A Phase 2, Randomized, Open-label Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Hepatocellular Carcinoma Who Are Naive to IO Therapy But Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073)
Phase: PHASE2
Conditions: Hepatocellular Carcinoma, Hepatoma, Liver Cancer, Adult, Liver Cell Carcinoma, Liver Cell Carcinoma, Adult
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 2, Randomized, Open-label Study of Relatlimab in Combination with Nivolumab in 
Participants with Advanced Hepatocellular Carcinoma who are Naive to IO Therapy but 
Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073) 
 
NCT Number: NCT04567615 
Document Date (Date in which document was last revised): 26 May 2022 

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Protocol Number: CA224073 
Date: 29-May-2020 
Revised Date: 26-May-2022 
 
REGULATORY AGENCY IDENTIFIER NUMBER(S) 
 
EudraCT: 2018-003151-38 
UTN: U1111-1218-6499 
 
CLINICAL PROTOCOL CA224073 
A Phase 2, Randomized, Open-label Study of Relatlimab in Combination with Nivolumab in 
Participants with Advanced Hepatocellular Carcinoma who are Naive to IO Therapy but 
Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073) 
Short Title: Phase 2 study of relatlimab and nivolumab in IO-naive 2nd/3rd-line HCC 
Protocol Amendment 04 
 
 
 
Medical Monitor 
Bristol-Myers Squibb Company 
Bristol-Myers Squibb Company 
Route de Perreux 1 
2017 Boudry, Switzerland 
Telephone (mobile): 
Email: 
3401 Princeton Pike 
Lawrenceville, NJ, USA 
Telephone (mobile): 
Email: 
24-hr Emergency Telephone Number 
USA: 
International: 
Japan: 
 
Bristol Myers Squibb Company 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
 
Avenue de Finlande 4 
B-1420 Braine-l’Alleud, Belgium 
 
6-5-1 Nishi-Shinjuku, Shinjuku-ku, 
Tokyo, 163-1327, Japan 
 
This document is the confidential and proprietary information of Bristol Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 

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confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations (eg, a Contract Research 
Organization [CRO]). 
© 2022 Bristol-Myers Squibb Company 

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DOCUMENT HISTORY 
 
Document 
Date of Issue 
Summary of Change 
Protocol 
Amendment 04 
26-May-2022 
Additional updates, including personnel changes and changes to sections 
of the Synopsis, have been made to align the protocol with respect to these 
changes. This protocol amendment applies to all participants. 
Administrative 
Letter 01 
10-Mar-2022 
The purpose of this administrative letter is to communicate the change of 
the Medical Monitor and Clinical Scientist. 
Protocol 
Amendment 03 
29-Jul-2021 
Additional updates, including to sections of the Synopsis, have been made 
to align the protocol with respect to these changes. This protocol 
amendment applies to all participants. 
Protocol 
Amendment 02 
15-Apr-2021 
The primary reasons for these changes are to include participants with 
advanced immuno-oncology (IO) therapy-naive hepatocellular carcinoma 
(HCC) who have received one or two lines of tyrosine kinase inhibitor 
(TKI) therapies and have shown radiographic progression on or after the 
last line of TKI therapy; clarify expectations for sample collection, study 
assessments, and participant eligibility; 
. 
Revised Protocol 
01 
28-Oct-2020 
The primary reasons for these changes are to align dose modification 
criteria 
with the 
current Common Terminology Criteria for Adverse Event (CTCAE) 
version (v5); add serologic testing for severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) status; and incorporate additional updates to 
improve alignment across protocol sections and/or clarify expectations for 
eligibility, assessments, sample collections, treatment administration, and 
country-specific requirements. 
Original Protocol 
29-May-2020 
Not applicable 

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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 04: 
The primary rationale for Protocol Amendment 04 is to make overall study design changes and 
clarify several items throughout the protocol. 
The original design of CA224-073 was a 3-arm study randomized 2:1:2 with the following 
treatment arms: 
• Arm A: nivolumab 480 mg every 4 weeks (Q4W) 
• Arm B: nivolumab 480 mg Q4W + relatlimab 480 mg Q4W 
• Arm C: nivolumab 480 mg + relatlimab 960 mg Q4W 
 
 
 
 
24 participants were randomized in Arm C. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
 
Section Number & Title 
Title page 
Description of Change 
Changed Medical Monitor from 
, to 
, Clinical 
Scientist from 
to 
, and their associated contact 
Brief Rationale 
To report important 
personnel changes. 
information. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 2-1: Screening 
Procedural Outline 
(CA224073) 
Removed the following text from notes 
corresponding to the “Pre-screening for Tumor 
Tissue Sample” row: 
“All other procedures may be performed within 14 
days if pre-screening ICF is used.” 
Modified the language from “Most" to "All" 
inclusion/exclusion criteria in notes corresponding to 
the Inclusion/Exclusion Criteria row. 
To avoid confusion 
regarding procedures that 
can be done with pre- 
screening informed consent 
form (ICF). 
 
For clarity. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & Title 
Description of Change 
Brief Rationale 
Added the following text to notes corresponding to 
the row Physical Examination: 
“Full physical examination including height, weight, 
and BMI. Any findings during the PE will be 
recorded as medical history in the participant’s 
medical records and on the appropriate CRF.” 
Clarified requirements for 
physical examination. 
Oxygen saturation was added to vital sign 
assessments. 
Clarified requirements for 
vital sign assessments. 
Added the following text to notes corresponding to 
the row 12-lead ECG: 
“ECGs must be collected and assessed using the 
site’s own ECG machine.” 
To maintain consistency 
with the text stated in future 
visits. 
Replaced “24 hours” with “1 day” in the notes 
corresponding to the row, Pregnancy Test (WOCBP 
only). 
To update window to 1 day 
instead of 24 hours and 
maintain consistency among 
sections. 
Section 5.1.1: Screening 
Period 
Added the following text: 
If the subject is awaiting central laboratory results, 
then the participant does not have to reconsent until 
day 42 (additional +14 days beyond screening 
window). Other screening procedures should be 
conducted within the windows specified in Table 2-1. 
For clarity. 
Table 2-2: On-Treatment 
Assessments (CA224073) 
• 
Clarified on-treatment monitoring requirements 
between Arm A and B. 
• 
• 
• 
Added: Assessments of PR and CR must be 
confirmed at least 4 weeks (28 days) after initial 
response. 
To clarify that the enhanced 
monitoring requirements are 
specific to Arm B. 
To clarify confirmatory 
imaging requirements. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & Title 
Description of Change 
Brief Rationale 
• 
Replaced “24 hours” with “1 day” in the notes 
corresponding to the row, Pregnancy Test 
(WOCBP only). 
• 
Added the following text to notes corresponding 
to the row Body Imaging: 
"  disease progression (unless treatment beyond 
progression) 
or 
treatment 
discontinuation 
(including 
treatment 
beyond 
progression), 
whichever occurs later.” 
To maintain consistency 
among sections. 
To clarify imaging 
requirements and maintain 
consistency across protocol. 
Table 2-3: Follow-up 
Procedural Outline 
(CA224073) 
Added the following text to notes corresponding to 
the row Targeted Physical Examination: 
“Any findings during the PE will be evaluated for 
AEs and reported as such.” 
To emphasize adverse event 
(AE) reporting requirements 
during follow-up. 
Added the following text to notes corresponding to 
the row Body Imaging: 
“Participants with SD, PR, or CR at the time of the 
EOT visit or at the time of study treatment 
discontinuation will continue to have radiologic and 
clinical tumor assessments every 8 weeks (± 7 days) 
after discontinuation of study treatment/EOT visit, 
until the start of subsequent therapy, disease 
progression (unless treatment beyond progression), or 
withdrawal of study consent.” 
Assessments of PR and CR must be confirmed at 
least 4 weeks (28 days) after initial response.” 
To clarify and maintain 
consistency across 
protocol-regarding imaging 
requirements. 
Section 5.1.3: Follow-up 
Period 
Section 7.7.1 Prohibited 
and/or Restricted Treatments 
Section 9.2.1: Time Period 
and Frequency for Collecting 
AE and SAE Information 
Section 9.2.2: Methods of 
Detecting AEs and SAEs 
Updated duration of clinical safety follow-up from 
100 days to 135 days. 
Safety follow-up period 
extension to cover 5 half- 
lives of relatlimab. 
Section 3.2.3: Relatlimab 
Combined with Nivolumab 
Clinical Activity 
Updated the section with results from Study 
CA224047, a global, double-blind, randomized, 
Phase 2/3 study comparing a fixed-dose combination 
(FDC) formulation of nivolumab 480 mg + relatlimab 
160 mg FDC Q4W to nivolumab 480 mg Q4W in 
participants with previously untreated advanced 
melanoma. 
To provide background 
information on recent Phase 
3 trial results in melanoma 
with nivolumab + relatlimab. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & Title 
Description of Change 
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 1: Synopsis 
Section 5.1: Overall Design 
Figure 5.1-1: Study Design 
Schematic for CA224073 
Updated sample size to total approximately 250 
participants, with 226 in Arm A and B, and 24 in 
Arm C. 
 
 
Section 5.2: Number of 
Participants 
 
Section 6.1: Inclusion Criteria 
Updated sample size to total approximately 250 
participants, with 226 in Arm A and B and 24 in Arm 
C. 
To clarify total sample size 
plan. 
 
 
 
• 
Excluded participants with prior chemotherapy in To clarify that only patients 
inclusion criterion 2) b) iii). 
with prior tyrosine kinase 
inhibitor (TKI) treatment, 
not chemotherapy, are 
eligible to enroll. 
• 
Added to inclusion criterion 3) b) i): “No For clarity. 
contraception is required for male participants.” 
Section 6.1: Inclusion Criteria Removed language allowing participant re- 
To prevent re-randomization 
Section 6.4.1: Retesting 
During Screening Period 
 
 
 
 
Section 1 Synopsis 
Section 6.2: Exclusion 
Criteria 
 
Section 7.1.3: Palliative 
Therapy 
randomization from inclusion criterion 1) c. 
The term "pre-treatment failure" was changed to 
"screen failure" for further clarification. 
 
 
 
Added “pregnant or” to the existing 
exclusion criterion 2) a). 
 
 
Clarified palliative therapy language. 
to the trial which would 
impact the intent-to-treat 
population; this does not 
change language allowing 
re-enrollment of pre- 
treatment/screen failures. 
To make it consistent with 
Section 6.1 Inclusion 
Criterion 3) a) x) of the 
protocol. 
To better define 
circumstances when 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & Title 
Description of Change 
Brief Rationale 
palliative therapy is 
permitted. 
Section 7.3: Blinding 
Clarified blinding language regarding open-label 
design. 
To clarify that study has 
been treated as open label 
per design. 
Section 7.7.1: Prohibited 
and/or Restricted Treatments 
Clarified that “systemic” chemotherapy is prohibited 
while on study treatment. 
To clarify that locally 
administered chemotherapy 
that is not directed at 
hepatocellular carcinoma 
may be permissible. 
Section 8.1.3: Criteria to 
Resume Treatment 
Clarified the criterion, as shown below, to resume 
To fix an inconsistency in 
this protocol regarding 
requirements for re-initiation 
of treatment 
treatment in participants 
. 
. 
Section 9.2.1: Time Period 
and Frequency for Collecting 
AE and SAE Information 
Clarified the requirement to report deaths occurring 
within the follow-up period as SAEs. 
To continue to report deaths 
within the follow-up period 
as SAEs regardless of 
initiation of new anti- 
neoplastic treatment. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 9.8.4: Additional 
Research Collection 
Clarified that additional research collection and 
analysis will not occur 
Amendment 04. 
as per Protocol 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & Title 
Description of Change 
Brief Rationale 
 
 
 
 
Section 10.3.3: Other 
Analyses 
Language added 
 
 
Language describing the plan to conduct 
analyses using data obtained from 
the study was added. 
 
 
 
 
 
Appendix 2: Study 
Governance Considerations 
Added 2 new sections: BMS Commitment to 
Diversity in Clinical Trials and Data Protection, Data 
Privacy, and Data Security. 
Added to align with BMS 
commitment to diversity in 
clinical trials and to comply 
with European Union 
Clinical Trials Regulation 
requirement. 
 
 
 
 
Section 11 References 
All 
3 new literature references. 
 
Changed references to protocol amendment 03 to be 
in the past tense. 
Minor, therefore, have not 
been summarized. 
To clarify statements 
referencing protocol 
amendment 03 have already 
been implemented or are no 
longer relevant. 
 
Minor formatting and typographical corrections. 
Minor, therefore, have not 
been summarized. 

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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
1 
DOCUMENT HISTORY.............................................................................................. 
3 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 04: ............................ 
4 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04................ 
6 
TABLE OF CONTENTS.............................................................................................. 
13 
1 SYNOPSIS................................................................................................................. 
17 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
25 
3 INTRODUCTION ..................................................................................................... 
40 
3.1 Study Rationale ................................................................................................. 
40 
3.1.1 Research Hypothesis ................................................................................ 
43 
3.2 Background ....................................................................................................... 
43 
3.2.1 Relatlimab Mechanism of Action ............................................................. 
46 
3.2.2 Nivolumab Mechanism of Action ............................................................. 
46 
3.2.3 Relatlimab Combined with Nivolumab Clinical Activity ......................... 
47 
3.3 Benefit/Risk Assessment .................................................................................. 
48 
3.3.1 Introduction.............................................................................................. 
48 
3.3.2 Safety........................................................................................................ 
49 
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3.3.3 Safety Monitoring..................................................................................... 
52 
3.3.4 Efficacy .................................................................................................... 
53 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
54 
5 STUDY DESIGN....................................................................................................... 
55 
5.1 Overall Design .................................................................................................. 
55 
5.1.1 Screening Period...................................................................................... 
59 
5.1.2 Treatment Period ..................................................................................... 
59 
5.1.3 Follow-up Period ..................................................................................... 
60 
5.1.3.1 Survival Follow-up Period.............................................................. 
61 
5.1.4 Data Monitoring Committee and Other External Committees ................ 
61 
5.1.4.1 Data Monitoring Committee ........................................................... 
61 
5.2 Number of Participants ..................................................................................... 
62 
5.3 End of Study Definition .................................................................................... 
62 
5.4 Scientific Rationale for Study Design............................................................... 
63 
5.4.1 Rationale for Choice of Comparators...................................................... 
63 
5.4.2 Rationale for Use of Relatlimab in Combination with Nivolumab .......... 
63 
5.4.3 Rationale for Duration of Treatment ....................................................... 
64 
5.4.4 Rationale for Stratification Factors......................................................... 
64 
65 
5.5 Justification for Dose ........................................................................................ 
66 
5.5.1 Justification for Nivolumab Dose ............................................................ 
66 
67 
5.6 Clinical Pharmacology Summary ..................................................................... 
68 
5.6.1 Nivolumab Clinical Pharmacology Summary ......................................... 
68 
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6 STUDY POPULATION ............................................................................................ 
6.1 Inclusion Criteria .............................................................................................. 
6.2 Exclusion Criteria ............................................................................................. 
6.3 Lifestyle Restrictions ........................................................................................ 
6.4 Screen Failures.................................................................................................. 
6.4.1 Retesting During Screening Period ......................................................... 
7 TREATMENT ........................................................................................................... 
7.1 Treatments Administered.................................................................................. 
7.1.1 Relatlimab Combined with Nivolumab Dosing........................................ 
7.1.2 Best Supportive Care ............................................................................... 
7.1.3 Palliative Therapy.................................................................................... 
7.2 Method of Treatment Assignment .................................................................... 
7.3 Blinding............................................................................................................. 
7.4 Dosage Modification......................................................................................... 
 
7.4.2 Dose Delay Criteria ................................................................................. 
 
 
7.4.4 Management of Treatment-related Infusion Reactions............................ 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
7.5.1 Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
7.6 Treatment Compliance...................................................................................... 
7.7 Concomitant Therapy........................................................................................ 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
7.7.2 Other Restrictions and Precautions......................................................... 
7.7.2.1 Imaging Restriction and Precautions ............................................. 
7.7.3 Permitted Therapy ................................................................................... 
7.7.4 Antiviral Therapy ..................................................................................... 
7.8 Treatment After the End of the Study............................................................... 
8 DISCONTINUATION CRITERIA ........................................................................... 
8.1 Discontinuation from Study Treatment ............................................................ 
8.1.1 Relatlimab and Nivolumab Treatment Discontinuation .......................... 
8.1.2 Treatment Beyond Disease Progression .................................................. 
8.1.3 Criteria to Resume Treatment.................................................................. 
8.1.4 Post Study Treatment Study Follow-up.................................................... 
8.2 Discontinuation from the Study ........................................................................ 
8.3 Lost to Follow-Up............................................................................................. 
9 STUDY ASSESSMENTS AND PROCEDURES..................................................... 
9.1 Efficacy Assessments........................................................................................ 
9.1.1 Imaging Assessment for the Study............................................................ 
9.1.1.1 Methods of Measurement ................................................................ 
9.1.1.2 Imaging and Clinical Assessment ................................................... 
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9.2 Adverse Events ................................................................................................. 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
9.2.2 Method of Detecting AEs and SAEs......................................................... 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
9.2.4 Regulatory Reporting Requirements for SAEs......................................... 
9.2.5 Pregnancy ................................................................................................ 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
9.2.7 Potential Drug Induced Liver Injury (DILI) ............................................ 
9.2.8 Other Safety Considerations .................................................................... 
9.3 Overdose ........................................................................................................... 
9.4 Safety ................................................................................................................ 
9.4.1 Physical Examinations............................................................................. 
9.4.2 Vital signs................................................................................................. 
9.4.3 Electrocardiograms ................................................................................. 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
9.4.5 Imaging Safety Assessment ...................................................................... 
 
 
 
 
 
 
 
 
9.8.2 Tumor Samples......................................................................................... 
9.8.2.1 Tumor Sample Collection ............................................................... 
9.8.2.2 LAG-3 and PD-L1 Expression ........................................................ 
 
9.8.4 Additional Research Collection ............................................................... 
9.8.6 Other Assessments ................................................................................... 
9.9 Health Economics OR Medical Resource Utilization and Health Economics . 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.2 Populations for Analyses ................................................................................ 
10.3 Statistical Analyses ......................................................................................... 
10.3.1 Efficacy Analyses ................................................................................... 
10.3.2 Safety Analyses....................................................................................... 
10.3.4 Interim Analyses..................................................................................... 
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10.3.4.2 Bayesian Continuous Monitoring for Safety................................. 
11 REFERENCES ........................................................................................................ 
12 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW UP AND REPORTING......................................................................... 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION..................................................................... 
APPENDIX 5 CHILD-PUGH SCORE ........................................................................ 
APPENDIX 6 ECOG PERFORMANCE STATUS ..................................................... 
APPENDIX 7 COUNTRY SPECIFIC REQUIREMENTS/DIFFERENCES .............. 
 
APPENDIX 9 RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS ........................ 
APPENDIX 10 BARCELONA CLINIC LIVER CANCER (BCLC) 
CLASSIFICATION ................................................................................................ 
APPENDIX 11 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY 
................................................................................................................................. 
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1 
SYNOPSIS 
Protocol Title: A Phase 2, Randomized, Open-label Study of Relatlimab in Combination with 
Nivolumab in Participants with Advanced Hepatocellular Carcinoma who are Naive to IO Therapy 
but Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073) 
Short Title: Phase 2 study of relatlimab and nivolumab in IO-naive 2nd/3rd-line HCC 
Study Phase: 2a 
Rationale: 
Hepatocellular carcinoma (HCC) results in approximately 800,000 deaths globally per year. HCC 
has unique geographic, sex, and age distributions that are likely determined by specific etiologic 
factors. The preferred therapy for localized HCC is surgical resection, but the majority of patients 
are not eligible because of tumor extent or underlying liver dysfunction. For patients with disease 
that is not surgically resectable, liver transplantation is the only other potentially curative option. 
For patients with liver-limited disease who are not eligible for resection or liver transplantation, 
treatment options are locoregional therapies. Upon progression on locoregional therapy, systemic 
therapy is an option if performance status and underlying liver function are adequate. Currently, 
the standard of care for patients in first-line (1L) advanced/metastatic HCC are small molecule 
tyrosine kinase inhibitors (TKIs; eg, sorafenib and lenvatinib); however, with the data from the 
IMbrave 150 study, anti-programmed death-ligand 1 (PD-L1) and vascular endothelial growth 
factor (VEGF) inhibitor (atezolizumab and bevacizumab) combination therapy has reshaped the 
current landscape and also the subsequent therapies. 
Individually targeting immune checkpoint receptors, such as cytotoxic T-lymphocyte-associated 
protein-4 (CTLA-4) and programmed cell death-1 (PD-1), has been clinically successful across 
multiple tumor types, including HCC. It is possible, however, that combination therapies could 
potentially lead to greater depth of response and overall survival (OS), as has been noted with 
anti-PD-1 and anti-CTLA-4 combination therapy in advanced melanoma patients. Targeting 
additional checkpoints, such as lymphocyte activation gene 3 (LAG-3), is considered a promising, 
novel approach. Dual blockade of LAG-3 and PD-1 has potential to improve efficacy in 
comparison with blocking PD-1 alone, without adding significant toxicity. 
 
 
There is also evidence that fibrinogen-like protein 1 (FGL-1), a liver-secreted protein, is a 
major LAG-3 functional ligand independent from major histocompatibility complex (MHC) Class 
II. FGL-1 inhibits antigen-specific T-cell activation, and ablation of FGL-1 in mice promotes T- 
cell immunity. Blockade of the FGL-1:LAG-3 interaction by monoclonal antibodies stimulates 
tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand, 
inter-dependent manner. FGL-1 is highly produced by human cancer cells, and elevated FGL-1 in 
the plasma of cancer patients is associated with a poor prognosis and resistance to 
anti-PD-1/B7-H1 therapy. 
 

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Nivolumab is currently in development and has been registered in a variety of tumors. 
Development of nivolumab for HCC was initiated in 2012 with CA209040, which is a Phase 1/2 
clinical trial evaluating the safety and efficacy of nivolumab in advanced HCC. Data from the 
dose-escalation and expansion cohorts of this study led initially to the accelerated approval of 
nivolumab for the second-line (2L) therapy of advanced HCC patients who progressed on or were 
intolerant to sorafenib in many, but not all (eg, not approved in Japan), countries. As of the most 
recent analysis, with 27 months of follow-up, with 154 participants treated with nivolumab 
3 mg/kg every 2 weeks (Q2W), the objective response rate (ORR) was 14%, the median 
progression-free survival (mPFS) was 2.83 months, and the median OS (mOS) was 15.6 months. 
Most recently, the doublet combination of nivolumab and ipilimumab received accelerated 
approval in the United States in the same setting in HCC. This approval was based on data from 
the 28-month follow-up, demonstrating an ORR of 33% among the 49 participants treated with 
nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses, followed by 
nivolumab 240 mg Q2W. 
After the approval of atezolizumab and bevacizumab combination in 1L HCC, the treatment 
recommendations shifted to indicate that previously approved 1L TKI therapies are now 
recommended after atezolizumab and bevacizumab therapies, and agents that were recommended 
after failure of 1L TKI therapies are now recommended in subsequent settings, according to the 
most recent guidelines. Although, for patients who are not eligible or cannot get access to 
atezolizumab 
and 
bevacizumab 
regimen, 
the 
recommendations 
remain 
the 
same. 
Recommendations for 2L therapy differ depending on which regimen was administered 1L. 
 
This Phase 2 study will evaluate the safety and efficacy of relatlimab in combination with 
nivolumab in 2L/third-line (3L) IO-naive HCC. Efficacy will be evaluated in the all-comer patient 
population for 480 mg relatlimab in combination with 480 mg nivolumab compared to 
nivolumab 480 mg monotherapy. 
Approximately 226 participants will be 
randomized into Arm A and Arm B. 
Study Population: 
Adult (≥ 18 years) male and female participants with histologically confirmed HCC of any 
etiology (hepatitis C virus [HCV]-HCC, hepatitis B virus [HBV]-HCC, or non-viral related-HCC) 
who have never been exposed to prior IO therapy but progressed on TKI therapy in the 
advanced/metastatic setting. 
• Key inclusion criteria: 
− Male and female participants must be ≥ 18 years at the time of informed consent. 

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− Participants with histologic confirmed advanced/metastatic 2L or 3L HCC. 
 
− Participants who have experienced progression that was demonstrated radiographically on 
or after one or two prior TKI therapies without prior exposure to IO agents. 
− Child-Pugh score of 5 or 6 points (ie, Child-Pugh A). 
− Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 
• Key Exclusion Criteria: 
− Women who are pregnant or breastfeeding. 
− Untreated symptomatic central nervous system metastases or leptomeningeal metastases. 
− Participants with uncontrolled or significant cardiovascular disease. 
− Participants with clinically significant ascites defined by any prior (within 1 year) or 
current clinically significant ascites as measured by physical examination and that requires 
active paracentesis for control. 
− Participants with evidence of portal hypertension with bleeding esophageal or gastric 
varices within the past 6 months prior to randomization. 
− Episodes of hepatic encephalopathy (≥ Grade 2) within 12 months prior to randomization. 
− Prior organ allograft or allogeneic bone marrow transplantation. 
− Participants with an active, known or suspected autoimmune disease. Participants with 
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin 
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or 
conditions not expected to recur in the absence of an external trigger are permitted to enroll. 
− Participants 
with 
a 
condition 
requiring 
systemic 
treatment 
with 
either 
corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive 
medications within 14 days of randomization. Inhaled or topical steroids, and adrenal 
replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the 
absence of active autoimmune disease. 
− Participants with active co-infection with: 
♦ Both hepatitis B and C as evidenced by detectable HBV surface antigen or HBV 
deoxyribonucleic acid (DNA) and HCV ribonucleic acid (RNA), OR 
♦ Hepatitis D infection in participants with HBV. 
− Participants with symptomatic severe acute respiratory syndrome coronavirus 
2 (SARS-CoV-2) infection. 
♦ Additionally, in the case of prior SARS-CoV-2 infection, acute symptoms must have 
resolved and, in consultation with Medical Monitor, there are no sequelae that would 
place the participant at a higher risk of receiving investigational treatment. 
− Prior treatment with relatlimab or any other LAG-3 targeted agents. 
− Prior exposure to IO therapies such as, but not limited to, an anti-PD-1, anti-PD-L1, or 
anti-CTLA-4 antibody, oncolytic viruses, or any other antibody or drug specifically 
targeting T-cell co-stimulation or checkpoint pathways. 

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Table 1-1: 
Objectives and Endpoints 
 
Objective 
Endpoint 
Primary 
• 
To evaluate the efficacy of relatlimab in 
combination 
with 
nivolumab 
relative 
to 
nivolumab monotherapy in IO therapy-naive 
participants after prior treatment with TKI 
therapy 
• 
ORR assessed by BICR using RECIST v1.1 
Key Secondary 
• 
To investigate safety and tolerability of 
relatlimab in combination with nivolumab in 
participants with advanced HCC 
• 
Incidence of AEs, SAEs, and AEs leading to 
discontinuation, deaths, and clinical laboratory test 
abnormalities 
• 
To further evaluate the preliminary efficacy of 
relatlimab in combination with nivolumab 
• 
DCR, DOR, and PFS assessed by BICR per 
RECIST v1.1 
• 
ORR, DCR, DOR, and PFS assessed by Investigator 
per RECIST v1.1 
• 
OS 
Abbreviations: AE = adverse event; BICR = Blinded Independent Central Review; DCR = disease control rate; DOR 
= duration of response; HCC = hepatocellular carcinoma; IO = immuno-oncology; ORR = objective response rate; 
OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors; 
SAE = serious adverse event; TKI = tyrosine kinase inhibitor. 
 
Overall Design: 
This Phase 2 study will evaluate the safety and efficacy of relatlimab in combination with 
nivolumab in participants with 2L or 3L IO-naive HCC. 
As of 19-July-2021, participants are being randomized 1:1 to receive: 
• Arm A: Nivolumab 480 mg Q4W 
• Arm B: Nivolumab 480 mg Q4W+ Relatlimab 480 mg Q4W 
 
• 
Arm C: Nivolumab 480 mg Q4W+ Relatlimab 960 mg Q4W 
24 participants were randomized to Arm C. 

