A Phase 1b/2 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ociperlimab (BGB-A1217) in Combination With Tislelizumab (BGB-A317) or Rituximab in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma
Phase: PHASE1
Conditions: Relapsed Diffuse Large B-cell Lymphoma, Refractory Diffuse Large B-cell Lymphoma
Sponsor: BeiGene

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 1 
CLINICAL STUDY PROTOCOL 
TITLE PAGE  
Protocol Title:  
A Phase 1b/2 Study Investigating the Safety, Tolerability, 
Pharmacokinetics, and Preliminary Antitumor Activity of 
Ociperlimab (BGB-A1217) in Combination With Tislelizumab 
(BGB-A317) or Rituximab in Patients With Relapsed or Refractory 
Diffuse Large B-Cell Lymphoma 
Protocol Number: 
AdvanTIG-101 
Phase: 
1b/2 
Investigational Product(s): 
Ociperlimab (BGB-A1217), Tislelizumab (BGB-A317), and 
Rituximab 
Proposed Indication(s): 
Diffuse Large B-Cell Lymphoma 
Sponsor: 
BeiGene, Ltd. 
c/o BeiGene USA, Inc. 
1840 Gateway Drive 
3rd Floor  
San Mateo, CA 94404 USA  
 
BeiGene (Guangzhou) Biologics Manufacturing Co., Ltd. 
No. 83 South Kangyao Road 
Huangpu District 
Guangzhou, P.R. China 
 
Sponsor Medical Monitor: 
 
Telephone: 
 
Email: 
 
Original Protocol Version 0.0: 
Protocol Amendment 1.0: 
Protocol Amendment 2.0: 
Protocol Amendment 3.0: 
24 September 2021 
02 September 2022 
15 June 2023 
22 May 2024 
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 
confidential 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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 2 
FINAL PROTOCOL APPROVAL SHEET  
A Phase 1b/2 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary 
Antitumor Activity of Ociperlimab (BGB-A1217) in Combination With Tislelizumab 
(BGB-A317) or Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell 
Lymphoma 
BeiGene (Guangzhou) Biologics Manufacturing Co., Ltd., Approval: 
 
See electronic signature 
Development Core Team Lead 
 
See electronic signature 
Date 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 3 
INVESTIGATOR SIGNATURE PAGE  
 
Protocol Title: 
A Phase 1b/2 Study Investigating the Safety, Tolerability, 
Pharmacokinetics, and Preliminary Antitumor Activity of Ociperlimab 
(BGB-A1217) in Combination With Tislelizumab (BGB-A317) or 
Rituximab in Patients With Relapsed or Refractory Diffuse Large 
B-Cell Lymphoma 
Protocol Identifier: 
AdvanTIG-101 
 
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 prior to 
implementation of this sponsor-approved protocol. 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: 
_______________________________ 
 
_______________________________ 
 
_______________________________ 
 
_______________________________ 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 4 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
FINAL PROTOCOL APPROVAL SHEET ....................................................................................2 
INVESTIGATOR SIGNATURE PAGE .........................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES .........................................................................................................................11 
LIST OF FIGURES .......................................................................................................................11 
SYNOPSIS ....................................................................................................................................12 
LIST OF ABBREVIATIONS AND TERMS ................................................................................22 
1. 
INTRODUCTION AND RATIONALES ..................................................................24 
1.1. 
Introduction .................................................................................................................24 
1.1.1. 
Diffuse Large B-Cell Lymphoma ...............................................................................24 
1.1.2. 
Current Treatment of DLBCL ....................................................................................24 
1.1.3. 
Anti-PD-1 Inhibitors in DLBCL .................................................................................25 
1.2. 
Ociperlimab as a TIGIT Inhibitor ...............................................................................26 
1.2.1. 
Nonclinical Summary .................................................................................................26 
1.2.1.1. 
Pharmacology .............................................................................................................26 
1.2.1.2. 
Toxicology ..................................................................................................................27 
1.2.2. 
Prior Clinical Experience With Ociperlimab ..............................................................27 
1.2.2.1. 
Clinical Pharmacology ................................................................................................27 
1.2.2.2. 
Safety Assessment of Ociperlimab .............................................................................28 
1.2.2.3. 
Preliminary Efficacy Profile .......................................................................................29 
1.3. 
Tislelizumab as a PD-1 Inhibitor ................................................................................30 
1.3.1. 
Nonclinical Summary .................................................................................................30 
1.3.1.1. 
Pharmacology .............................................................................................................30 
1.3.1.2. 
Toxicology ..................................................................................................................30 
1.3.2. 
Prior Clinical Experience With Tislelizumab .............................................................31 
1.3.2.1. 
Clinical Pharmacology ................................................................................................31 
1.3.2.2. 
Pooled Safety Assessment of Tislelizumab Monotherapy in Solid Tumors ..............31 
1.3.2.3. 
Pooled Safety Assessment of Tislelizumab Monotherapy in Hematological 
Malignancies ...............................................................................................................32 
1.3.3. 
Regulatory Status ........................................................................................................33 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 5 
1.4. 
Rituximab as a CD20 Inhibitor ...................................................................................35 
1.5. 
Study Rationale ...........................................................................................................35 
1.5.1. 
Rationale for the Selection of Ociperlimab Dose .......................................................35 
1.5.2. 
Rationale for Selection of Tislelizumab Dose ............................................................36 
1.5.3. 
Rationale for the Combination of Ociperlimab and Tislelizumab in the 
Treatment of DLBCL With PD-L1 Positive ...............................................................36 
1.5.4. 
Rationale for Ociperlimab and Rituximab in the Treatment of DLBCL ....................37 
1.5.5. 
Rationale for Biomarker Strategy ...............................................................................38 
1.6. 
Benefit-Risk Assessment ............................................................................................39 
1.7. 
Study Conduct ............................................................................................................40 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................41 
3. 
STUDY DESIGN .......................................................................................................43 
3.1. 
Summary of Study Design ..........................................................................................43 
3.2. 
Details of Dose Confirmation .....................................................................................46 
3.2.1. 
Starting Dose and Dose Confirmation Approach .......................................................46 
3.2.2. 
Rules for Dose Confirmation ......................................................................................46 
3.2.3. 
Assessment of Dose-Limiting Toxicity ......................................................................47 
3.2.4. 
Dose-Limiting Toxicity Definition .............................................................................47 
3.2.5. 
Recommended Phase 2 Dose Confirmation ...............................................................48 
3.3. 
Details of Dose Expansion ..........................................................................................48 
4. 
STUDY POPULATION .............................................................................................50 
4.1. 
Inclusion Criteria ........................................................................................................50 
4.2. 
Exclusion Criteria .......................................................................................................51 
5. 
STUDY TREATMENT ..............................................................................................54 
5.1. 
Formulation, Packaging, and Handling ......................................................................54 
5.1.1. 
Ociperlimab ................................................................................................................54 
5.1.2. 
Tislelizumab ...............................................................................................................54 
5.1.3. 
Rituximab ...................................................................................................................54 
5.2. 
Dosage, Administration, and Compliance ..................................................................55 
5.2.1. 
Dose Confirmation Stage ............................................................................................55 
5.2.2. 
Dose Expansion Stage ................................................................................................56 
5.3. 
Incorrect Administration or Overdose ........................................................................56 
5.4. 
Dose Delay or Modification .......................................................................................56 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 6 
5.4.1. 
Dose Interruption or Delay for Ociperlimab, Tislelizumab, and Rituximab ..............56 
5.4.2. 
Dose Modification for Ociperlimab, Tislelizumab, and Rituximab ...........................57 
6. 
PRIOR AND CONCOMITANT THERAPY .............................................................58 
6.1. 
Prior Therapy ..............................................................................................................58 
6.2. 
Permitted Concomitant Medications/Procedures .......................................................58 
6.3. 
Prohibited Concomitant Medications/Procedures ......................................................59 
7. 
STUDY PERIODS, VISITS, OR PROCEDURES ....................................................60 
7.1. 
Screening Period .........................................................................................................60 
7.1.1. 
Informed Consent and Screening Log ........................................................................60 
7.1.2. 
Patient Numbering ......................................................................................................60 
7.2. 
Enrollment ..................................................................................................................60 
7.3. 
Treatment Period ........................................................................................................61 
7.4. 
Follow-up Periods .......................................................................................................61 
7.4.1. 
Safety Follow-up Period .............................................................................................61 
7.4.2. 
Efficacy Follow-up Period ..........................................................................................61 
7.4.3. 
Survival Follow-up .....................................................................................................61 
7.4.4. 
Lost to Follow-up .......................................................................................................61 
7.5. 
Discontinuation From Study Treatment or From the Study .......................................62 
7.5.1. 
Patient Discontinuation From Study Treatment (End of Treatment for an 
Individual Patient) ......................................................................................................62 
7.5.2. 
Patient Discontinuation From the Study (End of Study for an Individual 
Patient) ........................................................................................................................62 
7.6. 
End of Study ...............................................................................................................63 
7.6.1. 
Management and Monitoring for Patients Remaining on Treatment After 
Study Termination ......................................................................................................64 
8. 
STUDY ASSESSMENTS ..........................................................................................65 
8.1. 
Screening Assessments ...............................................................................................65 
8.1.1. 
Pulmonary Function Tests ..........................................................................................65 
8.2. 
Safety Assessments .....................................................................................................65 
8.2.1. 
Vital Signs ..................................................................................................................65 
8.2.2. 
Physical Examinations ................................................................................................66 
8.2.3. 
Ophthalmologic Examination .....................................................................................66 
8.2.4. 
Eastern Cooperative Oncology Group Performance Status ........................................66 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 7 
8.2.5. 
Laboratory Safety Tests ..............................................................................................66 
8.2.5.1. 
Cardiac Enzyme Monitoring .......................................................................................67 
8.2.6. 
Electrocardiograms .....................................................................................................67 
8.2.7. 
Echocardiogram/Multiple Gated Acquisition Scan ....................................................67 
8.2.8. 
Adverse Events ...........................................................................................................67 
8.2.9. 
Hepatitis B and Hepatitis C Testing ...........................................................................68 
8.3. 
Tumor and Response Evaluations ..............................................................................68 
8.4. 
Bone Marrow Examination .........................................................................................69 
8.5. 
Quantitative Serum Immunoglobulin Assessment .....................................................70 
8.6. 
Pharmacokinetic Assessment and Antidrug Antibody Testing ..................................70 
8.7. 
Biomarkers ..................................................................................................................70 
8.8. 
Visit Windows ............................................................................................................71 
8.9. 
Unscheduled Visits .....................................................................................................71 
9. 
SAFETY MONITORING AND REPORTING .........................................................72 
9.1. 
Risks Associated With Study Drug ............................................................................72 
9.1.1. 
Risks Associated With Ociperlimab and Tislelizumab ..............................................72 
9.1.2. 
Risks Associated With Rituximab ..............................................................................72 
9.2. 
General Plan to Manage Safety Concerns ..................................................................72 
9.2.1. 
Eligibility Criteria .......................................................................................................72 
9.2.2. 
Abnormal Liver Function Tests ..................................................................................73 
9.2.3. 
Safety Monitoring Plan ...............................................................................................73 
9.3. 
Adverse Events ...........................................................................................................74 
9.3.1. 
Definitions and Reporting ...........................................................................................74 
9.3.2. 
Assessment of Severity ...............................................................................................74 
9.3.3. 
Assessment of Causality .............................................................................................75 
9.3.4. 
Follow-up of Adverse Events .....................................................................................76 
9.3.5. 
Laboratory Test Abnormalities ...................................................................................76 
9.4. 
Definition of a Serious Adverse Event .......................................................................77 
9.5. 
Suspected Unexpected Serious Adverse Reaction .....................................................77 
9.6. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ...........................................................................................................78 
9.6.1. 
Adverse Event Recording Period ................................................................................78 
9.6.2. 
Reporting Serious Adverse Events .............................................................................79 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 8 
9.6.2.1. 
Prompt Reporting of Serious Adverse Events ............................................................79 
9.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report ........................80 
9.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events .............................80 
9.6.3. 
Eliciting Adverse Events ............................................................................................81 
9.6.4. 
Progressive Disease ....................................................................................................81 
9.6.5. 
Deaths .........................................................................................................................81 
9.6.6. 
Recording Pregnancies ...............................................................................................81 
9.6.7. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Independent Ethics Committees ................................................81 
9.6.8. 
Assessing and Recording Immune-Mediated Adverse Events ...................................82 
9.6.9. 
Recording Infusion-Related Reactions .......................................................................82 
9.7. 
Management of Adverse Events of Special Interest ...................................................82 
9.7.1. 
Managing Infusion-Related Reactions .......................................................................82 
9.7.2. 
Severe Hypersensitivity Reactions and Flu-Like Symptoms .....................................84 
9.7.3. 
Immune-Mediated Adverse Events ............................................................................84 
9.7.4. 
Management of Immune-mediated AEs in Patients With Pre-Existing Renal 
Dysfunction .................................................................................................................85 
10. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION .................87 
10.1. 
Statistical Analysis ......................................................................................................87 
10.1.1. 
Analysis Sets ...............................................................................................................87 
10.1.2. 
Patient Disposition ......................................................................................................87 
10.1.3. 
Demographic and Other Baseline Characteristics ......................................................87 
10.1.4. 
Prior and Concomitant Medications ...........................................................................87 
10.2. 
Efficacy Analyses .......................................................................................................88 
10.3. 
Safety Analyses ..........................................................................................................89 
10.3.1. 
Extent of Exposure .....................................................................................................89 
10.3.2. 
Adverse Events ...........................................................................................................89 
10.3.3. 
Laboratory Analyses ...................................................................................................90 
10.3.4. 
Vital Signs ..................................................................................................................90 
10.3.5. 
Electrocardiograms .....................................................................................................90 
10.3.6. 
Eastern Cooperative Oncology Group (ECOG) Performance Status .........................90 
10.4. 
Pharmacokinetic Analyses ..........................................................................................90 
10.5. 
Immunogenicity Analyses ..........................................................................................91 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 9 
10.6. 
Other Exploratory Analyses .......................................................................................91 
10.7. 
Sample Size Consideration .........................................................................................91 
10.8. 
Interim Analyses .........................................................................................................91 
11. 
STUDY COMMITTEES ............................................................................................93 
11.1. 
Safety Monitoring Committee ....................................................................................93 
12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ...............................................................................................94 
12.1. 
Access to Information for Monitoring ........................................................................94 
12.2. 
Access to Information for Auditing or Inspections ....................................................94 
13. 
QUALITY ASSURANCE AND QUALITY CONTROL .........................................95 
13.1. 
Regulatory Authority Approval ..................................................................................95 
13.2. 
Quality Assurance .......................................................................................................95 
13.3. 
Study Site Inspections.................................................................................................95 
13.4. 
Drug Accountability ...................................................................................................95 
14. 
ETHICS/PROTECTION OF HUMAN PATIENTS ..................................................97 
14.1. 
Ethical Standard ..........................................................................................................97 
14.2. 
Institutional Review Board/Independent Ethics Committee ......................................97 
14.2.1. 
Protocol Amendments ................................................................................................97 
14.3. 
Informed Consent .......................................................................................................98 
14.4. 
Patient and Data Confidentiality .................................................................................98 
14.5. 
Financial Disclosure .................................................................................................100 
15. 
DATA HANDLING AND RECORD KEEPING ....................................................101 
15.1. 
Data Collection and Management Responsibilities ..................................................101 
15.1.1. 
Data Entry in the Electronic Case Report Form .......................................................101 
15.1.2. 
Data Collection .........................................................................................................101 
15.1.3. 
Data Management/Coding ........................................................................................101 
15.2. 
Study Records Retention ..........................................................................................102 
15.3. 
Protocol Deviations ..................................................................................................103 
15.4. 
Study Report and Publications..................................................................................103 
15.5. 
Study and Study Center Closure ...............................................................................103 
15.6. 
Information Disclosure and Inventions ....................................................................104 
16. 
REFERENCES .........................................................................................................106 
17. 
APPENDICES ..........................................................................................................112 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 10 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ..................................................................113 
APPENDIX 2. CLINICAL LABORATORY ASSESSMENTS ..............................................123 
APPENDIX 3. EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
STATUS ...................................................................................................................124 
APPENDIX 4. PRE-EXISTING IMMUNE DEFICIENCIES OR AUTOIMMUNE 
DISEASES ................................................................................................................125 
APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL,” “NO CHILDBEARING 
POTENTIAL” ...........................................................................................................126 
APPENDIX 6. NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION ..................................................................................................128 
APPENDIX 7. COCKCROFT-GAULT FORMULA ...............................................................129 
APPENDIX 8. LUGANO CLASSIFICATION FOR NON-HODGKIN LYMPHOMA .........130 
APPENDIX 9. IMMUNE-MEDIATED ADVERSE EVENT EVALUATION AND 
MANAGEMENT .....................................................................................................133 
APPENDIX 10. DRUGS WITH A KNOWN RISK OF QT 
PROLONGATION/TORSADES DE POINTES .....................................................154 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 11 
LIST OF TABLES 
Table 1: 
Planned Dose Levels for Ociperlimab, Tislelizumab, and Rituximab .......................55 
Table 2: 
Administration of Ociperlimab, Tislelizumab, and Rituximab and 
Monitoring Time .........................................................................................................55 
Table 3: 
Guidance for Duration of Recording New or Worsening Adverse Events in 
Cohort 1 and Cohort 2 ................................................................................................79 
Table 4: 
Timeframes and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee .............................................................................79 
Table 5: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due 
to Study Drug(s) .........................................................................................................83 
Table 6: 
Examples of Immune-Mediated Adverse Events .......................................................85 
 
LIST OF FIGURES  
Figure 1: 
Cycle 1 and 5 Mean (+ SD) Serum Concentration-Time Profiles of 
Ociperlimab in Study AdvanTIG-105 ........................................................................28 
Figure 2: 
Study Schema .............................................................................................................45 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 12 
SYNOPSIS  
Name of Sponsor/Company: BeiGene, Ltd.  
BeiGene (Guangzhou) Biologics Manufacturing Co., Ltd. 
Investigational Product(s): Ociperlimab (also known as BGB-A1217), Tislelizumab (also known as 
BGB-A317), and Rituximab 
Title of Study: A Phase 1b/2 Study Investigating the Safety, Tolerability, Pharmacokinetics, and 
Preliminary Antitumor Activity of Ociperlimab (BGB-A1217) in Combination With Tislelizumab 
(BGB-A317) or Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma 
Protocol Identifier: AdvanTIG-101 
Phase of Development: 1b/2 
Number of Patients: Approximately 66 to 80 patients in total 
Cohort 1 (patients with programmed cell death ligand-1 [PD-L1] positive on the surface of tumor cells 
for both Dose Confirmation and Dose Expansion Stages): Approximately 43 to 50 patients 
Cohort 2 (patients with PD-L1 negative on the surface of tumor cells for Dose Confirmation Stage and 
relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) patients regardless of PD-L1 
expression for Dose Expansion Stage): Approximately 23 to 30 patients  
Study Centers: Approximately 15 centers in China 
Study Objectives 
Primary: 
• 
To assess the safety and tolerability of ociperlimab (also known as BGB-A1217) in 
combination with tislelizumab (also known as BGB-A317) or rituximab in patients with 
R/R DLBCL 
• 
To confirm the recommended Phase 2 dose (RP2D) of ociperlimab when administered in 
combination with tislelizumab or rituximab in patients with R/R DLBCL 
Secondary: 
• 
To assess the preliminary antitumor activity of ociperlimab in combination with 
tislelizumab or rituximab in patients with R/R DLBCL as measured by 
investigator-assessed response using the Lugano Classification (2014) (as described in 
Section 10.2) 
• 
To characterize the pharmacokinetics (PK) of ociperlimab in combination with 
tislelizumab or rituximab 
• 
To assess the host immunogenicity to ociperlimab in combination with tislelizumab or 
rituximab 
Exploratory: 
• 
To explore the correlation of PD-L1 expression level and the preliminary antitumor 
activity of ociperlimab in combination with tislelizumab 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 13 
• 
To characterize the exploratory biomarkers and their association with preliminary 
antitumor activity of ociperlimab in combination with tislelizumab or rituximab 
Study Endpoints 
Primary: 
• 
Adverse events (AEs) and serious adverse events (SAEs) as characterized by type, 
frequency, severity (as graded by National Cancer Institute-Common Terminology Criteria 
for Adverse Events [NCI-CTCAE] Version 5.0), seriousness, and relationship to study 
drug(s); physical examinations, electrocardiograms (ECGs), laboratory abnormalities, and 
changes in laboratory assessments as needed; and AEs meeting protocol-defined dose-
limiting toxicity (DLT) criteria 
• 
RP2D of ociperlimab when administered in combination with tislelizumab or rituximab 
Secondary: 
• 
To evaluate the preliminary antitumor activity of ociperlimab in combination with 
tislelizumab or rituximab in patients with R/R DLBCL as measured by 
investigator-assessed response using the Lugano Classification (2014) (as described in 
Section 10.2) as measured by:  
– 
Overall response rate (ORR) 
– 
Complete response (CR) rate 
– 
Duration of response (DOR) 
– 
Time to response (TTR) 
– 
Progression-free survival (PFS) 
– Overall survival (OS) 
• 
Serum concentration and PK parameters (as appropriate) of ociperlimab in combination 
with tislelizumab or rituximab  
• 
Immunogenic responses to ociperlimab in combination with tislelizumab or rituximab, 
which will be evaluated through the detection of antidrug antibodies (ADAs) 
Exploratory: 
• 
Evaluate PD-L1 expression in archival or fresh patient-derived tumor tissue samples at 
screening and its association with the preliminary antitumor activity of ociperlimab in 
combination with tislelizumab. 
• 
Evaluate biomarkers from patient-derived tumor tissue and/or blood (or blood derivative) 
samples obtained before, during, and/or after treatment, and their association with 
preliminary antitumor activity of ociperlimab in combination with tislelizumab or 
rituximab. Biomarkers may include expression of T cell immunoglobulin and 
immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), CD226, CD155, and 
CD112, PD-L1/2 gene alteration, Epstein-Barr virus (EBV) status, tumor 
microenvironment, immune-related gene expression profile, and gene mutation profile in 
tumor tissue; immune-cell quantification and phenotypes, cytokine profiling, 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 14 
immune-related gene expression profiling, and DNA/ circulating tumor DNA (ctDNA) 
sequencing in peripheral blood 
Study Design 
• 
This is a Phase 1b/2, open-label, Dose Confirmation, and dose-expansion study to evaluate 
the safety, tolerability, PK, and preliminary antitumor activity of ociperlimab in 
combination with tislelizumab or rituximab in patients with R/R DLBCL.  
• 
First, each cohort will conduct Dose Confirmation Stage to confirm the RP2D of 
ociperlimab. Then, the confirmed RP2D will be implemented in Dose Expansion Stage. 
• 
Eligible patients will be allocated to 2 cohorts:  
− 
Cohort 1: R/R DLBCL patients with positive PD-L1 on the surface of tumor cells 
(with any expression level identified by local laboratory by immunohistochemistry) 
will receive ociperlimab in combination with tislelizumab 
− 
Cohort 2: R/R DLBCL patients with negative PD-L1 on the surface of tumor cells (for 
Dose Confirmation Stage) identified by local laboratory by immunohistochemistry and 
R/R DLBCL patients regardless of PD-L1 expression (for Dose Expansion Stage) will 
receive ociperlimab in combination with rituximab 
• 
Dose Confirmation Stage: Ociperlimab will be tested at the dose level of 900 mg initially. 
If ociperlimab 900 mg exceeds the maximum tolerated dose, ociperlimab 600 mg will be 
tested. Other dose levels of ociperlimab (eg, lower than 600 mg) may be explored to 
confirm the optimal dose level of ociperlimab in combination with tislelizumab or 
rituximab per the Safety Monitoring Committee’s (SMC’s) recommendation considering 
the totality of emerging data. The dose of tislelizumab and rituximab will be fixed at 200 
mg and 375 mg/m2, respectively. Every treatment cycle contains 21 days, and the 
combination regimen will be administrated intravenously on Day 1 of each cycle.  
Patients in both Cohort 1 and Cohort 2 will be monitored for DLTs for the first cycle 
(starting from the first dose of study treatment and ending on C1D21). RP2D confirmation 
will occur in accordance with the modified 3 + 3 principles.  
The RP2D of combination therapy will be confirmed from safety, tolerability, and any 
other relevant and available data (eg, PK and efficacy data). 
• 
Dose Expansion Stage: After the RP2D of ociperlimab in combination with tislelizumab or 
rituximab is confirmed, further enrollment of both cohorts will commerce to their target 
sample size. For Cohort 1, approximately 40 patients will be enrolled at RP2D. One futility 
interim analysis will be planned when approximately 20 patients have been enrolled and 
have ≥ 1 post-baseline disease evaluation. The SMC along with the sponsor will make the 
decision of proceeding or not. To reflect the natural distribution across PD-L1 expression 
given a relatively small sample size at interim analysis, the number of eligible patients with 
PD-L1 expression ≤ 5% on the surface of tumor cells as determined by local laboratory 
will be capped to ≤ 50% of the first 20 patients enrolled, and the benefit-risk profile may 
also be evaluated by the SMC and sponsor for these patients. After the interim analysis, the 
number of these patients with PD-L1 expression ≤ 5% on the surface of tumor cells as 
determined by local laboratory may be further capped per the SMC’s recommendation 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 15 
considering the totality of emerging data. For Cohort 2, approximately a total of 
20 patients regardless of PD-L1 expression will be enrolled at RP2D (refer to 
Section 1.5.4).  
• 
Patients will continue to receive study drug until they meet a study treatment 
discontinuation criterion (see Section 7.5).  
The study schema is as follows: 
 
