A Randomized, Double-Blind Phase 2/3 Study of Relatlimab Combined With Nivolumab Versus Nivolumab in Participants With Previously Untreated Metastatic or Unresectable Melanoma
Phase: PHASE2
Conditions: Melanoma
Sponsor: Bristol-Myers Squibb

Page: 1
Protocol Number: CA224047
IND Number: 136382
EX-US Non-IND
EUDRACT Number: 2017-003583-12
Date: 18-Dec-2017
Revised Date: 23-Nov-2020
Clinical Protocol CA224047
ARandomized, Double-Blind Phase 2/3 Study of Relatlimab Combined with Nivolumab versus 
Nivolumab in Participants with Previously Untreated Metastatic or Unresectable Melanoma
Protocol Amendment Number: 03
24-hrEmergency Telephone Number
Bristol-Myers Squibb Research and Development
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
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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 
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disclosure or dissemination of this information is strictly prohibited unless expressly 
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Clinical Protocol
CA224047
BMS-986213
relatlimab-nivolumab fdc
Protocol Amendment No.: 03
Date: 23-Nov-2020
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this document without due authorization from BMS is requested to return it to BMS or 
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to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).

Clinical Protocol
CA224047
BMS-986213
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Protocol Amendment No.: 03
Date: 23-Nov-2020
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol 
Amendment 03
23-Nov-2020
The following changes have been made to this protocol:
1) Revised the order of the Phase 3 secondary endpoints hierarchical 
testing strategy(1. Overall survival [OS] 2. Overall response rate 
[ORR]). 
2) Added two interim analyses of OS.
3) Revision of dose delay, criteria to resume treatment, and 
discontinuation criteria to align with CTCAE V5. 
4) Updatedcontraceptive guidance for participants. 
In addition, minor changes were made to improveoverallclarityand to 
clarify necessary
 communication with the BMS Medical 
Monitor/designee.
Revised Protocol 
02
22-Feb-2019
The following changes have been made to this protocol:
1) Incorporated changes from Administrative Letters 04, 05, and 06.
2) Added PFS2 as an exploratory objective.
3) Re-added pregnancy testing during follow-up visits.
Made additional minor changes to clarify timing of procedures and 
improve overall clarity of protocol.
Administrative 
Letter 06
05-Nov-2018
Updated Medical Monitor and Study Director information.
Administrative 
Letter 05
07-Sep-2018
Corrected study design statement error in Section 5.1.
Administrative 
Letter 04
05-Sep-2018
Updated CTCAEversion from 4 to 5. As such, also instructed sites that 
Grade 1 myocarditis is no longer an event term and all troponin elevations 
should be coded as troponin elevation regardless of myocardial 
inflammation.
Revised Protocol 
01
15-Aug-2018
The followingchanges have been made to this protocol:
Incorporated changes from Administrative Letters 01, 02, and 03.
Changed Phase 2 primary objective from ORR to PFS.
Updated interim analysis to include all 400 participants from Phase 2.
Clarified procedures for interim analysis and results.
Updated timing of procedures throughout for clarity.
Updated PK analyses for current preferred methods.
Updated Immuno-Oncology (IO) algorithms for current methods.
Added myocarditis IO algorithm.
Updated headers to include fullfixed-dose combination product.
Administrative 
Letter 03
18-Jun-2018
Corrected an error in Appendix 8, Country Specific Requirement. The 
section indicates that HIV testing at site is locally mandated in countries 
listed. The test is not required in Italyand Spain.
Administrative 
Letter 02
17-May-2018
Corrected an error in Appendix 8, Country Specific Requirement. The 
section indicates that HIV testing at site is locally mandated in countries 
listed. The test is not required in France.
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Document
Date of Issue
Summary of Change
Administrative 
Letter 01
09-Mar-2018
Corrected an error in Section 9.4.4, Safety Laboratory Assessment, Table 
9.4.4-1 section of the protocol. The serology tests indicate incorrectly that 
the HPV status should be done at screening. The test is not needed as part 
of the inclusion/exclusion criteria.