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For Protocol Amendment 03, all participants in Arm B and Arm C were re-consented. All new 
participants at the time had signed the updated informed consent for Protocol Amendment 03. 
This is an open-label, randomized Phase 2 study in adult (≥ 18 years) male and female participants 
with advanced, Child-Pugh A, IO-naive HCC who have experienced progression that was 
demonstrated radiographically on or after one or two prior TKI therapies in the 
advanced/metastatic setting. Participants must not be amenable for management with surgery or 
locoregional therapy or have progressed after surgery or locoregional therapy. 
Stratification will occur by region (Asia [excluding Japan] vs Rest of the World [including Japan]) 
and macrovascular invasion and/or extrahepatic spread (MVI/EHS; present or absent). For the 
purposes of randomization, LAG-3 will also be treated as a stratification factor. 
MVI is defined as: 
• Hepatic vein tumor thrombus, OR 
• Inferior vena cava tumor thrombus, OR 

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• Portal vein tumor thrombus; Vp3/Vp4 (presence of a tumor thrombus in the main trunk of the 
portal vein or a portal vein branch contralateral to the primarily involved lobe or first-order 
branches of the portal vein) participants are also eligible. 
EHS is defined as presence of metastatic disease in lymph nodes or distant sites outside the liver. 
All participants will be treated until disease progression or unacceptable toxicity. Treatment 
beyond initial Investigator-assessed RECIST v1.1-defined progression is permitted if the 
participant has Investigator-assessed clinical benefit and is tolerating study treatment. 
Individual participants with confirmed complete response (CR) will be given the option to 
discontinue study therapy on a case-by-case basis after specific consultation and agreement 
between the Investigator and BMS Medical Monitor in settings where benefit/risk justifies 
discontinuation of study therapy. 
 
Approximately 226 participants will be randomized into Arm A and Arm 
B. 
A study design schematic for CA224073 is provided in Figure 1-1. 

 
Clinical Protocol 
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CA224073 
relatlimab 
Figure 1-1: 
Study Design Schematic for CA224073 
 
 
Abbreviations: 
2L = second line; 3L = third line; ECOG = Eastern Cooperative Oncology Group; EHS = extrahepatic spread; 
FU = follow-up; HCC = hepatocellular carcinoma; IO = immuno-oncology; LAG-3 = lymphocyte activation gene 3; MVI = macrovascular invasion; N = number; 
Nivo = nivolumab; Q4W = every 4 weeks; Rela = relatlimab; TKI = tyrosine kinase inhibitor. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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b Total patients planned is approximately 250 with an additional 24 patients randomized to Arm C 
. 

 
Clinical Protocol 
CA224073 
BMS-986016 
relatlimab 
Number of Participants: 
Approximately 250 participants will be randomized (226 to Arm A and B, and 24 in Arm C). 
It is estimated that approximately 357 enrolled participants will be needed to achieve these 
250 randomized. 
Treatment Arms and Duration: 
Information on the treatment groups and duration is provided in Table 1-2. 
Table 1-2: 
Treatments Administered 
 
Study 
Arm 
Study 
Treatment 
Dose 
Level 
Frequency of Administration and 
Duration of Treatment 
Route of 
Administratio 
n 
Approximate 
Infusion 
Time, minutes 
Arm A 
Nivolumab 
480 mg 
Q4W 
Until progression, unacceptable 
toxicity, or withdrawal of consent 
IV 
30 
Arm B 
Nivolumab/ 
Relatlimaba 
480 mg/ 
480 mg 
Q4W 
Until progression, unacceptable 
toxicity, or withdrawal of consent 
IV 
60 
Arm C 
Nivolumab/ 
Relatlimaba 
480 mg/ 
960 mg 
Q4W 
Until progression, unacceptable 
toxicity, or withdrawal of consent 
IV 
60b 
Abbreviations: IV = intravenous; mg = milligram; Q4W = every 4 weeks. 
a Nivolumab and relatlimab are co-administered. 
b Infusions will occur over approximately 60 minutes for participants weighing equal to or greater than 45 kg, and 
for participants weighing less than 45 kg, infusions will occur over approximately 90 minutes. 
 
Study Treatment: 
Information on the study treatments is provided in Table 1-3. 
Table 1-3: 
Study Treatment for CA224073 
 
Medication 
Potency 
IP/Non-IP 
Relatlimaba Injection 
(10 mg/mL) 
10 mg/mL 
IP 
Nivolumaba Injection 
(10 mg/mL) 
10 mg/mL 
IP 
Abbreviations: IP = investigational product; mg = milligram; mL = milliliter. 
a Relatlimab is sometimes referred to as BMS-986016; Nivolumab is sometimes referred to as BMS-936558. 
 
Data Monitoring Committee: No. 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2 
SCHEDULE OF ACTIVITIES 
Table 2-1: 
Screening Procedural Outline (CA224073) 
 
Procedure 
Screening Visit 
-28 Days 
Day -14 to 
Day -1 Visits 
Notesa (All windows are based on calendar days.) 
Pre-screening for Tumor Tissue 
Samples 
X 
 
The participant may proceed to additional screening procedures after signing the 
main study ICF. 
Eligibility Assessments 
Pre-screening or Main Informed 
Consent 
X 
Prior to any screening procedures. 
Study allows for re-enrollment of a participant that has discontinued the study as a 
screen failure. If re-enrolled, the participant must be re-consented and assigned a 
new participant number from IRT. 
For Protocol Amendment 03, all current participants in Arm B and Arm C were re- 
consented. All new participants had signed the updated informed consent for 
Protocol Amendment 03. 
Contact IRT 
X 
For participant number assignment at time main or pre-screening informed consent 
is obtained. 
Inclusion/Exclusion Criteria 
X 
All inclusion/exclusion criteria should be assessed at screening and confirmed prior 
to randomization, including LAG-3 expression status (see Section 6). 
Medical History 
X 
All medical history relevant to HCC, including disease characteristics (including 
stratification factors, Barcelona Clinic Liver Cancer stage [see Appendix 10]), 
concomitant medications, prior cancer therapy, and alcohol history. 
Prior Systemic Therapies 
X 
Includes prior cancer treatment regimens and medications administered within 
4 weeks of study dose administration. 
Child-Pugh Score 
X 
Child-Pugh A score is required (see Appendix 5 and Section 6.1 for inclusion 
criteria). 

Clinical Protocol 
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CA224073 
relatlimab 
Table 2-1: 
Screening Procedural Outline (CA224073) 
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Procedure 
Screening Visit 
-28 Days 
Day -14 to 
Day -1 Visits 
Notesa (All windows are based on calendar days.) 
Required Tumor Tissue Samples 
X 
An FFPE tumor tissue block (preferred) or a minimum of 20 freshly cut unstained 
slides* of tumor tissue obtained from core biopsy, incisional biopsy, excisional 
biopsy, or surgical specimen prior to enrollment is required. 
Fine needle aspirates or other 
cytology samples and biopsies of bone lesions that do not have a soft tissue 
component are not acceptable. Note the following for the required tumor sample: 
• 
Samples should be collected within 3 months of enrollment. Biopsy can be 
taken any time during or after TKI treatment, with no intervening systemic 
anti-cancer treatment between time of acquisition and randomization. 
• 
If a tumor sample (as described above) is not available, then a fresh 
pre-treatment biopsy may be obtained. This fresh biopsy should be excisional, 
incisional, or core needle. 
• 
If the first 2 options are not feasible, then, in rare instances, an archival tissue 
sample may be submitted if approval from BMS (Medical Monitor or Clinical 
Scientist) is obtained. 
Tumor sample must be sent to the central laboratory. 
Other screening procedures should be 
conducted within the windows specified. 
*If despite best efforts, a minimum of 20 slides are not obtainable, submission of 
fewer slides may be acceptable in some circumstances following discussion with 
BMS Medical Monitor or Clinical Scientist. 
Safety Assessments 
Physical Examination 
X 
Full physical examination, including height, weight, and BMI. Any findings during 
the PE will be recorded as medical history in the participant’s medical records and 
on the appropriate CRF. 

Clinical Protocol 
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CA224073 
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Table 2-1: 
Screening Procedural Outline (CA224073) 
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Procedure 
Screening Visit 
-28 Days 
Day -14 to 
Day -1 Visits 
Notesa (All windows are based on calendar days.) 
Physical Measurements 
X 
Includes height and weight. 
Performance Status 
X 
ECOG performance status (see Appendix 6). 
Vital Signs 
X 
Including BP, heart rate, oxygen saturation by pulse oximetry, and temperature. BP 
and heart rate should be measured after the participant has been seated quietly for at 
least 5 minutes. 
Assessment of Signs and 
Symptoms 
X 
Within 14 days of randomization. 
Concomitant Medication Use 
X 
Concomitant medication use within 28 days of randomization and vaccine use 
within 30 days prior to randomization. 
2D-Echocardiogram 
X 
LVEF assessment with documented LVEF ≥ 50% by either TTE (preferred test) or 
MUGA scan within 6 months from first study drug administration. If more than 
1 scan is performed, the most recent scan is applicable. 
12-lead ECG 
X 
12-lead ECGs should be recorded after the participant has been supine for at least 
5 minutes. ECGs must be collected and assessed using the site’s own ECG machine. 
Chest Radiograph 
X 
Posterior-anterior and lateral (either side) chest x-ray to establish baseline. 
Serious Adverse Events 
Assessment 
X 
SAEs collected from time of consent (pre-screening and/or main ICF). 
All AEs (SAEs or non-serious AEs) associated with SARS-CoV-2 infection 
collected from time of consent. See Section 9.2. AEs are graded per CTCAE v5, 
except as described for hepatic and endocrinopathies 
. 
Laboratory Tests 
X 
Local laboratory testing, including testing for symptomatic SARS-CoV-2 infection. 
Hematology, serum chemistry, and urinalysis, as outlined in Section 9.4.4. 
Urinalysis 
X 
See Section 9.4.4. 
Thyroid Function Tests 
X 
See Section 9.4.4. 
Serology 
X 
Hep B surface antigen, Hep B surface antibody, Hep B core antibody, Hep B DNA 
viral load (PCR), Hep C RNA viral load (PCR), Hep C antibody, and Hep D 
antibody (if chronic HBV infection). See Section 9.4.4. 

Clinical Protocol 
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Table 2-1: 
Screening Procedural Outline (CA224073) 
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Procedure 
Screening Visit 
-28 Days 
Day -14 to 
Day -1 Visits 
Notesa (All windows are based on calendar days.) 
HIV (when required by local regulations [see Appendix 7]), must be done at local 
laboratory within 28 days prior to randomization. See Section 9.4.4. 
Coagulation Profile 
X 
Including PT/INR and aPTT. If screening laboratory test samples are drawn within 
4 days of first treatment, then these laboratory samples will also qualify as Day 1 
(predose) laboratory samples. See Section 9.4.4. 
Disease Assessment: Serum 
Alpha-fetoprotein 
X 
See Section 9.4.4. 
Pregnancy Test (WOCBP only) 
X 
Local laboratory testing 
Serum or urine (minimum sensitivity equivalent units 25 IU/L or equivalent units of 
HCG) to be done at screening visit and repeated within 1 day prior to first dose of 
study treatment. An extension up to 72 hours prior to the start of study treatment is 
permissible in situations where results cannot be obtained within the standard 
24-hour window. 
Follicle-stimulating Hormone 
X 
If needed to document post-menopausal status, as defined in Section 9.4.4. 
Females under the age of 55 years must have a serum FSH level > 40 mIU/mL to 
confirm menopause. 
Efficacy Assessments 
Body Imaging: Baseline Tumor 
Assessments 
X 
Contrast-enhanced CT of the chest, CT or MRI of abdomen and pelvis (including 
required tri-phasic CT or MRI of the liver), and all other known and/or suspected 
sites of disease should be performed within 28 days prior to randomization. See 
Section 9.1.1 for further details. 
Brain Imaging 
X 
MRI of the brain with and without contrast is required for participants with known 
or suspected brain metastases, unless participant has completed an imaging study of 
the brain within 28 days of randomization. CT of the brain (without and with 
contrast) can be performed if MRI is contraindicated. See Section 9.1.1 for further 
details. 

Clinical Protocol 
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CA224073 
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Table 2-1: 
Screening Procedural Outline (CA224073) 
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See Section 9.1.1; as clinically indicated per local standards. 
Abbreviations: 2D = 2-dimensional; AE = adverse event; BMS = Bristol Myers Squibb; BP = blood pressure; 
CRF = case report 
form; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; DNA = deoxyribonucleic acid; ECG = electrocardiogram; 
ECOG = Eastern Cooperative Oncology Group; FFPE = formalin-fixed paraffin embedded; FSH = follicle-stimulating hormone; HBV = hepatitis B virus; 
HCC = hepatocellular carcinoma; HCG = human chorionic gonadotropin; Hep = hepatitis; HIV = human immune deficiency virus; ICF = informed consent form; 
IgG = immunoglobulin G; 
INR = international normalized ratio; IRT = Interactive Response Technology; IU = international unit; 
L = liter; LAG-3 = lymphocyte activation gene 3; LVEF = left ventricular ejection fraction; mL = milliliter; MRI = magnetic resonance imaging; 
MUGA = multiple-gated acquisition; PCR = polymerase chain reaction; PT = prothrombin time; RNA = ribonucleic acid; SAE = serious adverse event; 
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TKI = tyrosine kinase inhibitor; TTE = transthoracic echocardiogram; WOCBP = women of 
child bearing potential. 
a Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 
Notesa (All windows are based on calendar days.) 
Day -14 to 
Day -1 Visits 
Screening Visit 
-28 Days 
Procedure 
X 
Other Imaging: Bone Scan 

Clinical Protocol 
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Table 2-2: 
On-Treatment Assessments (CA224073) 
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Procedurea 
Cycle 1 
(4 weeks) 
Cycle 2+ 
(4 weeks) 
End of 
Treatment 
(EOT)b 
Notesc (All windows are based on calendar days.) 
D1 
D15 
(± 3 
days) 
D1 
(± 3 
days) 
D15 
(± 3 
days) 
Eligibility Assessments 
Inclusion/Exclusion Criteria 
X 
Cycle 1 Day 1 only: All inclusion/exclusion criteria should be 
confirmed prior to first dose. 
Safety Assessments 
Targeted Physical Examination 
X 
X 
X 
X 
X 
To be performed only as clinically indicated prior to dosing, 
using local oncology/hepatology physical examination guidelines 
when new symptoms or laboratory abnormalities occur. 
Child-Pugh Score 
X 
X 
X 
See Appendix 5. 
Vital Signs 
X 
X 
X 
X 
X 
Including BP, heart rate, and temperature prior to dosing. BP and 
heart rate should be measured after the participant has been seated 
quietly for at least 5 minutes. 
Oxygen Saturation 
X 
X 
X 
Prior to dosing; collect at rest via pulse oximetry. Oxygen levels 
will be used in combination with clinical signs and symptoms and 
radiographic images to evaluate pulmonary/respiratory status. 
Changes in O2 levels will not be used in isolation to document or 
diagnose pulmonary toxicity. 
Physical Measurements and 
Performance Status 
X 
X 
X 
Weight and ECOG (see Appendix 6), prior to dosing. 
Adverse Event and Serious Adverse 
Event Assessments 
Continuously 
All AEs (SAEs or non-serious AEs), including those associated 
with SARS-CoV-2 infection, must be collected continuously 
during the treatment period. See Section 9.2. AEs are graded per 
CTCAE v5, except as described for hepatic and endocrinopathies 
. 
Concomitant Medication Use 
Continuously 

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Table 2-2: 
On-Treatment Assessments (CA224073) 
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Cycle 1 
(4 weeks) 
Cycle 2+ 
(4 weeks) 
 
End of 
Procedurea 
D15 
D1 
(± 3 
days) 
D1 
(± 3 
days) 
D15 
(± 3 
days) 
Treatment 
(EOT)b 
Notesc (All windows are based on calendar days.) 
 
 
Locally performed: Within 3 calendar days prior to dosing, 
including hematology, serum chemistry, urinalysis, thyroid 
function tests, 
and coagulation profile, as outlined 
in Section 9.4.4. 
 
 
 
 
 
Laboratory Tests 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Thyroid Function Tests 
X 
X 
X 
See Section 9.4.4. 

Clinical Protocol 
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Table 2-2: 
On-Treatment Assessments (CA224073) 
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Procedurea 
Cycle 1 
(4 weeks) 
Cycle 2+ 
(4 weeks) 
End of 
Treatment 
(EOT)b 
Notesc (All windows are based on calendar days.) 
D1 
D15 
(± 3 
days) 
D1 
(± 3 
days) 
D15 
(± 3 
days) 
Coagulation Profile 
X 
X 
X 
X 
X 
Including PT/INR and aPTT. See Section 9.4.4. 
Disease Assessment: Serum 
Alpha-fetoprotein 
X 
X 
X 
See Section 9.4.4. 
12-lead ECG 
X 
X 
X 
12-lead ECGs should be recorded after the participant has been 
supine for at least 5 minutes. ECGs must be collected and 
assessed predose on Day 1 of each cycle using the site’s own 
ECG machine; done on Day 1 only starting with Cycle 2. 
2D Echocardiogram 
See notes. 
For all participants: performed locally as clinically indicated. 
Chest Radiograph 
See notes. 
As clinically indicated. 
Pregnancy Test (WOCBP only) 
X 
X 
Serum or urine (minimum sensitivity equivalent units 25 IU/L or 
equivalent units of HCG) within 1 day prior to administration of 
first dose of study treatment and then every 4 weeks (± 7 days), 
regardless of dosing schedule. An extension up to 72 hours prior 
to the start of study treatment is permissible in situations where 
results cannot be obtained within the standard 24-hour window. 
Efficacy Assessments 
Body Imaging 
See notes. 
Contrast-enhanced CT of the chest, CT or MRI of abdomen and 
pelvis (including required tri-phasic CT or MRI of the liver), and 
all other known and/or suspected sites of disease should occur 

Clinical Protocol 
BMS-986016 
CA224073 
relatlimab 
Table 2-2: 
On-Treatment Assessments (CA224073) 
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Procedurea 
Cycle 1 
(4 weeks) 
Cycle 2+ 
(4 weeks) 
End of 
Treatment 
(EOT)b 
Notesc (All windows are based on calendar days.) 
D1 
D15 
(± 3 
days) 
D1 
(± 3 
days) 
D15 
(± 3 
days) 
every 8 weeks starting from randomization (± 7 days). 
Imaging should continue as per schedule until disease progression 
(unless treatment beyond progression) or treatment 
discontinuation (including treatment beyond progression), 
whichever occurs later. 
Assessments of PR and CR must be confirmed at least 4 weeks 
(28 days) after initial response. 
See Section 9.1.1 for further details. 
Brain Imaging 
See notes. 
Participants with a history of brain metastasis or symptoms 
should have a surveillance MRI study per standard of care 
(approximately every 12 weeks from randomization), or sooner if 
clinically indicated. CT of the brain without and with contrast can 
be performed if MRI is contraindicated. See Section 9.1.1 for 
further details. 
Other Imaging: Bone Scan 
See notes. 
See Section 9.1.1; as clinically indicated per local standards. 

Clinical Protocol 
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Table 2-2: 
On-Treatment Assessments (CA224073) 
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Procedurea 
Cycle 1 
(4 weeks) 
Cycle 2+ 
(4 weeks) 
End of 
Treatment 
(EOT)b 
Notesc (All windows are based on calendar days.) 
D1 
D15 
(± 3 
days) 
D1 
(± 3 
days) 
D15 
(± 3 
days) 
Additional Research Sampling 
See notes. 
See Section 9.8.4. 

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1F1F
2F2F
3F3F
4F4F
 
 
Cycle 1 
(4 weeks) 
Cycle 2+ 
(4 weeks) 
 
End of 
Procedurea 
D15 
D1 
(± 3 
days) 
D1 
(± 3 
days) 
D15 
(± 3 
days) 
Treatment 
(EOT)b 
Notesc (All windows are based on calendar days.) 
 
 
 
 
 
 
 
 
 
 
 
 
Study Treatment 
Contact IRT to Randomize the 
Participant 
 
 
 
 
Administer Study Treatment 
X 
X 
 
 
 
 
Abbreviations: 2D = 2-dimensional; AE = adverse event; 
 
Only once eligibility is confirmed and treatment can be started. 
Only at Cycle 1. 
See Section 7.1 for treatment administration details. Treatment 
should begin within 3 days of randomization/contacting IRT. 
Washout period between end of TKI treatment and start of dosing 
is 10 days for sorafenib, 6 days for lenvatinib, 6 days for 
regorafenib, and 21 days for cabozatinib. 1, 2, 3, 4 The washout 
period for any other TKI therapies can be discussed with the 
Medical Monitor. 
Treatment will continue until disease progression, unacceptable 
toxicity, or study ends. 
aPTT = activated partial thromboplastin time; 
BP = blood pressure; 
CR = complete response; CRF = case report form; CT = computed tomography; CTCAE 
= Common Terminology Criteria for Adverse Events; 
D = day; 
ECG = 
electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; 
HCG = human chorionic gonadotropin; 
INR = International Normalized 
X

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Ratio; IRT = Interactive Response Technology; IU = international unit; L = liter; 
MRI = magnetic resonance imaging; O2 = oxygen; 
PR = partial response; 
SARS- 
CoV-2 = severe acute respiratory syndrome coronavirus 2; 
TKI = tyrosine kinase inhibitor; WOCBP = women of child bearing potential. 
a If a dose is delayed, then the procedures scheduled for that same time point should also be delayed to coincide with when that time point’s dosing actually 
occurs, except for body imaging and pregnancy testing, which need to be performed as scheduled. 
b EOT is defined as the last on-treatment visit or where a decision is made to discontinue the participant from treatment. 
c Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 
PT = prothrombin time; SAE = serious adverse event; 

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Procedure 
Safety Follow-up 
Visit 1 and 2a 
Survival 
Follow-up visitsb 
Notesc 
Safety Assessments 
Targeted Physical Examination 
X 
Targeted physical examination to be performed only as clinically indicated. 
Any findings during the PE will be evaluated for AEs and reported as such. 
Vital Signs 
X 
Weight, BP, heart rate, and temperature. 
Assessment of Signs and Symptoms 
X 
Adverse Event and Serious Adverse 
Event Assessments 
X 
See notes. 
All SAEs and non-serious AEs should be collected continuously during the 
treatment period and for a minimum of 135 days following discontinuation 
of study treatment. 
Participants will be followed for all SAEs, non-serious AEs of special 
interest (as defined in Section 9.2), and all AEs (SAEs and non-serious 
AEs) associated with confirmed or suspected SARS-CoV-2 infection until 
resolution, the condition stabilizes, the event is otherwise explained, the 
event is deemed irreversible, the participant is lost to follow-up (as defined 
in Section 8.3), or for suspected cases, until SARS-CoV-2 infection is ruled 
out. 
Review of Concomitant Medications 
X 
See Section 7.7. 
Performance Status 
X 
ECOG performance status Score (see Appendix 6). 
Laboratory Tests 
X 
(see notes) 
For Follow-up Visit 1, onsite/local including hematology, serum chemistry, 
and urinalysis, as outlined in Section 9.4.4. 
Repeat at Follow-up Visit 2 only if study treatment-related toxicity persists. 
Pregnancy Test (WOCBP only) 
X 
Serum or urine. Pregnancy testing is only required at Follow-up Visits 1 
and 2, unless increased frequency and duration is required per local 
regulations. 
Coagulation Profile 
X 
Including PT/INR and aPTT. 

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Procedure 
Safety Follow-up 
Visit 1 and 2a 
Survival 
Follow-up visitsb 
Notesc 
 
Efficacy Assessments 
Body Imaging 
See notes. 
Contrast-enhanced CT of the chest, CT or MRI of abdomen and pelvis 
(including required tri-phasic CT or MRI of the liver), and all other known 
and/or suspected sites of disease should occur every 8 weeks (± 7 days). 
Participants with SD, PR, or CR at the time of the EOT visit or at the time 
of study treatment discontinuation will continue to have radiologic and 
clinical tumor assessments every 8 weeks (± 7 days) after discontinuation 
of study treatment/EOT visit, until the start of subsequent therapy, disease 
progression (unless treatment beyond progression), or withdrawal of study 
consent. 
Assessments of PR and CR must be confirmed at least 4 weeks (28 days) 
after initial response. 
See Section 5.1.3 and Section 9.1.1 for further details. 
Brain Imaging 
X 
X 
Participants with a history of brain metastasis or symptoms should have 
surveillance MRIs per standard of care (approximately every 12 weeks) or 
sooner if clinically indicated. CT of the brain without and with contrast can 
be performed if MRI is contraindicated. See Section 9.1.1 for further 
details. 
Collection of Survival Status and 
Subsequent Therapy Information 
X 
X 
(see notes) 
Collect every 3 months during survival visits until death, lost to follow-up, 
or withdrawal of study consent. May be performed by phone contact or 
office visit. 
TSST/PFS2 Assessment 
X 
X 
Following first progression, participants will continue to be followed 
during the safety and survival follow-up visits. Timing of objectively 

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Procedure 
Safety Follow-up 
Visit 1 and 2a 
Survival 
Follow-up visitsb 
Notesc 
documented progression after the next line of therapy per Investigator 
assessment will be documented. The start of the second next-line therapy 
will also be collected. 
Abbreviations: AE = adverse event; aPTT = activated partial thromboplastin time; BMS = Bristol Myers Squibb; BP = blood pressure; CR = complete response; 
CRF = case report form; CT = computed tomography; 
ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment; 
INR = 
international normalized ratio; MRI = magnetic resonance imaging; PE = physical examination; PFS2 = progression-free survival 2 (second progression); 
PR = partial response; 
PT = prothrombin time; SD = stable disease; 
SAE = serious adverse event; SARS-CoV-2 = severe 
acute respiratory syndrome coronavirus 2; TSST = time to second subsequent therapy; WOCBP = women of child bearing potential. 
a Follow-up visits occur as follows: Follow-up Visit 1 = 30 days from the last dose of study treatment (± 7 days) or coincides with the date of 
discontinuation (± 11 days) if date of discontinuation is greater than 42 days after last dose. Follow-up Visit 2 = 135 days (± 7 days) from last dose of study 
treatment. Participants must be followed for at least 135 days after last dose of study treatment. Both follow-up visits should be conducted in person. 
b Survival follow-up visits may be conducted in clinic or by phone. Survival visits: first survival follow-up visit 3 months (± 14 days) after Follow-up Visit 2; 
subsequent survival follow-up visits every 3 months (± 14 days). BMS may request that survival data be collected on all treated participants outside of the 
3 months-specified window. See Section 5.1.3.1 for participants with stable disease, complete response, or partial response. 
c Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 

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3 
INTRODUCTION 
 
 
CA224073 is a Phase 2, randomized, open-label study of 
relatlimab (BMS-986016) in combination with nivolumab in participants with advanced HCC who 
are naive to prior immunotherapies, who have received one or two lines of tyrosine kinase 
inhibitor (TKI) therapies, and who have shown radiographic progression on or after the last line of 
TKI therapy in the advanced/metastatic setting. 
Individually targeting immune checkpoint receptors, such as programmed death-1 (PD-1), has 
demonstrated clinical activity across multiple tumor types; several studies to date have 
demonstrated activity of therapeutic compounds aimed at the PD-1 receptor and its ligand, 
programmed death-ligand 1 (PD-L1). This benefit is further extended by dual combination therapy 
of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and PD-1 inhibitors, as well as 
combination of anti-PD-L1 (atezolizumab) and anti-vascular endothelial growth factor (VEGF; 
bevacizumab) monoclonal antibodies showing superior efficacy to sorafenib monotherapy. 5 
Despite the demonstrated benefit of single or dual combinations of cancer immunotherapies on 
clinical outcome, a large proportion of patients with many tumor types do not respond or will 
relapse after an initial response to these agents. Substantial efforts are needed to provide therapy 
to patients who do not respond to currently approved single or dual combination 
immunotherapeutic agents. 
Lymphocyte activation gene 3 (LAG-3; cluster of differentiation [CD] 223) is a checkpoint and a 
potential cancer immunotherapeutic target due to its negative regulatory role on T-cells and its 
regulatory capacity. 6, 7 Relatlimab is a human LAG-3-specific antibody that was isolated from 
immunized transgenic mice expressing human immunoglobulin (Ig) genes. 8 It is expressed as an 
immunoglobulin G4 (IgG4) isotype antibody that includes a stabilizing hinge mutation (S228P) 
for attenuated Fc receptor binding in order to reduce or eliminate the possibility of antibody- or 
complement-mediated target cell killing. Relatlimab binds to LAG-3 with high affinity and inhibits 
the negative regulatory function of LAG-3 in vitro. Binding of relatlimab to LAG-3 prevents 
binding of this receptor to cells bearing its ligand, major histocompatibility complex (MHC) Class 
II, the peptide antigen presentation molecule recognized by CD4-positive (+) T cells. In addition, 
relatlimab enhances activation of human T cells in super-antigen stimulation assays when added 
alone or in combination with nivolumab (anti-PD-1 antibody). 
3.1 
Study Rationale 
Despite the demonstrated benefit of single or dual combinations of cancer immunotherapies on 
clinical outcome, a large proportion of cancer patients across many tumor types do not respond to 
these available therapies. The most encouraging efficacy data are coming from trials with 
combination regimens. The IMbrave 150 trial of atezolizumab and bevacizumab vs sorafenib met 
its primary endpoint, with a median progression-free survival (mPFS) of 6.8 vs 4.3 months; 
however, Grade 3-4 treatment-related adverse events (AEs) were reported in 36% of participants 
in the combination arm and 16% of the participants had AEs leading to withdrawal of any study 