Abbreviations: D, Day; IV, intravenous; Q3W, once every 3 weeks; RP2D, recommended Phase 2 dose. 
Note: Refer to Section 3.1 for dose confirmation details. 
Study Assessments 
The schedule of study assessments for both Dose Confirmation and Dose Expansion Stages are 
provided in Appendix 1. Patients will be closely monitored for safety and tolerability throughout the 
study. 
Dose-Limiting Toxicity Definitions  
All AEs will be graded according to the NCI-CTCAE Version 5.0.  
A DLT is defined as 1 of the following toxicities occurring during the DLT assessment window (the 
first cycle of the study treatment, starting from the first dose of study treatment and ending on C1D21) 
and considered by the investigator to be related to ociperlimab and/or tislelizumab or rituximab without 
a clear alternative cause to study treatment. 
Hematologic: 
1. Grade 4 neutropenia lasting > 7 days 
2. ≥ Grade 3 febrile neutropenia  
3. Grade 3 thrombocytopenia with ≥ Grade 2 bleeding (including but not limited to central 
nervous system bleeding of any grade) 
4. Grade 4 thrombocytopenia lasting > 7 days 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 16 
5. ≥ Grade 4 anemia 
Nonhematologic: 
1. ≥ Grade 4 toxicity 
2. Grade 3 toxicity that is clinically significant and does not resolve to baseline or ≤ Grade 1 
within 7 days after optimal supportive care is initiated 
Note: The following AEs will not be considered DLTs: 
• 
Grade 3 endocrinopathy that is adequately controlled by hormonal replacement 
• 
Grade 3 rash 
• 
Grade 3 infusion-related AE that is transient (resolving within 6 hours of onset) 
• 
Grade 3 nausea, vomiting, or diarrhea lasting for ≤ 72 hours with adequate antiemetic 
and/or other supportive care 
• 
Fatigue lasting for ≤ 7 days 
• 
Electrolyte abnormality that lasts for ≤ 72 hours, is not clinically complicated, and resolves 
spontaneously or responds to convention medical interventions 
• 
Asymptomatic biochemical laboratory abnormalities resolve to Grade 1 or baseline 
≤ 7 days with or without medical interventions 
During the DLT assessment window, any other grade of AEs occurred which is assessed to be related 
to study drug and leads to dose discontinuation or interruption of any study drug (ociperlimab, 
tislelizumab, or rituximab) for > 7 days will also be considered DLTs after review by the SMC. 
Clinically important or persistent AEs that are not part of the DLT criteria (Section 3.2.4) may also be 
considered a DLT after review by the SMC in consultation with the investigators. Additionally, any 
clinically significant AEs that occur after the DLT assessment window (eg, late immune-mediated AE 
[imAE]) for a given dose level may be considered a DLT regarding decisions of subsequent dose level.  
Patients who are not DLT-evaluable may be replaced if needed.  
Tumor Assessments 
Tumor imaging will be performed ≤ 28 days before the first dose of study drug(s). Screening 
assessments must include both contrast computed tomography (CT) and positron emission 
tomography-CT (PET-CT) scans of the neck, chest, abdomen, and pelvis. During the study, contrast 
CT will be performed every 9 weeks (± 7 days), from Day 1 of Cycle 1, for the first 54 weeks; every 
18 weeks (± 7 days) for additional 54 weeks; then every 24 weeks thereafter based on the Lugano 
Classification (2014) (Cheson et al 2014). For patients who are positive for PET-CT scans at screening, 
PET-CT should be repeated at Week 9 (± 7 days), Week 18 (± 7 days), at time when confirming CR or 
progressive disease (PD), and as clinically indicated. 
If a patient is known to have a contraindication to CT contrast media or develops a contraindication 
during the study, a magnetic resonance imaging (MRI) should be performed but must be used 
consistently throughout the study.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 17 
For immune therapies such as ociperlimab and tislelizumab, pseudoprogression may occur due to 
immune-cell infiltration and other mechanisms leading to an apparent increase of existing tumor 
masses or appearance of new tumor lesions. Also, some patients may benefit from additional immune 
therapies despite evidence of PD. If radiographic PD is suspected by the investigator to reflect 
pseudoprogression and the clinical condition is stable, patients may continue treatment of study drugs 
as long as they meet the criteria below and until PD is confirmed by a repeated imaging ≥ 4 weeks later 
(but not exceeding 12 weeks from the initial documentation of PD): 
• 
Absence of clinical symptoms and signs of PD (including clinically significantly 
worsening of laboratory values) 
• 
Stable Eastern Cooperative Oncology Group (ECOG) Performance Status 
• 
Absence of rapid progression of disease or of progressive tumor at critical anatomical sites 
(eg, cord compression) that requires urgent alternative medical intervention 
Tumor assessment should continue as planned in patients until the patient begins a new antitumor 
therapy, experiences PD, withdraws consent, is lost to follow-up, dies, or until the study terminates, 
whichever occurs first. Clinical suspicion of disease progression at any time will require a physical 
examination and radiological confirmation to be performed promptly, rather than waiting for the next 
scheduled tumor assessment. 
Tumor assessments must be performed on schedule regardless of whether study treatment has been 
administered or withheld. That is, they should not be adjusted for delays in cycles.  
Bone Marrow Examinations 
Bone marrow biopsy and aspirate are required to assess bone marrow involvement of patients during 
the screening period, unless they have been performed within 60 days before the first dose of study 
drug and there has been no intervening therapy from the time of the biopsy/aspirate until the first dose 
of study drug. For patients who have evidence of bone marrow disease at screening, repeated bone 
marrow biopsy may not be needed if PET-CT shows bone marrow clearance at CR. 
Duration of Patient Participation:  
This study will consist of 5 periods: 
1. Screening Period will be performed ≤ 28 days before first dose of study drug(s).  
2. Treatment Period starts with the first study drug administration and ends when the patient is 
discontinued from study treatment for any reason. 
3. Safety Follow-up Period: Patients who permanently discontinue study drugs will be asked to 
return to the clinic for the Safety Follow-up Visit, which is required to be conducted 30 days 
(± 7 days) after the last dose of study drugs unless otherwise specified or before the initiation 
of subsequent anticancer therapy, whichever occurs first. Additional Safety Follow-up Visits at 
60, 90, 120, 180 days after the last dose of study drugs (the visits at 120-day and 180-day are 
only required for women of childbearing potential) are required (in clinic or over the phone, as 
needed based on the assessments required). Patients will be contacted by telephone to assess 
imAEs and relevant concomitant medications (ie, those associated with an imAE or any new 
anticancer therapy). These contacts should be conducted 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 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 18 
anticancer therapy. For women of childbearing potential, an additional visit to perform a 
pregnancy test will occur at approximately 120 days after the last dose of tislelizumab and 
ociperlimab and 180 days after the last dose of rituximab (see Appendix 5). 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. 
4. Efficacy Follow-up Period: Patients who discontinue study drug(s) for reasons other than PD 
(eg, toxicity) will continue to undergo tumor assessments following the original tumor 
assessment schedule until the patient experiences PD, withdraws consent, dies, or starts a 
subsequent anticancer therapy, or for any other reason listed in Section 7.5.2, whichever occurs 
first. 
5. Survival Follow-up: Patients will be followed for survival and to obtain information on 
subsequent anticancer therapy after discontinuation of study treatment via telephone calls, 
patient medical records, and/or clinic visits approximately every 12 weeks (± 14 days) after the 
Safety Follow-up Visit or as directed by the sponsor until death, withdrawal of consent, loss to 
follow-up, or study termination by sponsor. 
Study Population:  
Patients with histologically confirmed R/R DLBCL who have previously received ≥ 1 line of adequate 
systemic anti-DLBCL therapy (defined as an anti-CD20 antibody-based chemoimmunotherapy for 
≥ 2 consecutive cycles, unless patients had PD before Cycle 2) 
Key Eligibility Criteria: 
Adult patients (≥ 18 years of age, at the time of voluntarily signing of informed consent) with 
histologically confirmed DLBCL NOS (Not Otherwise Specified), or EBV+ DLBCL NOS or 
high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL 
histology (double/triple-hit lymphoma [DHL/THL]) with R/R disease before study entry. All patients 
should be ineligible for high dose therapy/hematopoietic stem cell transplantation. All patients are also 
required to demonstrate an ECOG Performance Status score of ≤ 2 and adequate organ function. 
Patients who have current or history of central nervous system lymphoma or histologically transformed 
lymphoma will be excluded from the study.  
Investigational Product, Dose, and Mode of Administration: 
Dose Confirmation: Tislelizumab (200 mg, for Cohort 1) or rituximab (375 mg/m2, for Cohort 2) will 
be intravenously administered first followed by ociperlimab (900 mg or 600 mg) on Day 1 of each 
21-day cycle (once every 3 weeks). Lower dose levels of ociperlimab may be evaluated while the 
dosing regimen of tislelizumab and rituximab will remain fixed. 
Dose Expansion: Tislelizumab (200 mg, for Cohort 1) or rituximab (375 mg/m2, for Cohort 2) will be 
intravenously administered first followed by ociperlimab (RP2D) on Day 1 of each 21-day cycle (once 
every 3 weeks). 
Statistical Methods: 
Analysis Sets: 
• 
The Safety Analysis Set includes all patients who received any dose of any study drug(s). 
This will be the analysis set for the safety analyses. 
• 
The Efficacy Analysis Set includes all patients who received any dose of any study 
drug(s), have evaluable disease at baseline, and have ≥ 1 evaluable postbaseline tumor 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 19 
response assessment unless any clinical PD or death occurred before the first postbaseline 
tumor assessment. 
• 
The DLT-Evaluable Analysis Set includes patients who 1) experienced a DLT event or 2) 
received ≥ 80% each of the assigned dose of ociperlimab in combination with tislelizumab 
or rituximab and remained on study during the DLT assessment window. 
• 
The PK Analysis Set includes all patients who received any dose of any study drug(s) per 
the protocol, for whom any quantifiable postdose PK concentrations are available. 
• 
The Immunogenicity Analysis Set includes all patients who received any dose of any study 
drug(s), for whom both baseline ADA and ≥ 1 postbaseline ADA results are available. 
Efficacy Analysis: 
Efficacy analyses in both dose confirmation and dose expansion will be conducted based upon the 
investigators’ tumor assessments in the Efficacy Analysis Set using the Lugano Classification (2014) 
(Cheson et al 2014), performed by cohort and dose if necessary, and summarized with below endpoints 
to evaluate the preliminary antitumor activities of ociperlimab in combination with tislelizumab or 
rituximab: 
• 
ORR is defined as the proportion of patients who have best response is CR or PR  
• 
CR rate is defined as the proportion of patients whose best response is CR  
• 
DOR is defined as the time from the first documentation of an overall response until the 
first documentation of progression or death, whichever comes first 
• 
TTR is defined as time from the starting date of the therapy to the date of the first 
documentation of an overall response 
• 
PFS is defined as the time from the date of the first dose of study drug(s) to the date of the 
first documentation of PD or death, whichever occurs first 
• 
OS is defined as the time from the starting date of the therapy to the date of death due to 
any causes 
ORR and CR rate will be summarized along with their 95% CI using the Clopper-Pearson method. 
Kaplan-Meier methodology will be used to estimate DOR/PFS/OS medians or other quartiles, and their 
95% CI will be constructed using the Brookmeyer and Crowley method. Kaplan-Meier curves will also 
be provided. DOR will be analyzed only in responders. 
TTR will be summarized only in responders using sample statistics, such as sample mean, median, and 
standard deviation. 
For patients in the Efficacy Analysis Set but with clinical PD or death occurring before the first 
postbaseline tumor assessment, their best overall response will be considered as PD or Not Assessable, 
respectively. Their documented date of PD or death will be used in the PFS/OS analyses accordingly as 
event time.  
All PD-L1-related subgroups analyses, where deemed necessary, will be conducted using the same 
method as above and based on centrally tested PD-L1 expression level. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 20 
Safety Analyses: 
Safety data will be summarized using the Safety Analysis Set and DLT-Evaluable Analysis Set and by 
cohort and dose if necessary. 
Safety will be determined by the spontaneous reporting of AEs and by laboratory values (hematology, 
clinical chemistry, coagulation, and urinalysis). Vital signs, physical examinations, and ECG findings 
will also be used in determining the safety profile. The severity of AEs will be graded according to 
NCI-CTCAE Version 5.0. The incidence of DLT events and treatment-emergent adverse events 
(TEAEs) will be reported as the number (percentage) of patients with TEAEs by the Medical 
Dictionary for Regulatory Activities (MedDRA) System Organ Class, Preferred Term, and worst 
grade. Descriptive summary statistics (eg, n, mean, standard deviation, median, minimum, and 
maximum for continuous variables; n [%] for categorical variables) and changes from baseline will be 
provided for laboratory parameters and vital signs. 
Pharmacokinetic Analyses: 
Serum concentration data and PK parameters (as appropriate) of ociperlimab and tislelizumab will be 
tabulated and summarized by visit/cycle for each treatment. Additional PK analyses may be conducted 
as appropriate. 
Sample Size Consideration: 
The study plans to enroll approximately 66 to 80 patients: 
• 
Cohort 1: Approximately 43 to 50 patients  
• 
Cohort 2: Approximately 23 to 30 patients  
For Cohort 1, the sample size of approximately 40 patients at RP2D is based on the precision of the 
estimate of ORR, a consideration that a relatively sufficient number of patients is needed to justify 
performing further analysis (eg, the subgroup analysis based on the cutoff value of tumor PD-L1 
expression), and a probability that is high enough to observe certain AEs of interest (eg, rash). With 
40 patients, if the observed ORR is 60%, the corresponding Clopper-Pearson 95% CI will be 43.3% to 
75.1%. One futility interim analysis for ORR is planned to be conducted when approximately 
20 patients have been enrolled with a futility boundary of 35% (equivalent to observe ≤ 7 responders). 
For an AE with a rate of 10%, there is 98.5%of probability to observe ≥ 1 event of such an AE among 
all 40 patients (multiple same AE on one patient will be counted only once). To reflect the natural 
distribution across PD-L1 expression given a relatively small sample size at interim analysis, the 
number of eligible patients with PD-L1 expression ≤ 5% on the surface of tumor cells as determined by 
local laboratory will be capped to ≤ 50% of the first 20 patients enrolled, and the benefit-risk profile 
may also be evaluated by the SMC and sponsor for these patients. After the interim analysis, the 
number of these patients with PD-L1 expression ≤ 5% on the surface of tumor cells as determined by 
local laboratory may be further capped per the SMC’s recommendation considering the totality of 
emerging data. Considering the patients in the Dose Confirmation Stage that are not dosed at RP2D 
dose level (approximately 3 to 10 patients), approximately 43 to 50 patients in total will be enrolled in 
Cohort 1. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 21 
For Cohort 2, the sample size of approximately 20 patients at RP2D is based on the precision of the 
estimate of ORR. With 20 patients, if the observed ORR is 60%, the corresponding Clopper-Pearson 
95% CI will be 36.1% to 80.9%. Considering the patients in the Dose Confirmation Stage that are not 
dosed at RP2D dose level (approximately 3 to 10 patients), approximately 23 to 30 patients in total will 
be enrolled in Cohort 2. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 22 
LIST OF ABBREVIATIONS AND TERMS  
Abbreviation 
Definition 
ADA 
antidrug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
auto-HCT 
autologous hematopoietic cell transplantation 
BGB-A1217 
ociperlimab 
BGB-A317 
tislelizumab 
CL 
clearance 
CR 
complete response 
CT 
computed tomography 
ctDNA 
circulating tumor DNA  
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EBV 
Epstein-Barr virus 
GCB 
germinal center B-cell-like 
GCP 
Good Clinical Practice 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IHC 
immunohistochemistry 
imAE 
immune-mediated adverse event 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 23 
Abbreviation 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCCN 
National Comprehensive Cancer Network 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse Events 
NHL 
non-Hodgkin lymphomas 
NSCLC 
non-small cell lung cancer 
ORR 
overall response rate 
OS 
overall survival 
PD 
progressive disease 
PD-1 
programmed cell death protein-1 
PD-L1 
programmed cell death ligand-1 
PD-L1 TC 
PD-L1 expression by tumor cells 
PET 
positron-emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
R-CHOP 
rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone 
R/R 
relapsed or refractory 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SMC 
Safety Monitoring Committee 
TEAE 
treatment-emergent adverse event 
TIGIT 
T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif 
(ITIM) domain 
ULN 
upper limit of normal 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 24 
1. 
INTRODUCTION AND RATIONALES  
1.1. 
Introduction  
1.1.1. 
Diffuse Large B-Cell Lymphoma  
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease with a 
variable clinical outcome (Susanibar-Adaniya and Barta 2021) and is the most common subtype 
of aggressive non-Hodgkin lymphomas (NHL) in the Western Countries, accounting for around 
31% of NHL cases in adults (Thandra et al 2021). There were 544,352 new cases of NHL and 
259,793 deaths resulting from this disease worldwide in 2020 (Sung et al 2021). The incidence 
rate for DLBCL is approximately 6.9 cases per 100,000 person-years (Teras et al 2016). Based 
on the study report of National Central Cancer Registry of China, an estimated of 88,200 new 
lymphoma cases and 52,100 lymphoma deaths occurred in China in 2015, ranked in the 12th and 
11th place among all cancer cases, respectively (Chen et al 2016). Two locally retrospective 
studies for NHL distributions in China showed that DLBCL made up about 29.1% and 40.9% of 
NHL, respectively (Liu et al 2011; Gross et al 2008). According to the current Surveillance 
Epidemiology and End Results (SEER) data, the median age at diagnosis is 66 years 
(SEER 2020).  
Accordingly, there are 3 subtypes of DLBCL: the germinal center B-cell-like (GCB) subtype 
with expression of normal germinal center B cells, the activated B-cell-like subtype with 
expression of post-germinal or activated B cells, and the unclassified subtype. The GCB and 
activated B-cell-like subtypes are essentially different entities and are characterized by 
differences in survival, disease biology, and gene expression (Wilson et al 2015). Patients in the 
GCB subtype have a higher 5-year survival rate compared with those in the activated B-cell-like 
subtype (60% versus 35%, respectively) (Rosenwald et al 2002; Alizadeh et al 2000).  
Originally proposed in 1993, the International Prognostic Index still remains as the primary 
clinical tool to predict clinical outcome for patients with DLBCL (International NHL Prognostic 
Factors Project 1993). The specific factors are age > 60 years, stage III or IV disease (per the 
Ann Arbor classification [Carbone et al 1971]), Eastern Cooperative Oncology Group (ECOG) 
Performance Status ≥ 2, elevated lactate dehydrogenase (LDH) levels, and extranodal 
involvement > 1 site. These factors are combined in the International Prognostic Index into 
4 categories, with a 5-year progression-free survival (PFS) ranging from 40% to 70% and a 
5-year overall survival (OS) ranging from 26% to 73% among patients treated with 
cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (Ziepert 2010).  
1.1.2. 
Current Treatment of DLBCL  
Historically, the addition of rituximab to a chemotherapy regimen of cyclophosphamide, 
doxorubicin, vincristine, and prednisone (R-CHOP) has significantly improved the clinical 
outcome (Coiffier et al 2002; Sehn et al 2005). Recently, the Phase III POLARIX study 
comparing polatuzumab vedotin in combination with chemotherapy regimen R-CHP versus the 
standard of care R-CHOP in treatment of first-line DLBCL met its primary endpoint by 
demonstrating significantly improved and clinically meaningful PFS (Roche Group 2021). 
However, 30% to 40% of patients with DLBCL eventually relapse and 10% of them are primary 
refractory, which remains as a consistent clinical problem (Flowers et al 2010).  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 25 
The standard approach has been proceeded toward salvage therapy and consolidation with 
autologous hematopoietic stem cell transplantation (auto-HCT) for patients with 
relapsed/refractory (R/R) DLBCL (Philip et al 1995). Approximately 20% to 30% of patients 
who received auto-HCT can get long-term remission, but at the cost of high toxicity and 
treatment-related mortality (Gisselbrecht et al 2010). Generally, relapse and refractory cases still 
pose highly unmet medical needs, especially in patients who are not eligible for intensive 
therapeutic strategies based on hematopoietic stem cell transplantation. Both the US National 
Comprehensive Cancer Network (NCCN) (NCCN 2023) and the European Society for Medical 
Oncology (ESMO) recommend inclusion in a clinical study whenever possible (Tilly et al 2015). 
1.1.3. 
Anti-PD-1 Inhibitors in DLBCL  
Immune surveillance plays a critical role in preventing tumor progression and metastasis. 
However, tumors have developed resistance mechanisms to suppress and/or escape the host 
immune system, thereby enabling tumorigenesis to proceed unchecked (Schreiber et al 2011; 
Swann and Smyth 2007). One such resistance mechanism involves upregulation of immune 
checkpoint receptors expressed on immune cells (eg, effector T cells), such as programmed cell 
death protein-1 (PD-1). It is known that programmed cell death ligand-1 (PD-L1) is often 
upregulated in various types of solid tumors associated with poor prognosis (Wu et al 2019) and 
anti-PD-1/anti-PD-L1 monoclonal antibodies are demonstrated to have obvious antitumor effects 
(Armand et al 2013; Brahmer et al 2012). 
One retrospective study assessed the expression of PD-L1 in 1253 DLBCL samples and analyzed 
the clinicopathological features of DLBCL with PD-L1 positive (PD-L1+). The prevalence rates 
of PD-L1+ (with a 30% threshold) and microenvironment PD-L1+ (mPD-L1+with a 20% 
threshold) DLBCL was 11% and 15.3%, respectively. Regarding OS, patients with PD-L1+ 
DLBCL had inferior OS compared with that in patients with PD-L1- DLBCL, while the 
expression of mPD-L1+ showed limited influence on OS. Thus, blockade of the PD-1/PD-L1 
pathway may have the potential to exert antitumor effects in certain subsets of DLBCL (Kiyasu 
et al 2015).  
A Phase II study evaluated the efficacy and safety of nivolumab in patients with R/R DLBCL 
who were ineligible for auto-HCT or who had experienced failure with auto-HCT. Among the 
121 treated patients, 87 patients in the auto-HCT-failed cohort and 34 patients in the 
auto-HCT-ineligible cohorts reached the overall response rates (ORR) of 10% and 3%, and 
median duration of response (DOR) of 11 and 8 months, respectively. There were 3 patients in 
the auto-HCT-failed cohort with a durable response of > 11 months. The median PFS and OS 
were 1.9 and 12.2 months in the auto-HCT-failed cohort and 1.4 and 5.8 months in the 
auto-HCT-ineligible cohort, respectively (Ansell et al 2019). 
ORR to anti-PD-1 therapy in unselected patients with R/R DLBCL is modest. These mixed 
outcomes likely reflect the heterogeneous nature of DLBCL. Studies suggest that if anti-PD-1 
therapy is to impact the management of DLBCL, then future efforts should be focused on 
developing predictive biomarkers that accurately identify subsets of patients likely to benefit.  
In a prospective KEYNOTE-013 study, among 29 R/R DLBCL patients, pembrolizumab has 
shown ORR of 13.8%. Interestingly, 2 of 3 patients with PD-L1 gene-altered DLBCLs achieved 
a clinical response to pembrolizumab. In contrast, only 2 of 26 patients with PD-L1-unaltered 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 26 
DLBCLs responded. Thus, the presence of PD-L1 alterations significantly enriched for response 
to pembrolizumab (P = 0.005). Positive PD-L1 protein expression (PD-L1 H score ≥ 30) also 
enriched for response (2 of 5 patients), although this did not reach statistical significance 
(P = 0.062) (Godfrey et al 2019). 
Among the 45 patients with R/R DLBCL, nivolumab in combination with ibrutinib showed an 
ORR of 36%. Measurable PD-L1 expression was seen in 13 (50%) of 26 samples from the 
DLBCL cohort, eight of which had elevated (≥ 5%) PD-L1 expression. In post-hoc analyses, 
5 (63%) of 8 patients with elevated (≥ 5%) PD-L1 expression achieved an ORR compared with 
3 (19%) of 16 without elevated expression of PD-L1, although this finding was not significant 
(P = 0.065) (Younes et al 2019).  
A combination therapy of pembrolizumab and R-CHOP was designed to explore the safety and 
preliminary efficacy in previously untreated patients with DLBCL. Among the 30 patients 
treated, the overall and complete response (CR) rates were 90% and 77%, respectively, and the 
2-year PFS was 83%. Furthermore, correlative analysis suggested that PD-L1 expression was 
associated with non-GCB subtype and improved PFS and OS, supporting PD-L1 as a biomarker 
to identify patients with DLBCL who may benefit from this anti-PD-1 inhibitor contained 
regimen (Smith et al 2020). 
1.2. 
Ociperlimab as a TIGIT Inhibitor  
1.2.1. 
Nonclinical Summary  
1.2.1.1. 
Pharmacology  
Ociperlimab (also known as BGB-A1217) is a humanized IgG1 monoclonal antibody against T 
cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain 
(TIGIT) under clinical development for the treatment of human malignancies. 
Ociperlimab binds to the extracellular domain of human TIGIT with high specificity and affinity 
(equilibrium dissociation constant [KD] = 0.135 nM), as demonstrated by target binding assays 
and surface plasmon resonance (SPR) characterization. Ociperlimab has shown antitumor 
activity in both the GL261 mouse glioma tumor model and the CT26WT mouse colon cancer 
model in humanized TIGIT knock-in mice. In the MC38 mouse colon cancer model in 
humanized TIGIT knock-in mice, ociperlimab in combination with antimouse PD-1 significantly 
inhibited tumor growth compared with either therapy alone. 
Ociperlimab has the constant region of a wild-type human immunoglobulin G1 (IgG1) to enable 
the Fc-mediated effector functions. Ociperlimab has demonstrated competent binding to C1q and 
all gamma Fc receptors (FcγRs) and induces antibody-dependent cellular cytotoxicity (ADCC) 
against a TIGIT overexpressing cell line, but no antibody-dependent cellular cytotoxicity or 
complement-dependent cytotoxicity against primary T effector cells in the cell-based assays. 
Cynomolgus monkeys and humanized TIGIT knock-in mice (ie, mice expressing the human 
TIGIT gene) were selected for nonclinical safety evaluation based on the homology of the TIGIT 
amino acid sequence, binding affinity, and efficacy studies. Ociperlimab inhibits GL261 tumor 
growth significantly in humanized TIGIT knock-in mice at doses ≥ 0.4 mg/kg administered once 
weekly. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 27 
Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for detailed information 
regarding pharmacology studies. 
1.2.1.2. 
Toxicology  
The toxicity and safety profile of ociperlimab was characterized in 4- and 13-week repeated-dose 
toxicity studies in humanized TIGIT knock-in mice and in a 13-week repeated-dose toxicity 
study in cynomolgus monkeys.  
No apparent toxicity was observed in the 4- or 13-week humanized TIGIT knock-in mouse 
studies or in the13-week cynomolgus monkey study. A dose-proportional increase in systemic 
exposure (area under the concentration-time curve [AUC] and maximum observed serum 
concentration [Cmax]) was noted in both species, without apparent sex difference, while 
excluding the impact of positive antidrug antibodies (ADAs) in individual animals with lower 
systemic exposure and/or faster clearance. No accumulation was observed in monkeys following 
once-every-2-weeks dosing for 13 weeks. A trend of accumulation was shown in mice following 
once-weekly dosing for 4 and 13 weeks. The no-observed-adverse-effect level (NOAEL) of 
ociperlimab was 50 mg/kg in mice and 100 mg/kg in monkeys, which were the highest doses 
tested in each species. 
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 (IHC) 
method. 
In an in vitro cytokine release assay using human peripheral blood mononuclear cells (PBMCs), 
ociperlimab did not induce significant increases in interferon gamma (IFN-γ), interleukin (IL)-2, 
IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, or granulocyte-macrophage colony-
stimulating factor (GM-CSF) as commonly seen in the “cytokine storm.” Selective induction of 
monocyte chemoattractant protein-1 (MCP-1) and IFN-γ-inducible protein 10 (IP-10) in PBMCs 
by ociperlimab were observed and were not considered to be a risk in causing acute cytokine 
release syndrome. 
The safety profile of ociperlimab was considered adequate to support human studies. 
Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for detailed information 
regarding toxicology studies. 
1.2.2. 
Prior Clinical Experience With Ociperlimab  
1.2.2.1. 
Clinical Pharmacology  
Preliminary pharmacokinetic (PK) data are available from a total of 52 patients in Phase 1 (dose 
escalation and dose verification in China) portion of Study AdvanTIG-105. In the dose escalation 
part, 32 patients were treated with ociperlimab at 50 mg, 150 mg, 450 mg, 900 mg, or 1800 mg 
dose levels on Day 1, and on Day 8 tislelizumab 200 mg once every 3 weeks was added for the 
first cycle. Cycle 2 was initiated on Day 28, and the dose regimen of once every 3 weeks was 
followed thereafter for the combination. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 28 
In the China dose verification part, 20 patients were treated with 900 mg ociperlimab, either as 
monotherapy (n = 9) or in combination with tislelizumab 200 mg (n = 11). 
Ociperlimab exposures increased approximately dose proportionally from the 50 mg dose to 
1800 mg dose for Cmax and AUC. There was minimal accumulation observed in Cycle 5 
following multiple doses. Across dose groups, serum concentrations of ociperlimab decreased in 
a biexponential manner after administration. The geometric mean terminal half-life estimate 
following the first dose ranged from approximately 7 days to 11 days. Postdose PK sampling 
duration may not be sufficient for robust characterization of elimination half-life using 
noncompartmental analysis (NCA); hence, the reported half-life values should be interpreted 
with caution. The mean serum concentration-time profiles of ociperlimab from dose escalation 
are shown in (Figure 1). 
As of 13 August 2023, treatment-emergent ADAs for ociperlimab at doses of 50 to 1800 mg 
once every 3 weeks have been observed for 0.3% (1 of 324) of ADA-evaluable patients.  
Peripheral TIGIT receptor occupancy data were available for 32 enrolled patients treated with 
ociperlimab at 50 mg, 150 mg, 450 mg, 900 mg, and 1800 mg dose levels in Study 
AdvanTIG-105. Complete TIGIT receptor occupancy (100%) at all tested dose levels was 
observed on CD8+, CD4+, and regulatory T cells in peripheral blood. 
Refer to the Ociperlimab (BGB-A1217) Investigator’s Brochure for detailed information on 
ociperlimab clinical PK and pharmacodynamics. 
Figure 1: 
Cycle 1 and 5 Mean (+ SD) Serum Concentration-Time Profiles of 
Ociperlimab in Study AdvanTIG-105  
 
Note: For the 1800 mg dose, only 3 concentrations were available on Day 28. 
1.2.2.2. 
Safety Assessment of Ociperlimab  
As of the data cutoff date of 28 July 2023, 729 patients had received at least one dose of 
ociperlimab, either as monotherapy (n = 9 patients), in combination with tislelizumab only 
(n = 370 patients), in combination with tislelizumab plus chemotherapy (n = 214 patients), in 
combination with tislelizumab plus concurrent chemoradiotherapy (n = 63 patients), in 
combination with tislelizumab plus BAT1706 (n = 62 patients), or in combination with rituximab 
(n = 11 patients) across a variety of tumor types. Refer to the Ociperlimab (BGB-A1217) 
Investigator’s Brochure for detailed information. 
Cycle 1
Cycle 5
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 29 
1.2.2.2.1. Treatment-Emergent Adverse Events Assessed as Related to Ociperlimab  
A total of 534 patients (73.3%) experienced adverse events assessed by the investigator as 
related to ociperlimab treatment, with 152 patients (20.9%) having experienced an event 
≥ Grade 3 in severity. 
The most frequently reported (≥ 10%) ociperlimab-related adverse events were rash (17.7%), 
pruritus (12.9%), aspartate aminotransferase (AST) increased (12.3%), alanine aminotransferase 
(ALT) increased (11.2%), and hypothyroidism (10.7%). The most frequently reported (≥ 3%) 
ociperlimab-related adverse event of ≥ Grade 3 was rash (3.0%). 
1.2.2.2.2. Treatment-Emergent Serious Adverse Events as Related to Ociperlimab  
Serious adverse events assessed by the investigator as related to ociperlimab treatment were 
experienced by 103 of 729 patients (14.1%). The most frequently reported (≥ 1%) ociperlimab-
related serious adverse events were immune-mediated lung disease (1.6%) and pneumonitis 
(1.1%). 
1.2.2.2.3. Treatment-Emergent Adverse Events Leading to Death as Related to 
Ociperlimab  
A total of 7 patients experienced adverse events leading to death that were assessed by the 
investigator as related to ociperlimab. Ociperlimab-related adverse event leading to death was 
experienced by a single patient each (1 of 729 patients; 0.1%). These were: blood creatine 
phosphokinase increased, cardiac failure, immune-mediated lung disease, multiple organ 
dysfunction syndrome, pneumonitis, septic shock, and upper gastrointestinal perforation. 
1.2.2.2.4. Immune-Mediated Adverse Events  
A total of 312 patients (42.8%) experienced immune-mediated adverse events, with 79 patients 
(10.8%) having experienced an event of ≥ Grade 3 in severity. The most frequently reported 
(≥ 10%) immune-mediated adverse events were rash (18.7%) and hypothyroidism (12.5%). The 
most frequently reported (≥ 3%) immune-mediated adverse event of ≥ Grade 3 was rash (3.3%). 
1.2.2.2.5. Infusion-Related Reactions  
A total of 79 patients (10.8%) experienced infusion-related reactions (IRRs), with 8 patients 
(1.1%) having experienced an event of ≥ Grade 3 in severity. The most frequently reported 
(≥ 1%) infusion-related reactions were chills (5.1%), pyrexia (4.7%), and dyspnoea (1.0%). 
Other important, but less common, IRRs experienced by patients included flushing (0.3%), 
palpitations (0.3%), urticaria (0.3%), anaphylactic reaction (0.1%), dizziness (0.1%), and 
infusion-related reaction (0.1%). The most frequently reported (≥ 0.5%) event of ≥ Grade 3 
infusion-related reactions was dyspnoea (0.5%). 
1.2.2.3. 
Preliminary Efficacy Profile  
As of the data cutoff date of 29 September 2022, a total of 30 evaluable patients had received 
ociperlimab in combination with tislelizumab 200 mg intravenously once every 3 weeks 
(Frentzas et al 2023). Ociperlimab doses consisted of 50 mg (1 patient), 150 mg (3 patients), 
450 mg (5 patients), 900 mg (16 patients), and 1800 mg (5 patients). Unconfirmed partial 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 30 
responses were observed in 3 patients (10.0% of the 30 efficacy-evaluable patients). Each patient 
had received a different dose of ociperlimab: 450 mg, 900 mg, or 1800 mg. The overall response 
rate was 10.0% (95% CI: 2.11% to 26.53%). The median duration of response was 3.6 months 
(95% CI: 2.8 months to not evaluable). Stable disease was observed in 12 patients (40.0%) 
(2 patients receiving ociperlimab 150 mg, 2 receiving 450 mg, 7 receiving 900 mg, and 
1 receiving 1800 mg). The disease control rate was 50.0% (95% CI: 31.30% to 68.70%). 
As of the data cutoff date of 05 April 2022, efficacy data from Study AdvanTIG-105 Dose 
Expansion Cohort 3 (a total of 39 evaluable patients with PD-L1 expression by tumor cells 
(PD-L1 TC) ≥ 1%, untreated metastatic squamous or non-squamous non-small cell lung cancer 
(NSCLC) received ociperlimab 900 mg plus tislelizumab 200 mg) were presented at the 2022 
meeting of the World Conference of Lung Cancer (Rajiv et al 2022). The unconfirmed objective 
response rate was 53.8% (95% CI: 37.2, 69.9); in patients with PD-L1 TC 1% to 49% and PD-L1 
TC ≥ 50%, the unconfirmed ORR was 44.0% and 71.4%, respectively. The overall disease 
control rate (DCR) was 89.7%; in patients with PD-L1 TC 1% to 49% and PD-L1 TC ≥ 50%, the 
DCR was 88.0% and 92.9%, respectively. The median DOR was not evaluable (NE), and the 
median PFS was 5.4 months (95% CI: 4.2, NE), with 5.2 months and 5.6 months in the PD-L1 
TC 1% to 49% and PD-L1 TC ≥ 50% subgroups, respectively. 
1.3. 
Tislelizumab as a PD-1 Inhibitor  
1.3.1. 
Nonclinical Summary  
1.3.1.1. 
Pharmacology  
Tislelizumab is a humanized, immunoglobulin G4 (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 
and affinity (dissociation constant [KD] = 0.15 nM). It competitively blocks binding of both 
PD-L1 and PD-L2, thus inhibiting PD-1-mediated negative signaling in T cells.  
In vitro assays with tislelizumab suggest either low or no antibody-dependent cellular 
cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity 
effects in humans (Labrijn et al 2009; Zhang et al 2018a). Tislelizumab was specifically 
engineered to abrogate these potential mechanisms of T cell clearance and potential resistance to 
anti-PD-1 therapy. 
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for additional details 
regarding nonclinical studies of tislelizumab. 
1.3.1.2. 
Toxicology  
The nonclinical toxicity and toxicokinetic 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 dosed once every 2 weeks for 13 weeks. Tissue cross-
reactivity in normal human and cynomolgus monkey frozen tissues was also evaluated.  In 
addition, the potential off-target binding of tislelizumab was screened using the Retrogenix 
microarray assay.  The single-dose regimens spanned from the intended human dose to 10-fold 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 31 
higher than the maximum of the intended human dose, and the repeated-dose regimens spanned 
to 3-fold higher than the maximum of the intended human dose. 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. Based on the Retrogenix cell microarray 
screening of more than 6400 different proteins, tislelizumab clearly exhibited relatively high 
selective binding to the intended target, PD-1 protein, and had weak binding to only one off 
target protein. 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 of tislelizumab in the 13-week monkey toxicity study was considered to be 
30 mg/kg. The toxicity profile of tislelizumab is considered adequate to support the current study 
of BGB-A317-A1217-101. 
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed 
information on the toxicology of tislelizumab. 
1.3.2. 
Prior Clinical Experience With Tislelizumab  
1.3.2.1. 
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 half-
life was estimated to be approximately 23.8 days, and the steady state is expected to be reached 
after 12 weeks.  
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed 
information on the clinical pharmacology of tislelizumab. 
1.3.2.2. 
Pooled Safety Assessment of Tislelizumab Monotherapy in Solid Tumors  
As of 27 October 2023, 2377 patients with solid tumors had been treated with tislelizumab 
monotherapy in 9 clinical studies. The patients in the pooled solid tumor monotherapy studies 
had a median treatment exposure duration of 4.0 months (range: 0 to 64 months) and median 
study follow-up duration of 11.9 months (range: 0 to 64 months).  
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed 
information on the clinical safety of tislelizumab. 
1.3.2.2.1. Treatment-Emergent Adverse Events Assessed as Related to Tislelizumab  
A total of 1690 (71.1%) patients experienced ≥ 1 treatment-related TEAE. The most commonly 
occurring (≥ 10%) treatment-related TEAEs were AST increased (14.5%) and ALT increased 
(13.0%). 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 32 
Three hundred and fifty-one patients (14.8%) experienced a tislelizumab-related TEAE of 
≥ Grade 3. The most commonly occurring (≥ 1%) ≥ Grade 3 TEAEs were AST increased (1.6%) 
and ALT increased (1.1%). 
1.3.2.2.2. Treatment-Emergent Serious Adverse Events as Related to Tislelizumab  
As of 27 October 2023, 245 (10.3%) patients experienced tislelizumab-related treatment-
emergent SAE. The most commonly occurring treatment-related SAE was pneumonitis (1.1%). 
All other events occurred in less than 1% of patients. 
1.3.2.2.3. Treatment-Emergent Adverse Events Leading to Death as Related to 
Tislelizumab  
A total of 22 (0.9%) patients experienced tislelizumab-related TEAE leading to death. The most 
commonly occurring tislelizumab-related TEAEs leading to death were hepatic failure (0.2%), 
and pneumonitis, death, multiple organ dysfunction syndrome, and pneumonia (0.1% each). All 
other events occurred in single patients. 
1.3.2.2.4. Immune-Mediated Adverse Events  
A total of 768 (32.3%) patients experienced immune-mediated adverse event (imAE), with 115 
(4.8%) patients having experienced an imAE of ≥ Grade 3 in severity. The most commonly 
occurring (≥ 1%) imAEs of any grade were hypothyroidism (10.9%), rash (8.8%), 
hyperthyroidism (4.4%), pneumonitis (3.2%), and rash maculo-papular (1.6%). The most 
commonly occurring (≥ 0.5%) ≥ Grade 3 imAEs were pneumonitis (0.8%) and rash (0.5%). 
1.3.2.2.5. Infusion-Related Reactions  
A total of 109 (4.6%) patients experienced IRR, with 4 (0.2%) patients having experienced IRR 
of ≥ Grade 3 in severity. The most commonly occurring (≥ 1%) IRRs were rash (2.3%) and 
infusion-related reaction (1.2%). 
1.3.2.3. 
Pooled Safety Assessment of Tislelizumab Monotherapy in Hematological 
Malignancies  
As of 27 October 2023, 192 patients with hematologic malignancies had been treated with 
tislelizumab monotherapy in 3 clinical studies. The patients in the pooled hematologic 
malignancies monotherapy studies had a median treatment exposure duration of 7.0 months 
(range: 1 to 39 months) and a median study follow-up duration of 20.7 months (range: 1 to 
39 months). 
Please refer to the Tislelizumab (BGB-A317) Investigator’s Brochure for more detailed 
information on the clinical safety of tislelizumab. 
1.3.2.3.1. Treatment-Emergent Adverse Events Assessed as Related to Tislelizumab  
A total of 153 (79.7%) patients experienced ≥ 1 treatment-related TEAE, with 38 (19.8%) 
patients having experienced TEAE of ≥ Grade 3. The most commonly occurring (≥ 10%) 
treatment-related TEAEs were pyrexia (26.6%), hypothyroidism (19.3%), and pruritus (11.5%). 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 33 
The most commonly occurring (≥ 2%) ≥ Grade 3 treatment-related TEAEs were anaemia (2.6%) 
as well as neutropenia, neutrophil count decreased, and pneumonia (2.1% each). 
1.3.2.3.2. Treatment-Emergent Serious Adverse Events as Related to Tislelizumab  
Thirty-six (18.8%) patients experienced tislelizumab-related treatment-emergent SAE. The most 
commonly occurring (≥ 1%) treatment-related SAEs were pneumonia and pyrexia (2.1%), and 
interstitial lung disease and pneumonitis (1.0% each). 
1.3.2.3.3. Immune-Mediated Adverse Events  
Seventy-four (38.5%) patients experienced imAE, with 8 (4.2%) patients having experienced 
imAE of ≥ Grade 3.  The most commonly occurring imAEs were hypothyroidism (20.3%), rash 
(6.8%), hyperthyroidism (3.6%), rash maculo-papular (3.1%), and pneumonitis (2.1%).  All 
other imAEs occurred in ≤ 2 patients. The most commonly occurring ≥ Grade 3 imAE was 
pneumonitis (1.0%). All other ≥ Grade 3 imAEs occurred in a single patient each. 
1.3.2.3.4. Infusion-Related Reactions  
Twenty-two (11.5%) patients experienced IRR, with none of them having experienced an IRR of 
≥ Grade 3. The most commonly occurring IRRs were rash (3.6%), chills (2.6%), and infusion-
related reaction, cytokine release syndrome, and eyelid oedema (1.0% each). All other IRRs 
occurred in a single patient each.  
1.3.2.3.5. Treatment-Emergent Adverse Events Leading to Death as Related to 
Tislelizumab  
Of the 192 patients in the hematologic malignancy group of pooled tislelizumab monotherapy 
studies, no patient experienced tislelizumab-related TEAE leading to death. 
1.3.3. 
Regulatory Status  
As of the data cutoff date of 27 October 2023, tislelizumab has been approved and is currently 
marketed in Europe, South Korea, China, and Macao, China, for various indications, including 
for solid tumor and hematologic malignancies. 
Tislelizumab is approved for the following indication in Europe: 
• for use in adult patients with unresectable locally advanced or metastatic esophageal 
squamous cell carcinoma (ESCC) after prior platinum-based chemotherapy 
Tislelizumab is approved for the following indication in South Korea: 
• for use in adult patients with unresectable, recurrent, locally advanced or metastatic 
ESCC who are unable to continue prior platinum-based chemotherapy or relapsed or 
progressed after administration 
Tislelizumab is approved for the following indications in China as well as in Macao, China, 
except for the first-line gastric/gastroesophageal junction adenocarcinoma and first-line ESCC 
indications: 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 34 
• for use in combination with paclitaxel plus carboplatin or paclitaxel for injection 
(albumin bound) plus carboplatin as first-line treatment in patients with unresectable, 
locally advanced, or metastatic squamous NSCLC (both China and Macao, China) 
• for use in combination with pemetrexed and platinum chemotherapy as first-line 
treatment in patients with unresectable, locally advanced, or metastatic nonsquamous 
NSCLC with EGFR genomic tumor aberrations negative or ALK genomic tumor 
negative status (both China and Macao, China) 
• for use in adult patients with locally advanced or metastatic nonsquamous NSCLC, 
with EGFR genomic tumor aberrations negative and ALK genomic tumor negative 
status, that has progressed after or did not tolerate prior platinum-based chemotherapy 
and in adult patients with locally advanced or metastatic squamous NSCLC, with 
EGFR and ALK negative or unknown status, that has progressed after or did not 
tolerate prior platinum-based chemotherapy (both China and Macao, China) 
• for use in patients with locally advanced or metastatic ESCC who have disease 
progression or are intolerant to first-line standard chemotherapy (both China and 
Macao, China) 
• for use in combination with gemcitabine and cisplatin as first-line treatment in 
patients with recurrent or metastatic nasopharyngeal cancer (both China and Macao, 
China) 
• for use in combination with fluoropyrimidine and platinum chemotherapy as first-line 
treatment of patients with locally advanced unresectable or metastatic gastric or 
gastroesophageal junction adenocarcinoma with PD-L1-high expression (China only) 
• for use in combination with paclitaxel and platinum- or fluoropyrimidine- and 
platinum-based chemotherapy as first-line treatment in patients with unresectable 
locally advanced, recurrent or metastatic ESCC (China only) 
In addition, the following indications are conditionally approved in China and Macao, China, 
based on data from single-arm pivotal clinical studies (1 study for each indication). Full approval 
of these indications depends on demonstration of a significant clinical benefit of tislelizumab 
over the standard of care in ongoing randomized confirmatory clinical studies: 
• treatment of patients with relapsed or refractory classical Hodgkin lymphoma who 
received ≥ 2 lines of systemic chemotherapy regimens 
• treatment of patients with locally advanced or metastatic urothelial carcinoma with 
PD-L1-high expression whose disease progressed during or after platinum-containing 
chemotherapy or have disease progression within 12 months of neoadjuvant or 
adjuvant treatment with platinum-containing chemotherapy 
• treatment of patients with hepatocellular carcinoma who have been previously treated 
with ≥ 1 systemic therapy 
• treatment of adult patients with advanced unresectable or metastatic microsatellite 
instability-high or mismatch-repair-deficient solid tumors, including patients with 
advanced colorectal cancer who had been treated with fluoropyrimidine, oxaliplatin, 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 35 
and irinotecan and patients with other advanced solid tumors who develop disease 
progression after prior treatment and have no satisfactory alternative treatment 
options.  
1.4. 
Rituximab as a CD20 Inhibitor  
Rituximab is a genetically engineered, chimeric murine/human monoclonal IgG1 kappa antibody 
directed against the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. 
Upon binding to CD20, rituximab mediates B cell lysis, with possible mechanisms of lysis 
including complement-dependent cytotoxicity (CDC) and ADCC. Most common AEs associated 
with rituximab (≥ 25%) in clinical trials for NHL were infusion reaction, fever, lymphopenia, 
chills, infection, and asthenia. Tumor lysis syndrome (TLS) can be associated with rituximab 
treatment in patients with NHL, with a high number of circulating malignant cells 
(≥ 25,000/mm3) or high tumor burden conferring a greater risk of TLS (Rituximab prescribing 
information 2021).  
Rituximab is currently approved in China for the treatment of CD20+ NHL, including the CD20+ 
DLBCL. 
1.5. 
Study Rationale  
1.5.1. 
Rationale for the Selection of Ociperlimab Dose  
The ociperlimab dose of 900 mg once every 3 weeks combined with tislelizumab 200 mg once 
every 3 weeks was selected as the RP2D for further investigation based on clinical safety, 
tolerability, PK, and pharmacodynamic data from the ongoing Phase 1/1b Study AdvanTIG-105.  
Complete TIGIT receptor occupancy was observed in circulating T cells in peripheral blood at 
all the tested doses of ociperlimab in Study AdvanTIG-105. However, the correlation between 
TIGIT receptor occupancy in the periphery and in tumor tissues is unknown. In a previous 
Phase 1 study of tiragolumab, another anti-TIGIT antibody, complete peripheral receptor 
occupancy was reached at the 30 mg dose level, but the clinical dose of 600 mg was determined 
as the RP2D, which was 20 times the 30 mg dose (Bendell et al 2020). Similarly, although 
complete peripheral receptor occupancy was observed at the 50 mg dose level of ociperlimab, 
the RP2D of 900 mg is approximately 20 times the dose of 50 mg, to ensure sufficient TIGIT 
receptor occupancy in the tumor tissue. 
As of 12 May 2021, a total of 3 patients were assessed to have a confirmed PR, including 
1 patient each in the 450 mg, 900 mg, and 1800 mg cohorts. Ociperlimab exposure in all 
3 patients with a PR is consistent with that expected at the 900 mg dose level. The confirmed 
DCRs observed in the 450 mg, 900 mg, and 1800 mg cohorts were 60% (3 of 5 patients), 64.3% 
(9 of 14 patients), and 60% (3 of 5 patients), respectively.  
Although the best overall response rate 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 patients enrolled in Study AdvanTIG-105 
• Exposure in all 3 patients with a PR was consistent with that expected at the 900 mg 
dose 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 36 
• Lack of sufficient information on the impact of immunogenicity on ociperlimab PK 
• An overall intent to minimize exposure overlap with doses < 450 mg. 
1.5.2. 
Rationale for Selection of Tislelizumab Dose  
The dosage of 200 mg intravenously once every 3 weeks was selected based on safety, efficacy, 
and PK assessments in the first-in-human Study BGB-A317_Study_001. A wide range of 
dosages were investigated in this study, including 2 mg/kg or 5 mg/kg on schedules of once 
every 2 weeks or once every 3 weeks. For the once-every-3-week schedule, a fixed dose of 
200 mg was also investigated, and was ultimately selected for the following reasons: 
• All dosages tested, including 200 mg once every 3 weeks, were tolerated. The MTD 
was not reached with dosages up to 10 mg/kg once every 2 weeks. The observed 
serum concentration after 200 mg dosing was within the range seen after the 2 mg/kg 
and 5 mg/kg dosing. 
• Preliminary clinical activity was observed at this dosage. 
• Exposure-response relationships were flat for ORR and safety endpoints across a 
variety of tumor types (data from studies BGB-A317_Study_001 and BGB-A317-102 
in solid tumors, and BGB-A317-203 in classical Hodgkin lymphomas). In addition, 
no clinically significant covariates were identified in population PK analysis. 
• Compared with doses based on patient’s body 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. 
1.5.3. 
Rationale for the Combination of Ociperlimab and Tislelizumab in the 
Treatment of DLBCL With PD-L1 Positive  
TIGIT and PD-1 function as immune checkpoint receptors in the overlapping regulation of 
immune tolerance. Blockade of the TIGIT receptor alone or in combination with PD-1/PD-L1 
blockade has been shown both in vitro and in vivo to rescue functionally “exhausted” T cells 
(Johnston et al 2014; Chauvin et al 2015). In mouse models, TIGIT blockade in combination 
with anti-PD-1/PD-L1 antibodies demonstrated significantly better antitumor efficacy than either 
monotherapy (Johnston et al 2014; Dixon et al 2018). Clinically, treatment with anti-TIGIT 
antibody in combination with anti-PD-1/PD-L1 therapy has the potential to be more effective 
than anti-PD-1/PD-L1 alone in metastatic NSCLC without prior checkpoint inhibitor therapy. 
The combination of tiragolumab plus atezolizumab reported an ORR of 31% and a PFS of 
5.42 months versus placebo plus atezolizumab with an ORR of 16% and a PFS of 3.58 months in 
first-line Stage IV NSCLC patients with PD-L1 Tumor Proportion Score ≥ 1% (Rodriguez-
Abreu et al 2020). Similarly, the vibostolimab plus pembrolizumab combination reported an 
unconfirmed and confirmed ORR of 29% and 24%, respectively, in patients with NSCLC who 
were untreated or had been treated with at least 1 line of platinum-containing chemotherapy and 
had not previously received anti-PD-1/PD-L1 therapy (Niu et al 2020).  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 37 
Gene expression analysis has previously verified upregulation of TIGIT and PD-L1 in DLBCL 
compared with normal controls (Laurent et al 2015). Characterization of coinhibitory receptor 
expression in intratumoral T cells from DLBCL revealed that both TIGIT and PD-1 were 
expressed at higher frequency than all other receptors (eg, T cell immunoglobulin domain and 
mucin domain-3 [TIM-3] and lymphocyte-activation-gene-3 [LAG-3]). The co-expression 
pattern of TIGIT and PD-1 not only contributes to impaired T cell effector function as tested by 
cytokine production, but also inhibits the antitumor activity of T cell through interaction with 
ligand-expressing tumor cells in DLBCL (CD155 and CD122 expression). All these indicate the 
value of combinatorial blockade of TIGIT and PD-1 in DLBCL and exploration for mechanisms 
of immune escape by characterizing the tumor microenvironment (Josefsson et al 2019).  
However, the limitation of single agent of anti-PD-1 is also observed in patients with 
R/R DLBCL, with the ORR of approximately 10%. A trend of increasing ORR and CR rate was 
observed in patients with high PD-L1 expression on the surface of tumor cells in a combination 
therapy of nivolumab and ibrutinib (Section 1.1.3). Given the tolerable and manageable safety 
profile of tislelizumab in DLBCL (Section 1.1.1) and the scientific rationale of synergistic 
antitumor effects between anti-TIGIT and anti-PD-1 therapies, the combination of ociperlimab 
and tislelizumab may bring significant clinical benefit in R/R DLBCL with PD-L1 positive and 
support further clinical development. 
1.5.4. 
Rationale for Ociperlimab and Rituximab in the Treatment of DLBCL   
As a monoclonal antibody with intact Fc effector function, rituximab can be responsible for 
rapidly killing tumor targets via FcγR-mediated ADCC or antibody-dependent cellular 
phagocytosis (ADCP), a short-term process mediated by natural killer cells and myeloid effector 
cells from innate immune system (Taylor and Lindorfer 2008, Minard-Colin et al 2008). Studies 
also reveal that the therapeutic function and long-term immune memory of rituximab require 
active crosstalk with adaptive immunity. Evidence in lymphoma patients suggests that rituximab 
can induce a strong antitumor vaccinal effect by priming antitumor T cell responses, resulting in 
durable response (Cartron et al 2004). Using a murine lymphoma model to express human CD20, 
CD4+ and CD8+ T cells are demonstrated to be required for anti-CD20 mAb-mediated 
long-term memory immune response (Abès et al 2010), and the mechanism of rituximab is 
proved to engage the macrophage for immediate ADCC and dendritic cells for long-term 
antitumor cellular immune response (DiLillo et al 2015). Furthermore, adaptive resistance is 
gradually developed through Treg accumulation in larger lymphomas; and blockade of CTLA-4 
can synergize with anti-CD20 treatment to overcome the resistance associated with adaptive 
immune response in advanced B cell lymphoma (Ren et al 2017).  
TIGIT is an immune checkpoint receptor primarily expressed on immune cells, such as T cells 
and natural killer (NK) cells. TIGIT plays a key role in promoting T cell exhaustion and 
maintaining immune tolerance, in both chronic viral infections and the tumor microenvironment 
(Johnston et al 2014). NK cells from TIGIT-deficient mice produce more IFNγ in the presence of 
poliovirus receptor (PVR)-expressing target cells (Li et al 2014). TIGIT blockade also prevents 
NK cell exhaustion and elicits potent antitumor immunity (Zhang et al 2018b). Therefore, TIGIT 
blockade may have potential to promote NK-cell activation against poliovirus receptor+ (PVR+) 
tumor cells and to synergize the therapeutic monoclonal antibody (such as rituximab) mediated 
ADCC activity.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 38 
TIGIT is also highly expressed on tumor infiltrated Treg cells (Joller et al 2014; Kurtulus et al 
2015). TIGIT-positive Treg cells demonstrated greater suppressive functions when compared to 
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 outcome upon immune checkpoint blockade 
(Fourcade et al 2018). Moreover, as a therapeutic monoclonal antibody with human IgG1, TIGIT 
blockade antibody is proved to be able to deplete suppressive TIGIThi Treg cells while spare 
TIGITlow/mid effector T cells in tumor microenvironment (Preillon et al 2021 and data on file). 
Thus, targeting TIGIT provides a potential strategy to rescue the immunosuppressive 
microenvironment, thereby inducing an efficient antitumor immune response.  
Rituximab is recommended as the backbone of R/R DLBCL treatment per treatment guidelines 
(NCCN 2023; Tilly et al 2015), ociperlimab may synergize with rituximab by enhancing 
T-cell/NK-cell activation and Treg depletion/inhibition to promote both immediate tumor killing 
and long-term memory immune response. Hence, ociperlimab is designed to be used in 
combination with rituximab in this study. 
At the Dose Confirmation Stage of Cohort 2 (in R/R DLBCL with PD-L1 negative), ociperlimab 
of 900 mg was confirmed by SMC as being safe and RP2D to be used in combination with 
rituximab, similar safety profile is expected in R/R DLBCL with PD-L1 positive population 
under this combination treatment.   
Based on the observed preliminary anticancer activity from the Dose Confirmation Stage of 
Cohort 2, in order to explore more potential treatment regimen and to potentially maximize 
clinical benefit for all R/R DLBCL patients, the target population in Cohort 2 is considered to 
extend to all R/R DLBCL patients regardless of PD-L1 expression at the Dose Expansion Stage. 
1.5.5. 
Rationale for Biomarker Strategy  
PD-L1 expression has been demonstrated to be positively correlated with response to anti-PD-1 
therapy across tumor types (Cristescu et al 2018). Although PD-L1 expression has not been 
widely approved to be a predictive factor for anti-PD(L)-1 treatment in patients with DLBCL. 
Higher PD-L1 expression was shown to be associated with better response and survival benefit 
(Section 1.1.3), indicating the potential role of PD-L1 in predicting response to anti-PD(L)-1 
therapies. In summary, these data support further exploration of the correlation of PD-L1 
expression with response to tislelizumab and ociperlimab. 
Meanwhile, mechanisms of resistance to immunotherapies are also not well understood and need 
more exploration. Identification of tumor and immune-related features associated with disease 
progression or acquired resistance to ociperlimab in combination with tislelizumab or rituximab 
may increase the understanding of disease pathobiology and provide biological evidence for the 
combination strategy. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 39 
Thus, for Cohort 1, archival or fresh tumor samples at screening will be collected for PD-L1 
expression analysis to explore its association with the preliminary efficacy of ociperlimab in 
combination with tislelizumab. Other biomarker analyses in tumor tissues will include the 
expression of TIGIT, CD226, CD155, and CD112, PD-L1/2 gene alteration, Epstein-Barr virus 
(EBV) status, tumor microenvironment, immune-related gene expression profile, and gene 
mutation profile to explore potential predictive and prognostic biomarkers and mechanisms of 
action and resistance.  
In addition, blood-based biomarkers will be analyzed, including immune-cell quantification and 
phenotypes, cytokine profiling, immune-related gene expression profiling, and DNA/circulating 
tumor DNA (ctDNA) sequencing. The association of these biomarkers with clinical response to 
ociperlimab in combination with tislelizumab or rituximab will be further explored. 
1.6. 
Benefit-Risk Assessment  
Patients with R/R DLBCL represent a population with high unmet medical needs: although 
R-CHOP in first-line treatment and auto-HCT in second-line treatment have significantly 
improved the survival and the recently released positive result of Phase III POLARIX study may 
impact the treatment landscape, patients who relapse after auto-HCT or are ineligible for 
auto-HCT have poor outcomes with limited treatment options. As discussed earlier 
(Section 1.1.3), although the clinical benefits of anti-PD-1 antibodies are limited in R/R DLBCL, 
patients with tumor PD-L1 positive may achieve improved survival after being treated with 
anti-PD-1 antibody as first-line treatment, supporting to identify PD-L1 as a biomarker for 
clinical benefit. The coexpressed PD-L1 and TIGIT in DLBCL lymphocytes are observed to 
correlate with inhibiting the antitumor activity of T cell, suggesting the potential value of 
combined blockade of TIGIT and PD-1 for R/R DLBCL (Section 1.1.3 and Josefsson et al 2019).  
The safety profile of tislelizumab monotherapy is similar across tumor types. There is no pattern 
in the incidence, severity, or causality of AEs to tislelizumab dose level. The safety profile for 
single-agent tislelizumab is similar to those observed with other PD-1 inhibitors.  
Based on the safety profile in 9 patients with ociperlimab monotherapy and 268 patients with 
ociperlimab in combination with tislelizumab as of 20 July 2022, ociperlimab in combination 
with tislelizumab was well tolerated and the toxicities were manageable, with no DLTs reported, 
most TEAEs were Grade 1 or Grade 2, and most ≥ Grade 3 TEAEs and all serious TEAEs were 
recovered. In addition, the RP2D of combination regimen has been determined to be 900 mg 
ociperlimab in combination with 200 mg tislelizumab once every 3 weeks.  
As has been shown for other anti-PD-1-based immune-oncology combinations, the risk of 
observing augmented safety signals remains. Therefore, a monitoring plan derived from the 
European Society for Medical Oncology and American Society for Clinical Oncology has been 
established to monitor, diagnose, and manage imAEs (Appendix 9).  
Rituximab has been used in clinical practice for more than 20 years. The well-established clinical 
efficacy and safety profiles drive its backbone role on DLBCL treatment. To maximize the 
clinical benefit in patients with PD-L1 negative, rituximab in combination with anti-TIGIT 
antibodies are expected to exert synergetic effect on relieving the immunosuppressive 
microenvironment (Section 1.5.4).  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 40 
In summary, there is a strong scientific rationale that the combined blockade of TIGIT and PD-1 
or CD20 may result in enhanced antitumor activity without a major increase in the risk of 
immune-mediated toxicities. The benefit/risk of the combination of ociperlimab and tislelizumab 
or rituximab is considered favorable. 
A SMC will be established to regularly monitor the safety of ociperlimab in combination of 
tislelizumab or rituximab. Refer to Section 8.2 and Section 9 for information regarding safety 
monitoring and considerations related to potential risk. 
Based on the historical data of prevalence of PD-L1 expression in patients with DLBCL through 
the literature research (Younes et al 2019; Smith et al 2020; Ansell et al 2019; Xing et al 2016; 
Sun et al 2019; Dong et al 2016; Hu et al 2017), the enrollment strategy of capping patients with 
PD-L1 expression ≤ 5% on the surface of tumor cells in Cohort 1 is adopted to secure that the 
small sample size of patients enrolled at interim analysis could reflect the natural distribution of 
patients with DLBCL across PD-L1 expression level as much as possible. The benefit-risk 
profile may also be evaluated by the SMC and sponsor for these patients. 
1.7. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 41 
2. 
STUDY OBJECTIVES AND ENDPOINTS  
Objectives 
Endpoints 
Primary 
To assess the safety and tolerability of 
ociperlimab in combination with tislelizumab or 
rituximab in patients with relapsed or refractory 
diffuse large B-cell lymphoma (R/R DLBCL) 
AEs and serious adverse events (SAEs) as 
characterized by type, frequency, severity (as 
graded by National Cancer Institute-Common 
Terminology Criteria for Adverse Events 
[NCI-CTCAE] Version 5.0), seriousness, and 
relationship to study drug(s); physical 
examinations, electrocardiograms (ECGs), 
laboratory abnormalities, and changes in 
laboratory assessments as needed; and AEs 
meeting protocol-defined DLT criteria 
To confirm the RP2D of ociperlimab when 
administered in combination with tislelizumab or 
rituximab in patients with R/R DLBCL 
RP2D of ociperlimab when administered in 
combination with tislelizumab or rituximab 
Secondary 
To assess the preliminary antitumor activity of 
ociperlimab in combination with tislelizumab or 
rituximab in patients with R/R DLBCL as 
measured by investigator-assessed response using 
the Lugano Classification (2014) (as described in 
Section 10.2) 
To evaluate the preliminary antitumor activity of 
ociperlimab in combination with tislelizumab or 
rituximab in patients with R/R DLBCL as 
measured by investigator-assessed response using 
the Lugano Classification (2014) as measured by:  
− Overall response rate (ORR) 
− Complete response (CR) rate 
− Duration of response (DOR) 
− Time to response (TTR) 
− Progression-free survival (PFS) 
− Overall survival (OS) 
To characterize the PK of ociperlimab in 
combination with tislelizumab or rituximab 
Serum concentration and PK parameters (as 
appropriate) of ociperlimab in combination with 
tislelizumab or rituximab  
To assess the host immunogenicity to ociperlimab 
in combination with tislelizumab or rituximab  
Immunogenic responses to ociperlimab in 
combination with tislelizumab or rituximab, 
which will be evaluated through the detection of 
ADAs 
Exploratory 
To explore the correlation of PD-L1 expression 
level and the preliminary antitumor activity of 
ociperlimab in combination with tislelizumab 
Evaluate PD-L1 expression in archival or fresh 
patient-derived tumor tissue(s) samples at 
screening and its association with the preliminary 
antitumor activity of ociperlimab in combination 
with tislelizumab  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 42 
Objectives 
Endpoints 
To characterize the exploratory biomarkers and 
their association with preliminary antitumor 
activity of ociperlimab in combination with 
tislelizumab or rituximab 
Evaluate biomarkers from patient-derived tumor 
tissue(s) and/or blood (or blood derivative) 
samples obtained before, during, and/or after 
treatment, and their association with preliminary 
antitumor activity of ociperlimab in combination 
with tislelizumab or rituximab. Biomarkers may 
include expression of TIGIT, CD226, CD155, and 
CD112, PD-L1/2 gene alteration, EBV status, 
tumor microenvironment, immune-related gene 
expression profile, and gene mutation profile in 
tumor tissue; immune-cell quantification and 
phenotypes, cytokine profiling, immune-related 
gene expression profiling, and DNA/ctDNA 
sequencing in peripheral blood 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 43 
3. 
STUDY DESIGN  
3.1. 
Summary of Study Design  
This is a Phase 1b/2, open-label, dose-confirmation, and dose-expansion study to evaluate the 
safety, tolerability, PK, and preliminary antitumor activity of ociperlimab in combination with 
tislelizumab or rituximab in patients with R/R DLBCL (Figure 2). 
Eligible patients will be allocated to 2 cohorts. First, each cohort will conduct Dose Confirmation 
Stage to confirm the RP2D of ociperlimab. Then, the confirmed RP2D will be implemented in 
Dose Expansion Stage. 
• Cohort 1: R/R DLBCL patients with positive PD-L1 on the surface of tumor cells (with 
any expression level) will receive ociperlimab in combination with tislelizumab 
• Cohort 2:  
− Dose Confirmation Stage: R/R DLBCL patients with negative PD-L1 on the 
surface of tumor cells. 
− Dose Expansion Stage: R/R DLBCL patients regardless of PD-L1 expression. 
Patients will receive ociperlimab in combination with rituximab. 
Approximately 43 to 50 patients in Cohort 1 and approximately 23 to 30 patients in Cohort 2 will 
be enrolled in the entire study. Every treatment cycle contains 21 days. The combination of 
ociperlimab with tislelizumab in Cohort 1 and ociperlimab with rituximab in Cohort 2 will be 
administrated intravenously on Day 1 of each 21-day cycle continuously until confirmed PD, 
death, withdrawal of consent, loss of follow-up, or study termination by sponsor, whichever 
occurs first.  
As of 30 November 2023, the study recruitment was complete; a total of 53 patients have been 
enrolled in 19 activated study sites, with 24 patients in Cohort 1 and 29 patients in Cohort 2. 
Dose Confirmation Stage: Because ociperlimab 900 mg in combination with tislelizumab 
200 mg administered on Day 1 of each 3-week cycle has been determined as the RP2D in 
multiple malignancies from the AdvanTIG-105 study, 2 dose levels (900 mg and 600 mg) of 
ociperlimab are selected as candidates for Dose Confirmation Stage.  
Ociperlimab will be tested at the dose level of 900 mg initially. If ociperlimab 900 mg exceeds 
the MTD, ociperlimab 600 mg will be tested. Other dose levels of ociperlimab (eg, lower than 
600 mg) may be explored to confirm the optimal dose level of ociperlimab in combination with 
tislelizumab or rituximab per the SMC’s recommendation considering the totality of emerging 
data. The dose of tislelizumab or rituximab will be fixed at 200 mg or 375 mg/m2, respectively. 
Patients in both Cohort 1 and Cohort 2 will be monitored for DLTs for the first cycle (starting 
from the first dose of study treatment and ending on C1D21).  
RP2D confirmation will occur in accordance with the following modified 3 + 3 principles 
(Section 3.2.2).  
RP2D will be confirmed after discussion with SMC before the initiation of dose expansion. 
Refer to Section 3.2.5 for the result of RP2D confirmation. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 44 
Dose Expansion Stage: After the RP2D of ociperlimab in combination with tislelizumab or 
rituximab are confirmed, further enrollment of both cohorts will commerce to their target sample 
size. Based on the safety profile and observed preliminary anticancer activity from the Dose 
Confirmation Stage of Cohort 2, the target population in Cohort 2 is considered to extend to R/R 
DLBCL patients regardless of PD-L1 expression at the Dose Expansion Stage. 
Refer to Section 3.3 for details of Dose Expansion Stage. 
All AEs will be graded according to the NCI-CTCAE Version 5.0. Refer to Section 9 for 
additional and specific information regarding AE monitoring and reporting. Patients who, at time 
of confirmed disease progression, have an ongoing AE that leads to treatment discontinuation 
and has completed the scheduled Safety Follow-up Visit will be followed until the event 
resolves, the investigator assesses the event as stable, the patient is lost to follow-up, or the 
patient starts a new antitumor therapy, whichever occurs first. 
Preliminary antitumor activity will be evaluated by the investigator using the Lugano 
Classification (Cheson et al 2014 and Appendix 8). If a patient discontinues study drug(s) due to 
reasons other than PD or death, tumor assessments should continue to be performed following 
the assessment schedule until the start of new antitumor therapy, PD, death, lost to follow-up, or 
withdrawal of consent for efficacy follow-up, whichever occurs first (Section 7.4.2). 
Samples for PK and ADA assessment will be collected for ociperlimab and tislelizumab 
(Section 8.6). Biomarker analysis will include expression of TIGIT, CD226, CD155, PD-L1, and 
CD112, PD-L1/2 gene alteration, EBV status, tumor microenvironment, immune-related gene 
expression profile, and gene mutation profile in tumor tissues; immune-cell quantification and 
phenotype, cytokine profiling, immune-related gene expression profiling, and DNA/ctDNA 
sequencing in peripheral blood (Section 8.7). 
Patients will have scheduled follow-up visits for safety and, if applicable, for efficacy per the 
Schedule of Assessments (Appendix 1). 
Study procedures and assessments are further detailed in Section 7 and Section 8, respectively, 
and the Schedule of Assessments can be found in Appendix 1. Specific details regarding dose 
confirmation and dose expansion are described in the following sections. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 45 
Figure 2: 
Study Schema  
 