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10F10
11F11
13F13
14F14F
component.5 The combination of ipilimumab and nivolumab also showed improved 
efficacy (overall objective response rate [ORR]: 31%; median duration of response [DOR]: 
17 months); 37% of participants had a Grade 3-4 treatment-related AEs and 5% had Grade 3-4 
treatment-related AEs leading to discontinuation. 9 There is an unmet need to develop an 
efficacious combination regimen with an improved safety profile. 
LAG-3 (CD223) is a checkpoint and a potential cancer immunotherapeutic target due to its 
negative regulatory role on T-cells and its regulatory capacity.6,7 Relatlimab is a human 
LAG-3-specific antibody that was isolated from immunized transgenic mice expressing human Ig 
genes.8 
1) HCC has a unique tumor microenvironment (TME) that is typically driven by either viral or 
other chronic infections/inflammations, which create a moderately inflamed environment. 10 
Chronic inflammation causes a unique immune tolerogenic TME. 11 LAG-3 has been shown 
to play multiple roles in this context. In addition, relatlimab enhances activation of human T 
cells in super-antigen stimulation assays when added alone or in combination with 
nivolumab (anti-PD-1 antibody).8 
a) Comprehensive profiling of commercially sourced tumor specimens was performed to 
investigate and characterize expression of LAG-3 and MHC Class II in the context of 
inflammatory biomarkers (Bristol Myers Squibb [BMS] data on file). Relatlimab binds to 
LAG-3 with high affinity and inhibits the negative regulatory function of LAG-3 in vitro. 
Binding of relatlimab to LAG-3 prevents binding of this receptor to cells bearing its ligand, 
MHC Class II, the peptide antigen presentation molecule recognized by CD4+ T cells.8 
Fibrinogen-like protein 1 (FGL-1) is another potential ligand for LAG-3 that is highly 
 
b) To characterize the immune microenvironment in HCC, immunohistochemistry (IHC) 
staining was performed for CD8+ T lymphocytes, PD-1+ and LAG-3+ lymphocytes, 
CD163+ macrophages, and PD-L1 expression in tumor and liver backgrounds from 
29 cases of resected HCC. LAG-3 and PD-L1, 2 inhibitory molecules implicated in CD8 
T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating 
combinatorial checkpoint blockade with LAG-3 and PD-L1 inhibitors in HCC. 13 
2) Immunotherapeutic compounds, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents, 
either as monotherapy or as combination therapy, have already shown added benefit in 
different lines and settings of advanced/metastatic HCC. 
a) Nivolumab (anti-PD-1 monoclonal antibody) as a single agent or in combination with 
ipilimumab is indicated for the treatment of patients with HCC who have been previously 
treated with sorafenib. 14 These approvals were based on the CA209040 study. Nivolumab 
showed clinically meaningful efficacy in the pooled subgroup of 154 participants who were 
given 3 mg/kg nivolumab every 2 weeks (Q2W) until disease progression or unacceptable 
toxicity. With 27 months of follow-up, the ORR was 14% per blinded independent central 
review (BICR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and 18% 
per BICR by modified RECIST (mRECIST). DOR was 91% at ≥ 6 months, 59% at 
expressed in the liver and is a tumor suppressor gene in HCC. 12 
12F12F 

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≥ 12 months, and 32% at ≥ 24 months.14 Pembrolizumab (anti-PD1 monoclonal antibody) 
is also an approved immuno-oncology (IO) agent for second-line (2L) HCC. 15 Based on 
the study result in KEYNOTE-224, 104 participants were treated with 200 mg/kg 
pembrolizumab every 3 weeks (Q3W) until unacceptable toxicity, progression, or 
24 months of treatment in the same setting in HCC. The approval was based on ORR and 
DOR per RECIST v1.1. ORR was 17%, and DOR was 89% at 6 months and 56% at 
12 months. 
b) Nivolumab (anti-PD-1 monoclonal antibody) and ipilimumab (anti-CTLA-4 monoclonal 
antibody) combination received accelerated approval in 2L HCC, 16 showing promising 
efficacy. In CA209040, 49 participants received nivolumab 1 mg/kg in combination with 
ipilimumab 3 mg/kg Q3W for 4 doses, followed by single-agent nivolumab 240 mg Q2W 
until disease progression or unacceptable toxicity. The main efficacy outcome measures 
were ORR and DOR as determined by BICR using RECIST v1.1. ORR was 33% (n = 16; 
95% confidence interval [CI]: 20, 48). DOR was 88% at ≥ 6 months, 56% at ≥ 12 months, 
and 31% at ≥ 24 months. 
 
4) A systematic meta-analysis was conducted with 15 studies (n = 6306) exploring the effect of 
LAG-3 on overall survival (OS; for early-stage cancers) and disease-free survival (DFS) 
concluded that high expression of LAG-3 may be associated with favorable OS in several solid 
tumor types. 17 
 
 
This open-label, Phase 2 study will randomize participants with LAG-3+ 
 and 
LAG-3- 
advanced HCC. The study will evaluate the efficacy of relatlimab 480 mg 

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19F19
20F20
21F21
22F22
and in combination with nivolumab 480 mg administered every 4 weeks (Q4W) compared to 
nivolumab 480 mg Q4W monotherapy. 
Safety, 
will also be evaluated for relatlimab 480 mg in 
combination with nivolumab 480 mg Q4W and for relatlimab 960 mg in combination with 
nivolumab 480 mg Q4W for participants who were treated prior to Protocol Amendment 03. 
3.1.1 
Research Hypothesis 
It is anticipated that relatlimab in combination with nivolumab will demonstrate a favorable 
benefit/risk profile compared to nivolumab monotherapy to support further clinical testing in IO 
treatment-naive advanced/metastatic HCC patients. 
3.2 
Background 
HCC is the fifth most common cancer worldwide and the second leading cause of cancer-related 
death. The incidence of HCC varies geographically, largely due to variations in hepatitis B 
virus (HBV) and hepatitis C virus (HCV) infection. HCC incidence rates and death rates are 
increasing in many parts of the world, including North America, Latin America, and central 
Europe. In almost all populations, males have higher rates of liver cancer than females, with an 
overall sex ratio of around 2.4. 18 
Treatment of HCC is challenging because the disease is highly heterogeneous, with different 
etiologies, varying approaches to diagnosis and treatment, and variations in responses to 
therapy. 19 The patient’s underlying liver function has an important influence on HCC treatment 
decisions. A total of 90% of HCC patients have an underlying cirrhosis requiring management of 
both the malignancy and the cirrhosis. Additionally, many patients require ongoing support for 
concomitant underlying disease, such as HBV or HCV, or non-viral related liver disease (eg, non- 
alcoholic steatohepatitis). Treatment strategies are therefore complex and best served by a 
multidisciplinary team. 20, 21, 22 
Relatively few patients are eligible for curative treatment because of the late appearance of 
symptoms.20 For patients with liver-isolated disease who are not eligible for resection or liver 
transplantation, treatment options include local nonsurgical methods of liver-directed tumor 
ablation (radiofrequency ablation [RFA], microwave ablation, or cryoablation), irreversible 
electroporation (where available), embolization (including bland embolization, transarterial 
chemoembolization [TACE], and transarterial radioembolization), percutaneous injection 
therapy (with ethanol or acetic acid), and external beam radiation therapy. For patients who 
progress after locoregional liver-directed therapy, additional liver-directed therapy might be 
possible, depending upon tumor location and underlying liver function. However, the benefit of 
additional locoregional therapy vs early initiation of systemic therapy in these patients is unclear. 
The prognosis for these patients is poor. 
Until 2008, no effective therapy existed for advanced HCC. In 2007, the multinational randomized 
SHARP trial demonstrated a modest but statistically significant survival benefit for 
sorafenib (a multitargeted TKI) over supportive care alone in participants with advanced HCC. 

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OS, the primary endpoint, was significantly longer in the sorafenib-treated participants (10.7 vs 
7.9 months), as was time to radiologic progression (5.5 vs 2.8 months). A survival benefit was also 
demonstrated in Asian participants. 23, 24 These results established sorafenib monotherapy as a 
new reference standard systemic treatment for advanced HCC and formed the basis for approval 
of sorafenib for first-line (1L) treatment of unresectable HCC. Until May-2020, 2 TKIs, sorafenib 
and lenvatinib, were the only systemic agents approved to treat advanced HCC as 1L therapy. 
Lenvatinib demonstrated noninferiority to sorafenib in the REFLECT study, and is a treatment 
option, particularly for patients that do not tolerate sorafenib. 25 Post-marketing clinical studies of 
sorafenib showed that only a portion of patients show real benefits, while the incidence of drug- 
related significant adverse effects and the economic costs are relatively high. 26 
In 2019, the results of the CA209459 study were presented, showing meaningful clinical benefit 
with nivolumab therapy in 1L HCC compared to sorafenib therapy; although, results did not meet 
the statistical thresholds. Nivolumab compared to sorafenib was associated with a 2-fold higher 
ORR (15% vs 7%) and more complete responses (CRs; 4% vs 1%), but was not translated into 
statistical benefit with mPFS (3.7 vs 3.8 months) nor mOS (16.4 vs 14.7 months). In the sorafenib 
arm, 20% of participants received subsequent IO therapy after progressing on sorafenib. 
Grade 3 or 4 treatment-related AEs were reported in fewer nivolumab-treated participants than 
sorafenib-treated participants (22% vs 49%), who were also less likely to discontinue therapy 
because of side effects (4% vs 8%). 27 
In Oct-2019, preliminary data from the IMbrave 150 study (Phase 3) was presented with the 
combination of an anti-PD-L1 agent (atezolizumab) and an anti-VEGF monoclonal 
antibody (bevacizumab) for the 1L treatment of advanced HCC. There were significant 
improvements in mOS and mPFS with the combination therapy.5 At a median follow-up of 
8.6 months, mOS with combined therapy was not reached vs 13.2 months with 
sorafenib (estimated hazard ratio [HR] for survival, 0.58 [95% CI: 0.42, 0.79]). mPFS was also 
significantly better with combined therapy (6.8 vs 4.3 months; HR, 0.59 [95% CI: 0.47, 0.76). 
ORR was 2-fold higher with combined therapy (27.6% vs 12%). With this combination, 85% of 
participants had any-grade treatment-related AEs, 36% had Grade 3-4 treatment-related AEs, and 
16% had AEs that led to discontinuation of any component of the regimen. In May-2020, the 
United States (US) Food and Drug Administration (FDA) granted approval to this regimen for 
patients with unresectable or metastatic HCC who have not received prior systemic therapy. 28 
Regorafenib is a TKI approved for patients with documented disease progression following 
sorafenib that showed moderate 2.8-month mOS improvement over placebo. A benefit for 
regorafenib in patients progressing after 1L treatment with sorafenib was suggested in the 
RESORCE trial, in which 573 participants were randomized to receive either regorafenib or 
placebo. Regorafenib was associated with significantly prolonged mOS (10.6 vs 7.8 months), as 
well as significantly higher rates of ORR (11 vs 4%). 29 Cabozantinib is also an approved TKI 
agent for patients who progressed on prior TKI therapy. In the CELESTIAL trial, 707 participants 
were enrolled to receive either cabozantinib or placebo. In the population of participants receiving 
2L or third-line (3L) treatment after prior treatment with sorafenib, mOS was significantly better 

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with cabozantinib (10.2 vs 8.0 months), and the difference was more pronounced when the analysis 
was limited to participants whose only prior therapy was sorafenib (mOS: 11.3 vs 7.2 months). 30 
Currently, 4 TKIs are approved for HCC globally: sorafenib, lenvatinib, regorafenib, and 
cabozantinib. 
Ramucirumab is a recombinant vascular endothelial growth factor receptor (VEGFR)-2 
monoclonal antibody that showed modest activity in the REACH trial in 2L HCC compared to 
placebo (mOS: 9.2 vs 7.6 months). 31 The follow-up REACH-2 trial in 2L HCC participants with 
≥ 400 ng/mL alpha-fetoprotein (AFP) level was associated with significantly better OS compared 
to placebo (mOS: 8.5 vs 7.3 months), 32 and ramucirumab was approved for this patient 
population. 33 
Nivolumab was approved at a dose of 3 mg/kg Q2W for the treatment of HCC in patients who 
have been previously treated with sorafenib,14 based on the escalation and expansion cohorts of 
the Phase 1/2 CA209040 study. Nivolumab monotherapy (at a dose of 3 mg/kg Q2W) in 
participants with advanced HCC produced durable responses and disease stabilization, irrespective 
of HCC etiology and regardless of prior therapy with sorafenib (see Section 3.1 [Study Rationale]). 
In Mar-2020, the combination therapy of nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W for 
4 doses was granted accelerated approval by FDA for HCC patients who have been previously 
treated with sorafenib, based on data from Cohort 4 of the CA209040 study (see Section 3.1 [Study 
Rationale]).16 The combination regimen showed an ORR of 33%, with response durations ranging 
from 4.6 to 30.5+ months and 31% of responses lasting at least 2 years. With this combination, 
94% of participants experienced any-grade treatment-related AEs (53% Grade 3-4) and 29% of 
the participants needed to discontinue treatment due to AEs. 
After the approval of atezolizumab and bevacizumab combination in 1L HCC, the treatment 
recommendations shifted to indicate that previously approved 1L TKI therapies are now 
recommended after atezolizumab and bevacizumab therapies, and agents that were recommended 
after failure of 1L TKI therapies are now recommended in subsequent settings, according to the 
most recent guidelines. Although, for patients who are not eligible or cannot get access to 
atezolizumab 
and 
bevacizumab 
regimen, 
the 
recommendations 
remain 
the 
same. 
Recommendations for 2L therapy differ depending on which regimen was administered 1L. 34 
 

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Based on these data, immunotherapies seem to play an important role in the treatment of HCC. 
Despite the recent approvals for patients diagnosed with advanced disease, the unmet medical need 
still remains for drugs with the potential to induce durable tumor responses and that can prolong 
mOS for advanced HCC patients as well as provide improved safety profile compared to existing 
therapeutic options in a patient population where liver function has already been compromised. 35 
Information  for  nivolumab (OPDIVO, BMS-936558,  anti-PD-1  antibody)  and 
relatlimab (BMS-986016, anti-LAG-3 antibody), is provided in the sections below; additional 
details are provided in the respective Investigator Brochures (IBs)/package inserts.8,14, 36 
3.2.1 
Relatlimab Mechanism of Action 
Relatlimab is a fully human antibody specific for human LAG-3 that was isolated from immunized 
transgenic mice expressing human Ig genes. It is expressed as an IgG4 isotype antibody that 
includes a stabilizing hinge mutation (S228P) for attenuated Fc receptor binding in order to reduce 
or eliminate the possibility of antibody- or complement-mediated target cell killing. Relatlimab 
binds to a defined epitope on LAG-3 with high affinity (dissociation constant [Kd], 0.25 to 0.5 nM) 
and specificity and potently blocks the interaction of LAG-3 with its ligand, MHC 
Class II (half maximal inhibitory concentration [IC50], 0.7 nM). The antibody exhibits potent 
in vitro functional activity in reversing LAG-3-mediated inhibition of an antigen-specific murine 
T cell hybridoma overexpressing human LAG-3 (IC50, 1 nM). In addition, relatlimab enhances 
activation of human T cells in superantigen stimulation assays when added alone or in combination 
with nivolumab (anti-PD-L1 antibody). 
For additional details, refer to Section 4.1 (nonclinical pharmacology studies with relatlimab) and 
Section 4.2 (nonclinical pharmacokinetics with relatlimab) in the relatlimab IB.8 
3.2.2 
Nivolumab Mechanism of Action 
Cancer immunotherapy rests on the premise that tumors can be recognized as foreign rather than 
as self and can be effectively attacked by an activated immune system. An effective immune 
response in this setting is thought to rely on immune surveillance of tumor antigens expressed on 
cancer cells that ultimately results in an adaptive immune response and cancer cell death. 
Meanwhile, tumor progression may depend upon acquisition of traits that allow cancer cells to 
evade immunosurveillance and escape effective innate and adaptive immune responses. 37, 38, 39 
Current immunotherapy efforts attempt to break the apparent tolerance of the immune system to 
tumor cells and antigens by either introducing cancer antigens by therapeutic vaccination or by 
modulating regulatory checkpoints of the immune system. T-cell stimulation is a complex process 
involving the integration of numerous positive as well as negative co-stimulatory signals in 
addition to antigen recognition by the T-cell receptor (TCR). 40 Collectively, these signals govern 
the balance between T-cell activation and tolerance. 
PD-1 is a member of the CD28 family of T-cell co-stimulatory receptors that also includes CD28, 
CTLA-4, inducible T cell co-stimulator (ICOS), and B- and T-lymphocyte attenuator (BTLA). 41 
PD-1 signaling has been shown to inhibit CD28-mediated upregulation of interleukin (IL)-2, 
IL-10, IL-13, interferon-γ (IFN-γ), and B-cell lymphoma-extra large (Bcl-xL). PD-1 expression 

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has also been noted to inhibit T-cell activation, and expansion of previously activated cells. 
Evidence for a negative regulatory role of PD-1 comes from studies of PD-1-deficient mice, which 
develop a variety of autoimmune phenotypes. 42 These results suggest that PD-1 blockade has the 
potential to activate anti-self T-cell responses, but these responses are variable and dependent upon 
various host genetic factors. Thus, PD-1 deficiency or inhibition is not accompanied by a universal 
loss of tolerance to self-antigens. 
In vitro, nivolumab (BMS-936558) binds to PD-1 with high affinity (half-maximal effective 
concentration [EC50], 0.39-2.62 nM), and inhibits the binding of PD-1 to its ligands PD-L1 and 
programmed death-ligand 2 (PD-L2; IC50, ± 1 nM). Nivolumab binds specifically to PD-1 and 
not to related members of the CD28 family, such as CD28, ICOS, CTLA-4 and BTLA. Blockade 
of the PD-1 pathway by nivolumab results in a reproducible enhancement of both proliferation and 
IFN-γ release in the mixed lymphocyte reaction (MLR). Using a cytomegalovirus (CMV) 
restimulation assay with human peripheral blood mononuclear cells (PBMCs), the effect of 
nivolumab on antigen specific recall response indicated that nivolumab augmented IFN-γ secretion 
from CMV-specific memory T cells in a dose-dependent manner vs isotype-matched control. In 
vivo blockade of PD-1 by a murine analog of nivolumab enhances the antitumor immune response 
and results in tumor rejection in several immunocompetent mouse tumor models (MC38, SA1/N, 
and PAN02). 43 
3.2.3 
Relatlimab Combined with Nivolumab Clinical Activity 
 

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CA224047, a global, double-blind, randomized, Phase 2/3 study comparing a fixed-dose 
combination (FDC) formulation of nivolumab 480 mg + relatlimab 160 mg FDC Q4W to 
nivolumab 480 mg Q4W in participants with previously untreated advanced melanoma 
demonstrated a statistically significant and clinically meaningful benefit by dual inhibition of the 
LAG-3 and PD-1 pathways. 45F 45F  45,
46F 46F46 The study achieved its primary endpoint, demonstrating 
statistically significant improvement in progression-free survival (PFS) by BICR with nivolumab 
480 mg + relatlimab 160 mg FDC Q4W compared to nivolumab monotherapy in all randomized 
participants (N = 714) (PFS hazard ratio [HR] = 0.75 [95% CI: 0.62, 0.92], P-value = 0.0055). 
With a median follow-up of 13.2 months, the median PFS in the nivolumab + relatlimab FDC (3:1) 
group was 10.1 months (95% CI, 6.4–15.7) compared to 4.6 months (95% CI, 3.4–5.6) in the 
nivolumab monotherapy arm. PFS rates at 12 months were 47.7% (95% CI, 41.8–53.2) and 36.0% 
(95% CI, 30.5–41.6) for nivolumab + relatlimab FDC (3:1) and nivolumab monotherapy, 
respectively. The PFS benefit of nivolumab + relatlimab FDC (3:1) was consistent across key 
prespecified subgroups. The secondary endpoint of overall survival (OS) showed clinically 
meaningful improvement with nivolumab + relatlimab FDC over nivolumab monotherapy (median 
OS non-estimable [34.20, not reached {NR}]) versus 34.1 months [25.23, NR]; HR = 0.80 [0.64- 
1.01]; p = 0.0593) in all randomized participants but was not statistically significant.45.46 
Due to the statistical non-significance of the secondary endpoint of OS, ORR was not formally 
tested per the statistical testing hierarchy; however, clinically meaningful numerical differences 
were observed with the nivolumab + relatlimab FDC arm over nivolumab monotherapy (43.1% vs 
32.6%). 47 
3.3 
Benefit/Risk Assessment 
3.3.1 
Introduction 
Patients with advanced/metastatic HCC who experience progressive disease after TKI therapies 
have limited treatment options and poor overall prognosis, even with adequate liver reserve, as 
measured by Child-Pugh A status. Treatment options for patients who have not received a previous 
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achieved an ORR of 14% and an mOS of 15 months (49% of participants experienced serious 
adverse events [SAEs]).14 Pembrolizumab achieved an ORR of 17%, and an mOS of 14 months.15 
The TKIs cabozantinib and regorafenib achieved ORRs of had 4% and 11%, respectively, but with 
Grade 3-4 AEs reported in 85% of participants with cabozantinib and 44% of participants with 
regorafenib. The only IO combination regimen examined in 2L HCC (nivolumab and ipilimumab) 
showed improved efficacy compared to monotherapy agents, but presented with increased 
toxicity.16 At present, other treatment modalities, such as the combination of IO with anti-VEGF 
therapies, are anticipated to be available only for patients without prior therapy; thus, the unmet 
need for patients who experience progressive disease after 1L and subsequent lines of TKI 
therapies remains. 
HCC has a unique TME that is typically driven by either viral or other chronic 
infections/inflammations, which create a moderately inflamed environment.10 Chronic 
inflammation causes a unique immune tolerogenic TME.11 LAG-3 has been shown to play 
multiple roles in this context. In addition, relatlimab enhances activation of human T cells in super- 
antigen stimulation assays when added alone or in combination with nivolumab (anti-PD-1 
antibody).8 
There is strong preclinical support for the combination of relatlimab + nivolumab in HCC, 
evidence of clinical efficacy and tolerability of the combination at a lower dose, and extensive 
clinical experience with the dose of 480-mg relatlimab/480-mg nivolumab across a range of tumor 
types. 
3.3.2 
Safety 
The combination of nivolumab and relatlimab has shown well-defined toxicity profiles based on a 
safety database comprised of participants treated with either relatlimab monotherapy or as a 
combination across multiple tumor types. 
 

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Safety results to date indicate that sequential, co-administration, and the FDC of nivolumab + 
relatlimab administration have similar manageable safety profiles that are consistent with the 
mechanisms of action of each agent, nivolumab and relatlimab. No new types of clinically 
important events have been identified.8,45 
Given the safety profile of relatlimab as monotherapy and combination therapy observed to date,8 
the positive benefit/risk of the pivotal Phase 2/3 study of nivolumab + relatlimab FDC (3:1) 
demonstrated in participants with previously untreated metastatic or unresectable advanced 
melanoma,46 and the significant unmet medical need in the advanced HCC population, the 
continuing evaluation of the combination of nivolumab + relatlimab is justified for the patient 
population in this protocol. 
 

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3.3.3 
Safety Monitoring 
A pattern of IMAEs has been defined, 
. Most high-grade IMAEs, including hepatic and cardiac AEs, 
are manageable with the use of corticosteroids or hormone replacement therapy (endocrinopathies) 
as instructed 
. Additional extensive details on the safety profiles of relatlimab 
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and will not be repeated herein. As relatlimab is an experimental agent, it is possible that 
unforeseen, unknown, or unanticipated reactions may occur; however, data exists that the 
combination of relatlimab and nivolumab is safe and tolerable, even at higher doses in other tumor 
types, including those used in this study. 
This protocol uses a Bayesian continuous monitoring strategy to assess criteria for stopping 
enrollment for each treatment arm. 
The criteria of < 30% TRSAEs, as assessed by Investigator among the total participants, is 
proposed. This is slightly higher than the 22% rate that was observed in CA209040 HCC study for 
nivolumab 1 mg/kg and ipilimumab 3 mg/kg that has been approved by FDA. 
The monitoring will be implemented by a monthly review of the CA224073 clinical trial data by 
the study team. 
TRSAEs per treatment arm will be assessed and cumulative frequency per current enrollment will 
be determined. A broader review of safety for CA224073 will also take place by the study team. 
If the posterior probability that the TRSAEs > 22% (resulting in the final boundary of 29 out of 
100 total participants) is greater than 95%, a more in-depth safety analysis will start, and a report 
listing the SAEs, preferred term, grade, and outcome will be provided to the BMS Safety 
Committee (SC). The SC members have expertise in drug safety, clinical trial conduct, and 
oncology. The SC will convene an ad hoc meeting to review the safety data and provide a 
recommendation whether to continue enrollment or discontinue a treatment arm. In the event of a 
review, the totality of clinical data will be examined. 
 
3.3.4 
Efficacy 
 

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The available data with relatlimab and nivolumab and other immunotherapies in advanced HCC, 
as well as well-described immune biology in HCC, support the rationale for relatlimab in 
combination with nivolumab in patients with advanced/metastatic HCC who experience 
progressive disease after TKI therapies. This remains a high unmet need patient population; the 
available evidence and the anticipated acceptable safety profile support the benefit/risk of 
participation in this study. 
4 
OBJECTIVES AND ENDPOINTS 
Objectives and endpoints are presented in Table 4-1. 
Table 4-1: 
Objectives and Endpoints 
 
Objective 
Endpoint 
Primary 
• 
To evaluate the efficacy of relatlimab in 
combination with nivolumab relative to nivolumab 
monotherapy in IO therapy-naive participants after 
prior treatment with TKI therapy 
• 
ORR assessed by BICR using RECIST v1.1 
Key Secondary 
• 
To investigate safety and tolerability of relatlimab 
in combination with nivolumab in participants with 
advanced HCC 
• 
Incidence of AEs, SAEs, and AEs leading to 
discontinuation, deaths, and clinical laboratory test 
abnormalities 
• 
To further evaluate the preliminary efficacy of 
relatlimab in combination with nivolumab 
• 
DCR, DOR, and PFS assessed by BICR per 
RECIST v1.1 
• 
ORR, 
DCR, 
DOR, 
and 
PFS 
assessed 
by 
Investigator per RECIST v1.1 
• 
OS 

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Table 4-1: 
Objectives and Endpoints 
Objective 
Endpoint 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE = adverse event; BICR = Blinded Independent Central Review; 
DCR = disease control rate; DOR = duration of response; 
 
HCC = hepatocellular carcinoma; 
IO 
= 
immuno-oncology; 
ORR = objective response rate; OS = overall 
survival; PFS = progression-free survival; 
RECIST = Response Evaluation Criteria in Solid Tumors; SAE = serious adverse event; 
TKI = tyrosine kinase inhibitor. 
 
5 
STUDY DESIGN 
5.1 
Overall Design 
This Phase 2 study will evaluate the safety and efficacy of relatlimab in combination with 
nivolumab in participants with 2L or 3L IO-naive HCC. 

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As of 19-July-2021, participants are being randomized 1:1 to receive: 
• Arm A: Nivolumab 480 mg Q4W 
• Arm B: Nivolumab 480 mg Q4W+ Relatlimab 480 mg Q4W 
 
• 
Arm C: Nivolumab 480 mg Q4W+ Relatlimab 960 mg Q4W 
24 participants were randomized to Arm C. 
 
 
Stratification will occur by region (Asia [excluding Japan] vs Rest of the World [including Japan]) 
and macrovascular invasion and/or extrahepatic spread (MVI/EHS; present or absent). For the 
purposes of randomization, LAG-3 will also be treated as a stratification factor. 
MVI is defined as: 
• Hepatic vein tumor thrombus, OR 
• Inferior vena cava tumor thrombus, OR 
• Portal vein tumor thrombus; Vp3/Vp4 (presence of a tumor thrombus in the main trunk of the 
portal vein or a portal vein branch contralateral to the primarily involved lobe or first-order 
branches of the portal vein) participants are also eligible. 
 
EHS is defined as presence of metastatic disease in lymph nodes or distant sites outside the liver. 
All participants will be treated until disease progression or unacceptable toxicity. Treatment 
beyond initial Investigator-assessed RECIST v1.1-defined progression is permitted if the 
participant has Investigator-assessed clinical benefit and is tolerating study treatment. 

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Individual participants with confirmed CR will be given the option to discontinue study therapy 
on a case-by-case basis, after specific consultation and agreement between the Investigator and 
BMS Medical Monitor, in settings where benefit/risk justifies discontinuation of study therapy. 
Efficacy will be evaluated in the all-comer patient populations for 480-mg relatlimab in 
combination with 480-mg nivolumab Q4W compared to nivolumab 480 mg monotherapy. 
Arm C (960-mg relatlimab in combination with 480-mg nivolumab) has 
24 patients   randomized. Approximately 226 participants will be randomized 
in Arm A and Arm B. 
The study design schematic is presented in Figure 5.1-1. 