Abbreviations: D, Day; IV, intravenous; Q3W, once every 3 weeks; RP2D, recommended Phase 2 dose. 
Note: Refer to Section 3.1 for dose confirmation details. 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 46 
3.2. 
Details of Dose Confirmation  
3.2.1. 
Starting Dose and Dose Confirmation Approach  
Approximately 2 dose levels of ociperlimab (with a starting dose of 900 mg) (Figure 2) are 
selected as candidates for Dose Confirmation Stage to confirm the RP2D for ociperlimab in 
combination with tislelizumab or rituximab. All dose levels of ociperlimab in combination of 
tislelizumab or rituximab will be administered intravenously on Day 1 of Cycle 1 and every 
21 days thereafter (ie, every 3 weeks) as outlined in Section 5.2 and Appendix 1. Each cycle will 
be 21 days in length, which may be modified based upon emerging data. 
Based upon emerging clinical data, if ociperlimab 900 mg exceeds the MTD, dose level of 
ociperlimab 600 mg may be evaluated while the dosing regimen of tislelizumab and rituximab 
will remain fixed. However, other dose levels of ociperlimab (eg. lower than 600 mg) may be 
explored to confirm the optimal dose level of ociperlimab in combination with tislelizumab or 
rituximab per the SMC’s recommendation considering the totality of emerging data. 
The SMC will review the accumulated safety data and other available data after the last patient 
of current cohort has completed the 21-day DLT observation period and will recommend the 
RP2D for ociperlimab in combination with tislelizumab or rituximab (Section 3.2.5). All patients 
will continue with their originally assigned dosing regimen until they meet 1 of the 
discontinuation criteria (Section 7.5).  
3.2.2. 
Rules for Dose Confirmation  
Dose confirmation and RP2D determination will occur in accordance with the following 
modified 3 + 3 principles. 
Three to 6 patients will be initially enrolled per dose level. 
• If none of the initial 3 patients enrolled at a given dose level experiences a DLT (0/3), 
this dose level of ociperlimab in combination of tislelizumab or rituximab will be 
confirmed as RP2D. 
• If 1 of the initial 3 patients enrolled at a given dose level experiences a DLT (1/3), at least 
3 additional patients will be enrolled at this dose level (for a total of at least 6 evaluable 
patients).  
− If less than one-third of patients enrolled at a given dose level experiences a DLT (eg, 
< 2/6), this dose level of ociperlimab in combination of tislelizumab or rituximab will 
be confirmed as RP2D. 
− If ≥ 2 of the initial 6 patients enrolled at a given dose level experience a DLT, the 
MTD will be considered as having been exceeded and a next lower dose level will be 
assessed for toxicity in the same manner as described above. If ≥ 2 of the initial 
6 patients enrolled at dose level of ociperlimab 600 mg experience DLT, other dose 
levels of ociperlimab (eg. lower than 600 mg) may be explored per the SMC’s 
recommendation considering the totality of emerging data. 
All available safety data, including AEs, laboratory assessments, PK, and preliminary efficacy 
analyses (as available), will be reviewed by the medical monitor and study team members from 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 47 
Pharmacovigilance/Drug Safety, Clinical Pharmacology, and Biostatistics with input from other 
members as appropriate. 
On the basis of a sponsor review of real-time safety data and after consultation with the 
investigators and SMC, the decision to proceed to other dose levels during the study may be 
made as deemed appropriate. 
3.2.3. 
Assessment of Dose-Limiting Toxicity  
For initial Dose Confirmation recommendations, AEs will be assessed per the DLT criteria 
below (Section 3.2.4) during the 21-day DLT assessment window, which starts with the first day 
of study drug administration and ends on C1D21. 
Patients will be considered evaluable for DLTs if they 1) experienced a DLT or 2) received 
≥ 80% of each scheduled study drug administration and remained on study during the DLT 
assessment window.  
Any patient who experiences a DLT may be withdrawn from treatment or may continue to 
receive tislelizumab or rituximab alone or the combination therapy with a lower dose level for 
ociperlimab after discussion with and approval by the medical monitor. 
3.2.4. 
Dose-Limiting Toxicity Definition  
All toxicities or AEs will be graded according to the NCI-CTCAE Version 5.0. A DLT is defined 
as 1 of the following toxicities occurring during the DLT assessment window (starting from the 
first dose of study treatment and ending on C1D21) and considered by the investigator to be 
related to ociperlimab and/or tislelizumab or rituximab without a clear alternative cause to study 
treatment.  
Hematologic: 
1. Grade 4 neutropenia lasting > 7 days 
2. ≥ Grade 3 febrile neutropenia  
3. Grade 3 thrombocytopenia with ≥ Grade 2 bleeding (including but not limited to central 
nervous system bleeding of any grade) 
4. Grade 4 thrombocytopenia lasting > 7 days 
5. ≥ Grade 4 anemia 
Nonhematologic: 
1. ≥ Grade 4 toxicity 
2. Grade 3 toxicity that is clinically significant and does not resolve to baseline or ≤ Grade 1 
within 7 days after optimal supportive care is initiated 
Note: The following AEs will not be considered DLTs: 
• Grade 3 endocrinopathy that is adequately controlled by hormonal replacement 
• Grade 3 rash 
• Grade 3 infusion-related AE that is transient (resolving within 6 hours of onset) 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 48 
• Grade 3 nausea, vomiting, or diarrhea lasting for ≤ 72 hours with adequate antiemetic 
and/or other supportive care 
• Fatigue lasting for ≤ 7 days 
• Electrolyte abnormality that lasts for ≤ 72 hours, is not clinically complicated, and 
resolves spontaneously or responds to convention medical interventions 
• Asymptomatic biochemical laboratory abnormalities resolve to Grade 1 or baseline 
≤ 7 days with or without medical interventions  
During the DLT assessment window, any other grade of AEs occurred which is assessed to be 
related to study drug and leads to dose discontinuation or interruption of any study drug 
(ociperlimab, tislelizumab, or rituximab) for > 7 days will also be considered DLTs after review 
by the SMC. 
Clinically important or persistent AEs that are not part of the DLT criteria (Section 3.2.4) may 
also be considered a DLT after review by the SMC in consultation with the investigators. 
Additionally, any clinically significant AEs that occur after the DLT assessment window (eg, 
late imAE) for a given dose level may be considered regarding decisions of subsequent dose 
level.  
3.2.5. 
Recommended Phase 2 Dose Confirmation  
The combination therapy RP2D will be confirmed from safety, tolerability, and any other 
relevant and available data (eg, PK and preliminary efficacy data) that is obtained from the Dose 
Confirmation Stage. Once the combination therapy RP2D is confirmed, it will then be evaluated 
in the Dose Expansion Stage. 
3.3. 
Details of Dose Expansion  
The Dose Expansion Stage of the study will begin once the RP2D has been confirmed from the 
Dose Confirmation Stage. Approximately 40 patients for Cohort 1 and 20 patients for Cohort 2 
will be enrolled in parallel at each RP2D dose level.  
Each cohort will be evaluated independently for study endpoints and may be closed due to lack 
of preliminary antitumor activity according to the Lugano Classification (Cheson et al 2014) or 
other reasons.  
Expansion Cohort 1: Approximately 40 patients will be enrolled at RP2D dose level. One futility 
interim analysis for ORR is planned to be conducted when approximately 20 patients have been 
enrolled with a futility boundary of 35% (equivalent to observe ≤ 7 responders). The SMC along 
with the sponsor will make the decision of proceeding or not. To reflect the natural distribution 
across PD-L1 expression given a relatively small sample size at interim analysis, the number of 
eligible patients with PD-L1 expression ≤ 5% on the surface of tumor cells as determined by 
local laboratory will be capped to ≤ 50% of the first 20 patients enrolled, and the benefit-risk 
profile may also be evaluated by the SMC and sponsor for these patients. Upon conducting the 
interim analysis, the enrollment may be paused according to sponsor's decision, provided that the 
required number of patients for the interim analysis has been reached. After the interim analysis, 
the number of these patients with PD-L1 expression ≤ 5% on the surface of tumor cells as 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 49 
determined by local laboratory may be further capped per the SMC’s recommendation 
considering the totality of emerging data. 
The interim analysis was conducted in July 2023. During its 21 July 2023 meeting, the SMC 
reviewed all available data of the 24 patients enrolled in Cohort 1. Because the futility boundary 
for ORR was not exceeded, the SMC recommended to terminate the enrollment of Cohort 1 
immediately. 
Expansion Cohort 2: Based on the safety profile and observed preliminary anticancer activity 
from the Dose Confirmation Stage, the target population is considered to extend to all R/R 
DLBCL patients. Approximately 20 patients regardless of PD-L1 expression will be enrolled at 
RP2D dose level. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 50 
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. Signed informed consent form (ICF) and able to comply with study requirements 
2. Age ≥ 18 years on the day of signing the ICF 
3. Histologically confirmed DLBCL NOS (Not Otherwise Specified), EBV+ DLBCL NOS, 
or high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with 
DLBCL histology (double/triple-hit lymphoma [DHL/THL]), based on the World Health 
Organization (WHO) 2016 classification of tumors of hematopoietic and lymphoid tissue 
a. Cohort 1: Patients must have positive tumor PD-L1 IHC testing results as determined 
by local pathologist 
b. Cohort 2:  
− Dose Confirmation Stage: Patients must have negative tumor PD-L1 IHC testing 
results as determined by local pathologist.  
− Dose Expansion Stage: All R/R DLBCL patients with confirmed pathology 
diagnosis regardless of PD-L1 expression on tumor cells. 
4. Previously received ≥ 1 line of adequate systemic anti-DLBCL therapy, defined as an 
anti-CD20 antibody-based chemoimmunotherapy for ≥ 2 consecutive cycles, unless 
patients had PD before Cycle 2 
5. Relapsed or refractory disease before study entry, defined as either: 
a. Recurrent disease after having achieved disease remission (CR or PR) during or at the 
completion of the latest treatment regimen  
b. Stable disease or PD at the completion of the latest treatment regimen  
6. Ineligible for high dose therapy/hematopoietic stem cell transplantation 
7. Measurable disease as assessed by computed tomography (CT) or magnetic resonance 
imaging (MRI) and defined as at least 1 lymph node > 1.5 cm in the longest diameter 
and/or at least 1 extranodal lesion > 1.0 cm in the longest diameter, and measurable 
lesion (s) in 2 perpendicular diameters  
8. Available for archival tissue or consented to obtain fresh tumor tissue sample through an 
evaluable core or excisional biopsy. 
9. ECOG Performance Status ≤ 2 
10. Adequate bone marrow function as indicated by the following laboratory values:  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 51 
a. Absolute neutrophil count ≥ 1.0 x 109/L (≥ 0.75 x 109/L for patients with bone 
marrow involvement by DLBCL), without growth factor support ≥ 7 days before 
sample collection 
b. Platelet count ≥ 75 x 109/L (≥ 50 x 109/L for patients with bone marrow involvement 
by DLBCL), without blood transfusion or growth factor support ≥ 7 days before 
sample collection 
c. Hemoglobin ≥ 80 g/L, without blood transfusion or growth factor support ≥ 7 days 
before sample collection 
11. Adequate organ function as indicated by the following laboratory values: 
a. Creatinine clearance ≥ 30 mL/min (as estimated by Cockcroft-Gault equation or as 
measured by nuclear medicine scan or 24-hour urine collection) 
b. Serum total bilirubin ≤ 2.0 x ULN (unless with documented Gilbert syndrome) 
c. AST and ALT ≤ 2.5 x ULN (unless due to DLBCL) 
12. Women of childbearing potential must have a negative urine or serum pregnancy test 
≤ 7 days of the first dose of study drug(s) and be willing to use highly effective method of 
birth control for the duration of the study, and ≥ 120 days after the last dose of 
ociperlimab or tislelizumab, or ≥ 12 months after the last dose of rituximab, whichever is 
longer (Appendix 5). 
13. Nonsterile men must be willing to use highly effective method of birth control for the 
duration of the study and for ≥ 120 days after the last dose of ociperlimab or tislelizumab, 
or ≥ 12 months after the last dose of rituximab, whichever is longer (Appendix 5). 
a. A sterile man is defined as one for whom azoospermia has been previously 
demonstrated in a semen sample examination as definitive evidence of infertility 
b. Men with known “low sperm counts” (consistent with “subfertility”) 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. Current or history of central nervous system lymphoma 
2. Histologically transformed lymphoma 
3. Receipt of the following treatment: 
a. Systemic chemotherapy, targeted small molecule therapy or radiation therapy within 
4 weeks (or 5 half-lives, whichever is shorter) before first dose of study drug 
b. Recent treatment with another monoclonal antibody within 4 weeks before first dose 
of study drug 
c. Investigational treatment within 4 weeks (or 5 half-lives, whichever is shorter) before 
first dose of study drug 
d. Treatment with autologous stem cell transplantation within 6 months before first dose 
of study drug 
e. Treatment with allogeneic hematopoietic stem cell transplantation or organ 
transplantation 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 52 
f. Treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-TIGIT, anti-CTLA4 or other 
antibody or drug specifically targeting T cell costimulation or checkpoint pathways 
4. Toxicities (as a result of prior antitumor therapy) that have not recovered to baseline, 
≤ Grade 1, or stabilized, except for AEs that are not considered a likely safety risk 
(eg, alopecia, neuropathy, and specific laboratory abnormalities [see Inclusion Criterion 
#10 and #11 in Section 4.1]) 
5. Active autoimmune diseases or history of autoimmune diseases that may relapse, with the 
following exceptions: 
a. Controlled Type 1 diabetes 
b. Hypothyroidism (provided that it is managed with hormone replacement therapy 
only) 
c. Controlled celiac disease 
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia) 
e. Any other disease that is not expected to recur in the absence of external triggering 
factors 
6. 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 localized or locally recurring 
cancer that has been treated with curative intent (eg, resected basal or squamous cell skin 
cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized 
Gleason score 6 prostate cancer) 
7. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily 
of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before 
the first dose of study drug(s), with the following exceptions: 
a. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) 
b. Topical, ocular, intra-articular, intranasal, or inhalational 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 nonautoimmune condition (eg, delayed-type 
hypersensitivity reaction caused by contact allergen) 
8. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung 
diseases including but not limited to pulmonary fibrosis, acute lung diseases, or evidence 
of dyspnea at rest or pulse oximetry < 92% while breathing room air. 
9. Severe chronic or active fungal, bacterial and/or viral infection requiring systemic 
therapy ≤ 14 days prior to the first dose of study drug(s). 
10. Serologic status reflecting active hepatitis B virus (HBV) or hepatitis C virus (HCV) 
infection, defined as positive hepatitis B surface antigen (HBsAg) and/or detectable HBV 
DNA (≥ 20 IU/mL) or HCV RNA (≥ 15 IU/mL).  
11. Known history of HIV and human T cell lymphotropic virus infection 
12. Any major surgical procedure ≤ 4 weeks before the first dose of study drug(s).  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 53 
13. Any of the following cardiovascular risk factors: 
a. Acute myocardial infarction ≤ 6 months before screening 
b. Unstable angina ≤ 3 months before screening 
c. Heart failure meeting New York Heart Association Classification III or IV 
(Appendix 6) ≤ 6 months before the first dose of study drug(s) 
d. Clinically significant arrhythmia (eg, sustained ventricular tachycardia, ventricular 
fibrillation, or torsade de pointes). 
e. QTcF interval (QT interval corrected for heart rate by Fridericia’s formula) 
> 480 msec 
f. History of Mobitz II second-degree or third-degree heart block without a 
permanent pacemaker in place 
g. Uncontrolled hypertension as indicated by at least 2 consecutive blood pressure 
measurements showing systolic blood pressure > 170 mm Hg and diastolic blood 
pressure > 105 mm Hg at screening 
14. Hypersensitivity to ociperlimab, tislelizumab, rituximab, or any of their ingredients 
15. History of severe hypersensitivity reactions to other monoclonal antibodies 
16. Live vaccine ≤ 4 weeks before the first dose of study drug(s) 
• Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. 
Intranasal vaccines are live vaccines and are not allowed. 
17. Underlying medical conditions or alcohol or drug abuse or dependence that will be 
unfavorable for the administration of study drug(s), or will affect the explanation of drug 
toxicity or AEs, or result in insufficient or impaired compliance with study conduct 
18. Concurrent participation in another therapeutic clinical study 
• Concurrent participation in observational or noninterventional studies is allowed. In 
addition, patients who have completed active treatment in a clinical study and are in 
the follow-up period can be enrolled in this study. 
19. Women who are pregnant, are breastfeeding, or expecting to conceive or father children 
within the projected duration of the trial, starting with the prescreening or screening visit 
through at least 120 days after the last dose of tislelizumab or ociperlimab, or 12 months 
after the last dose of rituximab, whichever is longer 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 54 
5. 
STUDY TREATMENT  
5.1. 
Formulation, Packaging, and Handling  
5.1.1. 
Ociperlimab  
Ociperlimab is a monoclonal antibody formulated for intravenous injection in a single-use vial 
(20 mL glass vial, USP Type I) containing a total of 200 mg antibody in 10 mL or 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 (BGB-A1217) Investigator’s Brochure for other details 
regarding ociperlimab. 
5.1.2. 
Tislelizumab  
Tislelizumab is a monoclonal antibody formulated for intravenous injection 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 (BGB-A317) Investigator’s Brochure for other details 
regarding tislelizumab. 
5.1.3. 
Rituximab  
Rituximab will be provided by the sponsor, in a single dose vial containing a total of 100 mg 
antibody in 10 mL or 500 mg antibody in 50 mL of clear solution for intravenous infusion. The 
labels will include any additional clinical requirements as appropriate. Refer to the Pharmacy 
Manual for specifics on packaging and label content. The contents of the label will be in 
accordance with all applicable local regulatory requirements. 
Rituximab must be stored in the original package per storage requirements and temperature 
specified on the label. For more information regarding stability and storage refer to the Pharmacy 
Manual. Refer to the Rituximab prescribing information 2021 for other details regarding 
rituximab.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 55 
5.2. 
Dosage, Administration, and Compliance  
Study treatment begins on Cycle 1 Day 1. Treatment modifications (eg, dose delay/holds) will be 
based on specific laboratory and AE criteria, as described in Section 5.4. Guidelines for study 
treatment modification, delay, or discontinuation as well as management of imAEs or IRRs are 
provided in Section 9.7 and Appendix 9. 
Accurate records of all study drug(s) received, dispensed, returned, and disposed of 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. 
5.2.1. 
Dose Confirmation Stage  
Planned dose level(s) for ociperlimab, tislelizumab and rituximab are presented in Table 1. 
Table 1: 
Planned Dose Levels for Ociperlimab, Tislelizumab, and Rituximab 
Study drug(s) 
Dose 
Ociperlimab 
900 mg 
600 mg 
(Lower dose levels may be explored.) 
Tislelizumab (for Cohort 1 only) 
200 mg 
Rituximab (for Cohort 2 only) 
375 mg/m2 
As shown in Table 1, 200 mg of tislelizumab (for Cohort 1) or 375 mg/m2 rituximab (for 
Cohort 2) will be administered first followed by ociperlimab on Day 1 of each 21-day cycle 
(once every 3 weeks). Ociperlimab, tislelizumab, and rituximab must be 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. Ociperlimab and tislelizumab or 
rituximab must be prepared and administered as separate infusions and may not be administered 
with any other drug. Tislelizumab or rituximab should be administered first followed by 
ociperlimab.  
Table 2 outlines the infusion as well as postinfusion monitoring times for combination of 
ociperlimab and tislelizumab or rituximab. Monitoring must occur in an area where emergency 
medical equipment and appropriately trained staff are available. Duration of infusion and 
postinfusion monitoring can be decreased if tislelizumab or rituximab infusion is well tolerated. 
Premedication consisting of acetaminophen and an antihistamine could be administered before 
each rituximab infusion. Steroids may also be administered before the start of the rituximab 
infusion according to institutional practice.  
Table 2: 
Administration of Ociperlimab, Tislelizumab, and Rituximab and 
Monitoring Time 
Cycle 
Ociperlimab and tislelizumab 
combination (for Cohort 1) 
Ociperlimab and rituximab combination 
(for Cohort 2) 
C1D1 and 
C2D1 
Tislelizumab infusion over 60 minutes  
Ociperlimab infusion over 60 minutes 
Rituximab infusion per local guidance and 
prescribed information 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 56 
Cycle 
Ociperlimab and tislelizumab 
combination (for Cohort 1) 
Ociperlimab and rituximab combination 
(for Cohort 2) 
Patient monitoring for ≥ 120 minutes 
Ociperlimab infusion over 60 minutes 
Patient monitoring for ≥ 120 minutes 
C3D1a            
Tislelizumab infusion over 30 minutes  
Ociperlimab infusion over 60 minutes  
Patient monitoring for ≥ 60 minutes 
Rituximab infusion per local guidance and 
prescribed information 
Ociperlimab infusion over 60 minutes  
Patient monitoring for ≥ 60 minutes 
C4D1 
onwardsa 
Tislelizumab infusion over 30 minutes  
Ociperlimab infusion over 30 minutes  
Patient monitoring for ≥ 60 minutes 
Rituximab infusion per local guidance and 
prescribed information 
Ociperlimab infusion over 30 minutes  
Patient monitoring for ≥ 60 minutes 
Abbreviations: C, cycle; D, day. 
Note: The infusion rate may be decreased or the infusion may be stopped in the event of an infusion-related reaction. 
See Section 9.7.1 for details. 
a Subsequent decrease(s) in study drug infusion time and/or postinfusion monitoring time is contingent upon the 
tolerability of prior study drug administrations. If a cycle is missed, the equivalent number of study drug infusions 
must be met before a decrease in time can occur. 
5.2.2. 
Dose Expansion Stage  
The RP2D of ociperlimab to be used in combination with tislelizumab or rituximab will be 
confirmed based upon the available clinical data derived from Dose Confirmation Stage as 
described in Section 3.2.5.  
5.3. 
Incorrect Administration or Overdose  
Any incorrect administration of ociperlimab or overdose of tislelizumab (defined as ≥ 600 mg in 
a 24-hour period) or rituximab (defined as more than 110% of the precise calculated dose) 
should be noted in the patient’s chart and on the appropriate electronic case report form (eCRF). 
AEs associated with an incorrect administration or overdose of study drug(s) 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 9.6.2. Supportive care measures should be administered as appropriate. 
5.4. 
Dose Delay or Modification  
5.4.1. 
Dose Interruption or Delay for Ociperlimab, Tislelizumab, and Rituximab  
In Dose Confirmation Stage, prior to Cycle 1 Day 21, if any toxicity which is assessed to be 
related to study drug(s) and leads to dose interruption > 7 days of any study drug (ociperlimab, 
tislelizumab, or rituximab), should be considered as a DLT. 
Except Cycle 1 of Dose Confirmation Stage, if a dose delay is required, both study drugs are to 
be delayed (ie, ociperlimab and tislelizumab or rituximab must both be delayed and if applicable 
restarted at the same time). As a result, the initiation of the new treatment cycle will be 
postponed.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 57 
In general, dose delays for reasons other than management of AEs is prohibited. A dose delay of 
≤ 3 weeks is allowed under the following guidance and at the discretion of the investigator after 
consultation with the medical monitor or designee. If treatment-related AEs are persistent 
without any improvement for more than 3 weeks, permanent discontinuation of the study drug 
should be considered. If the patient recovers from the treatment-related AE after 3 weeks, 
re-initiation of study drug 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. 
If treatment is delayed due to AEs, 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 worsening of 
hematologic or biochemical parameters, the frequency of relevant blood tests should be 
increased as clinically indicated. 
Two occurrences of dose delays because of treatment-related AEs will be permitted. In the event 
of a third occurrence of a dose delay due to toxicity, permanent discontinuation of study drug 
should be considered after consultation with the medical monitor. 
The tumor assessment schedule will not be altered even if the administration of study drug is 
delayed.  
5.4.2. 
Dose Modification for Ociperlimab, Tislelizumab, and Rituximab  
There will be no dose reductions allowed for tislelizumab and rituximab. No dose reductions for 
ociperlimab are allowed, except if patients are receiving a dose level of ociperlimab that is 
determined to be beyond the MTD in Dose Confirmation Stage, the dose level of ociperlimab 
may be reduced following discussion and agreement with the medical monitor.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 58 
6. 
PRIOR AND CONCOMITANT THERAPY  
6.1. 
Prior Therapy  
All prior therapy, dates of administration, best response, and date of progression for DLBCL will 
be collected at study entry and entered into the eCRF. 
Per the study eligibility exclusion criteria (Section 4.2), patients who received prior therapies for 
DLBCL (including autologous hematopoietic stem cell transplantation within 6 months before 
the first dose of study drugs and allogeneic hematopoietic stem cell transplantation) or 
antibody/drug specific targeting T cell costimulation or checkpoint pathways are excluded from 
study participation. 
6.2. 
Permitted Concomitant Medications/Procedures  
The potential for drug-drug interaction between the study drugs (ociperlimab, tislelizumab, or 
rituximab) and other small molecule drugs is very low because all these are therapeutic 
monoclonal antibody and are expected to be degraded into amino acids and recycled into other 
proteins. Thus, it is unlikely to have an effect on drug-metabolizing enzymes or transporters.  
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. 
All concomitant medications, including all prescription and over-the-counter drugs, supplements, 
and intravenous medications and fluids, taken by or administered to the patient within 28 days 
before the first dose of study drug(s) and 30 days after the last dose of study drug(s) or the 
initiation of a new anticancer therapy will be recorded. 
Tumor lysis syndrome has been infrequently reported in patients with DLBCL. Patients with 
high tumor burden should be monitored closely and adopt prophylactic measures, including 
allopurinol, may be instituted per institutional standards.  
Patients with hematologic malignancies, particularly patients having received prior 
lymphodepleting chemotherapy or having prolonged corticosteroid exposure, are predisposed to 
opportunistic infections because of disease and treatment-related factors.  In patients with a high 
risk for opportunistic infections, including Pneumocystis jirovecii pneumonia (PJP), prophylaxis 
should be considered as per institutional standards. 
Bisphosphonates and RANKL inhibitors are allowed for bone metastases if initiated before 
enrollment and at a stable dose. Bisphosphonates are permitted during the study for a 
nonmalignant indication. 
Systemic Corticosteroids  
Systemic corticosteroids for non-NHL diseases are allowed as follows: 
• Systemic corticosteroids administered for the control of imAEs must be tapered gradually 
(see Appendix 9 and must be administered at nonimmunosuppressive doses (≤ 10 mg/day 
of prednisone or equivalent) before the next drug administration.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 59 
• Patients should not receive treatment with systemic corticosteroid other than 
intermittently to control or prevent infusion reactions or for short durations (< 2 weeks) to 
treat non-NHL-related condition(s) (eg, to treat a flare of chronic obstructive pulmonary 
disease). 
• A short course (≤ 7 days) of systemic corticosteroid treatment for control of 
lymphoma-related symptoms is allowed prior to enrollment provided that it is tapered off 
within 5 days after initiation of study treatment. 
• Chronic systemic corticosteroid use is not permitted, except for adrenal replacement, 
which requires consultation with the medical monitor. 
• To reduce or control symptoms per standard of care and institutional guidelines. 
Hepatitis B Treatment  
Patients with active hepatitis B, defined as positive HBsAg or positive hepatitis B core antibody 
(HBcAb) with detectable HBV DNA (≥ 20 IU/mL) are excluded from study. Patients with 
negative HBsAg, positive HBcAb, and undetectable HBV DNA (< 20 IU/mL) are eligible but 
must receive at least monthly HBV reactivation monitoring during treatment, and patients should 
be considered for prophylactic antiviral treatment in consultation with a local HBV expert. Such 
medications must be documented in the patient’s chart and recorded in the eCRF. If a patient is 
being treated prophylactically with antivirals, HBV DNA monitoring by PCR must be done at 
least every 3 months. HBV DNA monitoring should continue until the patient starts new 
antitumor therapy, or for any other reason listed in Section 7.5.2, whichever occurs first. 
6.3. 
Prohibited Concomitant Medications/Procedures  
The following medications are prohibited during the study or as otherwise noted: 
• Any concurrent antitumor therapy, including radiation therapy, chemotherapy, 
hormonal therapy, immunotherapy, standard or investigational agents (including 
Chinese or other country herbal medicine and Chinese or other country patent 
medicines for the treatment of cancer [regardless of cancer type]), ≤ 14 days (or 
≤ 5 half-lives, if applicable, whichever is shorter) before the first dose of study 
drug(s) and during the study. 
• Drugs known to prolong QT/QTc interval should be avoided in the study. See 
Appendix 10. 
• Live vaccines ≤ 28 days before the first dose of study drug(s) and ≤ 60 days following 
the last dose of study drug(s). 
• Immunosuppressive agents (except to treat a drug-mediated AE). 
• Patients should not abuse alcohol or other drugs. 
Herbal remedies with immune-stimulating properties (eg, mistletoe extract) or that 
are known to potentially interfere with liver or other major organ functions 
(eg, hypericin) ≤ 14 days (or ≤ 5 half-lives, if applicable, whichever is shorter) before 
the first dose of study drug(s) and during the study. Patients must notify the 
investigator of all herbal remedies used during the study.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 60 
7. 
STUDY PERIODS, VISITS, OR PROCEDURES  
7.1. 
Screening Period  
Screening evaluations will be performed ≤ 28 days before the first dose of study drug(s). A 
patient who agrees to participate in this study will sign the ICF before undergoing any 
study-specific screening assessment. Refer to Section 8.1 for instructions regarding screening 
assessments. 
In some conditions (depends on study design and sponsor’s decision), patient number may be 
limited, prescreening evaluations of PD-L1 on the surface of tumor cells status by local 
laboratory (with sponsor pre-approval, local laboratory collection may be substituted with central 
laboratory assessments) will be performed for patients who have histologically confirmed 
DLBCL and show a trend of lack of efficacy in their latest systemic anti-DLBCL treatments.  
7.1.1. 
Informed Consent and Screening Log  
Voluntary, written informed consent for participation in the study must be obtained before 
performing any study-specific procedures. ICFs for enrolled patients and for patients who are 
screened but not enrolled will be maintained at the study site.  
The investigator will maintain a screening log to record details of all patients screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
7.1.2. 
Patient Numbering  
After obtaining informed consent, study site personnel will access the Interactive Response 
Technology (IRT) system to assign a unique patient number to a potential study participant. 
Patient number will be assigned in chronological order starting with the lowest number. Once a 
patient number has been assigned to a patient, it cannot be reassigned to any other patient. If a 
patient is allowed to be rescreened, a new patient number will be assigned to the patient after 
reobtaining informed consent. 
7.2. 
Enrollment  
Prior to enrollment, the investigator is responsible for assessing and confirming that each patient 
meets all inclusion criteria for this study and that none of the exclusion criteria apply. All results 
from the screening procedure and relevant medical history must be available and reviewed by the 
investigator before eligibility can be determined. No eligibility waivers will be granted.  
Sponsor verification of patient eligibility will be managed by way of source data verification in 
accordance with International Council for Harmonisation (ICH) E6. 
The sponsor’s medical monitor will support the investigator and/or site staff by answering any 
queries or questions relating to protocol eligibility criteria. 
Participating women of childbearing potential should be placed on effective birth control as soon 
as medically reasonable and before initiation of study treatment. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 61 
7.3. 
Treatment Period  
Patients enrolled by the sponsor will be treated as described in Section 5.2. 
Refer to Section 7.5 and Section 8.3 for additional considerations regarding treatment 
discontinuation and withdrawal. 
7.4. 
Follow-up Periods  
7.4.1. 
Safety Follow-up Period  
Patients who permanently discontinue all study drugs will be asked to return to the clinic for the 
Safety Follow-up Visit, which is required to be conducted within 30 days (± 7 days) after the last 
dose of study drugs or before the initiation of new antitumor therapy, whichever occurs first. 
Additional Safety Follow-up Visits at 60, 90, 120, 180 days after the last dose of study drugs (the 
visits at 120-day and 180-day are only required for women of childbearing potential) are required 
(in clinic or over the phone, as needed based on the assessments required). Patients will be 
contacted by telephone to assess imAEs and relevant concomitant medications (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 after the last dose of tislelizumab and ociperlimab and 180 days after the last dose of 
rituximab. 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. 
All AEs, including SAEs, will be collected as described in Section 9.6. 
See Appendix 1 for assessments to be performed at the Safety Follow-up Visit. 
7.4.2. 
Efficacy Follow-up Period  
Patients who discontinue study drug(s) for reasons other than PD (eg, toxicity) will continue to 
undergo tumor assessments following the original plan until the patient experiences PD, starts 
new antitumor therapy, or for any other reason listed in Section 7.5.2, whichever occurs first. 