 
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Figure 5.1-1: 
Study Design Schematic for CA224073 
 
Abbreviations: 
2L = second line; 3L = third line; ECOG = Eastern Cooperative Oncology Group; EHS = extrahepatic spread; 
FU = follow-up; HCC = hepatocellular carcinoma; IO = immuno-oncology; LAG-3 = lymphocyte activation gene 3; MVI = macrovascular invasion; N = number; 
Nivo = nivolumab; Q4W = every 4 weeks; Rela = relatlimab; TKI = tyrosine kinase inhibitor. 
 
 
 
 
b Total patients planned is approximately 250 with an additional 24 patients randomized to Arm C 
. 
 
 
 
 
 
 
 
 
 
 
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5.1.1 
Screening Period 
The Screening Period will be up to 28 days and begins by establishing the participant’s initial 
eligibility and signing of the informed consent form (ICF) or pre-screening ICF, if allowed. 
Informed consent will be obtained prior to any study-specific procedures. Participants will be 
evaluated based on the assessments as outlined in Table 2-1 and the Inclusion and Exclusion 
criteria (see Section 6). If a participant exceeds the 28-day Screening Period due to a study-related 
procedure (eg, scheduling of a tumor biopsy, waiting for a study-related laboratory value), the 
participant must be re-consented. If the subject is awaiting central laboratory results, then the 
participant does not have to re-consent until Day 42 (additional +14 days beyond screening 
window). Other screening procedures should be conducted within the windows specified in Table 
2-1. A new participant identification number will be assigned by Interactive Response Technology 
(IRT) at the time of re-enrollment. In this situation, the fewest number of procedures from the 
initial screening should be repeated to qualify the participant, while maintaining participant safety 
and eligibility. In these cases, the site should consult with the BMS Medical Monitor (or Clinical 
Scientist). 
A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (preferred) or a minimum of 
20 freshly cut unstained slides of tumor tissue obtained from core biopsy, incisional biopsy, 
excisional biopsy, or surgical specimen prior to enrollment is required. Fine needle aspirates or 
other cytology samples and biopsies of bone lesions that do not have a soft tissue are not 
acceptable. Note the following for the required tumor sample: 
• Samples should be collected within 3 months of enrollment. Biopsy can be taken on TKI 
treatment or after TKI treatment, with no intervening systemic anti-cancer treatment between 
time of acquisition and randomization. 
• If a tumor sample (as described above) is not available, then a fresh pre-treatment biopsy may 
be obtained. This fresh biopsy should be excisional, incisional, or core needle. 
• If the first 2 options are not feasible, then an archival tissue sample may be submitted if 
approval from BMS (Medical Monitor or Clinical Scientist) is obtained. This option should 
only be used in rare instances. 
 
If despite best efforts, a minimum of 20 slides are not obtainable, submission of fewer slides may 
be acceptable in some circumstances following discussion with BMS Medical Monitor or Clinical 
Scientist. 
 
5.1.2 
Treatment Period 
• The treatment phase begins with the randomization call to the IRT system. The participant is 
randomly assigned to 1 of the 2 treatment arms: 
− Arm A: Nivolumab 480 mg Q4W 
Tumor sample must be sent to the central laboratory. 

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− Arm B: Nivolumab 480 mg Q4W and Relatlimab 480 mg Q4W 
 
• 
− Arm C: Nivolumab 480 mg Q4W and Relatlimab 960 mg Q4W 
• Administration of study treatment (see Table 7-1) should begin within 3 days of 
randomization/contacting IRT. 
• Participants will receive treatment until disease progression (unless treatment beyond 
progressive disease is permitted), unacceptable toxicity, or withdrawn consent. 
• Women of child bearing potential (WOCBP) must have a documented negative pregnancy test 
within 1 day prior to the start of study treatment. An extension up to 72 hours prior to the start 
of study treatment is permissible in situations where results cannot be obtained within the 
standard 24-hour window. For additional assessments see Table 2-2. 
• On-study vital sign assessments should be performed at each on-treatment visit. Please see 
Table 2-2. 
• On-study laboratory assessments should be performed within 3 calendar days prior to dosing 
at each on-treatment visit and will be assessed at the local laboratory. Please see Table 2-2. 
• Tumor assessments will occur in accordance with Table 2-2, until disease progression (unless 
treatment beyond disease progression is permitted), or treatment discontinuation (including 
treatment beyond progression), whichever occurs later. Each site should submit scans on a 
rolling basis to a central vendor. 
• Treatment Period ends when the participant is discontinued from study therapy for any reason. 
Please refer to Section 8 for a complete list of possible reasons for discontinuation. 
• Individual participants with confirmed CR will be given the option to discontinue study therapy 
on a case-by-case basis, after specific consultation and agreement between the Investigator and 
BMS Medical Monitor, in settings where benefit/risk justifies discontinuation of study therapy. 
 
5.1.3 
Follow-up Period 
Upon completion of study treatment, or once the decision is made to discontinue the participant 
from treatment, that is, at end of treatment (EOT), all participants will enter a Safety Follow-up 
Period. 
EOT is defined as the last on-treatment visit or where a decision is made to discontinue the 
participant from treatment. 

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After the EOT visit, all participants will be evaluated for any new AEs for 135 days after the last 
dose of study treatment. Follow-up visits should occur at Days 30 and 135 (± 7 days for all study 
visits) after the last dose or at the date of discontinuation (± 11 days). All participants should 
complete the 2 clinical safety follow-up visits regardless of whether new anti-cancer therapy is 
started, except those participants who withdraw consent for study participation. 
Participants with SD, PR, or CR at the time of the EOT visit or at the time of study treatment 
discontinuation will continue to have radiologic and clinical tumor assessments every 
8 weeks (± 7 days) after discontinuation of study treatment/EOT visit, until the start of subsequent 
therapy, disease progression, or withdrawal of study consent. Radiological assessments for 
participants who have ongoing clinical benefit may continue to be collected after participants 
complete the Survival Follow-up Period of the study. Participants who have disease progression 
after an initial course of study therapy will not be evaluated for response beyond the EOT visit and 
will be allowed to receive other tumor-directed therapy as required. 
5.1.3.1 
Survival Follow-up Period 
In parallel with the safety follow-up period, all participants will start the Survival Follow-up 
Period. Participants will be followed until death, loss to follow-up, withdrawal of consent, or 
conclusion of the study, whichever comes first. Participants with SD, PR, or CR will have both the 
Response Follow-up Period and Survival Follow-up Period occur simultaneously during the 
Follow-up Period. The duration of this follow-up is 2 years following the first dose of study 
drug (and at least 1 year from last dose) for response assessment; although, a longer Follow-up 
Period may be considered in selected cases if an efficacy signal is apparent. Tumor assessment 
scans for participants who have ongoing clinical benefit beyond the 2-year period after the first 
dose of study treatment may continue to be collected as part of standard-of-care treatment, where 
permitted. Subsequent therapies will also be recorded in this Survival Follow-up Period. 
5.1.4 
Data Monitoring Committee and Other External Committees 
5.1.4.1 
Data Monitoring Committee 
Relative to the exploratory nature of this Phase 2 open-label study and the experience that already 
exists around the use of relatlimab and nivolumab, a Data Monitoring Committee is not needed for 
this study. In addition to the comprehensive safety monitoring plan outlined below, the following 
key points were considered for this decision: 
• This is an open-label study and there will be regularly scheduled Investigator meetings to 
review safety in an ongoing manner. 
• Aggregate safety will be continuously monitored for Arm B and Arm C and will be informed 
by a Bayesian framework (see Section 10.3.4 [Interim Analyses]), which will consider overall 
safety measures if an excessive number of safety events are observed. 
• The eligibility criteria exclude participants with disease characteristics that could predispose 
them to higher risk of morbidity. 
• Exclusion of participants with known autoimmunity also applies because they could be at risk 
for exacerbation of their condition by the administration of therapies that relieve immune 
suppression, such as those used in this study. 

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• Participants will be observed frequently for clinical evaluation and blood counts during the 
Treatment Period. 
• Well-defined discontinuation criteria are established in the protocol for individual participants 
for safety, with clear criteria for treatment discontinuation, dose delay, and toxicity 
management. 
• BMS has in place a multilayered process for ensuring participant safety through close 
collaboration of study site Investigators, the BMS study team, and the BMS Worldwide Patient 
Safety (WWPS)-led Safety Management Team (SMT). This collaborative process constitutes 
the Data Safety Monitoring Plan for the study as detailed below. 
• Study safety is evaluated continuously by representatives of BMS WWPS, who operate 
independently from the clinical team and monitor safety across all BMS protocols. AEs are 
monitored continuously by WWPS. Signal detection is performed at least monthly and ad hoc 
throughout the study by the SMT, composed, at a minimum, of the WS medical safety 
assessment physician (Chairman of the SMT) and WWPS single-case review physician, the 
study Medical Monitor(s), the study biostatistician, and epidemiologist. The SMT monitors 
actual or potential issues related to participant safety that could result in a significant change 
in the medical benefit/risk balance associated with the use of study treatments. Furthermore, 
Investigators will be kept updated of important safety information during teleconferences 
between Investigators and the BMS clinical team, which will be held on a regularly scheduled 
basis. If appropriate, select safety issues may be escalated to a senior level, multidisciplinary, 
BMS-wide Medical Review Group for further evaluation and action. To support safety 
oversight, BMS has established ongoing processes for collection, review, analysis, and 
submission of individual AE reports and their aggregate analyses. Because this is an open-label 
study, the BMS Medical Monitor and the Investigators will have access to all data necessary 
for safety evaluation. 
• All participants in this study represent individuals with high unmet medical need because the 
prognosis for advanced/metastatic solid tumors is generally very poor. 
 
5.2 
Number of Participants 
Approximately 250 participants will be randomized (226 to Arm A and B, and 24 in Arm C). 
It is estimated that approximately 357 enrolled participants will be needed to achieve these 
250 randomized. 
 
5.3 
End of Study Definition 
The start of the study is defined as first participant screened. End of study is defined as the end of 
the survival follow-up period for the last participant. Study completion is defined as the final date 
on which data for the primary endpoint was or is expected to be collected, if this is not the same. 
Additional follow-up for OS may be conducted up to approximately 5 years after the 
randomization of the last participant. 

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5.4 
Scientific Rationale for Study Design 
Preliminary efficacy was seen with a lower dose of relatlimab and nivolumab combination in a 
• Understand the added benefit of relatlimab to nivolumab monotherapy. 
 
 
5.4.1 
Rationale for Choice of Comparators 
Nivolumab was chosen to be the comparator treatment to explore efficacy in 2L and subsequent 
settings. Nivolumab initially received accelerated approval for use in HCC patients who have 
failed  sorafenib  treatment.14  Currently,  the  National  Comprehensive  Cancer 
Network (NCCN) guidelines recommend nivolumab in subsequent lines of therapy in certain 
circumstances.34 
5.4.2 
Rationale for Use of Relatlimab in Combination with Nivolumab 
Several studies conducted and consequent approvals of immunotherapy agents support the use of 
immunotherapies in HCC, as previously described. HCC is a primary liver tumor that typically 
develops a pattern of chronic liver disease, particularly in patients with cirrhosis or chronic viral 
infection.  The  viral  association  makes  it  suitable  for  combination  therapy 
BMS-986016 (relatlimab) and nivolumab. On one hand, it has been shown that LAG-3 is 
selectively up-regulated on tumor infiltrating CD8+ T cells and that HBV-specific CD8+ 
tumor-infiltrating lymphocytes (TILs) have an impaired effector function in participants with 
49 
48F48F 
 
 
 
 
 
 
 
 
Besides the already proven benefit of immunotherapies in HCC, 
 Phase 1/2 studies 
are supporting the efficacy of LAG-3 mechanism of action in HCC. Lymphocytic infiltration of the 
tumor and a high CD4+:CD8+ T-cell ratio have been associated with reduced risk of tumor 
recurrence following liver transplantation for HCC. 50 Adoptive immunotherapy with autologous 
lymphocytes activated with recombinant-2 and antibody to CD3 in patients who had undergone 
curative resection resulted in significantly longer recurrence-free and disease-specific survival, 
although OS did not differ significantly between treated and control groups. 51 The data 
nonetheless imply a central role of T cells in modulating tumor progression and provide strong 
justification for T-cell immunotherapy.20 There is also evidence that FGL-1, a liver-secreted 
protein, is a major LAG-3 functional ligand independent from MHC-II. FGL-1 inhibits antigen- 
specific T-cell activation, and ablation of FGL-1 in mice promotes T-cell immunity. Blockade of 
the FGL-1:LAG-3 interaction by monoclonal antibodies stimulates tumor immunity and is 
therapeutic against established mouse tumors in a receptor-ligand, inter-dependent manner. FGL- 
single-arm study. 
To further evaluate and understand these data, this study aims to: 
HCC.

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51F51
1 is highly produced by human cancer cells, and elevated FGL-1 in the plasma of cancer patients 
is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. 52 
 
5.4.3 
Rationale for Duration of Treatment 
All participants will be treated until progression or appearance of intolerable toxicities, or if 
confirmed CR is achieved. Continuous tumor assessment every 8 weeks and safety evaluation will 
guide the decision to treat a participant with additional cycles of study therapy if the participant 
has confirmed clinical benefit. 
Tumor assessments should continue until disease progression or treatment discontinuation, 
whichever occurs later. Participants with unconfirmed progressive disease, SD, or PR at the end 
of a given cycle will continue to the next treatment cycle. 
Individual participants with confirmed CR will be given the option to discontinue study therapy 
on a case-by-case basis, after specific consultation and agreement between the Investigator and 
BMS Medical Monitor, in settings where benefit/risk justifies discontinuation of study therapy. 
Participants will be allowed to continue study treatment until the first occurrence of any of the 
following situations: 
• Progressive disease defined by RECIST v1.1, unless participants meet criteria for treatment 
beyond progression (see Section 8.1.2). 
• Clinical deterioration suggesting that no further benefit from treatment is likely. 
• Intolerability to therapy. 
• Participant meets criteria for discontinuation of study treatment. 
 
5.4.4 
Rationale for Stratification Factors 
Stratification will occur by: 
• Region (Asia [excluding Japan] vs rest of the world [including Japan]) 
• MVI/EHS (yes or no) 
• LAG-3 expression 
 
Recent pivotal studies in this indication and line/setting of therapy used the following stratification 
factors: the CA209040 study that led to the approval in 2L stratified by HCC HCV vs non-HCV 
and presence of Investigator-assessed vascular invasion (VI) or EHS vs absence of VI/EHS; while 
the KEYNOTE-240 study, which did not meet its endpoints with pembrolizumab monotherapy 

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56F56
59F59
60F60
61F61
52F52F
53F53
54F54
55F55
57F57
58F58
approval, stratified by geographic region (Asia excluding Japan, vs non-Asia including Japan), 
MVI (yes or no) and AFP (< 200 ng/mL vs > 200 ng/mL). 
A number of randomized Phase 3 trials in HCC that followed the sorafenib pivotal trials have 
failed to demonstrate positive outcomes. These include 4 Phase 3 trials in the 1L setting with 
sunitinib, brivanib, linifanib, and erlotinib. 53, 54, 55, 56 The reasons for trial failure are considered 
heterogeneous 
and 
include 
lack 
of 
understanding 
of 
critical 
drivers 
of 
tumor 
progression/dissemination, liver toxicity, flaws in trial design, or marginal antitumor potency. 57 
With respect to trial design, publications have cited potential imbalances in prognostic baseline 
factors. 
The randomized Phase 3 trials were mostly stratified by the presence or absence of VI and/or EHS, 
geographic region, and Eastern Cooperative Oncology Group (ECOG) performance status. Despite 
stratification and randomization, notable differences were observed in the outcomes. Subset 
analysis of the 2 pivotal sorafenib trials showed differences in the outcomes of participants who had 
VI/EHS compared to those who did not have VI/EHS. Participants who had VI/EHS had worse 
outcomes than participants without VI/EHS. 58, 59 This study will therefore stratify by VI/EHS. 
The impact of differing HCC patient populations and different approaches to clinical practice in 
the different regions is still important to consider. Based on pivotal trial results, differences in 
outcome are also captured in outcome by infectious vs non-infectious etiology. Based on World 
Health Organization (WHO) data, the prevalence of HCV is highest in the eastern Mediterranean 
region (>2%), 60 and HBV prevalence is 2-7% in Mediterranean countries, Japan, central Asia, the 
Middle East, and parts of South America. 61 These regions where HBV and HCV infection and 
consequent HCC is prevalent are in the Asian region. The Japanese HCC population is different 
from the other non-Japanese Asian HCC populations, with a higher prevalence of HCV-HCC and 
a better screening system. The KEYNOTE-224 and IMbrave 150 studies stratified by region, 
including Japan to the rest of the world. 62 Therefore, this study will not stratify by etiology, 
assuming the majority of HCC with infectious origin comes from the Asian countries. This study 
will therefore stratify by region. 
 
 
To balance the expression across arms, LAG-3 
will also be treated as a stratification factor. 
 

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5.5 
Justification for Dose 
 
5.5.1 
Justification for Nivolumab Dose 
Nivolumab 480 mg Q4W has been approved in Europe for use as monotherapy in patients with 
melanoma and renal cell carcinoma (RCC) and in the US for use as monotherapy in patients with 
melanoma, RCC, non-small cell lung cancer (NSCLC), and other indications, including HCC. 
The nivolumab dose of 480 mg Q4W was selected based on clinical data and modeling and 
simulation approaches using population PK (PPK) and exposure-response (E-R) analyses of data 
from studies in multiple tumor types (melanoma, NSCLC, RCC, squamous cell carcinoma of the 
head and neck [SCCHN], urothelial carcinoma [UC], and classical Hodgkin lymphoma [cHL]), 
where body weight-normalized dosing (mg/kg) has been used. The PPK analyses have shown that 
exposure to nivolumab increased dose proportionally over the dose range of 0.1 to 10 mg/kg 
administered Q2W, and no clinically meaningful differences in PK across ethnicities and tumor 
types were observed. Nivolumab clearance (CL) and volume of distribution were found to increase 
as the body weight increases, but less than proportionally with increasing weight, indicating that 
mg-per-kg dosing represents an over adjustment for the effect of body weight on nivolumab PK. 
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The PPK model previously developed using data from NSCLC participants has recently been 
updated, using data from 3,203 participants from 19 studies investigating nivolumab in the 
treatment of melanoma, NSCLC, RCC, SCCHN, UC, and cHL. In this dataset, the 
median (minimum - maximum) weight was 76.7 kg (34.1 kg - 180 kg) and thus, an approximately 
equivalent dose of 3 mg/kg Q2W for an 80-kg participant, nivolumab 480 mg Q4W was selected 
for future studies. 
Nivolumab 480 mg Q4W is predicted to produce similar exposures to those of 3 mg/kg Q2W and 
240 mg Q2W regimens. The overall distributions of nivolumab average steady state exposures are 
comparable after treatment with either nivolumab 3 mg/kg Q2W or nivolumab 480 mg Q4W, 
although the flat-dose regimen of 480 mg Q4W is predicted to result in approximately 43% higher 
steady-state peak concentration (Cmaxss) and approximately 16% lower steady-state trough 
concentrations compared to the reference regimen of 3 mg/kg Q2W. Across the various tumor 
types in the clinical program, nivolumab has been shown to be safe and well tolerated up to a dose 
level of 10 mg/kg, and the relationship between nivolumab exposure produced by 3 mg/kg and 
efficacy and safety has been found to be relatively flat. Although nivolumab Cmaxss is predicted 
to be higher following 480 mg Q4W, these exposures are predicted to be lower than or within the 
exposure ranges observed at doses up to 10 mg/kg Q2W used in the nivolumab clinical program 
and are not considered to put patients at increased risk. In addition, there was no difference in AE 
profile by body weight groups when extensive evaluations were performed with available 3 mg/kg 
Q2W and 10 mg/kg Q2W data. The exposures predicted following administration of nivolumab 
480 mg Q4W are on the flat part of the E-R curves for previously investigated tumors (melanoma 
and NSCLC) and are not predicted to affect efficacy. Based on these data, nivolumab 480 mg Q4W 
is expected to have similar efficacy and safety profiles to nivolumab 3 mg/kg Q2W. For lower 
body weight patients, given the relatively flat E-R relationship of nivolumab, the increased 
exposures from 480 mg Q4W are not expected to pose an increased risk. 
Nivolumab 480 mg Q4W is currently being evaluated in various studies across the nivolumab 
clinical  development  program.  Preliminary  results  from pooled  analyses,  including 
310 participants who received nivolumab 480 mg IV over 30 minutes Q4W, showed that the safety 
profile is consistent with the established safety profile of nivolumab (240 mg Q2W or 3 mg/kg 
Q2W administered IV over 60 minutes) across multiple indications, and no new safety concerns 
were identified. In HCC, this dose schedule is currently approved for the treatment of advanced 
HCC in the US and it is also under evaluation in an ongoing trial of nivolumab monotherapy in 
the adjuvant setting (CA2099DX). Therefore, in this study, 480 mg Q4W will be used for the 
nivolumab dose; this dose will provide a more convenient dosing regimen for participants, without 
compromising safety. 
 

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5.6 
Clinical Pharmacology Summary 
5.6.1 
Nivolumab Clinical Pharmacology Summary 
The PK of single-agent nivolumab was studied in participants over a dose range of 0.1 to 20 mg/kg 
administered as a single dose or as multiple doses of nivolumab as a 60-minute IV infusion every 
2 or 3 weeks. Nivolumab CL decreases over time, with a mean maximal reduction (% coefficient 
of variation [CV%]) from baseline values of 24.5% (47.6%), resulting in a geometric mean 
steady-state clearance (CLss; CV%) of 8.2 mL/h (53.9%) in participants with metastatic tumors; 
the decrease in CLss is not considered clinically relevant. Nivolumab CL does not decrease over 
time in participants with completely resected melanoma, as the geometric mean population CL is 
24% lower in this patient population compared with patients with metastatic melanoma at steady 
state. The geometric mean volume of distribution at steady state (Vss; CV%) is 6.8 L (27.3%), and 
geometric mean elimination half-life (t1/2) is 25 days (77.5%). Steady-state concentrations of 
nivolumab were reached by 12 weeks when administered at 3 mg/kg Q2W, and systemic 
accumulation was 3.7-fold. The exposure to nivolumab increases dose proportionally over the dose 
range of 0.1 to 10 mg/kg administered Q2W. The predicted exposure (average 
concentration [Cavg] and maximum concentration [Cmax]) of nivolumab after a 30-minute 
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Specific Populations: The PPK analysis suggested that the following factors had no clinically 
important effect on the CL of nivolumab: age (29 to 87 years), weight (35 to 160 kg), gender, race, 
baseline LDH, PD-L1 expression, solid tumor type, tumor size, renal impairment, and mild hepatic 
impairment. 
Renal Impairment: The effect of renal impairment on the CL of nivolumab was evaluated by a 
PPK analysis in participants with mild (estimated glomerular filtration rate [eGFR] 60 to 
89 mL/min/1.73 m2), moderate (eGFR 30 to 59 mL/min/1.73 m2), or severe (eGFR 15 to 
29 mL/min/1.73 m2) renal impairment. No clinically important differences in the CL of nivolumab 
were found between participants with renal impairment and participants with normal renal 
function. 
Hepatic Impairment: The effect of hepatic impairment on the CL of nivolumab was evaluated by 
PPK analyses in participants with HCC and in participants with other tumors with mild hepatic 
impairment (total bilirubin less than or equal to the upper limit of normal [ULN] and AST greater 
than ULN or total bilirubin greater than 1 to 1.5× ULN and any AST) and in HCC participants 
with moderate hepatic impairment (total bilirubin greater than 1.5 to 3× ULN and any AST). No 
clinically important differences in the CL of nivolumab were found between participants with 
mild/moderate hepatic impairment. 
Full details on the clinical pharmacology aspects of nivolumab can be found in the IB.36 
 

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6 
STUDY POPULATION 
For entry into the study, the following criteria MUST be met. 
6.1 
Inclusion Criteria 
1) Signed Written Informed Consent 
a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC)-approved written ICF, in accordance with regulatory and 
institutional guidelines. This must be obtained before the performance of any 
protocol-related procedures that are not part of normal participant care. 
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory tests, tumor biopsies, and other requirements of the study. 
c) Participant Re-enrollment: This study permits the re-enrollment of a participant that has 
discontinued the study as a screen failure (ie, participant has not been randomized). If re- 
enrolled, the participant must be re-consented. 
d) For Protocol Amendment 03, all participants in Arm B and Arm C were re-consented due 
to updated safety information obtained in this study. 
2) Type of Participant and Target Disease Characteristics 
a) Participants must have a diagnosis of HCC based on histological confirmation. 
i) Participants with only a radiologic diagnosis of HCC may be enrolled for screening in 
the study but histological confirmation is mandatory prior to the start of study therapy. 
Note: If tumor samples are not available, participants must consent to a pre-treatment 
fresh biopsy for histological confirmation as a condition of protocol participation. 
b) Participants must have advanced/metastatic (Barcelona Clinic Liver Cancer stages B and 
C, Appendix 10) 2L or 3L HCC, defined as: 
i) Not Applicable per Protocol Amendment 02 (see new criterion iii) below): 
Progressive disease after sorafenib or lenvatinib therapies in the advanced/metastatic 
setting. 
ii) Disease not eligible for curative surgical and/or locoregional therapies. 
(1) If local or locoregional therapy of intrahepatic tumor lesions (eg, surgery, radiation 
therapy, hepatic arterial embolization, chemoembolization, radiofrequency 
ablation, percutaneous ethanol injection, or cryoablation) was provided, it must 
have been completed ≥ 4 weeks before the first dose of study medication. 
 
 
iii) Progressive disease in participants who received one or two lines of TKI therapies and 
who have evidence of radiographic progression on or after the last line of TKI therapy 
in the advanced/metastatic setting. Washout period between end of TKI treatment and 
start of dosing is 10 days for sorafenib, 6 days for lenvatinib, 6 days for regorafenib, 
and 21 days for cabozatinib.1,2,3,4 The washout period for any other TKI therapies can 

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be discussed with the Medical Monitor. Participants who have had prior systemic 
treatment with cytotoxic chemotherapy are not eligible. 
c) Participants with MVI are allowed to enroll, and MVI is defined as: 
i) Hepatic vein tumor thrombus, OR 
ii) Inferior vena cava tumor thrombus, OR 
iii) Portal vein tumor thrombus; Vp3/Vp4 (presence of a tumor thrombus in the main trunk 
of the portal vein or a portal vein branch contralateral to the primarily involved lobe or 
first-order branches of the portal vein) participants are also eligible. 
d) Participants with extrahepatic spread (EHS) are allowed to enroll. EHS is defined as 
presence of metastatic disease in lymph nodes or distant sites outside the liver. 
e) Participants have to be immunotherapy treatment-naive in the advanced/metastatic setting: 
No prior immunotherapies are permitted (such as, but not limited to anti-LAG-3, anti-PD- 
1, anti-PD-L1, or anti-CTLA-4 antibody, oncolytic viruses, or any other antibody or drug 
specifically targeting T-cell co-stimulation or checkpoint pathways) for the treatment of 
the advanced/metastatic disease. 
i) Therapies with immunotherapy in early and intermediate stage are allowed if at least 
6 months between the last dose and date of recurrence occurred prior to initiating 1L 
systemic therapy. 
 
 
 
g) Participants  must  be  LAG-3+ 
or 
LAG-3- 
. Both LAG-3+ and LAG-3- participants will be allowed to 
enroll. 
h) Tumor tissue from an unresectable or metastatic site of disease that has not been previously 
irradiated must be provided 
. 
i) Not applicable per Protocol Amendment 02 (see new criterion iv) below): An FFPE 
tumor tissue block (preferred) or a minimum of 20 freshly cut unstained slides of tumor 
tissue obtained from core biopsy, incisional biopsy, excisional biopsy, or surgical 
specimen prior to enrollment is required. Fine needle aspirates or other cytology 
samples are not acceptable. Preferably, the tumor sample will be recently collected 
within 3 months of enrollment. Biopsy can be taken any time after the end of TKI 
treatment, with no intervening systemic anti-cancer treatment between time of 
acquisition and randomization. If a recently collected tumor sample (as described 
above) is not available, then a fresh pre-treatment biopsy (excisional, incisional, or 
core needle) may be obtained. If the first 2 options are not feasible, then an archival 
tissue may be submitted if approval from BMS (Medical Monitor or Clinical Scientist) 
is obtained. Central laboratory must provide IRT with confirmation of receipt of 
evaluable tumor tissue prior to randomization. The tissue submitted will be assessed 
for quality with a hematoxylin and eosin (H&E) stain and only those participants who 
have met tissue quality thresholds can be randomized. If despite best efforts, a minimum 
of 20 slides are not obtainable, submission of fewer slides may be acceptable in some 
circumstances following discussion with BMS Medical Monitor or Clinical Scientist. 