If patients refuse to return for these visits or are unable to do so, every effort should be made to 
contact the patients by telephone to determine their disease status. 
7.4.3. 
Survival Follow-up  
Patients will be followed for survival and to obtain information on subsequent anticancer therapy 
after discontinuation of study treatment via telephone calls, mail or email, patient medical 
records, and/or clinic visits approximately every 12 weeks (± 14 days) after the Safety Follow-up 
Visit or as directed by the sponsor until death, withdrawal of consent, loss to follow-up, or end of 
study. 
7.4.4. 
Lost to Follow-up  
If attempts to contact the patient by telephone are unsuccessful, additional attempts should be 
made to obtain protocol-required follow-up information. It may be possible to obtain the 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 62 
information from other contacts, such as referring physicians or relatives. Attempts of contact 
should be documented in the patient’s source documents. If a patient cannot be contacted despite 
all attempts, the patient will be considered lost to follow-up, and death information should be 
obtained through a public record search if local agencies permit. 
7.5. 
Discontinuation From Study Treatment or From the Study  
7.5.1. 
Patient Discontinuation From Study Treatment (End of Treatment for an 
Individual Patient)  
Patients have the right to discontinue study treatment at any time for any reason. In addition, the 
investigator has the right to discontinue a patient from study treatment at any time. Patients who 
discontinue study treatment for reasons other than PD should be followed for assessments of 
preliminary antitumor activity (Section 8.3) and safety (Section 8.2), if possible. 
The primary reason for discontinuation from study treatment should be documented on the 
appropriate eCRF. Patients may discontinue study treatment for reasons including but not limited 
to the following: 
• PD 
• AE 
• Withdrawal of consent 
• Pregnancy 
• Investigator’s decision, including but not limited to: 
− Any medical condition that the investigator or sponsor determines may jeopardize 
the patient’s safety if he or she were to continue the study treatment 
− Use of any concurrent antitumor therapy, including chemotherapy, hormonal 
therapy, immunotherapy, standard or investigational agents (including Chinese or 
other country herbal medicine and Chinese or other country patent medicines) for 
the treatment of cancer [regardless of cancer type]) 
− Patient noncompliance 
Study 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. 
7.5.2. 
Patient Discontinuation From the Study (End of Study for an Individual Patient)  
Patients may discontinue from the study for reasons that include but are not limited to the 
following: 
• Patient withdrawal of consent 
• Death 
• Lost to follow-up 
• Study termination by sponsor 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 63 
7.6. 
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 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 
• Patients have very limited benefit from treatment (eg, unsatisfactory antitumor 
activity) 
The sponsor will notify each investigator if a decision is made to terminate the study. Should this 
be necessary, prematurely discontinued patients must be seen for a 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. 
The sponsor has the right to close a study site at any time. The decision will be communicated to 
the site in advance. Reasons for closing a site include but are not limited to the following:  
• Excessively slow recruitment 
• Poor protocol adherence 
• Inaccurate or incomplete data recording 
• Noncompliance with GCP or applicable laws and regulations 
• Completion of study activity (ie, all patients have completed the study and all 
obligations have been fulfilled) 
At the time of study termination as determined by the sponsor, any patient who is still on 
treatment and who, in the opinion of the investigator, continues to benefit from study drug(s) will 
be offered the option of continued access to study drug(s) without the need for further data 
collection via eCRFs. The study drug(s) will be administered per current assignment until disease 
progression is assessed by the investigator, any other reasons listed in Section 7.5.1 occur, or the 
patient has received the maximum of 2 years of study drug(s) after the first dose, whichever 
occurs first. Refer to Section 7.6.1 regarding the management and monitoring of patients who 
receive poststudy drug(s) after study termination by the sponsor. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 64 
7.6.1. 
Management and Monitoring for Patients Remaining on Treatment After Study 
Termination  
Safety Assessment, Monitoring, and Reporting 
• Safety assessments (eg, laboratory tests, ECGs, hepatitis B and C testing) will be 
performed at qualified local laboratories per investigator’s discretion. 
• All AEs should be adequately evaluated and recorded in the clinical source 
documents; only SAEs will be reported to BeiGene’s Global Patient Safety per safety 
reporting in Section 9.6.2.1. 
Tumor and Response Evaluations 
• Patients will continue to undergo tumor assessments per investigator’s discretion until 
they begin a subsequent anticancer treatment, experience disease progression, 
withdraw consent, are lost to follow-up, or die, whichever occurs first.  
Pharmacokinetic and Biomarker Testing 
• Blood or tissue samples will not be collected for PK, ADA, biomarker, or other 
exploratory analyses.  
Safety Follow-up 
• The Safety Follow-up Visit at 30 days after the last dose of study drug(s) will be 
performed per investigator's discretion.  
• Additional Safety Follow-up Visits at 60, 90, 120, and 180 days after the last dose of 
study drug(s) and Survival Follow-up Visits will not be conducted. 
Data Collection and Management 
• Data generated after study termination by the sponsor will not be collected in the 
eCRFs. 
• As a part of patient management, the investigator must collect and maintain patient 
clinical source documents per the requirements of local institutions. 
The investigator is encouraged to communicate with the sponsor for any questions regarding 
patient management and monitoring during treatment with study drug(s). Patient management 
and monitoring, including tumor and response evaluations, safety assessments, study drug 
modifications, and follow-up will be generally concordant with the current approved protocol or 
per the investigator’s discretion, with guidance provided above. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 65 
8. 
STUDY ASSESSMENTS  
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. 
Where applicable, 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. 
8.1. 
Screening Assessments  
Screening evaluations will be performed ≤ 28 days before the first dose of study drug(s) (refer to 
Appendix 1 for details). Patients who agree to participate will sign the ICF before undergoing 
any study-specific 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 the first dose of study drug(s) may be used for the purposes of 
screening rather than repeating the standard-of-care tests unless otherwise indicated. 
Procedures conducted only during the Screening Visit are described in this section. For the 
description of assessments that are conducted during screening as well as throughout the study, 
refer to Safety Assessments (Section 8.2), Tumor and Response Evaluations (Section 8.3), Bone 
Marrow Examination (Section 8.4), PK and ADA Assessments (Section 8.5) and Biomarkers 
(Section 8.7) sections. 
Rescreening is allowed only once. 
8.1.1. 
Pulmonary Function Tests  
Pulmonary function tests may include but are not limited to spirometry and assessment of 
diffusion capacity, and will be done during the screening period to assist with the determination 
of suitability for the study. 
Tests may be repeated as clinically indicated while on study. 
8.2. 
Safety Assessments  
8.2.1. 
Vital Signs  
Vital signs including measurements of body temperature (˚C), pulse rate, blood pressure (systolic 
and diastolic), and weight will be performed at each study visit. Pulse rate and blood pressure 
will be measured while the patient is in a seated position after resting for 10 minutes. Height 
assessment is required only at screening. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 66 
8.2.2. 
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. A complete 
physical examination also includes an assessment of systems per the standard of care at the study 
site and as clinically indicated by symptoms. Any abnormality identified during screening will be 
graded according to NCI-CTCAE Version 5.0 and recorded in the eCRF with appropriate 
disease/condition terms. 
A limited examination of liver, spleen, lymph nodes will be performed at each study visit. New 
or worsened clinically significant abnormalities are to be recorded as AEs in the eCRF. Refer to 
Section 9.3 regarding AE definitions and reporting and follow-up requirements. 
8.2.3. 
Ophthalmologic Examination  
Because immune checkpoint inhibitors like tislelizumab may be associated with imAEs, an eye 
examination (including visual acuity test) and optical coherence tomography (or equivalent 
diagnostic test for retinal examination) will be assessed by an appropriate specialist as clinically 
indicated (Appendix 1A).  
In addition, investigators should solicit patients regarding changes in vision, visual disturbance, 
or ocular inflammation at each scheduled study visit during study treatment. For any change in 
vision, referral to an appropriate specialist will be made for further management guidance (see 
Appendix 9). 
8.2.4. 
Eastern Cooperative Oncology Group Performance Status  
ECOG Performance Status (Appendix 3) will be assessed during the study. 
8.2.5. 
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 1A. 
An investigator may obtain safety laboratory results from the local laboratory as clinically 
indicated (eg, on the day of a patient’s visit before results are available from the central 
laboratory for dose modifications or AE/SAE monitoring). If required by local regulations, 
clinical laboratory evaluations performed by a local (instead of a central) laboratory are 
acceptable. 
If clinical chemistry, hematology, and coagulation at screening are not performed ≤ 7 days 
before study drug administration on Day 1 of Cycle 1, these tests should be repeated and 
reviewed before study drug administration. After Day 1 of Cycle 1, results are to be reviewed 
within 72 hours before study drug administration. 
For central laboratory assessments, details regarding sample collection and shipment will be 
provided in a separate laboratory manual. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 67 
The following tests will also be conducted in this study at timepoints shown in Appendix 1. 
• Serum or urine pregnancy test (for women of childbearing potential, including 
women who have had a tubal ligation) must be performed and documented as 
negative ≤ 7 days before the first dose of study drug(s). Furthermore, a negative 
serum or urine pregnancy test must be completed and recorded before administration 
of study drug(s) at each cycle. A serum pregnancy test must be performed if the urine 
pregnancy test is positive or equivocal. 
• Thyroid function testing (ie, thyroid stimulating hormone, free triiodothyronine [T3], 
and free thyroxine [T4])  
• Hepatitis serology and viral load (refer to Section 8.2.9) 
8.2.5.1. 
Cardiac Enzyme Monitoring  
Although immune-mediated myocarditis is a rare complication of immune checkpoint inhibitors, 
serum creatine kinase and creatine kinase-muscle/brain are monitored in all tislelizumab studies 
to protect study patients and to quantify the risk of muscle inflammation (see Appendix 1A for 
the blood collection schedule and Appendix 9 for guidelines for management of suspected 
immune-related myocarditis, respectively). Serum troponins may be substituted per local 
guidelines if used consistently throughout the study. 
8.2.6. 
Electrocardiograms  
For safety monitoring purposes, the investigator must review, sign, and date all ECG tracings. 
Paper or electronic copies of ECG tracings will be kept as part of the patient’s permanent study 
file at the site. 
All ECGs are to be obtained before other assessments scheduled at that same time (eg, vital sign 
measurements and blood draws). The patient should rest in a semirecumbent supine position for 
≥ 10 minutes in the absence of environmental distractions that may induce changes in heart rate 
(eg, television, radio, and conversation) before each ECG collection. 
The 12-lead ECGs will be performed at screening and when clinically indicated (see 
Appendix 1A). The ECG at screening must be performed in triplicate. 
8.2.7. 
Echocardiogram/Multiple Gated Acquisition Scan  
Echocardiogram/multiple gated acquisition (MUGA) scan assessments will be performed at the 
Screening Visit unless one has been performed within 28 days before the first dose of study drug, 
and as clinically indicated during the study (see Appendix 1A).  
8.2.8. 
Adverse Events  
AEs will be graded and recorded throughout the study according to NCI-CTCAE Version 5.0. 
Characterization of toxicities will include severity, duration, and time to onset.  
All AEs, including SAEs, will be collected as described in Section 9.6. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 68 
8.2.9. 
Hepatitis B and Hepatitis C Testing  
Hepatitis B/C serologic markers and/or viral load will be tested at screening. Hepatitis B and C 
testing may be performed by a local laboratory if the laboratory is able to perform the test to the 
required sensitivity (< 20 IU/mL and < 15 IU/mL for HBV and HCV, respectively); otherwise, 
the results must be confirmed by a central laboratory. The hepatitis B testing will include 
HBsAg, HBcAb, and hepatitis B surface antibody (HBsAb), as well as HBV DNA by PCR if the 
patient is negative for HBsAg but positive for HBcAb (regardless of HBsAb status). The 
hepatitis C testing will include HCV antibody as well as HCV RNA by PCR if the patient is 
positive for HCV antibody. Patients with positive HBsAg and/or detectable level of HBV DNA 
or detectable level of HCV RNA are not eligible. 
Patients who are HBsAg negative, HBcAb positive, and HBV DNA negative (< 20 IU/mL) at 
screening must be monitored for HBV DNA by PCR at a monthly frequency. These patients 
should be considered for prophylactic antiviral treatment in consultation with a local HBV 
expert. If a patient is being treated prophylactically with antivirals, HBV DNA by PCR must be 
monitored at least every 3 months.  
During monthly monitoring of HBV DNA by PCR, if the value is between 20 IU/mL and 
100 IU/mL, then the HBV DNA level should be rechecked within 2 weeks. Study drugs should 
be stopped, and antiviral therapy should be initiated if the repeated level is between 20 IU/mL 
and 100 IU/mL. If the HBV DNA by PCR is 100 IU/mL or higher, then study drugs should be 
stopped, and antiviral therapy should be initiated or continued. Resumption of study drugs in 
patients whose HBV reactivation resolves should be discussed with and approved by the medical 
monitor and physicians with expertise in managing hepatitis B.  
Patients who are HCV antibody positive and HCV RNA negative (< 15 IU/mL) at screening 
must be monitored for HCV RNA at a monthly frequency. Patients with HCV RNA of 15 IU/mL 
or higher should stop study drugs and initiate antiviral therapy. Resumption of study drugs in 
patients whose HCV reactivation resolves should be discussed with and approved by the medical 
monitor and physicians with expertise in managing hepatitis C.  
HBV DNA and HCV RNA monitoring should continue until the patient starts new antitumor 
therapy, or for any other reason listed in Section 7.5.2, whichever occurs first.  
The medical monitor should be informed of any suspected HBV or HCV reactivation  
8.3. 
Tumor and Response Evaluations  
Response will be assessed by the investigator using the Lugano Classification for NHL (see 
Appendix 8).  
Tumor imaging will be performed ≤ 28 days before the first dose of study drug(s). Results of 
standard-of-care tests or examinations performed before informed consent has been obtained and 
≤ 28 days before the first dose of study drug(s) may be used for the purposes of screening rather 
than repeating the standard-of-care tests. During the study, tumor imaging will be performed 
every 9 weeks (± 7 days), from Day 1 of Cycle 1, for the first 54 weeks; every 18 weeks 
(± 7 days) for additional 54 weeks; then every 24 weeks thereafter based on the Lugano 
Classification (2014) (Cheson et al 2014). For patients who are positive for PET-CT scans at 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 69 
screening, PET-CT should be repeated at Week 9 (± 7 days), Week 18 (± 7 days), at time when 
confirming CR or PD, and as clinically indicated. 
At screening, all patients must undergo positron-emission scan (PET)-CT scan and CT with 
contrast of neck, chest, abdomen, and pelvis. Contrast CT will be performed for each subsequent 
tumor assessment. If a patient is known to have a contraindication to CT contrast media or 
develops a contraindication during the study, an MRI should be performed but must be used 
consistently.  
PET-CT may be used in lieu of a CT with contrast only if the CT of the PET-CT has been 
performed with diagnostic quality and contrast is administered. When both PET-CT and CT 
evaluations are available for the same tumor assessment visit, the results of PET-CT shall 
prevail.  
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).  
For immune therapies such as ociperlimab and tislelizumab, pseudoprogression may occur due to 
immune-cell infiltration and other mechanisms leading to an apparent increase of existing tumor 
masses or appearance of new tumor lesions. Also, some patients may benefit from additional 
immune therapies despite evidence of PD. If radiographic PD is suspected by the investigator to 
reflect pseudoprogression and the clinical condition is stable, patients may continue treatment of 
study drugs as long as patients meet criteria below and until PD is confirmed by a repeated 
imaging ≥ 4 weeks later (but not exceeding 12 weeks from the initial documentation of PD).  
• Absence of clinical symptoms and signs of PD (including clinically significantly 
worsening of laboratory values) 
• Stable ECOG Performance Status  
• Absence of rapid progression of disease or of progressive tumor at critical anatomical 
sites (eg, cord compression) that requires urgent alternative medical intervention 
Tumor assessment should continue as planned in patients until the patient begins a new 
antitumor therapy, experiences PD, withdraws consent, is lost to follow-up, dies, or until the 
study terminates, whichever occurs first. Clinical suspicion of disease progression at any time 
will require a physical examination and radiological confirmation to be performed promptly, 
rather than waiting for the next scheduled tumor assessment. 
Tumor assessments must be performed on schedule regardless of whether study treatment has 
been administered or withheld. That is, they should not be adjusted for delays in cycles.  
8.4. 
Bone Marrow Examination  
Bone marrow biopsy and aspirate are required to assess bone marrow involvement of patients 
during the screening period, unless they have been performed within 60 days before the first dose 
of study drug and there has been no intervening therapy from the time of the biopsy/aspirate until 
the first dose of study drug. For patients who have evidence of bone marrow disease at screening, 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 70 
repeated bone marrow biopsy may not be needed if PET-CT shows bone marrow clearance at 
CR. 
8.5. 
Quantitative Serum Immunoglobulin Assessment  
Serum immunoglobulin, including IgG, IgM, and IgA will be quantitatively assessed at 
screening, together with tumor evaluations during the treatment period (every 9 weeks 
[± 7 days], from Day 1 of Cycle 1, for the first 54 weeks; every 18weeks [± 7 days] for 
additional 54 weeks; then every 24 weeks [± 7 days] thereafter [Appendix 1A]), and at the Safety 
Follow-up Visit. 
8.6. 
Pharmacokinetic Assessment and Antidrug Antibody Testing  
Blood samples will be collected for characterizing the PK of ociperlimab and tislelizumab. 
Serum samples will be assayed for ociperlimab and tislelizumab concentrations using validated 
immunoassays. Validated screening and confirmatory assays will be employed to detect ADAs at 
multiple timepoints throughout the study.  
Blood sampling for PK and ADA will be collected at the timepoints specified in the Schedule of 
Assessments (Appendix 1B and Appendix 1C). The actual time and date of each sample 
collected will be captured in the eCRF and recorded in the database. The samples will be sent to 
the sponsor or designee for storage and/or analysis. 
Refer to the laboratory manual for instructions regarding sample collection, handling, labeling, 
storage, and shipping of laboratory samples to the central laboratory. 
8.7. 
Biomarkers  
Shipping, storage, and handling of blood as well as archival tumor and/or fresh tumor tissue and 
blood sample for the assessment of biomarkers will be managed through a central laboratory. 
Refer to the laboratory manual for details of sample handling and the Schedule of Assessments 
(Appendix 1A) for sample collection timepoints. 
The archival or fresh tumor tissues are mandatory for all patients who consent to participate in 
the study. If no archival samples are available, a fresh tumor biopsy at baseline is required. Also, 
if the patient can provide eligible archival tumor tissues and is willing to undergo fresh tumor 
biopsy at screening, a fresh tumor biopsy is strongly recommended. Archival (within 1 year 
before signing the ICF) and/or fresh tumor tissues (approximately 15 unstained slides) at 
screening need to be sent to the central laboratory for diagnosis confirmation and biomarker 
analysis, including expression of PD-L1, TIGIT, CD226, CD155, and CD112, PD-L1/2 gene 
alteration, EBV status. Tumor microenvironment, immune-related gene expression profile, and 
gene mutation profile that are related to response or clinical benefit of ociperlimab in 
combination with tislelizumab or rituximab will also be evaluated. Baseline tissue samples 
collected during screening will be shipped to a central laboratory for biomarker testing after local 
regulatory approval. This may occur after the start of study treatment if necessary.  
An optional tumor biopsy will be taken from accessible tumor sites at C2D1 and C4D1 to 
explore tumor biomarkers, including tumor microenvironment and immune-related gene 
expression profile which may be associated with response and resistance to study drugs. Optional 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 71 
biopsies will also be obtained for patients treated with study drugs who have confirmed PD 
during the study from accessible tumor sites to obtain samples to explore tumor 
microenvironment and gene mutation/expression profiling associated resistance mechanism. If 
feasible, any follow-up biopsy should ideally be taken from the same tumor lesion as the baseline 
biopsy. Written patient consent is required for fresh tumor biopsies. 
Tumor tissue should be of good quality based on total and viable tumor content. Fine-needle 
aspiration, brushing, cell pellets from pleural effusion, and lavage samples are not acceptable. 
Bone marrow biopsy is not acceptable. Tumor biopsy from an inguinal lymph node is only 
acceptable when a tumor biopsy cannot be obtained from other sites. For fresh biopsy specimens, 
acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, 
punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. 
Blood samples will be collected for all patients at predose of C1D1, C1D2, C1D8, C2D1, and at 
the time of PD to explore the association of blood-based biomarkers with response, resistance, 
and prognosis to ociperlimab in combination with tislelizumab or rituximab. Blood-based 
biomarker analysis includes immune-cell quantification and phenotypes, cytokine profiling, 
immune-related gene expression profiling, and DNA/ctDNA sequencing. 
8.8. 
Visit Windows  
All visits must occur within ± 3 days from the scheduled date, unless otherwise noted (see 
Appendix 1). All assessments will be performed on the day of the specified visit unless an 
acceptable time window is specified. Assessments scheduled on the day of study treatment 
administration (Day 1) of each cycle should be performed before study treatment infusion 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 
event, 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 
from Day 1 of Cycle 1. 
8.9. 
Unscheduled Visits  
Unscheduled visits may be performed at any time at the patient’s or the investigator’s request 
and may include vital signs/focused physical examination; ECOG Performance Status; AE 
review; concomitant medications and procedures review; radiographic assessments; physical 
examination of liver, spleen, and lymph nodes; disease-related constitutional symptoms; and 
hematology and clinical chemistry laboratory assessments. The date and reason for the 
unscheduled visit must be recorded in the source documentation. 
If an unscheduled visit is necessary to assess toxicity or for suspected PD, then diagnostic tests 
may be performed based on the investigator assessment as appropriate, and the results of these 
tests should be entered on the unscheduled visit eCRF. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 72 
9. 
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. 
9.1. 
Risks Associated With Study Drug  
9.1.1. 
Risks Associated With Ociperlimab and Tislelizumab  
Ociperlimab and tislelizumab are investigational agents that are currently in clinical 
development. The first-in-human Study AdvanTIG-105 evaluating safety, tolerability, and 
clinical benefit of ociperlimab in combination with tislelizumab in solid tumors is still ongoing. 
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 9.7.3. 
Ociperlimab-mediated TIGIT inhibition may increase the risk of imAEs. However, no apparent 
immunotoxicity, or toxicity in general, have 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 evaluation and management guidelines for suspected imAEs are 
provided in Appendix 9. 
9.1.2. 
Risks Associated With Rituximab  
Rituximab is a CD20-directed cytolytic antibody, which had been received approval for the 
treatment of patients with CD20-positive DLBCL and other NHL. The important identified risks 
of rituximab included IRRs, severe mucocutaneous reactions, HBV reactivation, progressive 
multifocal leukoencephalopathy, tumor lysis syndrome, infections, cardiovascular adverse 
reactions, renal toxicity, bowel obstruction and perforation, immunizations, and embryo-fetal 
toxicity.  
Please refer to the Rituximab prescribing information 2021 for details. 
9.2. 
General Plan to Manage Safety Concerns  
9.2.1. 
Eligibility Criteria  
Eligibility criteria were selected to guard the safety of patients in this study. Results from the 
nonclinical toxicology studies and clinical data with ociperlimab and tislelizumab, as well as the 
nonclinical/clinical data from other PD-L1/PD-1 inhibitors, were considered. Specifically, 
patients at risk for study-emergent active autoimmune diseases or with a history of autoimmune 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 73 
diseases that may relapse, patients who have undergone allogeneic stem cell or organ 
transplantation, and patients who have received a live vaccine ≤ 4 weeks before the first dose of 
study drug(s) are excluded from the study. Patients with contraindications for study drugs and 
other monoclonal antibodies are also excluded from the study (see Section 4.2 for the full list of 
exclusion criteria). 
9.2.2. 
Abnormal Liver Function Tests  
The finding of an elevated ALT or AST (> 3 x baseline value) in combination with either an 
elevated total bilirubin (> 2 x ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury. Therefore, 
investigators must report as an AE the occurrence of either of the following: 
• Treatment-emergent ALT or AST > 3 x baseline value in combination with total 
bilirubin > 2 x ULN (of which 35% is direct bilirubin) 
• Treatment-emergent ALT or AST > 3 x baseline value in combination with clinical 
jaundice 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal laboratory 
values should be recorded on the AE eCRF and reported to the sponsor immediately (ie, 
≤ 24 hours after learning of the event). 
9.2.3. 
Safety Monitoring Plan  
Safety will be evaluated in this study through the monitoring of all AEs, defined and graded 
according to NCI-CTCAE Version 5.0.  
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 3), 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 infections or autoimmune conditions. 
At the start of each cycle, study drug(s) will be administered only after clinical laboratory results 
have been reviewed. Administration of study drug(s) 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 
patients for both the Dose Confirmation and Dose Expansion Stages of the study.  
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 9.7. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 74 
9.3. 
Adverse Events  
9.3.1. 
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 
drug(s), whether considered related to study drug(s) 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 
• Detection or diagnosis of a new condition after study drug(s) 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 
drug(s) 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. 
9.3.2. 
Assessment of Severity  
The investigator will assess the severity for each AE and SAE reported during the study. AEs 
and SAEs should be assessed and graded based upon NCI-CTCAE Version 5.0. 
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-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 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 75 
regulatory definitions. Seriousness serves as the guide for defining regulatory reporting 
obligations from the sponsor to applicable regulatory authorities as described in Section 9.6.2. 
9.3.3. 
Assessment of Causality  
The investigator is obligated to assess the relationship between the study drug(s) and the 
occurrence of each AE or SAE using best clinical judgment. Alternative causes, such as natural 
history of the underlying diseases, concomitant therapy, other risk factors, and the temporal 
relationship of the AE or SAE to the study drug(s) should be considered and investigated. The 
investigator should consult the Tislelizumab (BGB-A317) Investigator’s Brochure, Ociperlimab 
(BGB-A1217) Investigator’s Brochure, and Rituximab prescribing information 2021 in the 
determination of his/her assessment. 
There may be situations when an SAE has occurred, and the investigator has only limited 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assesses causality for every SAE before transmission of the SAE report to 
the sponsor because the causality assessment is 1 of the criteria used when determining 
regulatory reporting requirements. The investigator may subsequently change his/her opinion of 
causality considering follow-up information and may amend the SAE report accordingly. 
The causality of each AE should be assessed and classified by the investigator as “related” or 
“not related” based on all information available at the time of reporting. An AE is considered 
related if there is “a reasonable possibility” that the AE may have been caused by the study 
drug(s) (ie, there are facts, evidence, or arguments to suggest possible causation). A number of 
factors should be considered in making this assessment, including: 
• Temporal relationship of the AE to the administration of study treatment/study 
procedure 
• Whether an alternative etiology has been identified 
• Mechanism of action of the study drug(s) 
• Biological plausibility 
• An AE should be considered “related” to study drug(s) if any of the following criteria 
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 drug[s]). However, the 
influence of other factors may have contributed to the AE (eg, the patient’s 
clinical condition or other concomitant AEs). 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 76 
9.3.4. 
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 timeframes outlined in Section 9.6.2. 
9.3.5. 
Laboratory Test Abnormalities  
Abnormal laboratory findings (eg, clinical chemistry, complete blood count, coagulation, or 
urinalysis) or other abnormal assessments (eg, ECGs, x-rays, or vital signs) that are judged by 
the investigator as clinically significant will be recorded as AEs or SAEs. This includes clinically 
significant abnormal laboratory findings or other abnormal assessments that are present at 
baseline and significantly worsen during the study. The definition of clinically significant is left 
to the judgment of the investigator. In general, these are the laboratory test abnormalities or other 
abnormal assessments that: 
• are associated with clinical signs or symptoms, or  
• require active medical intervention, or  
• lead to treatment 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 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 77 
the event should be recorded, and the severity or seriousness should be updated any time the 
event worsens. 
9.4. 
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 to be 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 
9.5. 
Suspected Unexpected Serious Adverse Reaction  
A suspected unexpected serious adverse reaction is a serious adverse reaction that is both 
unexpected (ie, not present in the study drug’s reference safety information) and meets the 
definition of a serious adverse drug reaction, the specificity or severity of which is not consistent 
with those noted in the Tislelizumab (BGB-A317) Investigator’s Brochure, Ociperlimab 
(BGB-A1217) Investigator’s Brochure, and Rituximab prescribing information 2021. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 78 
9.6. 
Timing, Frequency, and Method of Capturing Adverse Events and 
Serious Adverse Events  
9.6.1. 
Adverse Event Recording Period  
After informed consent has been signed but before the administration of the study drug(s), only 
SAEs should be reported. 
After the first dose of study drug(s), all AEs and SAEs, regardless of relationship to study 
drug(s), will be reported until either 30 days after the last dose of study drug(s) or initiation of 
new antitumor therapy, whichever occurs first. Immune-mediated AEs (serious or nonserious) 
should be recorded until 90 days after the last dose of ociperlimab and tislelizumab, regardless of 
whether or not the patient starts a new antitumor 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. 
AEs and SAEs should be recorded according to the details in Table 3. For the follow-up period 
for AEs, see Section 9.3.4. For the definition of treatment-emergent adverse events (TEAEs), see 
Section 10.3.2. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 79 
Table 3: 
Guidance for Duration of Recording New or Worsening Adverse Events in 
Cohort 1 and Cohort 2 
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 antitumor 
therapy, death, withdrawal of 
consent, or loss to follow-up, 
whichever occurs first 
Treatment-related SAEs 
Signing of informed consent 
Patient death, withdrawal of 
consent, or loss to follow-up, 
whichever occurs first 
Nonserious AEs due to PD 
Do not record (see Section 9.6.4) 
All nonserious AEs, except 
those due to PD 
First dose of study drug 
Up to 30 days after last dose, 
initiation of new antitumor 
therapy, death, withdrawal of 
consent, or loss to follow-up, 
whichever occurs first 
Immune-mediated AEs (serious 
or nonserious) 
First dose of study drug 
Up to 90 days after last dose 
(regardless of initiation of new 
antitumor therapy), death, 
withdrawal of consent, or loss to 
follow-up, whichever occurs 
first 
Abbreviations: AE, adverse event; PD, progressive disease; SAE, serious adverse event. 
a． All SAEs considered related to the study drug(s) that are brought to the attention of the investigator should be 
reported regardless of time since the last dose of treatment. 
9.6.2. 
Reporting Serious Adverse Events  
9.6.2.1. 
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 4. 
Table 4: 
Timeframes and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee 
 