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ii) If an insufficient amount of tumor tissue from an unresectable or metastatic site is 
available prior to the start of the screening phase, participants must consent to allow 
the acquisition of additional tumor tissue during the Screening Period for performance 
of 
 analyses. 
iii) Biopsies of bone lesions that do not have a soft tissue component are not acceptable. 
ii) An FFPE tumor tissue block (preferred) or a minimum of 20 freshly cut unstained slides 
of tumor tissue obtained from core biopsy, incisional biopsy, excisional biopsy, or 
surgical specimen prior to enrollment is required. 
If there is only 1 measurable lesion, and a core-needle 
biopsy is done (instead of excisional), the lesion may be used as a measurable lesion. 
Fine needle aspirates or other cytology samples and biopsies that do not have a soft 
tissue component are not acceptable. The tumor sample should be collected within 
3 months of enrollment. Biopsy can be taken on TKI treatment or after TKI treatment, 
with no intervening systemic anti-cancer treatment between time of acquisition and 
randomization. If a tumor sample (as described above) is not available, then a fresh 
pre-treatment biopsy (excisional, incisional, or core needle) may be obtained. If the 
first 2 options are not feasible, then an archival tissue sample (collected > 3 months 
prior to enrollment) may be submitted as a third option if approval from BMS (Medical 
Monitor or Clinical Scientist) is obtained. The third option should be used only in rare 
instances. Central laboratory must provide IRT with confirmation of receipt of 
evaluable tumor tissue prior to randomization. The tissue submitted will be assessed 
for quality with a hematoxylin and eosin (H&E) stain and only those participants who 
have met tissue quality thresholds can be randomized. If despite best efforts, a 
minimum of 20 slides are not obtainable, submission of fewer slides may be acceptable 
in some circumstances following discussion with BMS Medical Monitor or Clinical 
Scientist. 
i) Participants must have at least 1 RECIST v1.1 measurable untreated lesion. 
i) The lesion must be accurately measured in at least one dimension by contrast-enhanced 
spiral computed tomography (CT) or contrast-enhanced dynamic magnetic resonance 
imaging (MRI) as ≥10 mm. Note: Malignant lymph nodes must be ≥15 mm on short 
axis. 
ii) The lesion must not have been previously treated with surgery, radiotherapy, and/or 
locoregional therapy (eg, RFA, percutaneous ethanol injection [PEI] or percutaneous 
acetic acid injection [PAI], cryoablation, high-intensity focused ultrasound [HIFU], 
TACE, transarterial embolization [TAE], etc.). 
j) Child-Pugh score of 5 or 6 (ie, Child-Pugh A; Appendix 5). 
k) ECOG performance status 0 or 1 for ECOG performance status scale (Appendix 6). 
l) Life expectancy of ≥ 3 months. 
m) Participants are eligible to enroll if they have non-viral HCC, or if they have HBV-HCC, 
or HCV-HCC defined as follows: 
i) HBV-HCC: Resolved HBV infection (as evidenced by detectable HBV surface 
antibody, detectable HBV core antibody, undetectable HBV deoxyribonucleic 
acid (DNA), and undetectable HBV surface antigen) or chronic HBV infection (as 

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evidenced by detectable HBV surface antigen or HBV DNA). Participants with chronic 
HBV infection must have HBV DNA < 500 IU/mL and must be on antiviral therapy. 
ii) HCV-HCC: Active or resolved HCV infection as evidenced by detectable HCV 
ribonucleic acid (RNA) or antibody. 
n) Adequate cardiac function with LVEF assessment with documented LVEF ≥ 50% by either 
TTE or MUGA (TTE preferred test) within 6 months from first study drug administration. 
o) All participants: Ability to comply with treatment, 
sample collection and required study follow-up. 
p) Screening laboratory values must meet the following criteria and should be obtained within 
14 days prior to randomization: 
i) Adequate hematologic function: 
(1) White blood cells ≥ 2000/µL (SI: ≥ 2.00 × 109/L; stable, off any growth factor 
within 4 weeks of study treatment administration) 
(2) Neutrophils ≥ 1500/µL (SI: ≥ 1.50 × 109/L; stable, off any growth factor within 
4 weeks of study treatment administration) 
(3) Not Applicable per Revised Protocol 01 (see new criterion (5) below): Platelets 
≥ 60×103/µL (SI: ≥ 100 × 109/L; transfusion or the use of platelet-stimulating 
agents to achieve this level is not permitted) 
(4) Hemoglobin ≥ 8.5 g/dL (SI: ≥ 85 g/L; may be transfused to meet this requirement; 
recombinant human erythropoietin not permitted within 3 weeks of first study drug 
administration) 
(5) Platelets ≥ 60×103/µL (SI: ≥ 60 × 109/L; transfusion or the use of platelet- 
stimulating agents to achieve this level is not permitted) 
ii) Adequate hepatic function as documented by: 
(1) Serum albumin ≥ 2.8 g/dL (SI: ≥ 28 g/L; transfusion to meet this level is not 
permitted) 
(2) Serum total bilirubin < 2 mg/dL 
(3) AST/ALT: ≤ 5.0× ULN 
iii) Prothrombin time (PT)-international normalized ratio (INR) ≤ 2.3 or PT ≤ 6 seconds 
above control. 
iv) Adequate renal function, defined as a serum creatinine < 1.5× ULN, or creatinine 
clearance (CrCl) > 40 mL/min (measured or calculated using the Cockcroft-Gault 
formula): 
Female CrCl = (140 - age in years) × weight in kg × 0.85 
72 × serum creatinine in mg/dL 
Male CrCl = (140 - age in years) × weight in kg × 1.00 
72 × serum creatinine in mg/dL 
3) Age and Reproductive Status (age ≥ 18 years or local age of majority) 
a) Female Participants 
i) Females, ages ≥ 18 years or local age of majority. 

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ii) Women who are not of childbearing potential are exempt from contraceptive 
requirements. 
iii) Women participants must have documented proof that they are not of childbearing 
potential. 
iv) Women of childbearing potential (WOCBP) must have a negative highly sensitive 
serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units 
of human chorionic gonadotropin [HCG]) within 1 day prior to the start of study 
treatment. 
(1) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the participant must be excluded from 
participation if the serum pregnancy result is positive. 
(2) An extension up to 72 hours prior to the start of study treatment is permissible in 
situations where results cannot be obtained within the standard 24-hour window. 
v) Additional requirements for pregnancy testing during and after study intervention are 
located in Section 2 (Schedule of Activities). 
vi) The Investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
vii) WOCBP must agree to follow instructions for method(s) of contraception defined in 
Appendix 4 and as described below and included in the ICF. See criterion x) (2) below 
for additional details. 
viii) 
WOCBP who are continuously not heterosexually active are exempt from 
contraceptive requirements, and still must undergo pregnancy testing as described in 
this section. 
ix) WOCBP are permitted to use hormonal contraception methods (as described in 
Appendix 4). 
x) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
(1) Is not a WOCBP 
OR 
(2) Not Applicable per Revised Protocol 01 (see new criterion (3) below): Is a 
WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of < 1% per year), preferably with low user dependency, as described in 
Appendix 4 during the intervention period and for at least 24 weeks after the last 
dose of study treatment (ie, 30 days [duration of ovulatory cycle] plus the time 
required for nivolumab and relatlimab to undergo approximately 5 half-lives) and 
agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the 
same time period. 
(3) Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of < 1% per year), preferably with low user dependency, as described 
in Appendix 4 during the intervention period and for at least 5 months after the last 
dose of study treatment (ie, 30 days [duration of ovulatory cycle] plus the time 
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agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the 
same time period. 
b) Male Participants 
i) Males, ages ≥ 18 years or local age of majority. No contraception is required for male 
participants. 
ii) Not Applicable per Revised Protocol 01: Males who are sexually active with WOCBP 
must agree to follow instructions for method(s) of contraception defined in Appendix 4 
for the duration of treatment with study treatment(s) plus 33 weeks after the last dose 
of the study treatment (ie, 90 days [duration of sperm turnover] plus the time required 
for nivolumab and relatlimab to undergo approximately 5 half-lives), and as described 
below. In addition, male participants must be willing to refrain from sperm donation 
during this time. 
iii) Not Applicable per Revised Protocol 01: Azoospermic males are not exempt from 
contraceptive requirements and will be required to always use a latex or other synthetic 
condom during any sexual activity (eg, vaginal, anal, oral) with WOCBP, even if the 
participant has undergone a successful vasectomy or if the partner is pregnant. 
iv) Not Applicable per Revised Protocol 01: Male participants will be required to always 
use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, 
oral) with WOCBP; even if the participants have undergone a successful vasectomy or 
if their partner is already pregnant or breastfeeding. Males should continue to use a 
condom during the intervention period and for at least 33 weeks after the last dose of 
study intervention. 
v) Not Applicable per Revised Protocol 01: Female partners of males participating in the 
study should be advised to use highly effective methods of contraception during the 
intervention period and for at least 33 weeks after the last dose of study intervention in 
the male participant. 
vi) Not Applicable per Revised Protocol 01: Male participants with a pregnant or 
breastfeeding partner must agree to remain abstinent from sexual activity or use a male 
condom during any sexual activity (eg, vaginal, anal, oral) even if the participants have 
undergone a successful vasectomy, during the intervention period and for at least 
33 weeks after the last dose of study intervention. 
vii) Not Applicable per Revised Protocol 01: Male participants must refrain from donating 
sperm during the intervention period and for at least 33 weeks after the last dose of 
study intervention. 
viii) 
Not Applicable per Revised Protocol 01: Breastfeeding partners should be 
advised to consult their health care providers about using appropriate highly 
effective contraception during the time the participant is required to use condoms. 
 
Investigators shall counsel WOCBP on the importance of pregnancy prevention, the implications 
of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of 
study drug to a developing fetus. 
• The Investigator shall evaluate the effectiveness of the contraceptive method in relationship to 
the first dose of study intervention. 

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• Local laws and regulations may require the use of alternative and/or additional contraception 
methods. 
6.2 
Exclusion Criteria 
1) Target Disease Exceptions 
a) Known 
fibrolamellar 
HCC, 
sarcomatoid 
HCC, 
or 
combined 
hepatocellular 
cholangiocarcinoma. 
b) Prior organ allograft or allogeneic bone marrow transplantation. 
c) Episodes of hepatic encephalopathy (≥ Grade 2) within 12 months prior to randomization. 
d) Clinically significant ascites as defined by: 
i) Not applicable per Protocol Amendment 02 (see new criterion iii) below): Prior 
ascites that required treatment and require ongoing prophylaxis, OR 
ii) Not applicable per Protocol Amendment 02: Current ascites requiring treatment. 
iii) Any prior (within 1 year) or current clinically significant ascites as measured by 
physical examination and that requires active paracentesis for control. 
e) Presence of portal hypertension with history of bleeding due to esophageal or gastric 
varices within the past 6 months prior to randomization. 
f) Not applicable per Revised Protocol 01 (see new criterion g) and h) below): Active brain 
metastases or leptomeningeal metastases. Participants with treated brain metastases are 
eligible if the following criteria are fulfilled: 
i) Not applicable per Revised Protocol 01: The brain lesions have been treated and there 
is no MRI evidence of progression for at least 4 weeks after treatment is complete and 
within 28 days prior to randomization. (If an MRI is contraindicated, a CT scan is 
acceptable after discussion with the study Medical Monitor or designee). 
ii) Not applicable per Revised Protocol 01: There is no requirement for 
immunosuppressive doses of corticosteroids (> 10 mg/day prednisone equivalents) for 
at least 2 weeks prior to study drug administration. 
iii) Not applicable per Revised Protocol 01: The case is discussed with the study Medical 
Monitor or designee. 
g) Untreated symptomatic central nervous system (CNS) metastases. Participants are eligible 
if CNS metastases are asymptomatic and do not require immediate treatment, or have been 
treated and participants have neurologically returned to baseline (except for residual signs 
or symptoms related to the CNS treatment). In addition, participants must have been either 
off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or 
equivalent) for at least 2 weeks prior to randomization. Imaging performed within 28 days 
prior to randomization must document radiographic stability of CNS lesions and be 
performed after completion of any CNS-directed therapy. 
h) Leptomeningeal metastases. 
2) Medical Conditions 
a) Women who are pregnant or breastfeeding. 

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b) Infections 
i) Active co-infection with: 
(1) Both hepatitis B and C as evidenced by detectable HBV surface antigen or HBV 
DNA and HCV RNA, OR 
(2) Hepatitis D infection in participants with hepatitis B. 
ii) Not Applicable per Revised Protocol 01 (see new criterion iv) below): Known history 
of positive test for human immunodeficiency virus (HIV) or known acquired 
immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at 
sites where mandated locally (see Appendix 7). 
iii) Active bacterial or fungal infections requiring systemic treatment within 7 days prior to 
study drug dosing. 
iv) Known human immunodeficiency virus (HIV) positive with an acquired human 
immunodeficiency syndrome (AIDS)-defining opportunistic infection within the last 
year, or a current CD4 count < 350 cells/μL. HCC participants with HIV are eligible if: 
(1) They do not have another active viral infection. 
(2) They have received antiretroviral therapy (ART) for at least 4 weeks prior to 
randomization, as clinically indicated. 
(3) They continue on ART as clinically indicated while enrolled on study. 
(4) CD4 counts and viral load are monitored per standard of care by a local health care 
provider. 
(5) NOTE: Testing for HIV must be performed at sites where mandated locally. 
HIV-positive participants must be excluded where mandated locally (refer to 
Appendix 7). 
v) Not applicable per Protocol Amendment 02 (see new criterion vii) below): Active 
SARS-CoV-2 infection. 
(1) Additionally, in the case of prior SARS-CoV-2 infection, acute symptoms must have 
resolved and based on Investigator assessment in consultation with the Medical 
Monitor, there are no sequelae that would place the participant at a higher risk of 
receiving investigational treatment (see Section 6.4.1). 
vi) Other active viral infection. 
vii) Symptomatic SARS-CoV-2 infection. 
(1) Additionally, in the case of prior SARS-CoV-2 infection, acute symptoms must 
have resolved and based on Investigator assessment in consultation with the 
Medical Monitor, there are no sequelae that would place the participant at a higher 
risk of receiving investigational treatment (see Section 6.4.1). 
c) Participants with a history of myocarditis, regardless of etiology. 
d) Interstitial lung disease that is symptomatic or may interfere with the detection and 
management of suspected drug-related pulmonary toxicity. 
e) Participants with an active, known, or suspected autoimmune disease. Participants with 
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin 
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or 
conditions not expected to recur in the absence of an external trigger are permitted to enroll. 

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f) Participants 
with 
a 
condition 
requiring 
systemic 
treatment 
with 
either 
corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive 
medications within 14 days of randomization. Inhaled or topical steroids, and adrenal 
replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the 
absence of active autoimmune disease. 
g) Not applicable per Revised Protocol 01 (see new criterion i) below): Prior malignancy 
active within the previous 3 years except for locally curable cancers that have been 
apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, 
or carcinoma in situ of the prostate, cervix, or breast. 
h) Participants with any serious or uncontrolled medical disorders that in the opinion of the 
Investigator may increase the risk associated with study participation or study drug 
administration, impair the ability of the participant to receive protocol therapy, or interfere 
with the interpretation of study results. 
i) Concurrent malignancy (present during screening) requiring treatment or history of prior 
malignancy active within 2 years prior to randomization (ie, participants with a history of 
prior malignancy are eligible if treatment was completed at least 2 years before 
randomization and the participant has no evidence of disease). Participants with history of 
prior early stage basal/squamous cell skin cancer or non-invasive or in situ cancers that 
have undergone definitive treatment at any time are also eligible. 
j) All toxicities attributed to prior anticancer therapy other than hearing loss, alopecia, and 
fatigue must have resolved to Grade 1 (National Cancer Institute [NCI] Common 
Terminology Criteria for Adverse Events [CTCAE] v5) or baseline before administration 
of study drug. 
3) Prior/Concomitant Therapy 
a) Prior treatment with relatlimab or any other LAG-3 targeted agents. 
b) Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, oncolytic 
viruses, or any other antibody or drug specifically targeting T-cell co-stimulation or 
checkpoint pathways. 
c) Participants with history of life-threatening toxicity related to prior systemic anti-cancer 
therapy, except those that are unlikely to re-occur with standard countermeasures. 
d) Radiotherapy within 4 weeks prior to start of study drug. Palliative radiotherapy for 
symptomatic control is acceptable (if completed at least 2 weeks prior to study drug 
administration) and no additional radiotherapy for the same lesion is planned. 
e) Participants who have received a live/attenuated vaccine within 30 days of 
randomization (eg, varicella, zoster, yellow fever, rotavirus, oral polio and measles, 
mumps, rubella [MMR]). 
f) Any of the following procedures or medications within 4 weeks prior to study drug 
administration: 
i) Any investigational cytotoxic drug. Exposure to any non-cytotoxic drug within 4 weeks 
or 5 half-lives (whichever is shorter) is prohibited. If 5 half-lives are shorter than 
4 weeks, agreement with Sponsor/Medical Monitor is mandatory. 
ii) Growth 
factors 
(eg, 
granulocyte-colony 
stimulating 
factor, 
granulocyte 
macrophage-colony stimulating factor, erythropoietin). 

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iii) Major surgery. 
g) Inability to comply with restrictions and prohibited treatments as listed in 
Section 7.7 (Concomitant Therapy). 
h) Not Applicable per Revised Protocol 01 (see new criterion j) below): Treatment with 
botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended 
for general health support or to treat the disease under study within 2 weeks prior to 
randomization/treatment. See Section 7.7.1 for prohibited therapies. 
i) Participants currently in other interventional trials, including those for coronavirus 
disease 2019 (COVID-19), may not participate in BMS clinical trials until the 
protocol-specific washout period is achieved. If a study participant has received an 
investigational COVID-19 vaccine prior to screening, enrollment must be delayed until the 
biologic impact of the vaccine is stabilized, as determined by discussion between the 
Investigator and the Medical Monitor. 
j) Any complementary medications (eg, herbal supplements or traditional Chinese 
medicines) intended to treat the disease under study. Such medications are permitted if they 
are used as supportive care. 
k) If participants who are currently enrolled in other BMS studies in HCC are being 
considered for enrollment in CA224073, they cannot enroll in CA224073 until the other 
BMS study has completed the analysis of the primary endpoint. 
4) Physical and Laboratory Test Findings 
a) Positive pregnancy test at enrollment or prior to administration of study medication. 
b) Participants who do not meet criteria for screening laboratory values described in 
Section 6.1 (Inclusion Criteria). 
c) 
 
 
 
 
 
 
 
 
d) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, electrocardiograms (ECGs), or clinical laboratory 
determinations beyond what is consistent with the target population. 
5) Allergies and Adverse Drug Reaction 
a) History of allergy or hypersensitivity to study drug components. 
6) Sex and Reproductive Status 
a) WOCBP who are pregnant or breastfeeding. 

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7) Other Exclusion Criteria 
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply and BMS approval is required. 
b) Participants who are compulsorily detained for treatment of either a psychiatric or 
physical (eg, infectious disease) illness. 
 
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria. 
6.3 
Lifestyle Restrictions 
Not applicable. No restrictions are required 
6.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently randomized in the study/included in the analysis population. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements, as applicable, and to respond to queries from regulatory authorities. Minimal 
information includes date of consent, demography, screen failure details, eligibility criteria, and 
any serious AEs. 
6.4.1 
Retesting During Screening Period 
Participant Re-enrollment: This study permits the re-enrollment of a participant that has 
discontinued the study as a screen failure (ie, participant has not been randomized). If re-enrolled, 
the participant must be re-consented. 
Retesting of laboratory parameters and/or other assessments within any single Screening Period 
will be permitted (in addition to any parameters that require a confirmatory value). 
The most current result prior to Randomization is the value by which study inclusion will be 
assessed, as it represents the participant’s most current, clinical state. 
Laboratory parameters and/or assessments that are included in Table 2-1 (Screening Procedural 
Outline) may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant. 
Testing for asymptomatic COVID-19, for example by reverse transcription polymerase chain 
reaction (RT-PCR) or viral antigen, is not required. However, some participants may develop 
suspected or confirmed symptomatic COVID-19 or be discovered to have asymptomatic 
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the study after meeting all inclusion/exclusion criteria related to symptomatic infection and after 
meeting the following criteria: 
• At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive RT-PCR or viral antigen test result, and 
• At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and 
• Acute symptoms (eg, cough, shortness of breath) have resolved, and 
• In the opinion of the Investigator and in consultation with the Medical Monitor or Clinical 
Scientist, there are no COVID-19-related sequelae (eg, cardiovascular) that may place the 
participant at a higher risk of receiving investigational treatment, and 
• Negative follow-up SARS-CoV-2 RT-PCR or viral antigen test based on institutional, local, 
or regional guidelines. 
 
7 
TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo or 
medical device intended to be administered to a study participant according to the study 
randomization or treatment allocation. 
Study  treatment  includes  both  Investigational  [Medicinal]  Product  (IP/IMP)  and 
Non-investigational [Medicinal] Product (Non-IP/Non-IMP) and can consist of the following: 
• Nivolumab 
• Relatlimab 
 
An IP, also known as IMP in some regions, is defined as a pharmaceutical form of an active 
substance or placebo being tested or used as a reference in a clinical study, including products 
already with a marketing authorization but used or assembled (formulated or packaged) differently 
than the authorized form, or used for an unauthorized indication, or when used to gain further 
information about the authorized form. 
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-IPs. 
IPs used in this trial are provided in Table 7-1. There are no non-IPs in this study. 

 
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Table 7-1: 
Study Treatments for CA224073 
 
Product Description/ 
Class and Dosage Form 
Potency 
IP/Non-IMP 
Blinded or 
Open Label 
Packaging/Appearance 
Storage Conditions 
(per label) 
Relatlimaba Injection 
(10 mg/mL) 
10 mg/mL 
IP 
Open-label, 4 vials per carton/ 
80 mg/vial (8 mL vial) 
Colorless to pale yellow liquid, clear 
to opalescent, light (few) particulates 
(consistent in appearance to protein 
particulates) may be present. 
Refer to the label on 
container and/or 
Pharmacy Manual. 
Nivolumaba Injection 
(10 mg/mL) 
10 mg/mL 
IP 
Open-label, 4 vials per carton/ 
100 mg/vial (10 mL vial) 
Clear to opalescent, colorless to pale 
yellow liquid. Light (few) 
particulates may be present. 
Refer to the label on 
container and/or 
Pharmacy Manual. 
Abbreviations: IMP = investigational medicinal product; IP = investigational product; mg = milligram; mL = milliliter. 
a Relatlimab is sometimes referred to as BMS-986016; Nivolumab is sometimes referred to as BMS-936558. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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7.1 
Treatments Administered 
The selection and timing of dose for each participant is provided in Table 7.1-1. 
 
Table 7.1-1: 
Treatments Administered 
 
Study 
Arm 
Study 
Treatment 
Dose 
Level 
Frequency of Administration 
and Duration of Treatment 
Route of 
Administratio 
n 
Approximate 
Infusion 
Time, minutes 
Arm A 
Nivolumab 
480 mg 
Q4W 
Until progression, unacceptable 
toxicity, or withdrawal of consent 
IV 
30 
Arm B 
Nivolumab/ 
Relatlimaba 
480 mg/ 
480 mg 
Q4W 
Until progression, unacceptable 
toxicity, or withdrawal of consent 
IV 
60 
Arm C 
Nivolumab/ 
Relatlimaba 
480 mg/ 
960 mg 
Q4W 
Until progression, unacceptable 
toxicity, or withdrawal of consent 
IV 
60b 
Abbreviations: IV = intravenous; mg = milligram; Q4W = every 4 weeks. 
a Nivolumab and relatlimab are co-administered. 
b Infusions will occur over approximately 60 minutes for participants weighing equal to or greater than 45 kg, and 
for participants weighing less than 45 kg, infusions will occur over approximately 90 minutes. 
 
7.1.1 
Relatlimab Combined with Nivolumab Dosing 
Relatlimab and nivolumab will be administered on Day 1 of each Q4W treatment cycle. For Q4W 
dosing cycles, participants may be dosed no less than 26 days from the previous dose. 
Participants should be carefully monitored for infusion reactions during administration. If an acute 
infusion reaction is noted, the participant should be managed according to Section 7.4.4. 
Participants should receive relatlimab and nivolumab until progression, unacceptable toxicity, 
withdrawal of consent/assent by the participant, or the study ends, whichever occurs first. 
There will be no dose escalations or reductions of relatlimab or nivolumab. Premedication for 
potential infusion reaction is not recommended for the first dose of either treatment. 
Doses of relatlimab or nivolumab may be interrupted, delayed, or discontinued depending on how 
well the participant tolerates the treatment. Dosing visits must not be skipped, only delayed. See 
Section 7.4 (Dosage Modification) and Section 8.1 (Discontinuation from Study Treatment). 
The relatlimab and nivolumab injections can be infused undiluted or diluted. The infusion must be 
promptly followed by a flush of diluent to clear the line. Instructions for dilution and infusion of 
relatlimab and nivolumab injections will be provided in the Pharmacy Manual. Care must be taken 
to assure sterility of the prepared solution as the product does not contain any antimicrobial 
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63F63
For details on prepared drug storage, preparation, and administration, please refer to the IBs8,36 
and/or Pharmacy Manual. The selection and timing of dose for each participant is provided in 
Table 7.1-1. 
For the 960-mg relatlimab/480-mg nivolumab dose, infusions will occur over approximately 
60 minutes for participants weighing equal to or greater than 45 kg, and for participants weighing 
less than 45 kg, infusions will occur over approximately 90 minutes. 
Study treatment will be dispensed by IRT at the study visits as listed in Section 2 (Schedule of 
Activities). 
7.1.2 
Best Supportive Care 
Recommendations for best supportive care (BSC) can be found in the European Association for 
the Study of the Liver (EASL) Clinical Practice Guidelines: Management of HCC. 64 These 
include up to 3 g/day acetaminophen (paracetamol) for management of mild pain. Nonsteroidal 
anti-inflammatory medications should be avoided in participants with cirrhosis. Pain of 
intermediate or severe intensity can be managed with opioids, with care taken to avoid 
opioid-induced constipation. 
7.1.3 
Palliative Therapy 
Palliative local therapy for clinically symptomatic tumor sites (ie, for pain, bleeding, spinal cord 
compression, brain metastasis, new or impending pathologic fracture, superior vena-cava 
syndrome, or obstruction) including palliative (limited-field) radiation and palliative surgical 
resection may be considered during trial therapy if the following criteria are met: 
• The participant is considered to have progressed at the time of palliative therapy and 
meets criteria to continue with treatment beyond progression. 
• OR 
• The lesion for palliative local therapy is a non-target lesion which has not met criteria for 
progression. 
• Tumor lesions requiring palliative local therapy should be evaluated for objective evidence of 
disease progression prior to the initiation of such therapy. The potential for overlapping 
toxicities with radiotherapy and nivolumab/nivolumab plus relatlimab currently is not known; 
however, anecdotal data suggest that radiotherapy with nivolumab is tolerable. If palliative 
radiotherapy is required, then study drugs should be withheld for at least 1 week before, during, 
and 1 week after radiation. Palliative therapy must be clearly documented in the source 
records and case report form (CRF). Details in the source records should include dates of 
treatment, anatomical site, dose administered and fractionation schedule, and AEs. 
 
7.2 
Method of Treatment Assignment 
Study treatment will be dispensed at the study visits as listed in Section 2 (Schedule of Activities). 
Before the study is initiated, each user will receive login information and instructions on how to 
access the IRT. After the participant’s ICF has been obtained and initial eligibility is established, 
the participant must be enrolled into the study by using IRT to obtain the participant number. Every 

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participant who signs the ICF must be assigned a participant number in IRT. The Investigator or 
designee will register the participant for enrollment by following the enrollment procedures 
established by BMS. All procedures will be clarified in the IRT manual. 
Study treatment will be dispensed at the study visits per the Section 2 (Schedule of Activities). 
During the screening visit, the investigative site will call into the enrollment option of the IRT 
designated by BMS for assignment of a 5-digit participant number that will be unique across all 
sites. Enrolled participants, including those not dosed, will be assigned sequential participant 
numbers starting with 
. The participant identification 
(PID) number will ultimately be comprised of the site number and participant number. For 
example, the first participant screened (ie, enrolled) at site number 1, will have a PID of 
. Once it is determined that the participant meets the eligibility criteria following the 
screening visit, the investigative site will call the IRT to assign the participant into the open dose 
level. 
Treatment assignments for eligible participants will alternate among the arms, with screened 
participants assigned to different parts through IRT. If a treatment arm becomes overly enrolled 
because of screen failures in alternate arms, it can be temporarily closed to allow enrollment in the 
other arms. Once balance is achieved, the temporary hold can be lifted. If there are no openings 
available in the part to which the participant would be assigned by this algorithm, the participant 
will be assigned to the next open part/cohort until respective dose levels or cohorts have completed 
accrual according to principles outlined in Section 5.1.2 (Treatment Period). 
Participants will not be replaced if they are discontinued from the study secondary to an AE unless 
the AE can be determined to be unrelated to treatment. 
7.3 
Blinding 
This is a randomized, Phase 2a study, that is open label to Sponsor and site. It has been determined 
that blinding is not required to meet study objectives. Blinding procedures are not applicable and 
access to treatment assignment information is unrestricted. The specific treatment to be taken by a 
participant will be assigned using IRT. The site will contact the Interactive Response system prior 
to the start of study intervention administration for each participant. The site will record the 
treatment assignment on the applicable Case Report Form (CRF). 
7.4 
Dosage Modification 
AE criteria for delaying, resuming, and discontinuing of study treatment is provided 
. 

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7.4.2 
Dose Delay Criteria 
For participants receiving nivolumab monotherapy or combination relatlimab and nivolumab, dose 
delay criteria apply for all drug-related AEs (regardless of whether the event is attributed to 
nivolumab, relatlimab, or both). Delay administration of nivolumab or both nivolumab and 
relatlimab if any of the delay criteria 
 are met. Delay nivolumab or combined 
nivolumab and relatlimab dosing for any AE, laboratory abnormality, or intercurrent illness that, 
in the judgment of the Investigator, warrants delaying the dose of study medication. 
Study treatment must also be delayed for SARS-CoV-2 infection, either confirmed or suspected. 
For participants who require delay of relatlimab or nivolumab, re-evaluate weekly, or more 
frequently if clinically indicated, and resume relatlimab or nivolumab dosing when the retreatment 
criteria are met 
. Continue tumor assessments per protocol, even if dosing is 
delayed. 
 
 
 

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7.4.4 
Management of Treatment-related Infusion Reactions 
Since relatlimab and nivolumab contain only human Ig protein sequences, they are unlikely to be 
immunogenic and induce infusion or hypersensitivity reactions; however, if such a reaction were 
to occur, it might manifest with 
. All Grade 3 or 4 
infusion reactions should be reported within 24 hours and reported as an SAE if it meets the 
criteria. 
Treatment recommendations are provided below based on CTCAE v5 and may be modified based 
on local treatment standards and guidelines, as appropriate. 

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7.5 
Preparation/Handling/Storage/Accountability 
For relatlimab and nivolumab, refer to the current version of the IBs8,36 and/or Pharmacy Manual 
for complete storage, handling, dispensing, and infusion information. 
The IP should be stored in a secure area according to local regulations. It is the responsibility of 
the Investigator to ensure that IP is only dispensed to study participants. The IP must be dispensed 
only from official study sites by authorized personnel according to local regulations. 
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. 
If concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and contact BMS immediately. 
Study treatment not supplied by BMS will be stored in accordance with the package insert. 
IP documentation (whether supplied by BMS or not) must be maintained that includes all processes 
required to ensure drug is accurately administered. This includes documentation of drug storage, 
administration, and, as applicable, storage temperatures, reconstitution, and use of required 
processes (eg, required diluents, administration sets). 

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• Further guidance and information for final disposition of unused study treatment are provided 
in Appendix 2 and the Pharmacy Manual. 
7.5.1 
Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
Not applicable. 
7.6 
Treatment Compliance 
Study treatment compliance will be periodically monitored by drug accountability. Relatlimab and 
nivolumab IV infusions will be administered to the participant in the clinical facility. Trained 
medical personnel will dispense study treatments to the participants. Drug accountability should 
be reviewed by the site study staff at each visit to confirm treatment compliance. 
7.7 
Concomitant Therapy 
Concomitant medications are recorded at baseline and throughout the treatment phase of the study 
in the appropriate section of the CRF. All medications (prescriptions or over-the-counter 
medications) continued at the start of the study or started during the study and different from the 
study treatment must be documented in the concomitant therapy section of the CRF. 
Care should be taken when using benzodiazepines in participants with advanced cirrhosis due to 
an increased risk of falls, injuries, or altered mental status. Participants should be provided with 
appropriate psychological and nutritional support.64 
The effect of COVID-19 vaccines on participants taking relatlimab and nivolumab is currently 
unknown. 
7.7.1 
Prohibited and/or Restricted Treatments 
The following medications are prohibited during the study (unless utilized to treat a drug-related 
AE): 
• Immunosuppressive agents. 
• Immunosuppressive doses of systemic corticosteroids (except as stated in Section 7.7.3 
[Permitted Therapy]). 
• Loco-regional therapies for HCC. 
• Any concurrent anti-neoplastic therapy (ie, systemic chemotherapy, hormonal therapy, 
immunotherapy, extensive, non-palliative radiation therapy, or standard or investigational 
agents for treatment of HCC). 
− Treatment with complementary medications (eg, herbal supplements or traditional Chinese 
medicines) intended to treat the disease under study. Such medications are permitted if they 
are used as supportive care. 
• Any live/attenuated vaccine (eg varicella, zoster, yellow fever, rotavirus, oral polio and 
measles, mumps, rubella [MMR]) within 30 days of initiating study treatment, during 
treatment, and until 135 days post last dose. 

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7.7.2 
Other Restrictions and Precautions 
Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg 
daily prednisone equivalent) or other immunosuppressive medications within 14 days of 
randomization are excluded. 
Participants who need anticoagulation treatment due to concomitant cardiovascular disease should 
be monitored closely; a maintenance of INR > 2 is recommended. 
7.7.2.1 
Imaging Restriction and Precautions 
It is the local imaging facility’s responsibility to determine, based on participant 
attributes (eg, allergy history, diabetic history, and renal status), the appropriate imaging modality 
and contrast regimen per imaging study. Imaging contraindications and contrast risks are to be 
considered in this assessment. Participants with renal insufficiency are to be assessed as to whether 
or not they should receive contrast and, if so, which contrast agent and dose is appropriate. Specific 
to MRI, participants with severe renal insufficiency (ie, eGFR < 30 mL/min/1.73 m2) are at 
increased risk of nephrogenic systemic fibrosis; therefore, MRI contrast is contraindicated. 
In addition, participants may be excluded from MRI if they have tattoos, metallic implants, 
pacemakers, etc. This will be outlined in the image manual. Site-specific imaging requirements 
that are different than those captured in the imaging manual may be considered after discussion 
with the BMS Medical Monitor or Clinical Scientist. 
Gentle hydration before and after IV contrast should follow local standard of care. The ultimate 
decision to perform MRI in an individual participant in this study rests with the site radiologist, 
the Investigator, and standards set by the local Ethics Committee. 
7.7.3 
Permitted Therapy 
Participants are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses > 10 mg 
daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for 
prophylaxis  (eg,  contrast  dye  allergy)  or  for  treatment  of  non-autoimmune 
conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted. 
7.7.4 
Antiviral Therapy 
Participants on antiviral therapy for hepatitis B or C should continue the treatment during the study. 
Changing of dosage and regimens of antiviral therapy will be at the discretion of the Investigator. 
If a participant has a > 1 log IU/mL increase in HBV DNA, then virologic breakthrough should be 
considered and HBV DNA confirmed. Adherence to current antiviral therapy should be assessed, 
and resistance testing performed according to local practices. If a participant has documented 
virologic breakthrough due to antiviral resistance, then this should be managed based on 
standardized regional guidelines and treatment with relatlimab and nivolumab temporarily held. 
The participant may resume treatment with relatlimab and nivolumab or nivolumab (monotherapy 
phase) once virologic control is reestablished (HBV DNA < 500 IU/mL). 

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For any participant who continues to be HCV RNA positive after receiving relatlimab plus 
nivolumab, current guidelines for management of chronic HCV infection, including those from 
American Association for the Study of Liver Disease (AASLD), EASL, or Asian Pacific 
Association for the Study of the Liver (APASL) may be consulted. Initiation of direct-acting 
antivirals (DAAs) for HCV is allowed at the discretion of the Investigator after discussion with 
the BMS Medical Monitor or Clinical Scientist. 
7.8 
Treatment After the End of the Study 
At the conclusion of the study, participants who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study treatment specified in protocol Section 7.1. Study treatment 
will be provided via an extension of the study, a rollover study requiring approval by responsible 
health authority and Ethics Committee, or through another mechanism at the discretion of BMS. 
BMS reserves the right to terminate access to BMS-supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986016 is 
terminated for other reasons, including but not limited to lack of efficacy and/or not meeting the 
study objectives; c) the participant can obtain medication from a government sponsored or private 
health program. In all cases, BMS will follow local regulations. 
8 
DISCONTINUATION CRITERIA 
8.1 
Discontinuation from Study Treatment 
Participants MUST discontinue IP (and non-IP product at the discretion of the Investigator) for 
any of the following reasons: 
• Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information. 
• Any clinical AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
Investigator, indicates that continued participation in the study is not in the best interest of the 
participant. 
• Termination of the study by BMS. 
• Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply and 
BMS approval is required.) 
• Documented radiographic disease progression per RECIST v1.1, unless the participant meets 
criteria for treatment beyond progression (Section 8.1.2). 
 
Refer to the Section 2 (Schedule of Activities) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that can be completed. 

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In the case of pregnancy, the Investigator must immediately, within 24 hours of awareness of the 
pregnancy, notify the BMS Medical Monitor/Clinical Scientist of this event. In most cases (all 
cases in Czech Republic, Argentina, or other countries where it is required), the study treatment 
will be permanently discontinued in an appropriate manner (eg, dose tapering if necessary for 
participant safety). Refer to Section 9.2.5 (Pregnancy). 
All participants who discontinue study treatment should comply with protocol specified follow-up 
procedures as outlined in Section 2 (Schedule of Activities). The only exception to this requirement 
is when a participant withdraws consent for all study procedures including post-treatment study 
follow-up or loses the ability to consent freely (ie, is imprisoned or involuntarily incarcerated for 
the treatment of either a psychiatric or physical illness). 
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page. 
8.1.1 
Relatlimab and Nivolumab Treatment Discontinuation 
If a participant in any of the nivolumab/relatlimab combination arms meets criteria for 
discontinuation 
, the participant must discontinue both nivolumab and relatlimab 
and be taken off the treatment phase of the study. 
Both nivolumab and relatlimab treatment must be permanently discontinued per criteria 
in Section 7.4 (Dosage Modification). Discontinue nivolumab (Arm A) or both nivolumab 
and relatlimab (Arm B or Arm C) for any AE, laboratory abnormality, or intercurrent illness that, 
in the judgment of the Investigator, presents a substantial clinical risk to the participant with 
continued nivolumab dosing. 
Study treatment must also be permanently discontinued for the following: 
 
• Tumor assessments should continue as per protocol even if dosing is delayed. Periodic study 
visits to assess safety and laboratory studies should also continue every 6 weeks or more 
frequently if clinically indicated during such dosing delays. 
 
8.1.2 
Treatment Beyond Disease Progression 
Accumulating evidence indicates a minority of participants treated with immunotherapy may 
derive clinical benefit despite initial evidence of progressive disease.43 

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Participants treated with study therapy in any arm will be permitted to continue treatment beyond 
initial RECIST v1.1-defined progressive disease, assessed by the Investigator, as long as they meet 
the following criteria: 
• Investigator-assessed clinical benefit. 
• Tolerance of study treatment. 
• Stable performance status. 
• Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, CNS metastases). 
• Participant provides written informed consent prior to receiving additional treatment. All other 
elements of the main consent including description of reasonably foreseeable risks or 
discomforts, or other alternative treatment options will still apply. 
 
Radiographic assessment/scan(s) should continue in accordance with the Section 2 (Schedule of 
Activities) for the duration of the treatment beyond progression and should be submitted to the 
central imaging vendor. 
If the Investigator feels that the participant continues to achieve clinical benefit by continuing 
treatment, the participant should remain on the trial and continue to receive monitoring according 
to Section 2 (Schedule of Activities). 
For the participants who continue study therapy beyond progression, further progression is defined 
as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time 
of initial progressive disease. This includes an increase in the sum of diameters of all target lesions 
and/or the diameters of new measurable lesions compared to the time of initial progressive disease. 
Treatment should be discontinued permanently upon documentation of further progression. 
New lesions are considered measureable at the time of initial progression if the longest diameter 
is at least 10 mm (except for pathological lymph nodes which must have a short axis of at least 
15 mm). Any new lesion considered non-measureable at the time of initial progression may 
become measureable and therefore included in the tumor burden if the longest diameter increases 
to at least 10 mm (except for pathological lymph nodes which must have a short axis of at least 
15 mm). In situations where the relative increase in total tumor burden by 10% is solely due to 
inclusion of new lesions which become measurable, these new lesions must demonstrate an 
absolute increase of at least 5 mm. 
8.1.3 
Criteria to Resume Treatment 
 
 
Continue tumor assessments per protocol even 
if dosing is delayed. Continue periodic study visits to assess safety and laboratory studies every 6 
weeks or more frequently if clinically indicated during such dosing delays. 

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When criteria to resume treatment are met, resume nivolumab and relatlimab on the same day for 
participants receiving combination therapy or resume nivolumab in participants receiving 
monotherapy. 
Participants may also resume treatment with study drug under the following criteria: 
 
• Participants with SARS-CoV-2 infection (either confirmed or suspected) may resume 
treatment after all of the following: 1) at least 10 days (20 days for severe/critical illness) have 
passed since symptoms first appeared or positive test result (eg, RT-PCR or viral antigen); 
2) resolution of acute symptoms (including at least 24 hours has passed since last fever without 
fever-reducing medications); 3) evaluation by the Investigator with confirmation that there are 
no sequelae that would place the participant at a higher risk of receiving investigational 
treatment; and 4) consultation by the Medical Monitor. For suspected cases, treatment may 
also resume if SARS-CoV-2 infection is ruled out and other criteria to resume treatment are 
met. 
 
 

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8.1.4 
Post Study Treatment Study Follow-up 
In this study, OS is a key endpoint of the study. Post study follow-up is of critical importance and 
is essential to preserving participant safety and the integrity of the study. Participants who 
discontinue study treatment must continue to be followed (in this study or a rollover study) for 
collection of outcome and/or survival follow-up data as required and in line with Section 5 (Study 
Design) until death or the conclusion of the study. 
BMS may request that survival data be collected on all treated/randomized participants outside of 
the protocol-defined window. At the time of this request, each participant will be contacted to 
determine their survival status, unless the participant has withdrawn consent for all contacts or is 
lost to follow-up. 
8.2 
Discontinuation from the Study 
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol-specified follow-up procedures. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 
• Participants should notify the Investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible. 
• The withdrawal of consent should be explained in detail in the medical records by the 
Investigator, as to whether the withdrawal is from further treatment with study treatment only 
or also from study procedures and/or post treatment study follow-up, and entered on the 
appropriate CRF page. 
• In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law. 
• If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
 
8.3 
Lost to Follow-Up 
• All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant. 
• Lost to follow-up is defined by the inability to reach the participant after a minimum of three 
documented phone calls, faxes, or emails, as well as lack of response by participant to one 
registered mail letter. All attempts should be documented in the participant’s medical records. 
• If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death. 
• If Investigator’s use of a third-party representative to assist in the follow-up portion of the 
study has been included in the participant’s informed consent, then the Investigator may use a 

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the 
. 
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Sponsor-retained third-party representative to assist site staff with obtaining participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 
• The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information. 
• If after all attempts, the participant remains lost to follow-up, then the last known alive date as 
determined by the Investigator should be reported and documented in the participant’s medical 
records. 
 
9 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and timing are summarized in Section 2 (Schedule of Activities). 
• Protocol waivers or exemptions are not allowed. 
• All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment. 
• Adherence to the study design requirements, including those specified in Section 2 (Schedule 
of Activities), is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before randomization. The Investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes, provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in Section 2 (Schedule of Activities). 
 
Additional measures, including non-study required laboratory tests, should be performed as 
clinically indicated or to comply with local regulations. Laboratory toxicities (eg, suspected 
drug-induced liver enzyme evaluations) will be monitored during the follow-up phase via 
onsite/local labs until all study drug-related toxicities resolve, return to baseline, or are deemed 
irreversible. 
If a participant shows pulmonary-related signs (hypoxia, fever) or symptoms (eg, dyspnea, cough, 
fever) consistent with possible pulmonary AEs, the participant should be immediately evaluated 
to rule out pulmonary toxicity, according to 
 
Some of the assessments referred to in this section may not be captured as data in the CRF. They 
are intended to be used as safety monitoring by the treating physician. Additional testing or 

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assessments may be performed as clinically necessary or where required by institutional or local 
regulations. 
9.1 
Efficacy Assessments 
9.1.1 
Imaging Assessment for the Study 
Images will be submitted to a central imaging vendor for BICR during the study. Prior to scanning 
the first participant, sites should be qualified and understand the image acquisition guidelines and 
submission process as outlined in the Imaging Manual provided by the central imaging vendor. 
Screening and on study images should be acquired as outlined in Section 2 (Schedule of 
Activities). 
Tumor assessments at other time points may be performed if clinically indicated and should be 
submitted to the central imaging vendor as soon as possible. Unscheduled CT/MRI should be 
submitted to central imaging vendor. X-rays and bone scans that clearly demonstrate interval 
progression of disease, for example, most commonly as unequivocal lesions that are unmistakably 
new since the prior CT/MRI, should be submitted to central imaging vendor. Otherwise, they do 
not need to be submitted centrally. 
9.1.1.1 
Methods of Measurement 
Contrast-enhanced CT of the chest, CT or MRI of abdomen and pelvis (including required 
tri-phasic CT or MRI of the liver), and all other known and/or suspected sites of disease should be 
performed for tumor assessments. Images should be acquired with slice thickness of 5 mm or less 
with no intervening gap (contiguous). Every attempt should be made to image each participant 
using an identical acquisition protocol on the same scanner for all imaging time points. Tumor 
measurements should be made by the same Investigator or radiologist for each assessment, 
whenever possible. Change in tumor measurements and tumor response to guide ongoing study 
treatment decisions will be assessed by the Investigator using the RECIST v1.1 criteria. 
If a participant has a contraindication for CT IV contrast, then a non-contrast CT of the chest and 
a contrast-enhanced MRI of the, abdomen, pelvis (including required tri phasic CT or MRI of the 
liver), and other known/suspected sites of disease should be obtained. 
Bone scan or positron emission tomography (PET) scan are not adequate for assessment of 
RECIST v1.1 response in target lesions. In selected circumstances where such modalities are the 
sole modality used to assess certain non-target organs, those non-target organs may be evaluated 
less frequently. For example, bone scans may need to be repeated only when CR is identified in 
target disease or when progression in bone is suspected. 
MRI of brain should be acquired as outlined in Section 2 (Schedule of Activities). CT of the 
brain (without and with contrast) can be performed if MRI is contraindicated. 
Use of CT component of a PET-CT scanner: Combined modality scanning, such as with 
PET-CT, is increasingly used in clinical care, and is a modality/technology that is in rapid 
evolution; therefore, the recommendations outlined here may change rather quickly with time. At 
present, low dose or attenuation correction CT portions of a combined PET-CT are of limited use 

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in anatomically-based efficacy assessments and it is therefore suggested that they should not be 
substituted for dedicated diagnostic contrast-enhanced CT scans for anatomically-based 
RECIST v1.1 measurements. However, if a site can document that the CT performed as part of a 
PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then the 
CT portion of the PET-CT can be used for RECIST v1.1 measurements. Note, however, that the 
PET portion of the CT introduces additional data which may bias an Investigator if it is not 
routinely or serially performed. 
Bone scans may be collected per local standards, as clinically indicated. 
9.1.1.2 
Imaging and Clinical Assessment 
Tumor assessments should continue on the protocol-defined imaging schedule, regardless if dosing 
is delayed or discontinued. Changes in tumor measurements and tumor responses will be assessed 
by the same Investigator or designee using RECIST v1.1 criteria. Investigators will report the 
number and size of new lesions that appear while on study. The time point of tumor assessments 
will be reported on the CRF based on the Investigator’s assessment using RECIST v1.1 criteria 
(See Appendix 9 for specifics of RECIST v1.1 criteria to be used in this study). Assessments of 
 
Imaging should continue as per schedule until treatment stop (including treatment beyond 
progressive disease) or start of subsequent systemic therapy, whichever is later. 
PR and CR must be confirmed at least 4 weeks (28 days) after initial response. 

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9.2 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 

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The Investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study. 
IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component 
for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. 
IMAEs can include events with an alternate etiology which were exacerbated by the induction of 
autoimmunity. Information supporting the assessment will be collected on the participant’s CRF. 
Contacts for SAE reporting specified in Appendix 3. 
9.2.1 
Time Period and Frequency for Collecting AE and SAE Information 
The collection of non-serious AE information (with the exception of non-serious AEs related to 
SARS-CoV-2 infection) should begin at initiation of study treatment until the time points specified 
in the Section 2 (Schedule of Activities). See Section 9.2.3 for additional details on Follow-up. 
• All SAEs, and all AEs (SAEs and non-serious AEs) associated with confirmed or suspected 
SARS-CoV-2 infection, must be collected from the date of the participant’s written consent 
until 135 days following discontinuation of dosing. 
• All SAEs must be collected from the time of signing the consent, including those thought to 
be associated with protocol-specified procedures and within 135 days of discontinuation of 
dosing, except in cases where a study participant has started a new anti-neoplastic therapy. 
However, any SAE occurring after the start of a new treatment that is suspected to be related 
to study treatment by the Investigator will be reported, and any deaths occurring within the 
135-day follow-up period must be reported regardless of initiation of new anti-neoplastic 
therapy. 
− For participants assigned to treatment and never treated with study drug, SAEs should be 
collected for 30 days from the date of treatment assignment. 
• The Investigator must report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure (eg, a follow-up skin biopsy). 
• Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the CRF module. 
• All SAEs will be recorded and reported to Sponsor or designee within 24 hours of site 
awareness, as indicated in Appendix 3. 
• The Investigator will submit any updated SAE data to the Sponsor or designee within 24 hours 
of updated information being available. 
 
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the Investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the Investigator must promptly notify the Sponsor. 
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3. 

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9.2.2 
Method of Detecting AEs and SAEs 
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
AEs, when appropriate for the program or protocol. 
Every AE must be assessed by the Investigator with regard to whether it is considered 
immune-mediated. For events which are potentially immune-mediated, additional information will 
be collected on the participant’s CRF. 
All non-serious AEs (not only those deemed to be treatment-related) should be collected 
continuously during the treatment period and for a minimum of 135 days following discontinuation 
of study treatment. 
9.2.3 
Follow-up of AEs and SAEs 
• Non-serious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3). 
• Follow-up is also required for non-serious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study treatment, as appropriate. 
• All identified non-serious AEs must be recorded and described on the non-serious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study. 
 
After the initial AE/SAE report, the Investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs, non-serious AEs of special interest (as defined in 
Section 9.2), and AEs (SAEs and non-serious AEs) associated with confirmed or suspected 
SARS-CoV-2 infection will be followed until resolution, until the condition stabilizes, until the 
event is otherwise explained, the event is deemed irreversible, or until the participant is lost to 
follow-up (as defined in Section 8.3), or for suspected cases, until SARS-CoV-2 infection is ruled 
out. 
Further information on follow-up procedures is given in Appendix 3. 
9.2.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
product under clinical investigation are met. 
• An Investigator who receives an Investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements. 
The Sponsor or designee will be reporting AEs to regulatory authorities and Ethics Committees 
according to local applicable laws, including European Directive 2001/20/EC and FDA Code of 
Federal Regulations 21 CFR Parts 312 and 320. A suspected, unexpected serious adverse 

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reaction (SUSAR) is a subset of SAEs and will be reported to the appropriate regulatory authorities 
and Investigators following local and global guidelines and requirements. 
9.2.5 
Pregnancy 
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least for 
5 half-lives (5 months) after study product administration, the Investigator must immediately 
notify the BMS Medical Monitor/Clinical Scientist of this event and complete and forward a 
Pregnancy Surveillance Form to the BMS designee within 24 hours of awareness of the event and 
in accordance with SAE reporting procedures described in Appendix 3. 
If the Investigator determines a possible favorable benefit/risk ratio that warrants continuation of 
study treatment, or re-initiation of study treatment, a discussion between the Investigator and the 
BMS Medical Monitor/Clinical Scientist must occur. In the Czech Republic and Argentina (or 
other countries where it is required), all pregnancies will require the participant to discontinue 
treatment. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form. 
9.2.6 
Laboratory Test Result Abnormalities 
The following laboratory test result abnormalities should be captured on the non-serious AE CRF 
page or SAE Report Form electronic, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning. 
• Any laboratory test result that is clinically significant or meets the definition of an SAE 
• Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted 
• Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy 
 
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting Investigator (eg, anemia vs low hemoglobin value). 
9.2.7 
Potential Drug Induced Liver Injury (DILI) 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI (p-DILI) event. All occurrences of p-DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section 9.2 and Appendix 3 for reporting 
details). 
 

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9.2.8 
Other Safety Considerations 
Any significant worsening noted during interim or final physical examinations, electrocardiogram, 
x-ray filming, any other potential safety assessment required or not required by protocol should 
also be recorded as a non-serious AE or SAE, as appropriate, and reported accordingly. 

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9.3 
Overdose 
For this study, any dose of relatlimab or nivolumab greater than the protocol-specified dose will 
be considered an overdose. 
• In the event of an overdose, the Investigator should do the following: 
− Contact the Medical Monitor immediately. 
− Closely monitor the participant for AEs/SAEs and laboratory abnormalities. 
− Document the quantity of the excess dose as well as the duration of the overdosing in the 
CRF. 
 
9.4 
Safety 
Planned time points for all safety assessments are listed in Section 2 (Schedule of Activities). 
Safety assessments include AEs, physical examinations, vital signs, performance status, 
assessment of signs and symptoms, laboratory tests, and pregnancy tests as outlined in 
Section 2 (Schedule of Activities). 
9.4.1 
Physical Examinations 
Refer to Section 2 (Schedule of Activities). 
9.4.2 
Vital signs 
Refer to Section 2 (Schedule of Activities). 
9.4.3 
Electrocardiograms 
Refer to Section 2 (Schedule of Activities). 
9.4.4 
Clinical Safety Laboratory Assessments 
Laboratory assessments are listed in Table 9.4.4-1. 
Investigators must document their review of each laboratory safety report. 
All clinical safety laboratory assessments will be performed locally per Section 2 (Schedule of 
Activities). 

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Hematology - Complete Blood Count (CBC) 
Hemoglobin 
Hematocrit 
Total leukocyte count, including differential 
Platelet count 
Chemistry 
Amylase 
Alpha-fetoprotein (AFP) 
Lactate dehydrogenase (LDH) 
Lipase 
Creatinine 
Blood urea nitrogen (BUN)/serum urea 
Glucose 
Liver laboratory tests: 
Aspartate aminotransferase (AST) 
Alanine aminotransferase (ALT) 
Alkaline phosphatase (ALP) 
Total bilirubin (T.bili) 
Direct bilirubin 
Albumin 
 
 
 
 
 
 
 
 
Total protein 
Sodium 
Potassium 
Chloride 
Calcium 
Phosphorus 
Magnesium 
TSH, free T3 and free T4 - screening; if free T3 is not 
available, total T3 is acceptable 
TSH, with reflexive free T3 and free T4 if TSH is 
abnormal - on treatment 
Creatinine clearance (CrCl) - if used, at screening only 
 
 
 
 
 
 
 
 
Urinalysis 
Protein 
Glucose 
Blood 
Leukocyte esterase 
Specific gravity 
pH 
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive on the dipstick 
Serology 
Hepatitis C antibody (if Hepatitis C antibody is positive reflex to hepatitis C RNA), hepatitis C RNA viral load 
(PCR), hepatitis B surface antigen (if hepatitis B surface antigen is positive reflex to hepatitis D), hepatitis B 
surface antibody, hepatitis B core antibody, hepatitis B DNA viral load (PCR), HIV-1 and -2 antibody (screening 
only; testing for HIV must be performed at sites where mandated by local requirements [see Appendix 7]). 

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Other Analyses 
Pregnancy test, serum or urine (WOCBP only; minimum sensitivity 25 IU/L or equivalent units of human 
chorionic gonadotropin (HCG); screening, predose, safety follow-up 
Follicle stimulating hormone (FSH) screening -only required to confirm menopause in women < age 55) 
Coagulation profile (INR or PT, and aPTT) 
SARS-CoV-2 viral test 
Abbreviations: aPTT = activated partial thromboplastin time; HIV = human immunodeficiency virus; 
INR = international normalized ratio; PT = prothrombin time; RNA = ribonucleic acid; T3 = triiodothyronine; 
T4 = thyroxine; TSH = thyroid stimulating hormone; WOCBP = women of child bearing potential. 
 
9.4.5 
Imaging Safety Assessment 
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the study Investigator as per standard 
medical/clinical judgment. 

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9.8.2 
Tumor Samples 
Tumor biopsy specimens will be obtained as stated in Table 2-1. 
 