Timeframe for sending 
initial/follow-up reporta     Documentation method 
Reporting method 
All SAEs before 
the study 
termination 
≤ 24 hours after first 
knowledge of the SAE 
SAE report 
Electronic submission of 
SAE form to portalb            
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 80 
All SAEs after 
the study 
termination 
≤ 24 hours after first 
knowledge of the SAE 
SAE report 
Email or fax SAE form 
Abbreviations: AE, adverse event; SAE, serious adverse event. 
a Report follow-up information that is clinically relevant and pertains to the SAE, which includes but is not limited 
to the following: Update to the SAE, new additional SAE, outcome, seriousness criteria, investigator causality, 
event start date/date of onset, date of death, relationship to each study drug. Follow-up information will also be 
reported as per the discretion of the investigator if the new or updated information changes the medical assessment 
of the case. 
b SAE reports should be submitted to the sponsor safety database electronically from within the electronic data 
capture system. If the electronic submission is not available for any reason, a paper SAE form should be submitted 
by email or fax. 
9.6.2.2. 
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 9.6.2.1. 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 timeframes. 
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 9.3.3. 
The sponsor will provide contact information for SAE receipt. 
9.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events  
The investigator will report all SAEs to the sponsor in accordance with the procedures detailed in 
Section 9.6.2.1. 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 suspected unexpected serious adverse reactions (as defined in Section 9.5) will be submitted 
to all applicable regulatory authorities and investigators for ociperlimab, tislelizumab, and 
rituximab 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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 81 
9.6.3. 
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? 
9.6.4. 
Progressive Disease  
Disease progression, which is expected in this study population and is measured as an efficacy 
endpoint, should not be recorded as an AE term. Similarly, nonserious AEs that are clearly 
consistent with the pattern of progression of the underlying disease and are considered 
unequivocally due to disease progression should not be recorded. However, if there is any 
uncertainty as to whether a nonserious AE is due to disease progression, it should be recorded as 
an AE (Section 9.6.2).  
9.6.5. 
Deaths  
When a patient dies, if the only information available is death and the cause of death is unknown, 
then the death is reported as an AE, eg, “death NOS.” In all other cases, death is captured as an 
outcome. 
9.6.6. 
Recording Pregnancies  
If a female patient or the partner of a male patient becomes pregnant while receiving study 
drug(s) or within 120 days after the last dose of ociperlimab and/or tislelizumab, or within 
12 months after the last dose of rituximab, 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 drug(s) should be recorded and reported as an SAE. 
9.6.7. 
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: 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 82 
• Ociperlimab (BGB-A1217) Investigator’s Brochure 
• Tislelizumab (BGB-A317) Investigator’s Brochure 
• Rituximab prescribing information 2021 
9.6.8. 
Assessing and Recording Immune-Mediated Adverse Events  
Since treatment with anti-PD-1 or ociperlimab therapy can cause autoimmune disorders, AEs 
considered by the investigator to be immune related (see Section 9.7.3) should be classified as 
imAEs and identified as such in the eCRF AE page. Not all tislelizumab studies include a section 
in the eCRF AE page where imAEs are clearly identified. Therefore, all studies will rely on the 
company list of potential imAEs to identify all cases in each study to be further assessed as 
imAEs by the sponsor, in addition to those imAEs reported by the investigator via the AE CRF 
page. 
Investigators should consult the guidance on diagnostic evaluation and management of imAEs, 
which are commonly seen with immune checkpoint inhibitors, in Appendix 9. 
An extensive list of potential imAEs appears in Table 6. All conditions similar to 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 9. 
9.6.9. 
Recording Infusion-Related Reactions  
The symptoms of IRRs 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. Individual signs and symptoms of an 
infusion reaction should be recorded each as a separate AE in the eCRF and identified as an IRR. 
Refer to the eCRF completion guidelines for details. 
9.7. 
Management of Adverse Events of Special Interest  
As a routine precaution, following completion of study drug(s) administration, patients must be 
monitored for a period afterward in a setting where emergency medical equipment and staff who 
are trained to respond to medical emergencies are available. 
The management for IRRs, severe hypersensitivity reactions, and imAEs according to the 
NCI-CTCAE criteria are outlined in the following subsections. 
9.7.1. 
Managing Infusion-Related Reactions  
Patients should be closely monitored for IRRs. 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 IRRs. 
Treatment modifications for symptoms of IRRs due to study drug(s) are provided in Table 5. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 83 
Table 5: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due to 
Study Drug(s) 
NCI-CTCAE grade 
Treatment modification for ociperlimab, 
tislelizumab, or rituximab 
Grade 1 - mild 
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated. 
Decrease infusion rate by 50%. Any worsening is 
closely monitored. Medical management as needed.  
Subsequent infusions should be given after 
premedication and at the reduced infusion rate. 
Grade 2 - moderate 
Therapy or infusion interruption indicated but responds 
promptly to symptomatic treatment (eg, antihistamines, 
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 reaction 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.  
Subsequent infusions should be given after 
premedication and at the reduced infusion rate. 
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 study drug 
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 study drug 
treatment. 
Hospitalization is recommended. 
Abbreviations: NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events. 
Once the ociperlimab, tislelizumab, or rituximab infusion rate has been decreased by 50% or 
suspended due to an IRR, it must remain decreased for all subsequent infusions and 
premedication must be administered. If the patient has a second IRR (≥ Grade 2) on the slower 
infusion rate, the infusion should be discontinued and the patient should be withdrawn from 
ociperlimab, tislelizumab, or rituximab treatment. 
NCI-CTCAE Grade 1 or 2 infusion reaction: Proper medical management should be 
instituted, as indicated per the type of reaction. This includes but is not limited to an 
antihistamine (eg, diphenhydramine or equivalent), antipyretic (eg, paracetamol or equivalent), 
and, if considered indicated, oral or intravenous glucocorticoids, epinephrine, bronchodilators, 
and oxygen. In the next cycle, the patient should receive oral premedication 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 antihistamines, antipyretics, glucocorticoids, epinephrine, bronchodilators, 
and oxygen. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 84 
9.7.2. 
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 must be 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 patient will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed. The patient should then 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 or 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. 
9.7.3. 
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 in the eCRF AE page should be checked. 
A list of potential imAEs is shown below in Table 6. All conditions similar to those listed should 
be evaluated in patients receiving tislelizumab or ociperlimab to determine whether they are 
immune related. 
Recommendation for diagnostic evaluation and management of imAEs is based on European 
Society for Medical Oncology and American Society of Clinical Oncology guidelines 
(Haanen et al 2017; Brahmer et al 2018) and common immune-mediated toxicities are detailed in 
Appendix 9. For any AEs not included in Appendix 9, please 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-related toxicities. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 85 
Table 6: 
Examples of Immune-Mediated Adverse Events 
Body system affected 
Events 
Skin (mild-common) 
pruritus or maculopapular rash; vitiligo 
Skin (moderate) 
follicular or urticarial dermatitis; erythematous/lichenoid rash; Sweet syndrome 
Skin (severe-rare) 
full-thickness necrolysis/Stevens-Johnson syndrome 
Gastrointestinal 
colitis (includes diarrhea with abdominal pain or endoscopic/radiographic evidence 
of inflammation); pancreatitis; hepatitis; aminotransferase (ALT/AST) elevation; 
bowel perforation 
Endocrine 
thyroiditis, hypothyroidism, hyperthyroidism; hypophysitis with features of 
hypopituitarism (eg, fatigue, weakness, weight gain); insulin-dependent diabetes 
mellitus; diabetic ketoacidosis; adrenal insufficiency 
Respiratory 
pneumonitis/diffuse alveolitis 
Eye 
episcleritis; conjunctivitis; iritis/uveitis 
Neuromuscular 
arthritis; arthralgia; myalgia; neuropathy; Guillain-Barre syndrome; aseptic 
meningitis; 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 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase. 
Recommendations for managing imAEs are detailed in Appendix 9. 
If a toxicity does not resolve to ≤ Grade 1 within 12 weeks, study drug(s) should be discontinued 
after consultation with the sponsor. Patients who experience a recurrence of any event at the 
same or higher severity grade after restart of study drug should permanently discontinue 
treatment. 
9.7.4. 
Management of Immune-mediated AEs in Patients With Pre-Existing Renal 
Dysfunction  
Patients with moderate renal dysfunction (as estimated by Cockcroft-Gault equation or as 
measured by nuclear medicine scan or 24-hour urine collection) may be enrolled into the study. 
For patients with baseline renal insufficiency, the following algorithm is proposed for the use of 
steroid treatment in the management of imAEs: 
• If the serum creatinine was normal at baseline, please see Section 9.7.3 and refer to 
Appendix 9 for the diagnosis and management of patients with abnormal renal 
laboratory values. 
• If the serum creatinine was Grade 1 at baseline and the increase in serum creatinine 
meets criteria for serum creatinine increase ≥ Grade 2 after starting treatment with 
study drug(s), refer to Appendix 9 for the diagnosis and management of patients with 
abnormal renal laboratory values. Check the estimated creatinine clearance using 
Appendix 7. In the setting of a Grade 2 serum creatinine increase only, study 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 86 
treatment can continue unless the serum creatinine increases by ≥ 50% from the 
baseline value. 
• If the serum creatinine is Grade 2 at baseline and the increase in serum creatinine 
meets criteria for serum creatinine increase ≥ Grade 3 after starting treatment with 
study drug(s), refer to Appendix 9 for the diagnosis and management of patients with 
abnormal renal laboratory values. In the setting of a Grade 3 serum creatinine 
increase only, study treatment will be held until serum creatinine improves to baseline 
and treatment may resume only after discussion with the medical monitor. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 87 
10. 
STATISTICAL METHODS AND SAMPLE SIZE 
DETERMINATION  
As described in the study objectives, this study is designed to establish the safety and tolerability 
of ociperlimab in combination with tislelizumab or rituximab and to assess preliminary antitumor 
activities in patients with R/R DLBCL. 
Details of the statistical analyses will be included in a separate statistical analysis plan. 
10.1. 
Statistical Analysis  
10.1.1. 
Analysis Sets  
The Safety Analysis Set includes all patients who received any dose of any study drug(s). This 
will be the analysis set for the safety analyses. 
The Efficacy Analysis Set includes all patients who received any dose of any study drug(s), have 
evaluable disease at baseline, and have ≥ 1 evaluable postbaseline tumor response assessment 
unless any clinical PD or death occurred before the first postbaseline tumor assessment. 
The DLT-Evaluable Analysis Set includes patients who 1) experienced a DLT event or 2) 
received ≥ 80% each scheduled study drug administration remained on study during the DLT 
assessment window in the dose confirmation stage. 
The PK Analysis Set includes all patients who received any dose of any study drug(s) per the 
protocol, for whom any quantifiable postdose PK concentrations are available. 
The Immunogenicity Analysis Set includes all patients who received any dose of any study 
drug(s), for whom both baseline ADA and ≥ 1 postbaseline ADA results are available. 
10.1.2. 
Patient Disposition  
The number of patients enrolled, treated (by each study drug), and discontinued from study 
drug(s) and/or the study will be counted. The primary reason for study drug(s) and/or study 
discontinuation will be summarized according to the categories in the eCRF. 
10.1.3. 
Demographic and Other Baseline Characteristics  
Demographic and other baseline characteristics will be summarized descriptively in the Safety 
Analysis Set. Continuous variables might include age, weight, and body mass index. Categorical 
variables might include sex, ECOG Performance Status, race, ethnicity, hepatitis B core 
antibody, and hepatitis C antibody. A listing of demographic and other baseline characteristics 
will be provided.  
10.1.4. 
Prior and Concomitant Medications  
Prior medications will be defined as medications that started before the day of first dose of study 
drug(s). Concomitant medications will be defined as medications that 1) started before the first 
dose of study drug(s) and were continuing at the time of the first dose of study drug(s), or 
2) started on or after the date of the first dose of study drug(s) and up to 30 days after the 
patient’s last dose or the initiation of a new anticancer therapy. Concomitant medications will be 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 88 
coded using the World Health Organization Drug Dictionary drug codes. Prior and concomitant 
medications will be summarized and listed by drug and drug class. A listing of prior and 
concomitant medications will be provided. 
10.2. 
Efficacy Analyses  
Efficacy analyses will be conducted based upon investigators’ tumor assessments using the 
Lugano Classification (2014) (Cheson et al 2014) in the Efficacy Analysis Set, performed by 
cohort and dose if necessary. 
ORR 
The primary efficacy endpoint is ORR. ORR is defined as the proportion of patients achieving a 
best overall response of CR or PR. The point estimate and corresponding two-sided 
Clopper-Pearson 95% CI for ORR will be presented.  
The best overall response is defined as the best response recorded from the date of first dose of 
study drug(s) to the date of documented PD or new anti-cancer therapy, whichever occurs first. 
The proportion for each response category (CR, PR, stable disease [SD], and PD) will be 
presented.  
For patients in the Efficacy Analysis Set but with clinical PD or death occurring before the first 
postbaseline tumor assessment, their best overall response will be considered as PD or Not 
Assessable, respectively.  
CR rate 
CR rate will be summarized with the same method as ORR. 
DOR  
DOR for responders (CR or PR) is defined as the time (months) from the date of the earliest 
qualifying response (PR or better) to the date of PD, as determined by the investigator, or death 
for any cause, whichever occurs earlier. The DOR censoring rule will follow the United States 
Food and Drug Administration Guidance for Industry Clinical Trial Endpoints for the Approval 
of Cancer Drugs and Biologics (US Food and Drug Administration 2018). Kaplan-Meier 
methodology will be used to estimate the median and other quartiles and 95% CI for DOR. Only 
responders will be included in this analysis. 
PFS 
PFS is defined as the time (months) from the date of first dose of study drug(s) to PD, as 
determined by the investigator, or death of any cause, whichever occurs first. The censoring rules 
for PFS will follow the DOR censoring rules.  
Kaplan-Meier methodology will be used to estimate the median and other quantiles of PFS. 
Kaplan-Meier curves will be constructed to provide a visual description of the PFS change with 
time. Two-sided 95% CIs of median and other quartiles, if estimable, will be constructed with a 
generalized Brookmeyer and Crowley method (Brookmeyer and Crowley 1982) with log-log 
transformation. PFS rates at selected landmark timepoints (eg, 6-month) will be provided with 
the corresponding 95% CIs calculated based on the Greenwood’s formula (Greenwood 1926) 
with log-log transformation. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 89 
The duration of the follow-up for PFS will be determined by reverse Kaplan-Meier method 
(Schemper and Smith 1996).  
TTR  
TTR for responders (CR or PR) is defined as the time (months) from the date of first dose of 
study drug(s) to the date of the earliest qualifying response (PR or better) as determined by the 
investigator. TTR will be summarized by sample statistics, such as mean, median, and standard 
deviation for responders only.   
OS 
OS is defined as the time (months) from the date of first dose of study drug(s) to death due to any 
cause. Patients who remain alive before data cutoff date or discontinuation of the study 
(discontinued study due to reasons other than “Death”) will be censored at the time of the last 
date the patient is known to be alive. OS will be analyzed using the similar method as described 
for PFS.  
All PD-L1-related subgroups analyses will be conducted using the same method as above and 
based on centrally tested PD-L1 expression level. 
10.3. 
Safety Analyses  
Safety analyses will be conducted in the Safety Analysis Set and DLT-Evaluable Analysis Set 
and by cohort and dose if necessary. 
10.3.1. 
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 (weeks), cumulative total 
dose received per patient (mg), actual dose intensity, and relative dose intensity. 
The number (percentage) of patients requiring treatment interruption and dose delay will be 
summarized for each study drug. Reasons for dose modifications will be summarized as well. 
Patient data listings will be provided for dosing records and for calculated summary statistics. 
10.3.2. 
Adverse Events  
The AE verbatim descriptions (investigator’s description from the eCRF) will be coded using 
MedDRA.  
DLTs will be summarized at each dose cohort in dose confirmation stage. 
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) and up to 30 days following study 
drug(s) discontinuation or initiation of new antitumor therapy, whichever occurs first. Worsening 
of any TEAE to Grade 5 beyond 30 days after the last dose of study drugs is also considered a 
TEAE (if it is prior to the initiation of new anticancer therapy). The TEAE classification also 
applies to imAEs that are recorded up to 90 days after the last dose of tislelizumab and/or 
ociperlimab, regardless of whether or not the patient starts a new antitumor therapy. Only AEs 
that were treatment emergent will be included in summary tables of TEAEs. All AEs, 
treatment-emergent or otherwise, will be presented in patient data listings. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 90 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs by 
System Organ Class and Preferred Term. A patient will be counted only once by the highest 
severity grade per NCI-CTCAE Version 5.0 within a System Organ Class and Preferred Term, 
even if the patient experienced ≥ 1 TEAE within a specific System Organ Class and Preferred 
Term. The number (percentage) of patients with TEAEs will also be summarized by relationship 
to the study drug(s). 
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, treatment 
interruption, or dose delay will be summarized. 
10.3.3. 
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 provided. Laboratory parameters that are graded by 
NCI-CTCAE Version 5.0 or higher will be summarized by NCI-CTCAE grade.  
A data listing of patients with Grade 3 or higher postbaseline toxicity for selected laboratory 
parameters will be provided. Other analysis such as descriptive summary statistics or changes 
from baseline by visit for laboratory parameters might be summarized if deemed necessary. 
10.3.4. 
Vital Signs  
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate, 
and body temperature) and changes from baseline might be presented if deemed necessary.  
10.3.5. 
Electrocardiograms  
Actual value and change from baseline for the ECG parameters (such as QT interval, heart rate, 
and QTcF interval) may be presented by visit if deemed necessary. 
10.3.6. 
Eastern Cooperative Oncology Group (ECOG) Performance Status  
A shift table from baseline to worst post-baseline score in ECOG Performance Status may be 
summarized if deemed necessary. 
10.4. 
Pharmacokinetic Analyses  
Serum concentration data and PK parameters (as appropriate) of ociperlimab and tislelizumab for 
each sampling time will be tabulated and summarized by visit/cycle for each treatment. 
Descriptive statistics will include means, medians, ranges, and standard deviations, as 
appropriate.  
Additional PK analyses such as population PK analyses may be conducted as appropriate, and 
the results of such analyses may be reported separately from the clinical study report.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 91 
10.5. 
Immunogenicity Analyses  
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 and reported separately from the main clinical 
study report. 
10.6. 
Other Exploratory Analyses  
Exploratory biomarker analyses will be performed in an effort to understand the association of 
these markers with study drug(s) response, such as efficacy. 
10.7. 
Sample Size Consideration  
The study plans to enroll approximately 66 to 80 patients: 
• Cohort 1: Approximately 43 to 50 patients  
• Cohort 2: Approximately 23 to 30 patients  
For Cohort 1, the sample size of approximately 40 patients at RP2D is based on the precision of 
the estimate of ORR, a consideration that a relatively sufficient number of patients is needed to 
justify performing further analysis (eg, the subgroup analysis based on cutoff value of tumor 
PD-L1 expression), and a probability that is high enough to observe certain AEs of interest (eg, 
rash). With 40 patients, if the observed ORR is 60%, the corresponding Clopper-Pearson 95% CI 
will be 43.3% to 75.1%. For an AE with a rate of 10%, there is 98.5%probability to observe 
≥ 1 event of such an AE among all 40 patients (multiple same AE on one patient will be counted 
only once). To reflect the natural distribution across PD-L1 expression given a relatively small 
sample size at interim analysis, the number of eligible patients with PD-L1 expression ≤ 5% on 
the surface of tumor cells as determined by local laboratory will be capped to ≤ 50% of the first 
20 patients enrolled, and the benefit-risk profile may also be evaluated by the SMC and sponsor 
for these patients. After the interim analysis, the number of these patients with PD-L1 expression 
≤ 5% on the surface of tumor cells as determined by local laboratory may be further capped per 
the SMC’s recommendation considering the totality of emerging data. Considering the patients 
in the Dose Confirmation Stage that are not dosed at RP2D dose level (approximately 3 to 
10 patients), approximately 43 to 50 patients in total will be enrolled in Cohort 1. 
For Cohort 2, the sample size of approximately 20 patients at RP2D is based on the precision of 
the estimate of ORR. With 20 patients, if the observed ORR is 60%, the corresponding 
Clopper-Pearson 95% CI will be 36.1% to 80.9%. Considering the patients in the Dose 
Confirmation Stage that may not be dosed at RP2D dose level (approximately 3 to 10 patients), 
approximately 23 to 30 patients in total will be enrolled in Cohort 2. 
10.8. 
Interim Analyses  
One futility interim analysis for ORR is planned to be conducted when approximately 20 patients 
have been enrolled and meet the definition of Efficacy Analysis Set with a non-binding futility 
boundary of 35% (equivalent to observe ≤ 7 responders) for Cohort 1. If the true ORR is as low 
as 30%, there is 77% of probability that the futility boundary is met; if the true ORR is otherwise 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 92 
deemed to be at least 60%, the probability of meeting the boundary is estimated to be ≤ 2%. The 
final decision will be made by the SMC along with the sponsor.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 93 
11. 
STUDY COMMITTEES  
11.1. 
Safety Monitoring Committee  
An SMC will be established and include both the sponsor (including the medical monitor and 
study team members from Pharmacovigilance/Drug Safety, Clinical Pharmacology, and 
Biostatistics with other members as appropriate) and investigators. The SMC will review all 
available safety, efficacy, PK, and exploratory data and make recommendations of RP2D on 
Dose Confirmation Stage.  
The SMC will continue monitoring safety data throughout the study and make the decision along 
with the sponsor at the interim analysis for Cohort 1. The SMC may also be called upon by the 
sponsor on an ad hoc basis where applicable to the conduct of the study. The details of SMC 
membership, responsibilities, and meeting schedule are outlined in a separate SMC Charter. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 94 
12. 
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. 
12.1. 
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 study monitor is responsible for routine review of the eCRFs at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any patient records needed to 
verify the entries in the eCRFs. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected during these monitoring visits are resolved. 
12.2. 
Access to Information for Auditing or Inspections  
Representatives of regulatory authorities or of BeiGene 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 representatives of a regulatory agency or 
BeiGene access to records, facilities, and personnel for the effective conduct of any inspection or 
audit. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 95 
13. 
QUALITY ASSURANCE AND QUALITY CONTROL  
13.1. 
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. 
13.2. 
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. 
13.3. 
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. 
13.4. 
Drug Accountability  
The investigator or designee (ie, pharmacist) is responsible for ensuring adequate accountability 
of all used and unused study drug(s). This includes acknowledgment of receipt of each shipment 
of study drug(s) (quantity and condition), patient drug dispensation records, and returned or 
destroyed study drug(s). Dispensation records will document quantities received from BeiGene’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 BeiGene 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 BeiGene’s requirements specified in the Pharmacy Manual 
for disposal, arrangements will be made between the site and BeiGene or its representative for 
destruction or return of unused study drug supplies. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 96 
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 97 
14. 
ETHICS/PROTECTION OF HUMAN PATIENTS  
14.1. 
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 patient. 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). 
14.2. 
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 IEC/IRB correspondence and approval of the amended ICF/other information and the 
approved amended ICF/other information must be forwarded to the sponsor promptly. 
The principal investigator is responsible for providing written summaries of the status of the 
study to the IRB/IEC annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC. Investigators are also responsible for promptly 
informing the IRB/IEC of any protocol amendments. In addition to the requirements for 
reporting all AEs to the sponsor, investigators must comply with requirements for reporting 
SAEs to the local health authority and IRB/IEC. Investigators may receive written 
Investigational New Drug 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. 
14.2.1. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 98 
14.3. 
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 reconsented to the most current version of the ICFs (or to a significant new 
information/findings addendum in accordance with applicable laws and IRB/IEC policy) during 
their participation in the study. For any updated or revised ICFs, the case history or clinical 
records for each patient shall document the informed consent process and that written informed 
consent was obtained using the updated/revised ICFs for continued participation in the study. 
A copy of each signed ICF must be provided to the patient or the patient’s legally authorized 
representative. All signed and dated ICFs must remain in each patient’s study file or in the site 
file and must be available for verification by study monitors at any time. 
14.4. 
Patient and Data Confidentiality  
The investigator, institution, sponsor, and site will maintain confidentiality and privacy standards 
for the collection, storage, transmission, and processing of patients’ personal and medical 
information by following applicable laws and regulations related to the confidentiality, use, and 
protection of such information, including the ICH Good Clinical Practice Guideline, as 
implemented locally.  Such laws may be more stringent than the requirements in this protocol. 
The investigator and site shall code the personal and medical information obtained during the 
study with a unique patient identification number assigned to each patient enrolled in the study.  
The investigator must ensure that patients’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties.  Unless required to be provided by laws or 
regulations or specifically requested in exceptional circumstances by the sponsor or its 
representatives, the investigator and site must ensure that any personal and medical information 
transmitted to sponsor or its service providers is: 1) required by the protocol, and 2) 
appropriately de-identified (eg, via redaction and/or coding with the patient identification 
number) to ensure the following information about patients are NOT shared: 
o names or initials (full or partial); 
o full dates of birth; 
o contact information (such as phone numbers or home or email addresses);  
o 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; 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 99 
o geographic identifiers smaller than a state, province, or local equivalent (such as 
city, county, zip code, or other equivalent geographic identifiers); or  
o information about marital status, family, or household members; employment, sex life, 
sexual preference, or other sensitive data that is not relevant to the study. 
Patient personal and medical information obtained during this study is confidential and may only 
be disclosed to third parties as permitted by the signed ICF (or a separate authorization for the 
use and disclosure of personal health information that has been signed by the patient), unless 
permitted or required by law. 
In limited circumstances, such as in connection with insurance purposes or patient support 
services ancillary to certain study sites (eg, for patient travel or reimbursement), the investigator 
and site may provide certain of this personal information to the sponsor or its representatives.  
Such personal information may not be provided as part of the study protocol (eg, as part of the 
eCRF, on samples or reports submitted to the central lab, on safety reporting forms [except in 
China], or on product dispensing logs provided to the sponsor, etc.). 
Investigator and site must use only the specific forms and clinical trial systems, (eg, the 
electronic data capture [EDC] system and any secure file transfer platforms [SFTPs]) designated 
by sponsor for sharing and transfers of personal and medical information.  
In the event of a breach of the confidentiality of a patient’s personal and medical information, the 
investigator, site, and sponsor, as appropriate, shall fulfill all mediation steps and reporting 
obligations under applicable laws.  If the sponsor identifies personal or medical information that 
was not properly de-identified, it may be required to report the disclosure under local applicable 
laws. 
Medical information may be given to a patient’s personal physician or other appropriate medical 
personnel responsible for the patient’s welfare for treatment purposes where allowed by local 
law or the patient’s signed ICF. 
Information generated during this study must be available for inspection upon request by 
representatives of the United States Food and Drug Administration (US FDA), the China 
National Medical Products Administration (China NMPA), and all other national and local 
health authorities; by sponsor monitors, representatives, and collaborators; and by the IRBs/IECs 
for each study site, as appropriate. 
The investigator agrees that all information received from the sponsor, including but not limited 
to the Investigator’s Brochure, this protocol, eCRFs, the investigational drugs, and any other 
study information, are confidential and remain the sole and exclusive property of the sponsor 
during the conduct of the study and thereafter.  This information is not to be disclosed to any 
third party (except employees or agents directly involved in the conduct of the study or as 
required by law) without prior written consent from the sponsor.  The investigator further agrees 
to take all reasonable precautions to prevent the disclosure by any employee or agent of the study 
site to any third party or otherwise into the public domain. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 100 
14.5. 
Financial Disclosure  
Investigators are required to provide the sponsor with sufficient accurate financial information in 
accordance with regulations to allow the sponsor to submit complete disclosure or certification to 
the absence of certain financial interest of the clinical investigators and/or disclose those 
financial interests, as required, to the appropriate health authorities. This is intended to ensure 
financial interests and arrangements of the clinical investigators with BeiGene 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). 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 101 
15. 
DATA HANDLING AND RECORD KEEPING  
15.1. 
Data Collection and Management Responsibilities  
15.1.1. 
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. 
15.1.2. 
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 e-signature of the investigator or designee must be 
provided in the electronic data capture system to attest to its accuracy, authenticity, and 
completeness. 
Data contained in the eCRFs are the sole property of BeiGene and should not be made available 
in any form to third parties without written permission from BeiGene, except for authorized 
representatives of BeiGene or appropriate regulatory authorities. 
15.1.3. 
Data Management/Coding  
All final patient data, both eCRF and external data (eg, laboratory data), collected according to 
the protocol will be stored by BeiGene at the end of the study. 
Standard procedures (including following data review guidelines, computerized validation to 
produce queries, and maintenance of an audit file that includes all database modifications) will 
be followed to support accurate data collection. Data will be reviewed for outliers, logic, data 
inconsistencies, and completeness. 
During the study, a study monitor will make site visits to review protocol compliance, compare 
eCRFs against individual patient’s medical records, and ensure that the study is being conducted 
according to pertinent regulatory requirements. 
The eCRF entries will be verified with source documentation. The review of medical records 
will be performed in a manner to ensure that patient confidentiality is maintained. Checking the 
eCRFs for completeness, clarity, and cross-checking with source documents is required to 
monitor the progress of the study. Direct access to source data is also required for inspections 
and audits and will be carried out with due consideration to data protection and medical 
confidentiality. 
The AE verbatim descriptions (the investigator’s description from the eCRF) will be coded using 
MedDRA. AEs will be coded to MedDRA by Lowest Level Term, Preferred Term, and primary 
System Organ Class. Concomitant medications will be coded using the World Health 
Organization Drug Dictionary. Concomitant diseases/medical history will be coded using 
MedDRA. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 102 
15.2. 
Study Records Retention  
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least 1 of the following 2 categories: 1) investigator’s study file and/or 
2) patient clinical source documents. 
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/IEC and governmental approval with correspondence, ICFs, drug records, staff curriculum 
vitae and authorization forms, and other appropriate documents and correspondence. 
Patient clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the eCRFs) would include 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, screening and enrollment logs, etc. 
Following closure of the study, the investigator must maintain all study records in a safe and 
secure location. The records must be maintained to allow easy and timely retrieval, when needed 
(eg, audit or inspection), and, whenever feasible, to allow any subsequent review of data in 
conjunction with assessment of the facility, supporting systems, and personnel. Where permitted 
by local laws/regulations or institutional policy, some or all of these records can be maintained in 
a format other than hard copy (eg, microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions are 
legible, are a true and accurate copy of the original, and meet accessibility and retrieval 
standards, including regenerating a hard copy, if required. Furthermore, the investigator must 
ensure there is an acceptable backup of these reproductions and that an acceptable quality control 
process exists for making these reproductions. 
The sponsor will inform the investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to that study center for the study, as dictated by any institutional 
requirements, local laws or regulations, or the sponsor’s standards/procedures; otherwise, the 
retention period will default to 15 years. 
The investigator must notify the sponsor of any changes in the archival arrangements including 
but not limited to the following: archival at an off-site facility or transfer of ownership of or 
responsibility for the records in the event the investigator leaves the study center. 
If the investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and BeiGene 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 CRO managing the biological samples, for the shorter of a period of up to 10 years or as 
allowed by your IRB/IEC. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 103 
15.3. 
Protocol Deviations  
The investigator is responsible for ensuring that the study is conducted in accordance with the 
procedures and evaluations described in this protocol. Investigators assert they will apply due 
diligence to avoid protocol deviations and shall report all protocol deviations to the sponsor. 
The investigator is to document and explain any deviations from the approved protocol. The 
investigator must promptly report any major deviations that might impact patient safety and/or 
data integrity to the sponsor and to the IRB/IEC, in accordance with established IRB/IEC 
policies and procedures. 
15.4. 
Study Report and Publications  
A clinical study report will be prepared and provided to the regulatory agency. BeiGene 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 Uniform 
Requirements for Manuscripts or stricter local criteria (International Committee of Medical 
Journal Editors 2016). 
Each investigator agrees to submit all manuscripts, abstracts, posters, publications, and 
presentations (both oral and written) to the sponsor for review before submission or presentation 
in accordance with the clinical study agreement. This allows the sponsor to protect proprietary 
information, provide comments based on information from other studies that may not yet be 
available to the investigator, and ensure scientific and clinical accuracy. The details of the 
processes of producing and reviewing reports, manuscripts, and presentations based on the data 
from this study will be presented in the investigator’s clinical study agreement. Each investigator 
agrees that, in accordance with the terms of the clinical study agreement, a further delay of the 
publication/presentation may be requested by the sponsor to allow for patent filings and/or 
protection in advance of the publication/presentation. 
15.5. 
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 all study data to the sponsor 
• Resolution and closure of all data queries 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 104 
• Accountability, reconciliation, and arrangements for unused study drug(s) 
• Review of study records for completeness 
• Collection of all study documents for the trial master file filing according to GCP and 
local regulation 
• Shipment of samples (including but not limited to those for PK, ADA, and 
biomarkers) to the assay laboratory for central laboratory analysis according to 
protocol and laboratory manual requirements 
In addition, the sponsor reserves the right to suspend the enrollment or prematurely discontinue 
this study either at a single study center or at all study centers at any time for any reason. 
Potential reasons for suspension or discontinuation include but are not limited to: safety or 
ethical issues or noncompliance with this protocol, GCP, the sponsor’s written instructions, the 
clinical study agreement, or applicable laws and regulations. If the sponsor determines such 
action is needed, the sponsor will discuss this with the investigator (including the reasons for 
taking such action) at that time. When feasible, the sponsor will provide advance notification to 
the investigator of the impending action before it takes effect. 
The sponsor will promptly inform all other investigators and/or institutions conducting the study 
if the study is suspended or terminated for safety reasons. The sponsor will also inform the 
regulatory authorities of the suspension or termination of the study and the reason(s) for the 
action. If required by applicable regulations, the investigator must inform the IEC/IRB promptly 
and provide the reason for the suspension or termination. 
If the study is prematurely discontinued, all study data must still be provided to the sponsor. In 
addition, arrangements will be made for the return of all unused study drug(s) in accordance with 
the applicable sponsor procedures for the study. 
Financial compensation to the investigators and/or institutions will be in accordance with the 
clinical study agreement established between the investigator and/or institutions and the sponsor. 
15.6. 
Information Disclosure and Inventions  
All rights, title, and interests in any inventions, know-how, or other intellectual or industrial 
property rights that are conceived or reduced to practice by the study center personnel during the 
course of or as a result of the study are the sole property of the sponsor and are hereby assigned 
to the sponsor. 
If a written contract for the conduct of the study, which includes ownership provisions 
inconsistent with this statement, is executed between the sponsor and the study center, that 
contract’s ownership provisions shall apply rather than this statement. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 105 
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 may be published as described in Section 15.4 
If a written contract for the conduct of the study, which includes provisions inconsistent with this 
statement is executed, that contract’s provisions shall apply rather than this statement. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 106 
16. 
REFERENCES  
Abès R, Gélizé E, Fridman WH, Teillaud JL. Long-lasting antitumor protection by anti-CD20 
antibody through cellular immune response. Blood. 2010;116(6):926-934.  
Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma 
identified by gene expression profiling. Nature. 2000;403(6769):503-511. 
Ansell SM, Minnema MC, Johnson P, et al. Nivolumab for Relapsed/Refractory Diffuse Large 
B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A 
Single-Arm, Phase II Study. J Clin Oncol. 2019;37(6):481-489. 
Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 
blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse 
large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31(33):4199-
4206.  
Bendell JC, Bedard P, Bang Y-J, et al. Phase Ia/Ib dose-escalation study of the anti-TIGIT 
antibody tiragolumab as a single agent and in combination with atezolizumab in patients with 
advanced solid tumors [AACR abstract CT302]. Cancer Res. 2020;80(suppl 16). 
Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in 
patients treated with immune checkpoint inhibitor therapy: American Society of Clinical 
Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36(17)1714-68. 
Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients 
with advanced cancer. N Engl J Med. 2012;366(26):2455-2465.  
Brookmeyer R and Crowley J. A confidence interval for the median survival time. Biometrics. 
1982; 38, 29-41. 
Carbone PP, Kaplan HS, Musshoff K, et al. Report of the committee on Hodgkin's disease 
staging classification. Cancer Res. 1971;31(11):1860-1. 
Cartron G, Watier H, Golay J, et al. From the bench to the bedside: ways to improve rituximab 
efficacy. Blood. 2004;104(9):2635-2642. 
Chauvin J, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen-specific CD8(+) 
T cells in melanoma patients. J Clin Invest. 2015;125:2046-58. 
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 
2016;66(2):115-132.  
Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and 
response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin 
Oncol. 2014;32(27):3059-3068.  
Clinical Trials Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. September 21, 2020. 
https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2020_09_HMA_CTFG_Contraception_guidance_Versio
n_1.1_updated.pdf 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 107 
Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP 
alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235-
242. 
Cristescu R, Mogg R, Ayers M, et al. Pan-tumor genomic biomarkers for PD-1 checkpoint 
blockade-based immunotherapy. Science. 2018;362(6411).  
DiLillo DJ, Ravetch JV. Differential Fc-Receptor Engagement Drives an Anti-tumor Vaccinal 
Effect. Cell. 2015;161(5):1035-1045.  
Dixon KO, Schorer M, Nevin J, et al. Functional anti-TIGIT antibodies regulate development of 
autoimmunity and antitumor immunity. J Immunol. 2018;200:3000-7. 
Dolgin M, Association NYH, Fox AC, Gorlin R, et al. Nomenclature and criteria for diagnosis of 
diseases of the heart and great vessels. 9th ed. Boston, MA: Lippincott Williams and Wilkins; 
March 1, 1994. 
Dong L, Lv H, Li W, et al. Co-expression of PD-L1 and p-AKT is associated with poor 
prognosis in diffuse large B-cell lymphoma via PD-1/PD-L1 axis activating intracellular 
AKT/mTOR pathway in tumor cells. Oncotarget. 2016;7(22):33350-33362.  
Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University 
School of Medicine. 2007. http://medicine.iupui.edu/clinpharm/ddis/main-table/. Accessed 01 
December 2020. 
Flowers CR, Sinha R, Vose JM. Improving outcomes for patients with diffuse large B-cell 
lymphoma. CA Cancer J Clin. 2010;60(6):393-408.   
Fourcade J, Sun Z, Chauvin J, et al. CD226 opposes TIGIT to disrupt Tregs in melanoma JCI 
Insight. 2018;3(14):e121157. 
Frentzas S, Kao S, Gao R, et al. ADVANTIG-105: A phase 1 dose escalation study of the anti-
TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with 
advanced solid tumors. J Immunother Cancer. 2023;11:e005829. 
Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for 
relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190. 
Godfrey J, Tumuluru S, Bao R, et al. PD-L1 gene alterations identify a subset of diffuse large B-
cell lymphoma harboring a T-cell-inflamed phenotype. Blood. 2019;133(21):2279-2290.  
Greenwood M. The natural duration of cancer. Reports of public health and medical patients. 
H.M.S.O. 1926;33:iv-26. 
Gross SA, Zhu X, Bao L, et al. A prospective study of 728 cases of non-Hodgkin lymphoma 
from a single laboratory in Shanghai, China. Int J Hematol. 2008;88(2):165-173.  
Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: 
ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 
2017:28(suppl 4):iv119-iv142. 
Hu LY, Xu XL, Rao HL, et al. Expression and clinical value of programmed cell death-ligand 1 
(PD-L1) in diffuse large B cell lymphoma: a retrospective study. Chin J Cancer. 2017;36(1):94.   
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 108 
Human Protein Atlas. https://www.proteinatlas.org/ENSG00000181847-TIGIT/tissue.  Accessed 
02 January 2019. 
International Committee of Medical Journal Editors. Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly Work in Medical Journals. 2016. Available 
online: http://www.icmje.org. Accessed 08 August 2017. 
International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for 
aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329(14):987-994.  
Johnston R, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor 
and antiviral CD8(+) T cell effector function. Cancer Cell. 2014;26:923-37. 
Joller N, Lozano E, Burkett P, et al. Treg cells expressing the coinhibitory molecule TIGIT 
selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity. 2014;40:569-81. 
Josefsson SE, Beiske K, Blaker YN, et al. TIGIT and PD-1 Mark Intratumoral T Cells with 
Reduced Effector Function in B-cell Non-Hodgkin Lymphoma. Cancer Immunol Res. 
2019;7(3):355-362.   
Kiyasu J, Miyoshi H, Hirata A, et al. Expression of programmed cell death ligand 1 is associated 
with poor overall survival in patients with diffuse large B-cell lymphoma. Blood. 
2015;126(19):2193-2201.   
Kurtulus S, Sakuishi K., Ngiow SF, et al. TIGIT predominantly regulates the immune response 
via regulatory T cells. J Clin Invest. 2015;125:4053-62. 
Labrijn AF, Buijsse AO, van den Bremer ET, et al. Therapeutic IgG4 Antibodies Engage in 
Fab-Arm Exchange With Endogenous Human IgG4 In Vivo. Nat Biotechnol. 2009;27(8):767-
71. 
Laurent C, Charmpi K, Gravelle P, et al. Several immune escape patterns in non-Hodgkin's 
lymphomas. Oncoimmunology. 2015;4(8):e1026530. 
Li M, Xia P, Du Y, et al. T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus 
receptor (PVR) ligand engagement suppresses interferon-γ production of natural killer cells via 
β-arrestin 2-mediated negative signaling. J Biol Chem. 2014;289(25):17647-17657. 
Liu J, Song B, Fan T, et al. Pathological and clinical characteristics of 1,248 non-Hodgkin's 
lymphomas from a regional cancer hospital in Shandong, China. Asian Pac J Cancer Prev. 
2011;12(11):3055-3061.  
Minard-Colin V, Xiu Y, Poe JC, et al. Lymphoma depletion during CD20 immunotherapy in 
mice is mediated by macrophage FcgammaRI, FcgammaRIII, and FcgammaRIV. Blood. 
2008;112(4):1205-1213.  
National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in 
oncology: B-cell lymphomas. Version 3.0. 2023. Accessed 18 May 2023. 
Niu J, Nagrial A, Voskoboynik M, et al. 1410P Safety and efficacy of vibostolimab, an anti-
TIGIT antibody, plus pembrolizumab in patients with anti-PD-1/PD-L1-naive NSCLC. Annals 
of Oncology 2020;31:S891-2. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 109 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and Response Criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-55. 
Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as 
compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's 
lymphoma. N Engl J Med. 1995;333(23):1540-1545. 
Preillon J, Cuende J, Rabolli V, et al. Restoration of T-cell Effector Function, Depletion of 
Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT 
Antagonist Antibodies. Mol Cancer Ther. 2021;20(1):121-131. 
Rajiv Kumar, Se Hyun Kim, DianSheng Zhong, et al. AdvanTIG-105: Phase 1b dose-expansion 
study of ociperlimab plus tislelizumab in patients with metastatic NSCLC. Poster presented at 
World Conference of Lung Cancer (WCLC); August 6-9, 2022; Vienna, Austria.  
Ren Z, Guo J, Liao J, et al. CTLA-4 Limits Anti-CD20-Mediated Tumor Regression. Clin 
Cancer Res. 2017;23(1):193-203.  
Rituximab [prescribing information]. South San Francisco, CA: Genentech, Inc; June 2021 
(Revised).  
Roche Group. Phase III study shows Roche's Polivy plus R-CHP is the first regimen in 20 years 
to significantly improve outcomes in previously untreated aggressive form of lymphoma 
compared to standard of care. https://www.roche.com/media/releases/med-cor-2021-08-09.htm. 
Accessed 18 August 2021. 
Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a randomized， 
double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab 
(atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected 
NSCLC (CITYSCAPE). J Clin Oncol. 2020;38(suppl 15):9503. 
Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after 
chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937-1947.  
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin 
Trials. 1996;17(4):343-346.   
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer 
suppression and promotion. Science. 2011;331(6024):1565-70. 
Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab 
therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J 
Clin Oncol. 2005;23(22):5027-5033. 
Smith SD, Till BG, Shadman MS, et al. Pembrolizumab with R-CHOP in previously untreated 
diffuse large B-cell lymphoma: potential for biomarker driven therapy. Br J Haematol. 
2020;189(6):1119-1126.  
Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines 
for healthcare providers. Resuscitation. 2008;77(2):157-69. 
Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007;117(5):1137-46. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 110 
Sun C, Jia Y, Wang W, et al. Integrative analysis of PD-L1 DNA status, mRNA status and 
protein status, and their clinicopathological correlation, in diffuse large B-cell 
lymphoma. Histopathology. 2019;74(4):618-628.  
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of 
Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 
2021;71(3):209-249. 
Surveillance Epidemiology and End Results (SEER), NCI, US National Institutes of Health, Fast 
Facts; Statistics Stratified by Cancer Site, 2020. 
Susanibar-Adaniya S, Barta SK. 2021 Update on Diffuse large B cell lymphoma: A review of 
current data and potential applications on risk stratification and management. Am J Hematol. 
2021;96(5):617-629.  
Taylor RP, Lindorfer MA. Immunotherapeutic mechanisms of anti-CD20 monoclonal 
antibodies. Curr Opin Immunol. 2008;20(4):444-449.   
Teras LR, DeSantis CE, Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World 
Health Organization subtypes. CA Cancer J Clin. 2016 Nov 12;66(6):443-459.  
Thandra KC, Barsouk A, Saginala K, et al. Epidemiology of Non-Hodgkin's Lymphoma. Med 
Sci (Basel). 2021;9(1):5.  
Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO 
Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 
5):v116-25. 
US Food and Drug Administration Center for Drug Evaluation Research (CDER) and Center for 
Biologics Evaluation and Research. Guidance for Industry: Clinical Trial Endpoints for the 
Approval of Cancer Drugs and Biologics. 2018. 
Wilson WH, Young RM, Schmitz R, et al. Targeting B cell receptor signaling with ibrutinib in 
diffuse large B cell lymphoma. Nat Med. 2015;21(8):922-926.  
Woosley RL, Heise CW, Gallo T, Tate J, Woosley D and Romero KA. QTdrugs List. 2013. 
www.CredibleMeds.org. Accessed 01 December 2020 
Wu Y, Chen W, Xu ZP, Gu W. PD-L1 Distribution and Perspective for Cancer Immunotherapy-
Blockade, Knockdown, or Inhibition. Front Immunol. 2019;10:2022.   
Xing W, Dresser K, Zhang R, et al. PD-L1 expression in EBV-negative diffuse large B-cell 
lymphoma: clinicopathologic features and prognostic implications. Oncotarget. 
2016;7(37):59976-59986. 
Yang Z. Expression and function of Tigit in B-cell Non-Hodgkin Lymphoma. Blood. 
2016;128:4138. 
Younes A, Brody J, Carpio C, et al. Safety and activity of ibrutinib in combination with 
nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: 
a phase 1/2a study. Lancet Haematol. 2019;6(2):e67-e78.  
Zhang Q, Bi J, Zheng X, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell 
exhaustion and elicits potent anti-tumor immunity. Nat Immunol. 2018b;19(7):723-732. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 111 
Zhang T, Song X, Xu L, et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound 
impact on its biological functions. Cancer Immunol Immunother. 2018a;67(7):1079-90 
Ziepert M, Hasenclever D, Kuhnt E, et al. Standard International prognostic index remains a 
valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab 
era. J Clin Oncol 2010; 28:2373-80. 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 112 
17. 
APPENDICES 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 113 
APPENDIX 1. SCHEDULE OF ASSESSMENTS  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 114 
Appendix 1A. Schedule of Assessments  
Study Phase or Visit 
Screening 
b 
Treatment (1 Cycle = 21 days) 
Safety Follow-up Visit c 
Long-term 
Follow-up d 
Cycle/Period 
Cycle 1 
Cycle 2 
≥ Cycle 3 
(Every 1 cycle) 
Day 
-28 to -1 
1 
8 
15 
1 
15 
1 
+30 days 
(visit) 
+60 days 
(phone call) 
+90 days 
(phone call) 
Every 
12 weeks 
Window (Days) 
- 
- 
± 1 
± 1 
± 2 
± 3 
± 7 
± 14 
± 14 
± 14 
Study Treatment 
Ociperlimab a 
 
X 
 
 
X 
 
X 
 
 
 
 
Cohort 1: Tislelizumab a 
 
X 
 
 
X 
 
X 
 
 
 
 
Cohort 2: Rituximab a 
 
X 
 
 
X 
 
X 
 
 
 
 
Procedure 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility confirmation 
X 
 
 
 
 
 
 
 
 
 
 
Medical and disease history 
e 
X 
 
 
 
 
 
 
 
 
 
 
Demographics/prior 
treatment history of DLBCL 
f 
X 
 
 
 
 
 
 
 
 
 
 
Biomarker tissue samples g 
X 
To be optionally collected at C2D1, C4D1, and the time of PD 
 
Biomarker blood samples h  
To be collected at predose of C1D1, C1D2, C1D8, C2D1, and the time of PD 
 
Safety Assessments 
Physical examination i 
X 
X 
 
 
X 
 
X 
X 
 
 
 
Vital signs and weight j 
X 
X 
 
 
X 
 
X 
X 
 
 
 
ECOG performance status 
X 
X 
 
 
X 
 
X 
X 
 
 
 
12-lead ECG k 
X 
As clinically indicated 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 115 
Study Phase or Visit 
Screening 
b 
Treatment (1 Cycle = 21 days) 
Safety Follow-up Visit c 
Long-term 
Follow-up d 
Cycle/Period 
Cycle 1 
Cycle 2 
≥ Cycle 3 
(Every 1 cycle) 
Day 
-28 to -1 
1 
8 
15 
1 
15 
1 
+30 days 
(visit) 
+60 days 
(phone call) 
+90 days 
(phone call) 
Every 
12 weeks 
Window (Days) 
- 
- 
± 1 
± 1 
± 2 
± 3 
± 7 
± 14 
± 14 
± 14 
Ophthalmologic 
examination l 
As clinically indicated 
 
Echocardiogram/MUGA m 
X 
As clinically indicated 
 
Adverse event reviews n 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant medication 
Reviews n 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Laboratory Assessments 
Hematology o 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Serum chemistry o 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Coagulation o 
X 
As clinically indicated 
 
Urinalysis o 
X 
As clinically indicated 
 
CK and CK-MB p 
X 
X 
 
 
X 
 
X 
X 
 
 
 
Thyroid function q 
X 
 
 
 
X 
 
X 
X 
 
 
 
Pregnancy tests r 
X 
X 
 
 
X 
 
X 
X 
 
 
 
Quantitative serum 
immunoglobulins (IgG, 
IgM, IgA) s 
X 
During treatment period, every 9 weeks (± 7 days) 
from Day 1 of Cycle 1 for the first 54 weeks, every 
18 weeks (± 7 days) for additional 54 weeks, then 
every 24 weeks (± 7 days) thereafter 
X 
 
 
 
Hepatitis serologies t 
X 
Refer to Note t below for details 
 
Pulmonary function tests u 
X 
As clinically indicated 
 
PK samples v 
Refer to Appendix 1B and Appendix 1C 
 
ADA samples v 
Refer to Appendix 1B and Appendix 1C 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 116 
Study Phase or Visit 
Screening 
b 
Treatment (1 Cycle = 21 days) 
Safety Follow-up Visit c 
Long-term 
Follow-up d 
Cycle/Period 
Cycle 1 
Cycle 2 
≥ Cycle 3 
(Every 1 cycle) 
Day 
-28 to -1 
1 
8 
15 
1 
15 
1 
+30 days 
(visit) 
+60 days 
(phone call) 
+90 days 
(phone call) 
Every 
12 weeks 
Window (Days) 
- 
- 
± 1 
± 1 
± 2 
± 3 
± 7 
± 14 
± 14 
± 14 
Efficacy Assessments 
Contrast CT (neck, chest, 
abdomen, and pelvis) w 
X 
From Day 1 of Cycle 1, every 9 weeks (± 7 days) for the first 54 weeks, every 18 weeks (± 7 days) 
for additional 54 weeks, then every 24 weeks (± 7 days) thereafter 
 
PET-CT w 
X 
For patients who are positive at screening: Week 9 (± 7 days), Week18 (± 7 days), at time when 
confirming CR or PD, and clinically indicated 
 
Bone marrow 
examination x 
X 
As clinically indicated 
 
Others 
Survival status d 
 
 
 
 
 
 
 
 
 
 
X 
Subsequent anticancer 
therapy d 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: ADA, antidrug antibodies; AE, adverse event; CK, creatine kinase; CK-MB, creatine kinase-muscle/brain; CR, complete response; CT, computed 
tomography; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; HBcAb, hepatitis B core antibody; HBsAb, hepatitis B surface antibody; 
HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; ICF, informed consent form; Ig, immunoglobulin; imAE, immune-mediated 
AE; MUGA, multiple gated acquisition; MRI, magnetic resonance imaging; NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse 
Events; PD, progressive disease; SAE, serious adverse event; T3, triiodothyronine; T4, thyroxine. 
Note: Timepoints containing numbers represent timepoints with special considerations for that respective assessment. 
a. 
Ociperlimab in combination with tislelizumab or rituximab will be given intravenously on Day 1 of each 21-day cycle (once every 3 weeks) (see 
Section 5.2 for details). Note: Tislelizumab must not be administered concurrently with any other drug. 
b. Written informed consent is required before performing any study-specific procedure. Results of standard-of-care tests or examinations performed before 
informed consent has been obtained and ≤ 28 days before the first dose of study drug(s) may be used for screening assessments rather than repeating such 
tests unless otherwise indicated. The ICF signature alone does not define the start of the screening period, but the first study-related assessment date is to be 
used for the date of the Screening Visit. 
c. 
Patients who permanently discontinue study drugs will be asked to return to the clinic for the Safety Follow-up Visit, which is required to be conducted 
within 30 days (± 7 days) after the last dose of study drugs or before the initiation of new antitumor therapy, whichever occurs first. In addition, telephone 
contacts with patients will be conducted to assess all imAEs and relevant concomitant medications (ie, associated with an imAE or is a new anticancer 
therapy) at 60 days (±14 days) and 90 days (±14 days) after the last dose of study treatment, regardless of whether or not the patient starts a new anticancer 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 117 
therapy. For women of childbearing potential (see Appendix 5), an additional visit to perform a pregnancy test will occur approximately 120 days after the 
last dose of ociperlimab and tislelizumab, and 180 days after the last dose of rituximab. Visits are performed in the clinic or over the phone, as needed, 
based on the assessments required. 
d. Patients will be followed for survival and to obtain information on subsequent anticancer therapy via telephone calls, mail or email, patient medical records, 
and/or clinic visits after the last dose of study treatment and approximately every 12 weeks (± 14 days) after the Safety Follow-up visit or as directed by the 
sponsor until death, withdrawal of consent, loss to follow-up, or end of study. 
e. 
Review any medical and disease history any time after obtaining informed consent, including presence or absence of disease-related constitutional 
symptoms, the date of initial diagnosis, and current disease status, and stage of disease. 
f. 
Includes year of birth (or age), sex, self-reported race, and history of treatment for DLBCL, including prior systemic treatment(s), locoregional treatment(s), 
and surgical treatment(s). 
g. The archival or fresh tumor tissues are mandatory for all patients who consent to participate in the study. If no archival samples are available, a fresh tumor 
biopsy at baseline is required. Also, if the patient can provide eligible archival tumor tissues and is willing to undergo fresh tumor biopsy at screening, a 
fresh tumor biopsy is strongly recommended. Archival (within 1 year before signing the ICF) and/or fresh tumor tissues (approximately 15 unstained slides) 
at screening need to be sent to the central laboratory for diagnosis confirmation and biomarker analysis, including expression of PD-L1, TIGIT, CD226, 
CD155, and CD112, PD-L1/2 gene alteration, EBV status, tumor microenvironment, immune-related gene expression profile, and gene mutation profile 
will be evaluated. Tumor tissue should be of good quality based on total and viable tumor content. Fine-needle aspiration, brushing, cell pellets from pleural 
effusion, and lavage samples are not acceptable. Bone marrow biopsy is not acceptable. Tumor biopsy from an inguinal lymph node is only acceptable 
when a tumor biopsy cannot be obtained from other sites. An optional tumor biopsy will be taken from accessible tumor sites at C2D1 and C4D1 to explore 
tumor biomarkers including tumor microenvironment and immune-related gene expression profile which may be associated with response and resistance to 
study drugs. Optional biopsies will also be obtained for patients treated with study drugs who have confirmed PD during the study from accessible tumor 
sites to obtain samples to explore tumor microenvironment and gene mutation/expression profiling associated resistance mechanism. If feasible, any 
follow-up biopsy should ideally be taken from the same tumor lesion as the baseline biopsy. Written patient consent is required for fresh tumor biopsies. 
h. Blood samples will be collected for all patients at predose of C1D1, C1D2, C1D8, C2D1, and at the time of PD to explore the association of blood-based 
biomarkers with response, resistance, and prognosis to ociperlimab in combination with tislelizumab or rituximab. Blood-based biomarker analysis includes 
immune-cell quantification and phenotypes, cytokine profiling, immune-related gene expression profiling, and DNA/ctDNA sequencing. 
i. 
Refer to Section 8.2.2 for details regarding physical examination assessment requirements for screening and subsequent timepoints. In addition, 
investigators should solicit patients regarding changes in vision, visual disturbance, or ocular inflammation at each scheduled study visit during study 
treatment. For any change in vision, referral to an appropriate specialist will be made for further management guidance. 
j. 
Height assessment is required only at screening. Vital signs including measurements of body temperature (˚C), pulse rate, blood pressure (systolic and 
diastolic), and weight will be performed at each study visit. Pulse rate and blood pressure will be measured while the patient is in a seated position after 
resting for 10 minutes. If coinciding with study drug infusions, the patient’s vital signs are required to be recorded within 60 minutes before, during, and 
30 minutes after the first infusion of study drug(s). For subsequent infusions, vital signs will be collected within 60 minutes before infusion of study drug(s), 
and if clinically indicated, during and 30 minutes after study drug(s) infusion. 
k. The 12-lead ECGs will be performed at screening and when clinically indicated. The ECG at screening must be performed in triplicate. All ECGs are to be 
obtained before other assessments scheduled at that same time (eg, vital sign measurements and blood draws). The patient should rest in semirecumbent 
supine position for ≥ 10 minutes in the absence of environmental distractions that may induce changes in heart rate (eg, television, radio, and conversation) 
before each ECG collection. 
l. 
Ophthalmologic examination includes eye examination (including visual acuity test) and optical coherence tomography (or equivalent diagnostic test for 
retinal examination); these will be assessed by an appropriate specialist as clinically indicated.  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 118 
m. An echocardiogram/MUGA is to be performed at screening unless one has been performed within 28 days before the first dose of study drug, and as 
clinically indicated during the study. 
n. The AEs and laboratory abnormalities will be graded per NCI-CTCAE Version 5.0. All AEs will also be evaluated for seriousness. After the ICF has been 
signed but before the administration of study drug(s), only SAEs should be reported. After the first dose of study drug(s), all AEs and SAEs, regardless of 
relationship to study drug, will be reported until either 30 days after the last dose of study drug(s) or initiation of new antitumor therapy, whichever occurs 
first. ImAEs (serious and nonserious) should be reported until 90 days after the last dose of tislelizumab or ociperlimab regardless of whether the patient 
starts a new antitumor 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. In addition, all concomitant medications taken by or administered to the patient within 28 days before the 
first dose of study drug(s) and 30 days after the last dose of study drug(s) or the initiation of a new anticancer therapy should be recorded. 
o. Local and/or central laboratory assessments of clinical chemistry, hematology, coagulation, and urinalysis will be conducted as outlined in Appendix 2. If 
clinical chemistry, hematology, and coagulation at screening are not performed ≤ 7 days before study drug(s) administration on Day 1 of Cycle 1, these tests 
should be repeated and reviewed before study drug administration. After Day 1 of Cycle 1, results are to be reviewed within 72 hours before study drug 
administration. Hematology and clinical chemistry will be performed on Day 1, Day 8 and Day 15 of the first cycle, on Day 1 and Day 15 of Cycle 2, then 
on Day 1 on each subsequent cycle. Urinalysis and coagulation tests will be conducted at screening and during the treatment period only if clinically 
warranted. Refer to Section 9.3.5 for additional information regarding clinical assessment and management of clinical laboratory abnormalities. 
p. CK and CK-MB levels will be evaluated at the timepoints specified within the table and when clinically indicated. If CK-MB fractionation is not available, 
troponin I and/or troponin T should be tested instead. If only 1 of the troponins is assessed per local standards that same test should be evaluated throughout. 
If significant abnormalities are detected, the affected patients should be evaluated for possible myocarditis/myositis per institutional guidelines, including 
additional serum CK/CK-MB, serum troponin levels, ECG, etc. 
q. Analysis of thyroid function, including free T3, free T4, and thyroid stimulating hormone will be performed by a central laboratory and/or the local study 
site laboratory. 
r. 
Serum or urine pregnancy test (for women of childbearing potential, including women who have had a tubal ligation) must be performed and documented as 
negative ≤ 7 days before the first dose of study drug(s). A negative urine or serum pregnancy test must be completed and recorded ≤ 72 hours before the 
administration of study drug(s) at each cycle. A serum pregnancy test must be performed if the urine pregnancy test is positive or equivocal. 
s. 
Serum immunoglobulin, including IgG, IgM, and IgA will be quantitatively assessed at screening, together with tumor evaluations during the treatment 
period [ every 9 weeks (± 7 days), from Day 1 of Cycle 1, for the first 54 weeks; every 18 weeks (± 7 days) for additional 54 weeks; then every 24 weeks 
(± 7 days) thereafter] and at the Safety Follow-up Visit. 
t. 
Hepatitis serologies will include hepatitis B/C serologic markers and/or viral load at screening. Testing will be performed by a central laboratory and/or the 
local laboratory (if the local laboratory is able to perform the test to the required sensitivity [< 20 IU/mL and < 15 IU/mL for hepatitis B and C, 
respectively]). The hepatitis B testing will include HBsAg, HBcAb, and HBsAb, as well as HBV DNA by PCR if the patient is negative for HBsAg but 
positive for HBcAb (regardless of HBsAb status). The hepatitis C testing will include HCV antibody as well as HCV RNA by PCR if the patient is positive 
for HCV antibody. Patients who are HBsAg negative, HBcAb positive, and HBV DNA negative (< 20 IU/mL) at screening must be monitored for HBV 
DNA by PCR at a monthly frequency. If a patient is being treated prophylactically with antivirals, HBV DNA by PCR must be monitored at least every 
3 months. Patients who are HCV antibody positive and HCV RNA negative (< 15 IU/mL) at screening must be monitored for HCV RNA at a monthly 
frequency. HBV DNA and HCV RNA monitoring should continue until the patient starts new antitumor therapy, or for any other reason listed in 
Section 7.5.2, whichever occurs first. See Section 8.2.9 for more information.  
u. Pulmonary function tests may include but are not limited to spirometry and assessment of diffusion capacity, and will be done during the screening period 
to assist with the determination of suitability for the study. 
v. Ociperlimab and tislelizumab PK and ADA: Refer to Appendix 1B and Appendix 1C. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 119 
w. Tumor imaging will be performed ≤ 28 days before the first dose of study drug(s). Results of standard-of-care tests or examinations performed before 
informed consent has been obtained and ≤ 28 days before the first dose of study drug(s) may be used for the purposes of screening rather than repeating the 
standard-of-care tests. During the study, tumor imaging will be performed every 9 weeks (± 7 days), from Day 1 of Cycle 1, for the first 54 weeks; every 
18 weeks (± 7 days) for additional 54 weeks; then every 24 weeks (± 7 days) thereafter based on the Lugano Classification (2014) (Cheson et al 2014). For 
patients who are positive for PET-CT scans at screening, PET-CT should be repeated at Week 9 (± 7 days), Week 18 (± 7 days), at time when confirming 
CR or PD, and as clinically indicated. Screening assessments must include both contrast CT and PET-CT scans (with oral/intravenous contrast, unless 
contraindicated) of the neck, chest, abdomen, and pelvis. Other known or suspected sites of disease must be included in the imaging assessments (brain, 
etc). Contrast CT will be performed for each subsequent tumor assessment. If a patient is known to have a contraindication to CT contrast media or 
develops a contraindication during the study, an MRI should be performed but must be used consistently. See Section 8.3 for more information. 
x. Bone marrow biopsy and aspirate are required to assess bone marrow involvement of patients during the screening period, unless they have been performed 
within 60 days before the first dose of study drug and there has been no intervening therapy from the time of the biopsy/aspirate until the first dose of study 
drug. For patients who have evidence of bone marrow disease at screening, repeated bone marrow biopsy may not be needed if PET-CT shows bone 
marrow clearance at CR. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 120 
Appendix 1B. Dose Confirmation Cohorts 1 and 2: Pharmacokinetic and Immunogenicity Sampling 
Schedule for Ociperlimab and Tislelizumab  
Study 
week 
Study visit 
Time 
Cohort 1 (Dose Confirmation) 
Cohort 2 (Dose Confirmation) 
PK 
ADA 
PK 
ADA 
1 
Cycle 1, Day 1 
 
Predose (-60 min to 
predose) 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA 
Ociperlimab PK  
Ociperlimab ADA  
Within 30 min after 
end of infusion 
Ociperlimab PK & 
Tislelizumab PK 
 
Ociperlimab PK  
 
2 
Cycle 1, Day 8 
(± 1 day) 
At visit 
Ociperlimab PK  
 
Ociperlimab PK  
 
3 
Cycle 1, 
Day 15(± 1 day) 
At visit 
Ociperlimab PK 
 
Ociperlimab PK 
 
4 
Cycle 2, Day 1 
Predose (-60 min to 
predose) 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA  
Ociperlimab PK  
Ociperlimab ADA  
Within 30 min after 
end of infusion 
Ociperlimab PK 
 
Ociperlimab PK 
 
13 
Cycle 5, Day 1 
Predose (-60 min to 
predose) 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA  
Ociperlimab PK  
Ociperlimab ADA  
Within 30 min after 
end of infusion 
Ociperlimab PK & 
Tislelizumab PK 
 
Ociperlimab PK  
 
14 
Cycle 5, Day 8 
(± 1 day) 
At visit 
Ociperlimab PK 
 
Ociperlimab PK 
 
15 
Cycle 5, Day 15 
(± 1 day) 
At visit 
Ociperlimab PK 
 
Ociperlimab PK 
 
16 
Cycle 6, Day 1 
Predose (-60 min to 
predose) 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA  
Ociperlimab PK  
Ociperlimab ADA  
25 
Cycle 9, Day 1 
Predose (-60 min to 
predose) 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA 
Ociperlimab PK  
Ociperlimab ADA  
49 
Cycle 17, Day 1 
Predose (-60 min to 
predose) 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA 
Ociperlimab PK  
Ociperlimab ADA  
Safety Follow-up 
30 days (± 7 days) 
after last dose 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA 
Ociperlimab PK  
Ociperlimab ADA  
Abbreviations: ADA, antidrug antibody; h, hour; min, minute; PK, pharmacokinetic.  
Note:  
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 121 
Sample collection must be from opposite arm to that used for study drug infusion. If drug was administered via a central venous catheter, sample collection for 
PK and ADA should be from a different site. 
Procedures for collection of blood samples to evaluate ociperlimab and tislelizumab PK are described in the laboratory manual.  
If a patient presents with any ≥ Grade 3 imAE, an additional blood PK sample may be taken. 
All ADA samples should be collected at the same time as blood collection for predose PK analysis.  
These tests are required when it is allowed by local regulations/IRBs/IECs.
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 122 
Appendix 1C. Dose Expansion Cohorts 1 and 2: Pharmacokinetic and Immunogenicity Sampling Schedule 
for Ociperlimab and Tislelizumab  
 
Study 
Week 
Study Visit 
Time 
Cohort 1 (Dose Expansion) 
Cohort 2 (Dose Expansion) 
PK 
ADA 
PK 
ADA 
1 
Cycle 1, Day 1 
Predose (-60 min to 
predose) 
Tislelizumab PK and 
Ociperlimab PK 
Tislelizumab ADA and 
Ociperlimab ADA 
Ociperlimab PK 
Ociperlimab ADA 
Within 30 min after 
end of infusion 
Tislelizumab PK and 
Ociperlimab PK 
 
Ociperlimab PK 
 
4 
Cycle 2, Day 1 
Predose (-60 min to 
predose) 
Tislelizumab PK and 
Ociperlimab PK 
Tislelizumab ADA and 
Ociperlimab ADA 
Ociperlimab PK 
Ociperlimab ADA 
13 
Cycle 5, Day 1 
Predose (-60 min to 
predose) 
Tislelizumab PK and 
Ociperlimab PK 
Tislelizumab ADA and 
Ociperlimab ADA 
Ociperlimab PK 
Ociperlimab ADA 
Within 30 min after 
end of infusion 
Tislelizumab PK and 
Ociperlimab PK 
 