9.8.2.1 
Tumor Sample Collection 
The Investigator, in consultation with the radiology staff, must determine the degree of risk 
associated with the procedure and find it acceptable. Biopsies may be done with local anesthesia 
or conscious sedation. Institutional guidelines for the safe performance of biopsies should be 
followed. Excisional biopsies may be performed to obtain tumor biopsy samples. Invasive 
procedures that require general anesthesia should not be performed to obtain a biopsy specimen; 
however, if a surgical procedure is performed for a clinical indication, excess tumor tissue may be 
used for research purposes with the consent of the participant. Detailed instructions of the 
obtaining, processing, labeling, handling, storing, and shipping of specimens will be provided in a 
separate Laboratory Manual. 
9.8.2.2 
LAG-3 and PD-L1 Expression 
Entry to this study requires assessment for LAG-3 expression in tumor specimens. LAG-3 
expression on immune cells and PD-L1 expression on tumor and immune cells will be measured 

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using analytically validated immunohistochemical assays. LAG-3 status, as determined using a 
threshold, will be stratification criteria for randomization. 
 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.8.4 
Additional Research Collection 
This protocol will include residual sample storage for additional research (AR). 
For All US sites: 

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AR is required for all study participants, except where prohibited by IRBs/Ethics Committees, or 
academic/institutional requirements. Where one or more of these exceptions occurs, participation 
in the AR should be encouraged but will not be a condition of overall study participation. 
• If the IRB/Ethics Committees and site agree to the mandatory AR retention and/or collection, 
then the study participant must agree to the mandatory AR as a requirement for inclusion in 
the study. 
• If optional participation is permitted and approved, then the study participants may opt out of 
the AR retention and/or collection. 
 
For non-US Sites 
AR is optional for all study participants, except where retention and/or collection is prohibited by 
local laws or regulations, Ethics Committees, or institutional requirements. 
This collection for AR is intended to expand the translational research and development (R&D) 
capability at BMS, and will support as yet undefined research aims that will advance our 
understanding of disease and options for treatment. It may also be used to support health authority 
requests for analysis, and advancement of pharmacodiagnostic development to better target drugs 
to the right patients. This may also include genetic/genomic exploration aimed at exploring disease 
pathways, progression and response to treatment etc. 
Note: Additional Research collection and analysis will not occur 
as per Protocol 
Amendment 04. 
Sample Collection and Storage 
All requests for access to samples or data for AR will be vetted through a diverse committee of the 
study Sponsor’s senior leaders in R&D (or designee) to ensure the research supports appropriate 
and well-defined scientific research activities. 
 
 
 
Samples kept for future research will be stored at the BMS Biorepository in 
or 
an independent, BMS-approved storage vendor. 
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than fifteen (15) 
years after the end of the study or the maximum allowed by applicable law. 
Transfers of samples by research Sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures. 
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual. 

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Further details of sample collection and processing will be provided to the site in the procedure 
manual. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.8.6 
Other Assessments 
 
9.9 
Health Economics OR Medical Resource Utilization and Health 
Economics 
Health care resource utilization data will not be collected in this study. 
10 
STATISTICAL CONSIDERATIONS 
 
Serum will be collected for potential future measurements 
. 

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10.2 
Populations for Analyses 
For purposes of analysis, populations for primary and secondary objectives are defined in Table 
Table 10.2-1: 
Populations for Analyses 
 
Population 
Description 
Enrolled 
All participants who sign informed consent and obtain a participant number. 
Randomized 
All participants who are randomized. 
Randomized LAG-3+ 
All participants who are randomized and have LAG-3+ status. 
Treated 
All participants who take at least 1 dose of any study treatment. 
Treated LAG-3+ 
All participants who take at least 1 dose of any study treatment and is LAG-3+. 
Abbreviations: + = positive; LAG-3 = lymphocyte activation gene 3. 
 
10.3 
Statistical Analyses 
The SAP will be developed and finalized before database lock and will describe the selection of 
participants to be included in the analyses, and procedures for accounting for missing, unused, and 
spurious data. Below is a summary of planned statistical analyses of the primary and secondary 
endpoints. 
A description of the participant population will be included in a statistical output report, including 
subgroups of age, gender and race. 
10.3.1 
Efficacy Analyses 
Efficacy Analyses are described in Table 10.3.1-1 and will be performed on the randomized 
population. If Arm C is closed or dropped and number of participants randomized in Arm C is 
small, the primary efficacy comparison will be performed between Arm B vs Arm A and the 
efficacy analysis in Arm C will be descriptive. 
10.2-1. 

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Table 10.3.1-1: 
Efficacy Analyses 
 
Endpoint 
Statistical Analysis Methods 
Primary 
The difference in ORR between relatlimab in combination with nivolumab (Arm B) vs 
nivolumab (Arm A) will be presented by BICR using RECIST v1.1 computed using a simple 
proportion and 95% Clopper-Pearson confidence interval for this study. In addition, posterior 
probability of the true difference of ORR assessed by BICR using RECIST v1.1 to fall in the 
activity interval given the data will be provided. Also, the posterior mean of the difference of 
ORR between the two arms and the corresponding 90% credible intervals will also be provided. 
The efficacy analysis in Arm C will be descriptive. 
Secondary 
ORR assessed by Investigator and DCR will be computed and analyzed using frequency 
statistics. 
DOR, PFS, and OS will be analyzed using the Kaplan-Meier method. 
Abbreviations: BICR = Blinded Independent Central Review; DCR = disease control rate; DOR = duration of 
response; LAG-3 = lymphocyte activation gene 3; OS = overall survival; PFS = progression-free survival; 
ORR = objective response rate; RECIST = Response Evaluation Criteria in Solid Tumors. 
 
10.3.2 
Safety Analyses 
All safety analyses described in Table 10.3.2-1 will be performed on the treated population. 
Table 10.3.2-1: 
Safety Analyses 
 
Endpoint 
Statistical Analysis Methods 
Primary 
Not applicable. 
Secondary 
Incidence of AEs, SAEs, AEs leading to discontinuation, death, and laboratory abnormalities 
will be analyzed using frequency statistics. 
Abbreviations: AE = adverse event; IMAE = immune-mediated adverse event; SAE = serious adverse event. 

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10.3.4 
Interim Analyses 
 
 
 
 
 
 
 
 
10.3.4.2 
Bayesian Continuous Monitoring for Safety 
A Bayesian continuous monitoring framework71F 71F72 will be utilized to detect safety signals that occur 
during the study that may lead to termination of Arm B or Arm C. 
. 

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These boundaries can be applied in a continuous basis (does not require the exact number of 
participants 
) and is intended to assist on the recommendation to the 
BMS SC for clinical interpretation. Other parameters may be considered, and other posterior 
probabilities and boundaries may be calculated, as deemed appropriate by the SC, without 
amending the protocol. 
The SAP will further describe the planned interim analyses. 

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72 Thall PF, Simon R. Practical Bayesian guidelines for phase IIB clinical trials. Biometrics 1994 
Jun;50(2):337-349. 

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12 
APPENDICES 

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APPENDIX 1 
ABBREVIATIONS AND TRADEMARKS 
 
Term 
Definition 
− 
negative 
+ 
positive 
°C 
degrees Celsius 
µg 
microgram 
µL 
microliter 
1L 
first line 
2D 
2-dimensional 
2L 
second line 
3L 
third line 
AASLD 
American Association for the Study of Liver Disease 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
AFP 
alpha-fetoprotein 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
APASL 
Asian Pacific Association for the Study of the Liver 
aPTT 
activated partial thromboplastin time 
AR 
additional research 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase 
BCLC 
Barcelona Clinic Liver Cancer 
Bcl-xL 
B-cell lymphoma-extra large 
BIC 
Bayesian information criterion 
BICR 
blinded independent central review 
BMI 
body mass index 
BMS 
Bristol Myers Squibb 

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Term 
Definition 
BP 
blood pressure 
BSC 
best supportive care 
BTLA 
B- and T-lymphocyte attenuator 
BUN 
blood urea nitrogen 
Cavg 
average concentration 
CBC 
complete blood count 
CD 
cluster of differentiation 
CFR 
Code of Federal Regulations 
cHL 
classical Hodgkin lymphoma 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
clearance 
CLss 
steady-state clearance 
Cmax 
maximum concentration 
Cmaxss 
steady-state maximum concentration 
CMV 
cytomegalovirus 
CNS 
central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CrCl 
creatinine clearance 
CRF 
case report form, paper or electronic 
CRO 
contract research organization 
CSR 
clinical study report 
CT 
computed tomography 
CTAg 
clinical trial agreement 
CTCAE 
Common Terminology Criteria for Adverse Events 

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Term 
Definition 
CTLA-4 
cytotoxic T-lymphocyte-associated protein-4 
CV 
coefficient of variation 
D 
day 
DAA 
direct-acting antiviral 
DCR 
disease control rate 
DFS 
disease-free survival 
DILI 
drug-induced liver injury 
dL 
deciliter 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
E-R 
exposure-response 
EASL 
European Association for the Study of the Liver 
EC50 
half-maximal effective concentration 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
eg 
exempli gratia (for example) 
eGFR 
estimated glomerular filtration rate 
EHR 
electronic health record 
EHS 
extrahepatic spreading 
EMR 
electronic medical record 
EOT 
end of treatment 
E-R 
exposure-response 
etc 
et cetera 

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Term 
Definition 
EUDRACT 
European Union Drug Regulating Authorities Clinical Trials Database 
FDA 
Food and Drug Administration 
FDC 
fixed-dose combination 
FFPE 
formalin-fixed, paraffin-embedded 
FGL-1 
fibrinogen-like protein 1 
FSH 
follicle-stimulating hormone 
FU 
follow-up 
g 
gram 
GC 
gastric cancer 
GCP 
Good Clinical Practice 
GFR 
glomerular filtration rate 
h 
hour 
H&E 
hematoxylin and eosin 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCC 
hepatocellular carcinoma 
HCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
Hep B 
hepatitis B 
Hep C 
hepatitis C 

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Term 
Definition 
Hep D 
hepatitis D 
HIFU 
high-intensity focused ultrasound 
HIV 
human immunodeficiency virus 
HR 
hazard ratio 
IB 
Investigator’s Brochure 
IC50 
half-maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
ICOS 
inducible T cell co-stimulator 
ie 
id est (that is) 
IEC 
Independent Ethics Committee 
IFN-γ 
interferon-γ 
Ig 
immunoglobulin 
IgG 
immunoglobulin G 
IgG4 
immunoglobulin G4 
IHC 
immunohistochemistry 
IL 
interleukin 
IMAE 
immune-mediated adverse event 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IO 
immuno-oncology 
IP 
investigational product 
Ipi 
ipilimumab 
IRB 
Institutional Review Board 
IRT 
interactive response technology 

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Term 
Definition 
ITT 
intent-to-treat 
IU 
international unit 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
IV 
intravenous 
kg 
kilogram 
Kd 
dissociation constant 
L 
liter 
LAG-3 
lymphocyte activation gene 3 
LDH 
lactate dehydrogenase 
LFT 
liver function test 
LVEF 
left ventricular ejection fraction 
m2 
meters squared 
mg 
milligram 
MG 
myasthenia gravis 
MHC 
major histocompatibility complex 
mL 
milliliter 
MLR 
mixed lymphocyte reaction 
MMR 
measles, mumps, rubella 
mOS 
median overall survival 
mPFS 
median progression-free survival 
mRECIST 
modified Response Evaluation Criteria in Solid Tumors 
MRI 
magnetic resonance imaging 
msec 
millisecond 
MUGA 
multiple-gated acquisition 

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Term 
Definition 
MVI 
macrovascular invasion 
N 
number of subjects or observations 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NE 
not estimable 
ng 
nanogram 
Nivo 
nivolumab 
nM 
nanomolar 
NR 
not reached 
NSCLC 
non-small cell lung cancer 
O2 
oxygen 
ORR 
objective response rate 
OS 
overall survival 
PAI 
percutaneous acetic acid injection 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PD-1 
programmed cell death-1 
PD-1+ 
programmed cell death-1-positive 
p-DILI 
potential drug-induced liver injury 
PD-L1 
programmed death-ligand 1 
PD-L2 
programmed death-ligand 2 
PE 
physical examination 
PEI 
percutaneous ethanol injection 
PET 
positron emission tomography 
PFS 
progression-free survival 
PFS2 
progression-free survival 2 

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Term 
Definition 
PID 
participant identification 
PK 
pharmacokinetic 
PPK 
population pharmacokinetics 
PR 
partial response 
PT 
prothrombin time 
Q2W 
every 2 weeks 
Q3W 
every 3 weeks 
Q4W 
every 4 weeks 
Q6W 
every 6 weeks 
Q12W 
every 12 weeks 
R&D 
research and development 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
Rela 
relatlimab 
RFA 
radiofrequency ablation 
RNA 
ribonucleic acid 
RT-PCR 
reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAP 
statistical analysis plan 

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Term 
Definition 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
safety committee 
SCCHN 
squamous cell carcinoma of the head and neck 
SD 
stable disease 
SDR 
Safety Data Review 
SI 
International System of Units 
SMT 
Safety Management Team 
SOP 
standard operating procedures 
SUSAR 
suspected, unexpected serious adverse reaction 
t1/2 
half-life 
T3 
T3 = triiodothyronine 
T4 
thyroxine 
TACE 
transarterial chemoembolization 
TAE 
transarterial embolization 
T.bili 
total bilirubin 
TCR 
T-cell receptor 
TKI 
tyrosine kinase inhibitor 
TIL 
tumor-infiltrating lymphocyte 
TME 
tumor microenvironment 
TSH 
thyroid-stimulating hormone 

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Term 
Definition 
TTE 
transthoracic echocardiogram 
TSST 
time to second subsequent therapy 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
US 
United States 
UTN 
Universal Trial Number 
VEGF 
vascular endothelial growth factor 
VEGFR 
vascular endothelial growth factor receptor 
VI 
vascular invasion 
vs 
versus 
Vss 
mean volume of distribution at steady state 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
WNOCBP 
women not of childbearing potential 
WWPS 
Worldwide Patient Safety 

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APPENDIX 2 
STUDY GOVERNANCE CONSIDERATIONS 
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the CRF is intended to refer to a person 
(Participant) who has consented to participate in the clinical research study. 
REGULATORY AND ETHICAL CONSIDERATIONS 
GOOD CLINICAL PRACTICE 
This study will be conducted in accordance with: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines Good Clinical Practice (GCP), 
• as defined by the International Council on Harmonisation (ICH) 
• in accordance with the ethical principles underlying European Union Directive 2001/20/EC 
• United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
• applicable local requirements. 
 
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study. 
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to 
affect, to a significant degree one or more of the following: (1) the physical, safety or mental 
integrity of one or more subjects/participants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s). 
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks. 
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
Before study initiation, the Investigator must have written and dated approval/favorable opinion 
from  the  IRB/IEC  for  the  protocol,  consent  form,  participant  recruitment 
materials (eg, advertisements), and any other written information to be provided to 
subjects/participants. The Investigator or BMS should also provide the IRB/IEC with a copy of 
the Investigator Brochure or product labeling information to be provided to subjects/participants 
and any updates. 

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The Investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures. 
COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS 
The Investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects/participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as soon 
as possible to: 
• IRB/IEC 
• Regulatory Authority(ies), if applicable by local regulations (per national requirements) 
 
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS. 
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
subjects/participants currently enrolled in the study if they are affected by the amendment; and (3) 
the new form must be used to obtain consent from new subjects/participants prior to enrollment. 
If the revision is done via an administrative letter, Investigators must inform their IRB(s)/IEC(s). 
FINANCIAL DISCLOSURE 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 
INFORMED CONSENT PROCESS 
Investigators must ensure that subjects/participants are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer 
to participate. 
In situations where consent cannot be given by subjects/participants, their legally acceptable 
representatives (as per country guidelines) are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which the participant 
volunteers to participate. 

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Sponsor or designee will provide the Investigator with an appropriate (ie, Global or Local) sample 
informed consent form which will include all elements required by ICH, GCP and applicable 
regulatory requirements. The sample informed consent form will adhere to the ethical principles 
that have their origin in the Declaration of Helsinki. 
Investigators must: 
• Provide a copy of the consent form and written information about the study in the language in 
which the participant is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 
• Allow time necessary for participant or participant's legally acceptable representative to 
inquire about the details of the study. 
• Obtain an informed consent signed and personally dated by the participant or the participant's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 
• Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects/participants, prior to the beginning of 
the study, and after any revisions are completed for new information. 
 
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant. 
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The Investigator, or a person designated by the Investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects’/participants’ signed ICF and, in the US, the subjects’/participants’ signed HIPAA 
Authorization. 
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
Subjects/participants unable to give their written consent (eg, stroke or subjects/participants with 
or severe dementia) may only be enrolled in the study with the consent of a legally acceptable 
representative. The participant must also be informed about the nature of the study to the extent 
compatible with his or her understanding, and should this participant become capable, he or she 
should personally sign and date the consent form as soon as possible. The explicit wish of a 
participant who is unable to give his or her written consent, but who is capable of forming an 
opinion and assessing information to refuse participation in, or to be withdrawn from, the clinical 
study at any time should be considered by the Investigator. 

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The rights, safety, and well-being of the study subjects/participants are the most important 
considerations and should prevail over interests of science and society. 
BMS COMMITMENT TO DIVERSITY IN CLINICAL TRIALS 
The mission of BMS is to transform patients’ lives through science by discovering, developing, 
and delivering innovative medicines that help them prevail over serious diseases. 
BMS is committed to doing its part to ensure that patients have a fair and just opportunity to 
achieve optimal health outcomes. 
BMS is working to improve the recruitment of a diverse participant population with the goal that 
the clinical trial becomes more reflective of the real-world population and the people impacted by 
the diseases studied. 
DATA PROTECTION, DATA PRIVACY, AND DATA SECURITY 
BMS collects and processes personal data of study participants, patients, health care providers, 
and researchers for biopharmaceutical research and development to advance innovative, high- 
quality medicines that address the medical needs of patients. BMS ensures the privacy, protection, 
and confidentiality of such personal data to comply with applicable laws. To achieve these goals, 
BMS has internal policies that indicate measures and controls for processing personal data. BMS 
adheres to these standards to ensure that collection and processing of personal data are limited and 
proportionate to the purpose for which BMS collects such personal data. This purpose is clearly 
and unambiguously notified to the individual at the time of collection of personal data. In the true 
spirit of science, BMS is dedicated to sharing clinical trial information and data with participants, 
medical/research communities, the media, policy makers, and the general public. This is done in a 
manner that safeguards participant privacy and informed consent while respecting the integrity of 
national regulatory systems. Clinical trial data, health-related research, and pharmacovigilance 
activities on key-coded health data transferred by BMS across national borders is done in 
compliance with the relevant data protection laws in the country and GCP requirements. 
BMS protects Personal Information with adequate and appropriate security controls as indicated 
under the data protection laws. To align with the recommended security standards, BMS has 
adopted internal security standards and policies to protect personal data at every stage of 
its processing. 
To supplement these standards, BMS enters into Clinical Trial Agreements (CTAgs) with 
confidentiality obligations to ensure proper handling and protection of personal data by third 
parties accessing and handling personal data. 
BMS takes unauthorized access and disclosure of Personal Information very seriously. BMS has 
adopted the security standards that include National Institute of Standards and Technology 
Cybersecurity Framework for studies in the US. BMS aligns with these standards to continuously 
assess and improve its ability to protect, detect, and respond to cyber attacks and other 
unauthorized attempts to access personal data. These standards also aid in mitigating possible 
adverse effects. Furthermore, BMS Information Technology has defined 6 principles to protect our 
digital resources and information: 

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1) Responsibilities of IT Personnel 
2) Securing the BMS Digital Infrastructure 
3) Identity and Access Management 
4) External Partner Connections 
5) Cyber Threat Detection and Response 
6) Internal Cyber Incident Investigation 
 
SOURCE DOCUMENTS 
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event tracking/reporting, protocol required assessments, and/or drug accountability 
records). 
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
STUDY TREATMENT RECORDS 
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority. 

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If 
Then 
Supplied by BMS (or its vendors): 
Records or logs must comply with applicable 
regulations and guidelines and should include: 
• amount received and placed in storage area 
• amount currently in storage area 
• label identification number or batch number 
• amount dispensed to and returned by each 
participant, including unique participant 
identifiers 
• amount transferred to another area/site for 
dispensing or storage 
• nonstudy disposition (eg, lost, wasted) 
• amount destroyed at study site, if applicable 
• amount returned to BMS 
• retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 
• dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form. 
Sourced by site, and not supplied by 
BMS or its vendors (examples include IP 
sourced 
from 
the 
sites 
stock or 
commercial supply, or a specialty 
pharmacy) 
The Investigator or designee accepts responsibility 
for documenting traceability and study treatment 
integrity in accordance with requirements applicable 
under law and the SOPs/standards of the sourcing 
pharmacy. 
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements. 
CASE REPORT FORMS 
An Investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study. 
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. 

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The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules in accordance with the applicable regulatory 
requirement(s). 
The Investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
Investigator or qualified physician who is a sub-Investigator and who is delegated this task on the 
Delegation of Authority Form. Sub-Investigators in Japan may not be delegated the CRF approval 
task. The Investigator must retain a copy of the CRFs including records of the changes and 
corrections. 
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user 
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals 
MONITORING 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality, such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring), are provided in the monitoring plan. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the Investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents. 
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential. 
The Investigator must notify BMS promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to Sponsor or designee. 
RECORDS RETENTION 
The Investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
Investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study. 
BMS or designee will notify the Investigator (or head of the study site in Japan) when the study 
records are no longer needed. 

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If the Investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another Investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
RETURN OF STUDY TREATMENT 
For this study, study treatments (those supplied by BMS, a vendor or sourced by the Investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site. 
 
If.. 
Then 
Study treatments supplied by BMS (including 
its vendors 
Any unused study treatments supplied by BMS 
can only be destroyed after being inspected and 
reconciled by the responsible Study Monitor 
unless study treatments containers must be 
immediately destroyed as required for safety, 
or to meet local regulations (eg, cytotoxics or 
biologics). 
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor. 
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or 
commercial 
supply, 
or 
a 
specialty 
pharmacy) 
It 
is 
the 
Investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures. 
 
It is the Investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met: 
• On-site disposal practices must not expose humans to risks from the drug. 
• On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances. 
• Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request. 
• Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented. 
• Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period. 

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It is the Investigator’s or designee’s responsibility to arrange for disposal of all empty containers. 
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non-study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the Investigator 
or designee. 
CLINICAL STUDY REPORT 
A Signatory Investigator must be selected to sign the clinical study report. 
For each CSR related to this protocol, the following criteria will be used to select the signatory 
Investigator: 
• Participant recruitment (eg, among the top quartile of enrollers) 
• Regional representation (eg, among top quartile of enrollers from a specified region or country) 
• Other criteria (as determined by the study team) 
 
SCIENTIFIC PUBLICATIONS 
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTAg) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTAg. 
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
principal Investigator, sub-Investigator or any other member of the study staff without the prior 
written consent of the Sponsor. 
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship: 
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights and conclusion); AND 
2) Drafting the work or revising it critically for important intellectual content; AND 
3) Final approval of the version to be published; AND 
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 

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Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered. 
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions. 

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APPENDIX 3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW UP AND REPORTING 
ADVERSE EVENTS 
 
Adverse Event Definition: 
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation participant administered study treatment 
and that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the Investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the Investigator), 
should not be reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and 
should specify "intentional overdose" as the verbatim term 
Events NOT Meeting the AE Definition 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
DEFINITION OF SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met. 

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SERIOUS ADVERSE EVENTS 
 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any 
dose: 
Results in death 
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe) 
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below) 
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
• a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event) 
• elective surgery, planned prior to signing consent 
• admissions as per protocol for a planned medical/surgical procedure 
• routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy) 
• medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases 
• admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason) 
• admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols) 
Results in persistent or significant disability/incapacity 
Is a congenital anomaly/birth defect 
Is an important medical event (defined as a medical event(s) that may not be immediately life- 
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization. Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.7 for the definition of potential DILI.) 
 
Pregnancy and potential drug induced liver injury (DILI) must follow the same transmission timing 
and processes to BMS as used for SAEs (see Section 9.2.5 for reporting pregnancies). 

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EVALUATING AES AND SAES 
 
Assessment of Causality 
• The Investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• The Investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated. 
• The Investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor. 
• The Investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
If only limited information is initially available, follow-up reports are required. (Note: Follow- 
up SAE reports must include the same Investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report. 
All SAEs must be followed to resolution or stabilization. 

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REPORTING OF SAES TO SPONSOR OR DESIGNEE 
 
• SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event. 
• SAEs must be recorded on the SAE Report Form. 
The required method for SAE data reporting is through the eCRF. 
The paper SAE Report Form is only intended as a back-up option when the electronic 
data capture (EDC) system is unavailable/not functioning for transmission of the eCRF 
to BMS (or designee). 
In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission 
When paper forms are used, the original paper forms are to remain on site 
• Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission 
SAE Email Address: Refer to Contact Information list. 
SAE Facsimile Number: Refer to Contact Information list. 
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list 

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APPENDIX 4 
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION 
DEFINITIONS 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
Women in the following categories are not considered WOCBP 
• Premenarchal 
• Premenopausal female with 1 of the following: 
Documented hysterectomy 
Documented bilateral salpingectomy 
Documented bilateral oophorectomy 
 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
• Postmenopausal female 
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 
years in the absence of other biological or physiological causes. In addition, females under 
the age of 55 years must have a serum follicle stimulating hormone, (FSH) level 
> 40 mIU/mL to confirm menopause. 
 
Note: Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the Investigators should use their 
judgement in checking serum FSH levels. 
• 1 week minimum for vaginal hormonal products (rings, creams, gels) 
• 4 week minimum for transdermal products 
• 8 week minimum for oral products 
 
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal. 

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End of Relevant Systemic Exposure 
• End of relevant systemic exposure is the time point where the IMP or any active major 
metabolites has decreased to a concentration that is no longer considered to be relevant for 
human teratogenicity or fetotoxicity. This should be evaluated in context of safety margins 
from the no-observed adverse effect level (NOAEL) or the time required for 5 half-lives of the 
IMP to pass. 
 
METHODS OF CONTRACEPTION 
Local laws and regulations may require use of alternative and/or additional contraception methods. 
 
Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of <1% per year when used consistently and correctly.a 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b 
• oral (birth control pills) 
• intravaginal (vaginal birth control suppositories, rings, creams, gels) 
• transdermal 
• Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy 
• Progestogen-only hormonal contraception associated with inhibition of ovulation (This 
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol)b 
• oral 
• injectable 
• Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy 
Highly Effective Methods That Are User Independent 
• 
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol)b 
• Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol)b,c 
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• Vasectomized partner 
Having a vasectomized partner is a highly effective contraception method provided that 
the partner is the sole male sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception should be 
used. 
• Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant. 
• Continuous abstinence must begin at least 30 days prior to initiation of study therapy 
• It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
• WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 
• Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence 
• Periodic abstinence (including but not limited to calendar, symptothermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study. 
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous. In this case, alternative 
methods of contraception should be utilized. 
c Intrauterine hormone releasing systems are acceptable methods of contraception in the absence of definitive drug 
interaction studies when hormone exposures from intrauterine devices do not alter contraception effectiveness 
 
Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of >1% per year when used consistently and correctly. 
• Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously 
• Diaphragm with spermicide 
• Cervical cap with spermicide 
• Vaginal Sponge with spermicide 

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• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited) 
Unacceptable Methods of Contraception 
• Periodic abstinence (calendar, symptothermal, post-ovulation methods) 
• Withdrawal(coitus interruptus). 
• Spermicide only 
• Lactation amenorrhea method (LAM) 
 
COLLECTION OF PREGNANCY INFORMATION 
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting. 

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APPENDIX 5 
CHILD-PUGH SCORE 
 
Score 
Points 
Child-Pugh A 
5 - 6 
Child-Pugh B 
7 - 9 
Child-Pugh C 
> 9 
 
Scoring 
 
Score 
Measure 
1 Point 
2 Points 
3 Points 
Ascites 
Absent 
Slight 
Moderate 
Serum bilirubin (mg/dl) 
< 2.0 
2.0 - 3.0 
> 3.0 
Serum albumin (g/dl) 
> 3.5 
2.8 - 3.5 
< 2.8 
PT prolongation 
or INR 
< 4 sec 
< 1.7 
4 - 6 sec 
1.7 - 2.3 
> 6 sec 
> 2.3 
Encephalopathy grade 
None 
1 - 2 
3 - 4 
 
Encephalopathy Grading 
 
Encephalopathy 
Grade 
Clinical Definition 
Grade 0 
Normal consciousness, personality, and neurological examination 
Grade 1 
Restless, sleep disturbed, irritable/agitated, tremor, and impaired 
handwriting 
Grade 2 
Lethargic, time-disoriented, inappropriate, asterixis, and ataxia 
Grade 3 
Somnolent, stuporous, place-disoriented, hyperactive reflexes, and 
rigidity 
Grade 4 
Unrousable coma, no personality/behavior, decerebrate 

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APPENDIX 6 
ECOG PERFORMANCE STATUS 
 
ECOG PERFORMANCE STATUS 1 
0F 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without 
restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to 
carry out work of a light or sedentary nature, e.g., light 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 
1 Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, and Carbone PP. 
Toxicity and Response Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 
1982;5:649–655. 