Ociperlimab PK 
 
25 
Cycle 9, Day 1 
Predose (-60 min to 
predose) 
Tislelizumab PK and 
Ociperlimab PK 
Tislelizumab ADA and 
Ociperlimab ADA 
Ociperlimab PK 
Ociperlimab ADA 
49 
Cycle 17, 
Day 1 
Predose (-60 min to 
predose) 
Tislelizumab PK and 
Ociperlimab PK 
Tislelizumab ADA and 
Ociperlimab ADA 
Ociperlimab PK 
Ociperlimab ADA 
Safety Follow-up 
30 days (± 7 days) 
after last dose 
Ociperlimab PK & 
Tislelizumab PK 
Ociperlimab ADA & 
Tislelizumab ADA 
Ociperlimab PK  
Ociperlimab ADA  
Abbreviations: ADA, antidrug antibody; min, minutes; PK, pharmacokinetic. 
Note:  
Sample collection must be from opposite arm to that used for study drug infusion. If drug was administered via a central venous catheter, sample collection for 
PK and ADA should be from a different site. 
Procedures for collection of blood samples to evaluate ociperlimab and tislelizumab PK are described in the laboratory manual.  
If a patient presents with any ≥ Grade 3 imAE, an additional blood PK sample may be taken.  
All ADA samples should be collected at the same time as blood collection for predose PK analysis.  
These tests are required when it is allowed by local regulations/IRBs/IECs. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 123 
APPENDIX 2. CLINICAL LABORATORY ASSESSMENTS  
Clinical chemistry 
Hematology 
Coagulation 
Urinalysis 
Alkaline phosphatase 
Alanine aminotransferase 
Aspartate aminotransferase 
Albumin 
Total bilirubin 
Direct bilirubin 
Blood urea nitrogen or urea 
Potassium 
Sodium 
Total calciuma  
Creatinine 
Glucose 
Lactate dehydrogenase 
Total protein 
Red blood cell count 
Hematocrit 
Hemoglobin 
Platelet count 
White blood cell count 
Lymphocyte count 
Neutrophil count 
Prothrombin time 
Partial thromboplastin 
time or activated partial 
thromboplastin time 
International 
normalized ratio 
Glucose 
Protein 
Blood 
 
a Total calcium values will be corrected for patients with hypoproteinemia. 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 124 
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 house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
Source: Oken et al 1982. Eastern Cooperative Oncology Group, Robert Comis MD, Group Chair. 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 125 
APPENDIX 4. PRE-EXISTING IMMUNE DEFICIENCIES OR 
AUTOIMMUNE DISEASES  
Prospective patients should be carefully questioned to determine whether they have any history 
of an acquired or congenital immune deficiency or autoimmune disease. Please contact the 
medical monitor regarding any uncertainty about immune deficiency/autoimmune disease 
exclusions. 
Acute disseminated encephalomyelitis 
Addison disease 
Ankylosing spondylitis 
Antiphospholipid antibody syndrome 
Aplastic anemia 
Autoimmune hemolytic anemia 
Autoimmune hepatitis 
Autoimmune hypoparathyroidism 
Autoimmune hypophysitis 
Autoimmune myocarditis 
Autoimmune oophoritis 
Autoimmune orchitis 
Autoimmune thrombocytopenic purpura 
Behcet disease 
Bullous pemphigoid 
Chronic inflammatory demyelinating polyneuropathy 
Chung-Strauss syndrome 
Crohn disease 
Dermatomyositis 
Dysautonomia 
Epidermolysis bullosa acquisita 
Gestational pemphigoid 
Giant cell arteritis  
Goodpasture syndrome 
Granulomatosis with polyangiitis  
Graves disease 
Guillain-Barré syndrome 
Hashimoto disease 
Immunoglobulin A (IgA) neuropathy 
Inflammatory bowel disease 
Interstitial cystitis 
Kawasaki disease 
Lambert-Eaton 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 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 126 
APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS 
OF “WOMEN OF CHILDBEARING POTENTIAL,” “NO 
CHILDBEARING POTENTIAL”  
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, or implantable 
Note: Oral birth control pills are not considered a highly effective form of birth 
control, and if they are selected, they must be used with a second, barrier method 
of contraception such as condoms with or without spermicide. 
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized male partner 
− Note: This is only considered a highly effective form of birth control when the 
vasectomized partner is the sole partner of the study participant and there has 
been a medical assessment confirming surgical success. 
− A sterile man is one for azoospermia has been demonstrated in a semen sample 
examination as definitive evidence of infertility. 
• 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 drug(s), 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,” and “Women of No Childbearing 
Potential” 
As defined in this protocol, “women of childbearing potential” are female patients who are 
physiologically capable of becoming pregnant. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 127 
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 > 30 IU/mL and all 
alternative medical causes for the lack of spontaneous menses for ≥ 12 months 
have been ruled out, such as polycystic ovarian syndrome, hyperprolactinemia, 
etc. 
If a follicle-stimulating hormone (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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 128 
APPENDIX 6. NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION  
Class 
Symptoms 
I 
No limitation of physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea (shortness of breath). 
II 
Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity 
results in fatigue, palpitation, dyspnea (shortness of breath). 
III 
Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity 
causes fatigue, palpitation, or dyspnea. 
IV 
Unable to carry on any physical activity without discomfort. Symptoms of heart failure at 
rest. If any physical activity is undertaken, discomfort increases. 
Adapted from Dolgin et al 1994. 
Original source: Criteria Committee, New York Heart Association, Inc. Diseases of the Heart and Blood Vessels. 
Nomenclature and Criteria for diagnosis, 6th edition Boston, Little, Brown and Co. 1964, p 114. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 129 
APPENDIX 7. COCKCROFT-GAULT FORMULA  
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 130 
APPENDIX 8. LUGANO CLASSIFICATION FOR NON-HODGKIN 
LYMPHOMA  
Response and site 
PET-CT-based response  
(patients with PET-avid disease at screening) 
CT-based response 
(patients without PET-avid disease at 
screening) 
Complete 
Lymph nodes 
and 
extra-lymphatic 
sites 
Complete metabolic response 
Score 1, 2, 3* with or without a residual mass on 
5-point scale□ 
It is recognized that in Waldeyer’s ring or 
extra-nodal sites with physiologic uptake or 
with activation within spleen or marrow (eg, 
with chemotherapy or myeloid 
colony-stimulating factors), uptake may be 
greater than normal mediastinum and/or liver. In 
this circumstance, complete metabolic response 
may be inferred if uptake at sites of initial 
involvement is no greater than surrounding 
normal tissue even if the tissue has high 
physiologic uptake 
Complete radiologic response (all of the 
following): 
• Target nodes/nodal masses must regress 
to ≤ 1.5 cm in longest transverse 
diameter of a lesion 
• No extra-lymphatic sites of disease 
Non-measured 
lesion 
Not applicable 
Absent 
Organ 
enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG-avid disease in marrow 
Normal by morphology, if indeterminate,  
immunohistochemistry negative 
Partial 
Lymph nodes 
and 
extra-lymphatic 
sites 
Partial metabolic response 
Score 4 or 5□ with reduced uptake compared with 
baseline and residual mass(es) of any size 
At interim, these findings suggest responding 
disease 
At end of treatment, these findings indicate 
residual disease 
Partial remission (all of the following): 
• 
≥ 50% decrease in sum of the product 
of the perpendicular diameters for 
multiple lesions of up to 6 target 
measurable nodes and extra-nodal sites 
• 
When a lesion is too small to measure 
on CT, assign 5 mm × 5 mm as the 
default value 
• 
When no longer visible, 0 × 0 mm 
• 
For a node > 5 mm × 5 mm, but smaller 
than normal, use actual measurement 
for calculation 
Non-measured 
lesions 
Not applicable 
Absent/normal, regressed, but no increase 
Organ 
enlargement 
Not applicable 
Spleen must have regressed by > 50% in length 
beyond normal 
New lesions 
None 
None 
Bone marrow 
Residual uptake higher than uptake in normal 
marrow but reduced compared with baseline 
(diffuse uptake compatible with reactive 
changes from chemotherapy allowed). If there 
are persistent focal changes in the marrow in the 
context of a nodal response, consideration 
should be given to further evaluation with MRI 
or biopsy or an interval scan 
Not applicable 
 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 131 
Response and site 
PET-CT-based response  
(patients with PET-avid disease at screening) 
CT-based response 
(patients without PET-avid disease at 
screening) 
No response or 
stable disease 
Target 
nodes/nodal 
masses, 
extra-nodal 
lesions 
No metabolic response 
Score 4 or 5 with no significant change in FDG 
uptake from baseline at interim or end of 
treatment 
Stable disease 
< 50% decrease from baseline in sum of the 
product of the perpendicular diameters for 
multiple lesions of up to 6 dominant, 
measurable nodes and extra-nodal sites; no 
criteria for progressive disease are met 
Non-measured 
lesions 
Not applicable 
No increase consistent with progression 
Organ 
enlargement 
Not applicable 
No increase consistent with progression 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 
Progressive 
disease 
Individual 
target 
nodes/nodal 
masses 
Extra-nodal 
lesions 
Progressive metabolic disease 
Score 4 or 5 with an increase in intensity of 
uptake from baseline and/or new FDG-avid 
foci consistent with lymphoma at interim or 
end of treatment assessment 
 
Progressive disease requires at least one of the 
following cross products of the longest 
transverse diameter of a lesion and 
perpendicular diameter progression: 
 
An individual node/lesion must be abnormal 
with: 
• Longest transverse diameter of a lesion 
> 1.5 cm and 
• Increase by ≥ 50% from cross product of 
the longest transverse diameter of a lesion 
and perpendicular diameter nadir and 
• An increase in longest transverse diameter 
of a lesion or shortest axis perpendicular 
to the longest transverse diameter of a 
lesion from nadir 
– 
0.5 cm for lesions ≤ 2 cm 
– 
1.0 cm for lesions > 2 cm 
• In the setting of splenomegaly, the splenic 
length must increase by > 50% of the 
extent of its prior increase beyond baseline 
(eg, a 15-cm spleen must increase to 
> 16 cm). If no prior splenomegaly, must 
increase by ≥ 2 cm from baseline 
• New or recurrent splenomegaly 
Non-measured 
lesions 
None 
New or clear progression of pre-existing 
non-measured lesions 
 
 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 132 
Response and site 
PET-CT-based response  
(patients with PET-avid disease at screening) 
CT-based response 
(patients without PET-avid disease at 
screening) 
New lesions 
New FDG-avid foci consistent with lymphoma 
rather than another etiology (eg, infection, 
inflammation). If uncertain regarding etiology of 
new lesions, biopsy or interval scan may be 
considered 
• Regrowth of previously resolved lesions 
• A new node > 1.5 cm in any axis 
• A new extra-nodal site > 1.0 cm in any 
axis; if < 1.0 cm in any axis, its presence 
must be unequivocal and must be 
attributable to lymphoma 
• Assessable disease of any size 
unequivocally attributable to lymphoma 
Bone marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
Abbreviations: CT, computed tomography; FDG, [18F] fluorodeoxyglucose; MRI, magnetic resonance imaging; 
PET, positron emission tomography. 
Modified from Cheson et al 2014. 
*A score 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an 
interim scan. However, in trials involving PET where de-finding is investigated, it may be preferable to consider a 
score of 3 as inadequate response (to avoid under treatment). Measured dominant lesions: Up to 6 of the largest 
dominant nodes, nodal masses, and extra-nodal lesions selected to be clearly measurable in 2 diameters. Nodes 
should preferably be from disparate regions of the body and should include, where applicable, mediastinal, and 
retroperitoneal areas. Non-nodal lesions include those in solid organs (eg, liver, spleen, kidneys, lungs), 
gastrointestinal involvement, cutaneous lesions, or those noted on palpation. Non-measured lesions: Any disease not 
selected as measured, dominant disease and truly assessable disease should be considered not measured. These sites 
include any nodes, nodal masses, and extra-nodal sites not selected as dominant or measurable or that do not meet 
the requirements for measurability but are still considered abnormal, as well as truly assessable disease, which is any 
site of suspected disease that would be difficult to follow quantitatively with measurement, including pleural 
effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other lesions that cannot be 
confirmed and followed by imaging. In Waldeyer’s ring or in extra-nodal sites (eg, gastrointestinal tract, liver, bone 
marrow), FDG uptake may be greater than in the mediastinum with complete metabolic response but should be no 
higher than surrounding normal physiologic uptake (eg, with marrow activation as a result of chemotherapy or 
myeloid growth factors). 
□PET 5-point scale (Deauville Criteria): 
• 
1. no uptake above background 
• 
2. uptake ≤ mediastinum 
• 
3. uptake > mediastinum but ≤ liver 
• 
4. uptake moderately > liver 
• 
5. uptake markedly higher than liver and/or new lesions 
X. new areas of uptake unlikely to be related to lymphoma 
Note: Temporary withholding of study drug (eg, for drug-related toxicity, surgery, or intercurrent 
illness) for as little as 7 days can cause a transient worsening of disease and/or of constitutional 
symptoms. In such circumstances, and if medically appropriate, patients may resume therapy and 
relevant clinical, laboratory, and/or radiologic assessments should be performed to document 
whether tumor control can be maintained or whether actual disease progression has occurred. 
Isolated increase in lymph nodes and/or splenomegaly during periods of study drug(s) hold will 
not be considered as progressive disease unless confirmed by a repeat imaging studies ≥ 6 weeks 
after restarting study drug administration. The response category “indeterminate due to study 
drug(s)hold” should be selected for such instances. Following the repeated imaging 6 weeks after 
restarting study drug, response should be in comparison to the imaging at baseline. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 133 
APPENDIX 9. IMMUNE-MEDIATED ADVERSE EVENT EVALUATION 
AND MANAGEMENT  
The recommendations below for the diagnosis and management of any immune-mediated AE 
(imAE) are intended as a guidance. This document should be used in conjunction with expert 
clinical judgement (by specialist physicians experienced in the treatment of cancer using 
immunological agents), and individual institutional guidelines or policies. 
Criteria used to diagnose imAEs include blood tests, diagnostic imaging, histopathology, and 
microbiology assessments to exclude alternative causes such as infection, disease progression, 
and adverse effects of concomitant drugs. In addition to the results of these tests, the following 
factors should be considered when making an imAE diagnosis: 
• What was the temporal relationship between initiation of tislelizumab and the AE? 
• How did the patient respond to withdrawal of tislelizumab? 
• Did the event recur when tislelizumab was reintroduced? 
• Was there a clinical response to corticosteroids? 
• Is the event an autoimmune endocrinopathy? 
• Is disease progression or an alternative diagnosis a more likely explanation? 
When alternative explanations to autoimmune toxicity have been excluded, the imAE field 
associated with the AE in the eCRF should be checked. If further diagnostic evaluations change 
the assessment, the eCRF should be updated accordingly. 
 
Recommended Diagnostic Tests in the Management of 
Possible Immune-Mediated Adverse Events 
Immune-mediated 
Toxicity 
Diagnostic Evaluation Guideline 
Thyroid Disorders 
Perform scheduled and repeated thyroid function tests (TSH and 
T4). 
Hypophysitis 
Check visual fields and consider pituitary endocrine axis blood 
profile. Perform pituitary and whole brain MRI in patients with 
headache, visual disturbance, unexplained fatigue, asthenia, weight 
loss, and unexplained constitutional symptoms. 
Consider consultation with an endocrinologist if an abnormality is 
detected. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 134 
 
Recommended Diagnostic Tests in the Management of 
Possible Immune-Mediated Adverse Events 
Immune-mediated 
Toxicity 
Diagnostic Evaluation Guideline 
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. 
Colitis 
Review dietary intake and exclude steatorrhea. Consider 
comprehensive testing, including the following: FBC, UEC, LFTs, 
CRP, TFTs, stool microscopy and culture, viral PCR, Clostridium 
difficile toxin, and cryptosporidia (drug-resistant organism). 
In case of abdominal discomfort, consider imaging, eg, X-ray, CT 
scan. If a patient experiences bleeding, pain, or distension, consider 
colonoscopy with biopsy and surgical intervention as appropriate. 
Eye Disorders 
If a patient experiences acute, new onset, or worsening of eye 
inflammation; blurred vision; or other visual disturbances, refer the 
patient urgently to an ophthalmologist for evaluation and 
management. 
Hepatitis 
Check ALT/AST/total bilirubin, INR/albumin; the frequency will 
depend on severity of the AE (eg, daily if Grade 3 to 4; every 
2 to 3 days if Grade 2, until recovering). Review medications (eg, 
statins, antibiotics) and alcohol history. Perform liver screen 
including Hepatitis A/B/C serology, Hepatitis E PCR and assess 
anti-ANA/SMA/LKM/SLA/LP/LCI, iron studies. Consider imaging 
(eg, ultrasound scan for metastases or thromboembolism).  Consult 
with a hepatologist and consider liver biopsy. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 135 
 
Recommended Diagnostic Tests in the Management of 
Possible Immune-Mediated Adverse Events 
Immune-mediated 
Toxicity 
Diagnostic Evaluation Guideline 
Renal Toxicity 
Review hydration status and medication history. Test and culture 
urine. Consider renal ultrasound scan, protein assessment 
(dipstick/24-hour urine collection), or phase-contrast microscopy. 
Refer to a nephrologist for further management assistance. 
Dermatology 
Consider other causes by conducting a physical examination.  
Consider dermatology referral for skin biopsy. 
Joint or Muscle 
Inflammation 
Conduct musculoskeletal history and perform complete 
musculoskeletal examination. Consider joint X-ray and other 
imaging as required to exclude metastatic disease. Perform 
autoimmune serology and refer to rheumatology for further 
management assistance. 
For suspected myositis/rhabdomyolysis/myasthenia include: CK, 
ESR, CRP, troponin, and consider a muscle biopsy. 
Myocarditis 
Perform ECG, echocardiogram, CK/CK-MB, troponin (I and/or T), 
and refer to a cardiologist. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; ANA, antinuclear antibody; AST, aspartate 
aminotransferase; CK, creatine kinase; CK-MB, creatine kinase cardiac isoenzyme; CNS, central nervous system; 
CRP, C-reactive protein; CT, computed tomography; Dlco, diffusing capacity for carbon monoxide; ECG, 
electrocardiogram; ESR, erythrocyte sedimentation rate; FBC, full blood count; HIV, human immunodeficiency 
virus; INR, international normalized ratio; LCI, liver cytosolic antigen; LFT, liver function test; LKM, liver kidney 
microsomal antibody; LP, liver pancreas antigen; MRA, magnetic resonance angiogram; MRI, magnetic resonance 
imaging; PCR, polymerase chain reaction; SLA, soluble liver antigen; SMA, smooth muscle antibody; T4, 
thyroxine; TFT, thyroid function tests; TSH, thyroid-stimulating hormone; UEC, urea electrolytes and creatinine. 
Treatment of Immune-Mediated Adverse Events 
• Immune-mediated AEs can escalate quickly. Study treatment interruption, close 
monitoring, timely diagnostic work-up, and treatment intervention as appropriate is 
required. 
• Immune-mediated AEs should improve promptly after introduction of 
immunosuppressive therapy. If this does not occur, review the diagnosis, seek further 
specialist advice, and contact the study medical monitor. 
• For some Grade 3 toxicities that resolve quickly, rechallenge with study drug may be 
considered if there is evidence of a clinical response to study treatment, after 
consultation with the study medical monitor. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 136 
• 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 until ≤ 
Grade 1 or 
baseline. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 137 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
3-4 
Severe symptoms, 
hospitalization required 
Refer patient to an 
endocrinologist. 
If hypothyroid, 
replace with 
thyroxine 
0.5-1.6 µg/kg/day 
(for the elderly or 
those with 
comorbidities, the 
suggested starting 
dose is 
0.5 µg/kg/day).  Add 
oral prednisolone 
0.5 mg/kg/day for 
thyroid pain. 
Thyrotoxic patients 
require treatment with 
a beta blocker and 
may require 
carbimazole until 
thyroiditis resolves. 
Hold study 
treatment; resume 
when 
resolved/improved 
to ≤ Grade 1 or 
baseline. 
 
Hypophysitis 
1-2 
Mild-moderate symptoms 
Refer patient to an 
endocrinologist for 
hormone 
replacement. 
Add oral 
prednisolone 
0.5-1 mg/kg/day for 
patients with pituitary 
inflammation.  Taper 
corticosteroids over at 
least 1 month. 
If there is no 
improvement in 
48 hours, treat as 
Grade 3 or 4. 
Continue study 
treatment. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 138 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
3-4 
Severe or life-threatening 
symptoms 
Refer patient to an 
endocrinologist for 
assessment and 
treatment. 
Initiate pulse 
intravenous 
methylprednisolone 
1 mg/kg for patients 
with headache/visual 
disturbance due to 
pituitary 
inflammation.  
Convert to oral 
prednisolone and 
taper over at least 
1 month. 
Maintain hormone 
replacement 
according to 
endocrinologist’s 
advice. 
Hold study 
treatment for 
patients with 
headache/visual 
disturbance due to 
pituitary 
inflammation until 
resolved/improved 
to ≤ Grade 1 or 
baseline. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 139 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
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.  
Retreatment is 
acceptable if 
symptoms resolve 
completely or are 
controlled (≤ 
Grade 1 or 
baseline) on 
prednisolone 
≤ 10 mg/day. 
Discontinue study 
treatment if 
symptoms persist 
with corticosteroid 
treatment. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 140 
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 intravenous 
methylprednisolone 
2-4 mg/kg/day. If 
there is no 
improvement, or 
worsening after 
48 hours, add 
infliximab 5 mg/kg 
(if no hepatic 
involvement). 
Convert to oral 
prednisolone and 
taper over at least 
2 months. 
Cover with empiric 
antibiotics and 
consider prophylaxis 
for Pneumocystis 
infection and other 
adverse steroid 
effects, eg, blood 
glucose monitoring, 
vitamin D/calcium 
supplement. 
Discontinue study 
treatment. 
Neurological 
Toxicity 
1 
Mild symptoms 
NA 
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 ≤ Grade1 or 
baseline. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 141 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
3-4 
Severe/life-threatening 
symptoms, Grade 3 or 4 
encephalitis, or Grade 3 or 4 
Guillain-Barré syndrome 
Initiate treatment with 
oral prednisolone or 
intravenous 
methylprednisolone 
1-2 mg/kg/day, 
depending on 
symptoms. Taper 
corticosteroids over at 
least 4 weeks. 
Consider 
azathioprine, MMF, 
cyclosporine if no 
response within 
72-96 hours. 
Guillain-Barré 
syndrome: Start 
intravenous 
immunoglobulin 
0.4 g/kg/day for 
5 days or 
plasmapheresis. 
Consider 
corticosteroids 
(methylprednisolone 
2 to 4 mg/kg/day) 
followed by a slow 
taper. Monitor for 
concurrent autonomic 
dysfunction. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 142 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
2 
Moderate symptoms: 4-6 
liquid stools per day over 
baseline, or abdominal pain, 
or blood in stool, or nausea, 
or nocturnal episodes 
Oral prednisolone 
0.5 mg/kg/day 
(nonenteric coated). 
Do not wait for any 
diagnostic tests to 
start treatment.  Taper 
steroids over 
2-4 weeks. 
Consider endoscopy 
if symptoms are 
recurring. 
Hold study 
treatment; resume 
when 
resolved/improved 
to ≤ Grade 1 or 
baseline. 
3 
Severe symptoms: > 6 liquid 
stools per day over baseline, 
or if episodic within 1 hour 
of eating 
Initiate intravenous 
methylprednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone and 
taper over at least 
4 weeks.  Consider 
prophylaxis for 
adverse steroid 
effects, eg, blood 
glucose monitoring, 
vitamin D/calcium 
supplement. 
If no improvement in 
72 hours or 
symptoms worsen, 
consider infliximab 
5 mg/kg if no 
perforation, sepsis, 
TB, hepatitis, NYHA 
Class III/IV CHF or 
other 
immunosuppressive 
treatment: MMF or 
tacrolimus. 
Consult 
gastroenterologist to 
conduct colonoscopy/ 
sigmoidoscopy. 
Hold study 
treatment; 
retreatment may 
be considered 
when 
resolved/improved 
to ≤ Grade 1 or 
baseline and after 
discussion with 
the study medical 
monitor. 
4 
Life-threatening symptoms 
Discontinue study 
treatment. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 143 
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. 
Consider holding 
study treatment 
and monitor 
weekly for 
improvement. If 
not resolved, 
interrupt treatment 
until improved to 
Grade. 1. 
3 
Rash covers > 30% BSA or 
Grade 2 with substantial 
symptoms 
Avoid skin irritants 
and sun exposure; 
topical emollients, 
oral antihistamines, 
and high-potency 
topical corticosteroids 
recommended. 
Initiate 
(methyl)prednisolone 
1-2 mg/kg (or 
equivalent), tapering 
for a period of ≥ 4 
weeks. 
Hold study 
treatment. 
Re-treat when AE 
is resolved or 
improved to mild 
rash (≤ Grade 1) 
or baseline or after 
discussion with 
the study medical 
monitor. 
 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 144 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
4 
Skin sloughing > 30% BSA 
with associated symptoms 
(eg, erythema, purpura, 
epidermal detachment) 
Initiate intravenous 
methylprednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone and 
taper over at least 
4 weeks. 
Admit to a hospital 
and seek urgent 
dermatology 
consultation. 
Discontinue 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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 145 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
2 
ALT or AST 3-5 x ULN 
Recheck LFTs every 
48-72 hours. 
Administer 
prednisolone at a 
dose of 
0.5-2 mg/kg/day for 
≥ Grade 2 liver 
enzyme elevations, 
with or without 
concomitant bilirubin 
elevations. 
For Grade 2 hepatitis, 
withhold tislelizumab 
until the event has 
resolved or improved 
to baseline and 
prednisolone has been 
tapered to 
≤ 10 mg/day over 2-4 
weeks. 
Hold study 
treatment; 
treatment may be 
resumed when 
resolved/improved 
to ≤ Grade 1 or 
baseline and 
prednisolone 
tapered to 
≤ 10 mg. 
3 
ALT or AST 5-20 x ULN 
Immediately start 
(methyl)prednisolone 
1-2 mg/kg/day (or 
equivalent). Monitor 
closely. If no 
improvement after 
3 days, consider 
additional treatment 
options 
(mycophenolate 
mofetil or 
azathioprine). 
If ALT and AST ≤ 
10 x ULN: Hold 
study treatment 
until improved to 
baseline grade; 
reintroduce only 
after discussion 
with the medical 
monitor. 
If ALT or AST > 
10 x ULN: 
Discontinue study 
treatment. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 146 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
4 
ALT or AST > 20 x ULN 
Initiate intravenous 
methylprednisolone 
2 mg/kg/day.  
Convert to oral 
prednisolone and 
taper over at least 
6 weeks. 
Discontinue study 
treatment. 
Worsening LFTs despite steroids: 
If on oral prednisolone, change to pulsed intravenous 
methylprednisolone. 
If on intravenous methylprednisolone, add mycophenolate mofetil 
(MMF) 500 to 1000 mg twice a day. 
If worsens on MMF, consider addition of tacrolimus. 
Duration and dose of steroid required will depend on severity of event. 
Nephritis 
1 
Creatinine 1.5 x baseline 
or > ULN to 1.5 x ULN 
Repeat creatinine 
weekly. 
If symptoms worsen, 
manage as per criteria 
below. 
Continue study 
treatment. 
2 
Creatinine > 1.5-3 x baseline 
or > 1.5-3 x ULN 
Ensure hydration and 
review creatinine in 
48-72 hours; if not 
improving, consider 
creatinine clearance 
measurement by 
24-hour urine 
collection. 
Discuss with 
nephrologist the need 
for kidney biopsy. 
If attributed to study 
drug, initiate oral 
prednisolone 
0.5-1 mg/kg and taper 
over at least 2 weeks. 
Repeat 
creatinine/U&E every 
48-72 hours. 
Hold study 
treatment. 
If not attributed to 
drug toxicity, 
restart treatment. 
If attributed to 
study drug and 
resolved/improved 
to ≤ Grade 1 or 
baseline, restart 
study drug if 
tapered to 
< 10 mg 
prednisolone. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 147 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
3 
Creatinine > 3 x baseline or 
> 3-6 x ULN 
Hospitalize patient 
for monitoring and 
fluid balance; repeat 
creatinine every 
24 hours; refer to a 
nephrologist and 
discuss need for 
biopsy. 
If worsening, initiate 
intravenous 
(methyl)prednisolone 
1-2 mg/kg. Taper 
corticosteroids over at 
least 4 weeks. 
Hold study 
treatment until the 
cause is 
investigated. 
If study drug 
suspected, 
discontinue study 
treatment. 
 
4 
Creatinine > 6 x ULN 
As per Grade 3, 
patient should be 
managed in a hospital 
where renal 
replacement therapy 
is available. 
Discontinue study 
treatment. 
Diabetes/ 
Hyperglycemia 
1 
Fasting glucose value ULN 
to 160 mg/dL; ULN to 
8.9 mmol/L 
Monitor closely and 
treat according to 
local guideline.  
Check for C-peptide 
and antibodies against 
glutamic acid 
decarboxylase and 
islet cells are 
recommended. 
Continue study 
treatment. 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 148 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
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. 
Hold study 
treatment until 
patient is 
hyperglycemia 
symptom-free, 
and blood glucose 
has been 
stabilized at 
baseline or 
Grade 0-1. 
 
Ocular Toxicity 
1 
Asymptomatic eye 
examination/test abnormality 
Consider alternative 
causes and prescribe 
topical treatment as 
required. 
Continue study 
treatment. 
2 
Anterior uveitis or mild 
symptoms 
Refer patient to an 
ophthalmologist for 
assessment and 
topical corticosteroid 
treatment. 
Consider a course of 
oral steroids. 
Continue study 
treatment or hold 
treatment if 
symptoms worsen 
or if there are 
symptoms of 
visual disturbance. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 149 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
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 or 
baseline; 
reintroduce only 
after discussion 
with the study 
medical monitor. 
 
4 
Blindness (at least 20/200) in 
the affected eyes 
Initiate intravenous 
(methyl)prednisolone 
2 mg/kg/day.  
Convert to oral 
prednisolone and 
taper over at least 
4 weeks. 
Discontinue 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 intravenous 
(methyl)prednisolone 
1-2 mg/kg/day.  
Convert to oral 
prednisolone when 
amylase/lipase 
improved to Grade 2 
and taper over at least 
4 weeks. 
Hold study 
treatment until 
improved to 
≤ Grade 1 or 
baseline; 
reintroduce only 
after discussion 
with the study 
medical monitor. 
 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 150 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
2 
Moderate pain with 
inflammation, swelling, 
limited instrumental (fine 
motor) activities 
Management as per 
local guideline.  
Consider referring 
patient to a 
rheumatologist. 
If symptoms worsen 
on treatment, manage 
as a Grade 3 event. 
Continue 
treatment or, if 
symptoms 
continue to 
worsen, hold 
study treatment 
until symptoms 
improve to 
baseline or 
≤ Grade 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 1 or 
baseline; 
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. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 151 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
3 
Severe pain, limited food and 
fluid intake, daily living 
activity limited 
Admit to hospital for 
appropriate 
management. 
Initiate intravenous 
(methyl)prednisolone 
1-2 mg/kg/day. 
Convert to oral 
prednisolone when 
symptoms improve to 
Grade 2 and taper 
over at least 4 weeks. 
Hold study 
treatment until 
improved to 
≤ Grade 1 or 
baseline. 
 
4 
Life-threatening 
complications or dehydration 
Admit to hospital for 
emergency care.  
Consider intravenous 
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 1 or 
baseline. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 152 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
3-4 
Severe weakness, limiting 
self-care 
Admit to hospital and 
initiate oral 
prednisolone 
1 mg/kg.  Consider 
bolus intravenous 
(methyl)prednisolone 
and 1-2 mg/kg/day 
maintenance for 
severe activity 
restriction or 
dysphagia. 
If symptoms do not 
improve, add 
immunosuppressant 
therapy. 
Taper oral steroids 
over at least 4 weeks. 
For Grade 3: Hold 
study treatment 
until improved to 
≤ Grade 1 or 
baseline. 
Discontinue upon 
any evidence of 
myocardial 
involvement. 
 
Myocarditis a 
< 2 
Asymptomatic but 
significantly increased 
CK-MB or increased 
troponin OR clinically 
significant intraventricular 
conduction delay 
Initiate cardiac 
evaluation under 
close monitoring with 
repeat serum testing 
and including ECG, 
cardiac echo/MUGA, 
and/or other 
interventions per 
institutional 
guidelines; consider 
referral to a 
cardiologist. 
If diagnosis of 
myocarditis is 
confirmed, treat as 
Grade 2. 
Hold study 
treatment. 
If a diagnosis of 
myocarditis is 
confirmed and 
considered 
immune-mediated, 
permanently 
discontinue study 
treatment in 
patients with 
moderate or 
severe symptoms. 
Patients with no 
symptoms or mild 
symptoms may 
not restart 
tislelizumab 
unless cardiac 
parameters have 
returned to 
≤ Grade 1 or 
baseline and after 
2 
Symptoms on mild-moderate 
exertion 
Admit to hospital and 
initiate oral 
prednisolone or 
intravenous 
(methyl)prednisolone 
at 1-2 mg/kg/day.  
Consult with a 
3 
Severe symptoms with mild 
exertion 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 153 
Autoimmune 
Toxicity 
Grade 
Treatment 
Guidelines (Subject 
to Clinical 
Judgement) 
Study Drug 
Management 
4 
Life-threatening 
cardiologist and 
manage symptoms of 
cardiac failure 
according to local 
guidelines. 
If no immediate 
response, change to 
pulsed doses of 
(methyl)prednisolone 
1 g/day and add 
MMF, infliximab, or 
anti-thymocyte 
globulin. 
discussion with 
the study medical 
monitor. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSA, body 
surface area; CHF, congestive heart failure; CK, creatine kinase; CK-MB, creatine kinase cardiac isoenzyme; ECG, 
electrocardiogram; INR, international normalized ratio; LFT, liver function test; MMF, mycophenolate mofetil; 
MUGA, multigated acquisition scan; NYHA, New York Heart Association; T4, thyroxine; TB, tuberculosis; TFT, 
thyroid function test; TSH, thyroid-stimulating hormone; U&E, urea and electrolytes; ULN, upper limit of normal. 
a. If clinically significant cardiac enzyme abnormalities are detected during laboratory assessment and serial cardiac 
enzyme assessments pose logistical hardship for the patient, then patient hospitalization should strongly be 
considered until immune-mediated myocarditis has been ruled out. 
Approved Date
5/22/2024

AdvanTIG-101 
BeiGene 
Protocol Amendment Version 3.0 
22 May 2024 
 
CONFIDENTIAL 
Page 154 
APPENDIX 10. DRUGS WITH A KNOWN RISK OF QT 
PROLONGATION/TORSADES DE POINTES  
The text below was obtained from the following sources: Woosley et al 2013 and Flockhart 
2007.  
Bold font indicates medications or substances that might be relatively commonly used. 
• amiodarone 
• anagrelide 
• arsenic trioxide 
• astemizole (off United States [US] 
market) 
• azithromycin 
• bepridil (off US market) 
• chloroquine 
• chlorpromazine 
• cilostazol 
• ciprofloxacin 
• cisapride (off US market) 
• citalopram 
• clarithromycin 
• cocaine 
• disopyramide 
• dofetilide 
• domperidone (not on US market) 
• donepezil 
• dronedarone 
• droperidol 
• erythromycin 
• escitalopram 
• flecainide 
• fluconazole 
• gatifloxacin (off US market) 
• grepafloxacin (not on US market) 
• halofantrine (not on US market) 
• haloperidol 
• ibogaine (not on US market) 
• ibutilide 
• levofloxacin 
• levomepromazine/ 
methotrimeprazine (not on US 
market) 
• levomethadyl (off US market) 
• levosulpiride (not on US market) 
• mesoridazine (off US market) 
• methadone 
• moxifloxacin 
• ondansetron 
• oxaliplatin 
• pentamidine 
• pimozide 
• probucol (off US market) 
• procainamide 
• propofol 
• quinidine 
• roxithromycin (not on US market) 
• sevoflurane 
• sotalol 
• sparfloxacin (off US market) 
• sulpiride (not on US market) 
• sultopride (non on US market) 
• terfenadine (off US market) 
• terlipressin (not on US market) 
• terodiline (not on US market) 
• thioridazine 
• vandetanib 
 
 
Approved Date
5/22/2024