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APPENDIX 7 
COUNTRY SPECIFIC REQUIREMENTS/DIFFERENCES 
 
Country/Location 
Requirement 
Original Language/ 
Section Number 
Country-specific Language or Differences 
Argentina, Czech 
Republic, 
Germany, 
Romania 
Section 2 Schedule of 
Activities 
Table 2-1: Screening 
Procedural Outline 
(CA224073); 
Laboratory Tests 
Add “HIV” to the list of laboratory tests. 
Section 6.2: Exclusion 
Criteria 
Exclusion 
criterion 
2) b) iv) (5) 
Table 9.4.4-1: 
Clinical Safety 
Laboratory 
Assessments 
Standard language in exclusion criterion add: “Countries where 
exclusion of HIV positive participants is locally mandated.” 
Serology information modified to read: 
• 
Serum for hepatitis C antibody, HCV RNA. 
• 
Hepatitis B surface antigen (screening only). 
• 
HIV testing must be performed at sites where mandated by 
local or country regulations (see Appendix 7). 
France, Germany 
Section 8.1: 
Discontinuation from 
Study Treatment 
Second paragraph following bulleted text modified to read: 
“In the case of pregnancy, the Investigator must immediately 
notify the BMS Medical Monitor/Clinical Scientist of this event. 
In most cases, the study treatment will be permanently 
discontinued in an appropriate manner (eg, dose tapering if 
necessary for participant safety). Please call the BMS Medical 
Monitor within 24 hours of awareness of the pregnancy.” 
France 
Add to discontinuation criteria bullets an item for discontinuation 
due to product inefficacy. 
France 
Add to discontinuation criteria bullets an item for discontinuation 
due to severe infection. 
Czech Republic 
Second paragraph following bulleted text modified to read: 
“In the case of pregnancy, the Investigator must immediately, 
within 24 hours of awareness of the pregnancy, notify the BMS 
Medical Monitor/Clinical Scientist of this event. In all cases, the 
study treatment will be permanently discontinued in an 
appropriate manner (eg, dose tapering if necessary for participant 
safety). Refer to Section 9.2.5 (Pregnancy).” 
Czech Republic 
Section 9.2.5: 
Pregnancy 
Second paragraph modified to read: 
“In the Czech Republic, all pregnancies will require the 
participant to discontinue treatment.” 

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Country/Location 
Requirement 
Original Language/ 
Section Number 
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APPENDIX 9 
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS 
1 
EVALUATION OF LESIONS 
Solid tumors will be evaluated using Response Evaluation Criteria In Solid Tumors version 1.1 
(RECIST 1.1) guideline with BMS modifications.1 
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows: 
1.1 
Measurable 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ≥2x slice thickness if 
greater than 5mm. 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be ≥ 15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm). 
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥ 10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed. 
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions. 
1.2 
Non-Measurable 
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10 mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques. 
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions. 

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1.3 
Special considerations regarding lesion measurability 
1.3.1 
Bone lesions 
• Bone scan, PET scan and plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above. 
• Blastic bone lesions are non-measurable. 
 
1.4 
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions 
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline (this means in 
instances where patients have only one or two organ sites involved a maximum of two and four 
lesions respectively will be recorded). 
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum of 
two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’). 

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RESPONSE CRITERIA 
2.1 
Evaluation of Target Lesions 
• Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm. 
• Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters. 
• Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression). 
• Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
• Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed 
as either fully resolved or too small to measure (due to missing or poor quality images), and 
the sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above. 
2.1.1 
Special Notes on the Assessment of Target Lesions 
2.1.1.1 
Lymph nodes 
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target lesions, 
the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a normal 
lymph node is defined as having a short axis of < 10 mm. Case report forms or other data collection 
methods may therefore be designed to have target nodal lesions recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions. 
2.1.1.2 
Target lesions that become ‘too small to measure’ 
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned 
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 

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default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm. 
2.1.1.3 
Lesions that split or coalesce on treatment 
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’. 
2.2 
Evaluation of Non-Target Lesions 
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need 
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol. 
• Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10 mm short axis). 
• Non-CR/Non-PD: Persistence of one or more non-target lesion(s) 
• Progressive Disease (PD): Unequivocal progression of existing non-target lesions. 
2.2.1 
Special Notes on Assessment of Progression of Non-Target Disease 
The concept of progression of non-target disease requires additional explanation as follows: 
2.2.1.1 
When the patient also has measurable disease 
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy A modest ‘increase’ in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. Pleural effusions, pericardial 
effusions and ascites will not be followed as target or non-target lesions and will not contribute to 
response or progression. The designation of overall progression solely on the basis of change in 
non-target disease in the face of SD or PR of target disease will therefore be extremely rare. 
2.2.1.2 
When the patient has only non-measurable disease 
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 
if all lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the change 

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in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in lymphangitic disease from localized to widespread, or may be 
described as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the 
patient should be considered to have had overall PD at that point. While it would be ideal to have 
objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore, the increase must be substantial. 
2.2.2 
New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some comments 
on detection of new lesions are important. There are no specific criteria for the identification of 
new radiographic lesions; however, the finding of a new lesion should be unequivocal: ie, not 
attributable to differences in scanning technique, change in imaging modality or findings thought 
to represent something other than tumor (for example, some ‘new’ bone lesions may be simply 
healing or flare of pre-existing lesions). This is particularly important when the patient’s baseline 
lesions show partial or complete response. For example, necrosis of a liver lesion may be reported 
on a CT scan report as a ‘new’ cystic lesion, which it is not. 
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new fluid 
collection is seen on a post-baseline imaging exam, a comment may be made, but the appearance 
of a new fluid collection alone should not result in an assessment of Progressive Disease (PD). A 
lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD). 
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. While FDG-PET 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according 
to the following algorithm: 
1) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion. 
2) No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 
CT scans are needed to determine if there is truly progression occurring at that site (if so, the 
date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET 

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at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD. 
2.3 
Response Assessment 
 
 
 
 
 
 
 
 
2.3.2 
Time Point Response 
At each protocol specified time point, a response assessment occurs. Table 2.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) disease 
only, Table 2.3.2-2 is to be used. 
 
Table 2.3.2-1: 
Time Point Response: Patients With Target (± Non-Target) Disease 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable 
 
 
Table 2.3.2-2: 
Time Point Response: Patients with Non-target Disease Only 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PDa 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 

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Table 2.3.2-2: 
Time Point Response: Patients with Non-target Disease Only 
Non-Target Lesions 
New Lesions 
Overall Response 
Any 
Yes 
PD 
CR = complete response, PD = progressive disease and NE = inevaluable 
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised. 

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2.3.4 
Confirmation Scans 
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a 
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation. 
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease. 
REFERENCES 
1 Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47. 

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APPENDIX 10 
BARCELONA CLINIC LIVER CANCER (BCLC) 
CLASSIFICATION 
 
 
Stage 
Performance Status* 
Tumor Stage 
Liver Function Status 
A 
0 
Single 
Child-Pugh A-B 
B 
0 
Large multinodular 
Child-Pugh A-B 
C 
1-2 
Vascular invasion/ 
Child-Pugh A-B 
extrahepatic spread 
D 
3-4 
Any 
Child-Pugh C 
 
REFERENCE: 
Llovet JM, Bru C, Bruix J. 
Prognosis of hepatocellular carcinoma: the BCLC staging 
classification. Semin Liver Dis 1999;19:329-38. 

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APPENDIX 11 
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY 
Overall Rationale for Protocol Amendment 03, 29-Jul-2021 
Additional updates, including to sections of the Synopsis, have been made to align the protocol 
with respect to these changes. This protocol amendment applies to all participants. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & Title 
Description of Change 
Brief Rationale 
Title Page 
Updated contact information for Medical 
Monitor. 
Provided current contact information for 
the study. 
Section 2: Schedule of 
Added BCLC staging for 
Clarified eligibility expectations for 
Activities; 
advanced/metastatic hepatocellular 
advanced/metastatic HCC. 
Section 6.1: Inclusion 
carcinoma (HCC) to Table 2-1 and 
Criteria; 
inclusion criterion 2) b) and included new 
Appendix 10: Barcelona 
Appendix for BCLC. 
Clinic Liver Cancer (BCLC) 
Classification 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 4: Objectives and 
Endpoints 
Updated objectives and endpoints to 
align with study design change 
Section 5.1: Overall Design 
Added language describing dose options 
for participants who were already enrolled 
Clarified treatment expectations for 
participants who have already received 
relatlimab 960 mg + nivolumab 480 mg 
Q4W. 
prior to Protocol 
Amendment 03. 
Section 5.1: Overall Design 
Updated number of participants planned 
for the study. 
Aligned approximate number of 
participants with study design change 
Section 6.1: Inclusion 
Criteria 
Added new criterion 1) d): “For 
amendment Protocol Amendment 03, all 
participants in Arm B and Arm C will be 
Provided expectations for participant 
consent for Protocol Amendment 03. 
re-consented 
” 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & Title 
Description of Change 
Brief Rationale 
 
Overall Rationale for Protocol Amendment 02, 15-Apr-2021 
The primary reasons for these changes are to include participants with advanced 
immuno-oncology (IO) therapy-naive hepatocellular carcinoma (HCC) who have received one or 
two lines of tyrosine kinase inhibitor (TKI) therapies and have shown radiographic progression on 
or after the last line of TKI therapy; clarify expectations for sample collection, study assessments, 
and participant eligibility; 
 
Additional amendments, including to sections of the Synopsis, have been made to align the 
protocol with respect to these changes. This protocol amendment applies to all participants. 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Title Page; 
Section 3: Introduction; 
Section 5.1: Overall 
Design; 
Section 6.1: Inclusion 
Criteria 
Broadened eligibility to include participants with 
advanced IO therapy-naive HCC who have 
received one or two lines of TKI therapies and 
have shown radiographic progression on or after 
the last line of TKI therapy. 
Updated study indication to include 
participants who are IO therapy- 
naive with ≤ 2 prior lines of TKI 
therapies with advanced/metastatic 
HCC. 
Section 2: Schedule of 
Activities 
The following modifications were made: 
• Table 2-1: Updated Notes for Chest Radiograph 
row to clarify either side for lateral chest x-ray. 
• Table 2-2: 
‒ Column headers: Updated windows from 
2 days to 3 days. 
‒ Vital Signs row: Removed “within 3 days.” 
‒ Laboratory Tests row: Removed note for liver 
function tests. 
‒ Body Imaging and Brain Imaging rows: 
Updated “first dose” to “randomization.” 
• Table 2-2 and Table 2-3: 
Clarified expectations for 
on-treatment and follow-up 
assessments. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 2: Schedule of 
Activities; Section 5.1.1: 
Screening Period; 
Section 6.1: Inclusion 
Criteria 
The following modifications were made: 
• Updated screening procedures and inclusion 
criteria for required tumor tissue samples to 
clarify expectations for collection and use of 
archival tissue. 
• Table 2-2 and inclusion criterion 2) b) iii): 
Provided washout periods between end of TKI 
treatment and beginning of study treatment for 
specific TKIs. 
These changes were made to clarify: 
• Expectations for tumor tissue 
sample collection at screening. 
• Timing for initiating treatment 
administration. 
Section 2: Schedule of 
Activities; 
Section 6.2: Exclusion 
Criteria; Section 6.4.1: 
Retesting During 
Screening Period 
Updated testing and exclusion criteria for severe 
acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) infection from “active” to 
“symptomatic.” 
Changed considerations for 
SARS-CoV-2 from “active” to 
“symptomatic” infection. 
Section 2: Schedule of 
Activities; Section 9.4.4: 
Clinical Safety 
Laboratory Assessments 
The following udpates were made: 
• Added serum alpha-fetoprotein (AFP) testing 
to on-treatment assessments. 
• Removed Epstein-Barr virus antibody serology 
testing. 
These changes were made to: 
• Include on-treatment serum AFP 
testing. 
• Remove Epstein-Barr virus 
antibody testing because it is no 
longer applicable to this study. 
Section 3: Introduction; 
Section 3.2: Background; 
Section 3.3.1: 
Introduction; 
Section 3.3.4: Efficacy; 
Section 6.1: Inclusion 
Criteria 
The following updates were made: 
• Updated “sorafenib or lenvatinib” to “TKI” and 
provided list of currently approved TKIs. 
• Added paragraph describing current treatment 
recommendations for 1L and 2L therapies in 
HCC. 
These changes were made to: 
• Generalize the description of TKI 
therapies. 
• Provide additional background 
information on current treatment 
guidelines for HCC. 
Section 5.4.1: Rationale 
for Choice of 
Comparators 
Added text describing current National 
Comprehensive Cancer Network (NCCN) 
guidelines recommendations for use of nivolumab 
in subsequent lines of therapy in HCC after 
disease progression. 
Clarified recommended use of 
nivolumab in HCC per current 
treatment guidelines. 
Section 6.1: Inclusion 
Criteria 
Added new criterion 2) e) i) related early- and 
intermediate-stage immunotherapy. 
Clarified eligibility for participants 
with early- or intermediate-stage 
immunotherapy. 
Section 6.2: Exclusion 
Criteria 
The following updates were made: 
• Replaced criterion 1) d) i) related to prior 
ascites with new criterion 1) d) iii) and removed 
criterion 1) d) ii). 
• Added new criterion 3) k) related to enrollment 
in other BMS studies. 
These changes were made to: 
• Provide more permissive 
language for clinically significant 
ascites. 
• Clarify eligibility of participants 
who are currently enrolled in 
other BMS studies in HCC. 

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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 7.1: Treatments 
Administered; 
Section 7.1.1: Relatlimab 
Combined with 
Nivolumab Dosing 
Removed information related to administering 
relatlimab and nivolumab sequentially and added 
footnote describing expectations for 
co-administration infusions. 
Updated treatment administration of 
relatlimab and nivolumab to 
co-administration only. 
Section 7.4: Dosage 
Modification; 
Section 7.4.2 Dose Delay 
Criteria; Section 8.1.3: 
Criteria to Resume 
Treatment 
Updated descriptions of combination relatlimab 
and nivolumab to reflect co-administration. 
Aligned language with updated 
treatment administration of 
relatlimab and nivolumab to 
co-administration only. 
Section 7.7: Concomitant 
Therapy 
Added text: “The effect of COVID-19 vaccines on 
participants taking relatlimab and nivolumab is 
currently unknown.” 
Included considerations for 
COVID-19 vaccines. 
Section 7.7.2.1: Imaging 
Restriction and 
Precautions 
Added text: “Site-specific imaging requirements 
that are different than those captured in the 
imaging manual may be considered after 
discussion with the BMS Medical Monitor or 
Clinical Scientist.” 
Clarified expectations for 
site-specific imaging requirements. 
Section 9.2.5: Pregnancy Removed last 2 paragraphs related to pregnancy 
surveillance and contraception measures for male 
participants. 
Updated section to fully align with 
the rest of the protocol, which does 
not include male contraceptive 
requirements. 
Section 9.8.2: Tumor 
Samples 
Updated paragraph to refer to Table 2-1 only. 
Removed repetitive text to improve 
readability. 
Appendix 2: Study 
Governance 
Considerations 
Updated first paragraph for Monitoring section to 
further describe that details on monitoring can be 
found in the monitoring plan. 
Clarified expectations for 
monitoring. 
Appendix 7: Country 
Specific Requirements/ 
Differences 
Added country-specific differences for Czech 
Republic related to Section 8.1 and Section 9.2.5. 
Aligned Appendix 7 with 
country-specific differences for 
Czech Republic described in the 
main text. 

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Overall Rationale for Revised Protocol 01, 28-Oct-2020 
 
improve alignment across protocol sections and/or clarify expectations for eligibility, assessments, 
sample collections, treatment administration, and country-specific requirements. 
Additional amendments, including to sections of the Synopsis, have been made to align the 
protocol with respect to these changes. This Revised Protocol applies to all participants. 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Title Page 
The following changes were made: 
• 
Removed Investigational New Drug (IND) 
number. 
• 
Updated “Study Director” to “Clinical 
Scientist.” 
Changes were made for these reasons: 
• 
Role name at Bristol Myers 
Squibb (BMS) has changed. 
Section 2: 
Schedule of 
Activities 
• 
Added/updated the following rows with 
notes related to SARS-CoV-2 within 
Section 2 tables: 
• 
Serum and AE/SAE collection in the 
context of 
was added 
in the event that coronavirus 
disease 2019 (COVID-19) sequelae 
may increase toxicity or impact 
interpretation of 
study events/results. 
• 
Updated or corrected Notes as 
needed to clarify expectations 
and/or to better align with protocol 
text. 
o Adverse Event and/or Serious Adverse 
Event Assessments 
• 
• 
Added or updated details to Notes columns 
for the following rows: 
o Table 2-1: Inclusion/Exclusion Criteria, 
Medical History, Required Tumor 
Tissue Samples, Concomitant 
Medication Use, Serious Adverse 
Events Assessment, Laboratory Tests, 
Serology, Disease Assessment: Serum 
Alpha-fetoprotein, Pregnancy 
Test (WOCBP only) 
o Table 2-2: Procedure, 
Inclusion/Exclusion Criteria, Targeted 
Physical Examination, Vital Signs, 
Adverse Event and Serious Adverse 
Event Assessments, Laboratory Tests, 
Thyroid Function Tests, Pregnancy 
Test (WOCBP only), Body Imaging, 
Brain Imaging, 
o Table 2-3: Laboratory Tests 
The  primary  reasons for  these  changes  are  to  align  dose  modification  criteria 
with the current Common Terminology 
Criteria for Adverse Event (CTCAE) version (v5); 
and incorporate additional updates to 

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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Section 2: 
Schedule of 
Activities 
(continued) 
• 
Added a footnote for the Notes column in 
each Section 2 table to indicate that 
assessments may not be captured as data in 
the case report form (CRF). 
• 
Added reference to Section 5.1.3.1 in 
footnote b of Table 2-3. 
• 
Clarified expectations for capturing 
assessments in the CRF. 
• 
Clarified expectations for survival 
follow-up in participants with stable 
disease, complete response, or 
partial response. 
Section 3.2: 
Background 
Added information for the CA209459 study on 
participants with subsequent IO therapy. 
Provided additional context for findings 
from the CA209459 study. 
Section 3.3.3: 
Safety Monitoring 
Added text referring to other sections in the 
protocol for risk mitigation for SARS-CoV-2. 
Aligned with updates to other parts of 
the protocol related to SARS-CoV-2. 
Section 4: 
Objectives and 
Endpoints 
Section 5.1.1: 
Screening Period 
Added to tumor sample language that biopsy can 
be taken any time after the end of tyrosine 
kinase inhibitor treatment. 
Clarified expectations the required tumor 
sample. 
Section 5.1.2: 
Treatment Period; 
Section 6.1: 
Inclusion Criteria 
Added to pregnancy text language in Section 
5.1.2 and added new sub-criterion 3) a) iv) (2) 
for women of childbearing potential (WOCBP): 
“An extension up to 72 hours prior to the start of 
study treatment is permissible in situations 
where results cannot be obtained within the 
standard 24-hour window.” 
Clarified expectations for eligibility 
related to pregnancy testing and results. 
Section 5.6.1: 
Nivolumab 
Clinical 
Pharmacology 
Updated text per more recent data 
in the 
context of specific populations/medical 
conditions. 
Updated pharmacology information for 
nivolumab and relatlimab to align with 
more recent clinical experience. 
Summary; 

Clinical Protocol 
BMS-986016 
CA224073 
relatlimab 
Protocol Amendment No: 04 
Date: 26-May-2022 
195 
Approved v 51.0 
930155190 5.0 
 
 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Section 6.1: 
Inclusion Criteria 
The following updates were made: 
• 
Added new sub-criterion 2) b) ii) (1) related 
to local or locoregional therapy. 
• 
Added new sub-criterion 2) h) iii) related to 
biopsies of bone lesions. 
• 
Replaced criterion 2) p) (3) with new 
criterion 2) p) (5) to update platelet 
requirements to SI: ≥ 60 × 109/L. 
• 
Added age requirements to 3) header. 
• 
Replaced criterion 3) x) (2) with new 
criterion 3) x) (3) to update “24 weeks” to 
“5 months.” 
• 
Criteria 3) b) ii) through 3) b) viii) are no 
longer applicable; removed text related to 
male contraception in last paragraph. 
These changes were made to: 
• 
Clarified expectations for eligible 
advanced HCC disease. 
• 
Clarified expectations for required 
tumor tissue sample. 
• 
Corrected platelet values in 
inclusion criteria. 
• 
Clarified age requirements. 
• 
Update timing of contraceptive use 
for WOCBP-based study treatment 
half-lives. 
• 
Remove contraceptive requirements 
for male participants based on 
current safety information. 
Section 6.2: 
Exclusion Criteria 
The following updates were made: 
• 
Replaced criterion 1) f) with new criteria 
1) g) and 1) h) related to central nervous 
system (CNS) and leptomeningeal 
metastases, respectively. 
• 
Replaced criterion 2) b) ii) with new criteria 
2) b) iv) related to human 
immunodeficiency virus. 
• 
Added new criteria 2) b) v) for active 
infection with SARS-CoV-2 and 2) b) vi) 
for other active viral infection. 
• 
Replaced criterion 2) g) with new criterion 
2) i) related to concurrent or prior 
malignancy. 
• 
Added new criterion 2) j) related to 
resolution of AEs related to prior anticancer 
therapy. 
• 
Replaced criterion 3) h) with new criterion 
3) j) related to complementary medications. 
• 
Added new criterion 3) i) for participants 
currently in other interventional trials, 
including those for COVID-19. 
These changes were made to include 
new clinical approaches for eligibility 
related to CNS metastases, viral 
infections, and concurrent or prior 
malignancies, prior anticancer therapy 
AEs, supportive care, and eligibility 
criteria for participants in interventional 
trials. 
Section 6.4.1: 
Retesting During 
Screening Period 
Added text describing testing and retesting for 
participants who may develop suspected or 
confirmed symptomatic COVID-19. 
Included language to clarify expectations 
for eligibility and retesting for 
participants with suspected or confirmed 
symptomatic COVID-19. 
Section 7.1: 
Treatments 
Administered 
Added text to footnote b of Table 7.1-1 
clarifying that nivolumab and relatlimab will be 
co-administered once allowable. 
Updated co-administration language to 
better align with Section 7.1.1. 

Clinical Protocol 
BMS-986016 
CA224073 
relatlimab 
Protocol Amendment No: 04 
Date: 26-May-2022 
196 
Approved v 51.0 
930155190 5.0 
 
 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Section 7.1.1: 
Relatlimab 
Combined with 
Nivolumab 
Dosing 
The following updates were made: 
• 
Added “approximately” for timing of 
administration. 
• 
Added text: “For Q4W dosing cycles, 
participants may be dosed no less than 
26 days from the previous dose.” 
• 
Added language describing potential 
co-administration infusion times for 
participants ≥ 45 kg and < 45 kg. 
These changes were made to: 
• 
Allow more flexibility for the timing 
of infusion administration. 
• 
Clarify expectations for dosing 
cycles. 
• 
Distinguish infusion times for 
co-administration based on weight. 
Section 7.1.3: 
Palliative Therapy 
The following updates were made: 
• 
Updated definition and lesion for palliative 
local therapy. 
• 
Moved last paragraph to Section 7.7: 
Concomitant Therapy. 
These changes were made to: 
• 
Clarify expectations for palliative 
therapy. 
• 
Relocate information related to 
concomitant therapy to a more 
appropriate location in the protocol. 
Section 7.4.2: 
Dose Delay 
Criteria 
Added suspected or confirmed SARS-CoV-2 
infection as a criterion to delay treatment. 
Updated dose delay criteria to include 
expectations in cases of confirmed or 
suspected SARS-CoV-2 infection. 
Section 7.7.1: 
Prohibited and/or 
Restricted 
Treatments 
Updated language related to herbal supplements 
and traditional Chinese medicines for supportive 
care. 
Aligned section with new exclusion 
criterion 3) j) in Section 6.2. 

Clinical Protocol 
BMS-986016 
CA224073 
relatlimab 
Protocol Amendment No: 04 
Date: 26-May-2022 
197 
Approved v 51.0 
930155190 5.0 
 
 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Section 8.1: 
Discontinuation 
for Study 
Treatment; 
Section 9.2.5: 
Pregnancy 
The following changes were made: 
• 
Section 8.1: Updated second sentence in 
second paragraph after bulleted list, related 
to pregnancy cases, to “In most cases (all 
cases in Czech Republic Argentina, or other 
countries where it is required), the study 
treatment will be permanently 
discontinued...” 
• 
Section 9.2.5: 
o 
Added text: In the Czech Republic and 
Argentina (or other countries where it is 
required) all pregnancies will require 
the participant to discontinue treatment. 
o 
Updated 24 weeks to 5 months. 
Clarified expectations for 
discontinuation in the case of pregnancy, 
including for countries in which it is 
required that the study treatment be 
permanently discontinued in all 
pregnancy cases. 
Section 8.1.3: 
Criteria to 
Resume 
Treatment 
Added text describing scenarios in which 
participants with suspected or confirmed 
SARS-CoV-2 infection may resume treatment. 
Included language to clarify expectations 
for resuming treatment in participants 
with suspected or confirmed 
SARS-CoV-2 infection. 
Section 9.1.1.2: 
Imaging and 
Clinical 
Assessment 
Removed all but last sentence from second 
paragraph. 
Removed repetitive text. 
Section 9.2.1: 
Time Period and 
Frequency for 
Collecting AE and 
SAE Information 
The following updates were made: 
• 
Removed bullet related to Reference Safety 
Information in Investigator’s Brochure (IB). 
• 
Added text to describe collection of AEs 
and SAEs in the context of SARS-CoV-2 
infection. 
• 
Removed bullet related to SAE collection 
for participants who signed a pre-screening 
consent. 
These changes were made to: 
• 
Align references to IB in the 
protocol with current IB template. 
• 
Include language for AE/SAE 
collection in the context of 
SARS-CoV-2 in the event that 
COVID-19 sequelae may increase 
toxicity or impact interpretation of 
study events/results. 
• 
Remove inconsistent text to ensure 
alignment of this section with 
Table 2-1. 
Section 9.2.3: 
Follow-up of AEs 
and SAEs 
Updated last paragraph to include details related 
to follow-up of SAEs and non-serious AEs 
associated with confirmed or suspected 
SARS-CoV-2 infection. 
Included language for AE/SAE 
follow-up in the context of 
SARS-CoV-2 in the event that 
COVID-19 sequelae may increase 
toxicity or impact interpretation of 
study events/results. 

Clinical Protocol 
BMS-986016 
CA224073 
relatlimab 
Protocol Amendment No: 04 
Date: 26-May-2022 
198 
Approved v 51.0 
930155190 5.0 
 
 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Section 9.4.4: 
Clinical Safety 
Laboratory 
Assessments 
The updates below were made to Table 9.4.4-1: 
• 
Updated “Blood Urea Nitrogen (BUN)” to 
“Blood Urea Nitrogen (BUN)/serum urea.” 
• 
Added hepatitis C RNA viral load and 
hepatitis B DNA viral load under Serology. 
• 
Added “serum or urine” for pregnancy test. 
• 
Added SARS-CoV-2 viral test. 
Clarified expectation for assessments 
related to urea (when urea measurements 
are required instead of BUN), serology, 
pregnancy testing, and added 
SARS-CoV-2 viral test to align with 
related changes made in Section 6.2 and 
Section 6.4.1. 

Clinical Protocol 
BMS-986016 
CA224073 
relatlimab 
Protocol Amendment No: 04 
Date: 26-May-2022 
199 
Approved v 51.0 
930155190 5.0 
 
 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 01 
Section Number 
& Title 
Description of Change 
Brief Rationale 
Section 9.8.6: 
Other 
Assessments 
Added section to describe potential use of 
collections. 
Included language for potential use of 
collections, 
in alignment with the endpoint/objective 
added to Table 4-1. 
Appendix 4: 
Women Of 
Childbearing 
Potential 
Definitions and 
Methods of 
Contraception 
Updated vasectomized partner row in methods 
of contraception table. 
Aligned methods of contraception with 
updates made to male contraceptive 
requirements in Section 6.1. 
Appendix 7: 
Country Specific 
Requirements/ 
Differences 
The following updates were made: 
• 
Removed Czech Republic from 
modifications for Section 8.1: 
Discontinuation from Study Treatment 
modifications. 
• 
Added difference 
for Section 6.2: 
Inclusion Criteria. 
All 
Minor formatting and typographical corrections. 
These changes were minor, and therefore 
have not been summarized.