Original Protocol
18-Dec-2017
Not applicable
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Clinical Protocol
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OVERALL RATIONALE FOR REVISED PROTOCOL03:
The key change to the protocol includes the secondary endpoints statistical hierarchy evaluation 
to overall survival (OS)followed by overall response rate (ORR). Importantly, the primary 
endpoint has not been changed. In addition, revisions including interim analyses to be performed 
during the study (1ofprogression-free survival [PFS]and up to 2ofOS) are included.
OS is considered a more relevant endpoint for evaluation of clinical benefit in the melanoma 
landscape compared withORR. In study CA209-067 in previously untreated metastatic melanoma, 
overall survival at 5 years was remarkable at 52% in the nivolumab-plus-ipilimumab group and 
44% in the nivolumab group, as compared with 26% in the ipilimumab group.
1In addition, in the 
eventof a statistically significantPFS result, evaluating OS more formally would be considered 
more clinically meaningful than ORR.
2Therefore,OS will be testedhierarchically at the time of 
statistically significant PFS followed by ORR(if OS is statistically significant and at the time that 
ORR data are mature).
The final target number of OS events is 300, and the OS interim analyses present the opportunity 
to identify if a clear statistical significance is present at earlier information fractions between both 
treatment arms, indicating a survival benefit.
In addition, dose modification criteria and immuno-oncology (IO) agent management algorithms 
have been updated to align with the current Common Terminology Criteria for Adverse Event
(CTCAE) version (v5). Monitoringfor severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2)-related AE/SAE has been added. In addition, minor changes were made to improve clarity 
throughout the protocol were made. This revised protocol applies to all participants. 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL03
Section Number & 
Title
Description of Change
Brief Rationale
Title Page
Updated Medical Monitor Contact 
Information
Update
Section 2, Schedule of 
Activities; Table 2-2: On-
Study Assessments; 
Section 9.8.2, Tumor 
Samples; Section 9.8.2.6, 
Tumor Sample Collection
Added a note regarding collection 
of SARS-Cov-2-associated 
AEs/SAEs
Added clarification regarding 
biopsied lesions
Added clarification regarding
pediatric participants; theywould 
only complete EQ-5D-3Land not 
the WPAI:GHor FACT-M 
assessments
AE/SAE collection in the context of 
SARS-CoV-2 was added in the event 
that coronavirus disease2019 
(COVID-19) sequelae may increase 
toxicity or impact interpretation of 
studyevents/results.
Biopsy language, clarificationonly.
Pediatric EQ-5D-3L clarification 
only.
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL03
Section Number & 
Title
Description of Change
Brief Rationale
Section 2, Schedule of 
Activities; Table 2-3: 
Follow-Up Procedural 
Outline
Added a note regarding collection and
follow-up of SARS-CoV-2 infection. 
AE/SAE collection in the context of 
SARS-CoV-2 was added in the event that 
COVID-19 sequelaemay increase 
toxicity or impact interpretation of 
studyevents/results.
Section 3.1, Study 
Rationale
Revised to remove ORR from Phase 2 
evaluationsand to include OS and 
response rate and duration in the Phase 
3 study evaluations.
This was a correction. This edit was part 
of revisions made in revised protocol 02. 
Synopsis; Section 4, 
Objective and Endpoints; 
Table 4-1:Objectives and 
Endpoints
Phase 3 Exploratory
Added an objective regarding 
evaluations of FACIT GP5
Added evaluation of TFI
Phase 2 Secondary Objectives
Added definition for OS rate
Removal of “median” DOR
Phase 2 Exploratory Objective
Removal of “median” DOR
Treatment-free interval(TFI)is an 
emerging exploratory endpoint of interest 
in melanoma. Data suggest that TFI can 
positively impact quality of life (QoL)
and may improve the cost-effectiveness 
of immune checkpoint inhibitors. TFI can 
be analyzed in conjunction with safety, 
health-related QoL to give another 
representation of outcomes for off-
treatment patients.
Section 5.1, Overall 
Design; Section 10.2.5,
Interim Analyses
Timing on PFS interim analysis has 
been added.
Clarification on PFS analysis timing as 
been added. 
Section 5.1.1,Data 
Monitoring Committee
Revised to clarify that Data Monitoring 
Committee (DMC)will convene for 
assessment of the interim analysis. 
Clarification regarding DMC involvement 
in interim analysis.
Section 5.2, Number of 
Participants 
Revised to clarify that the interim PFS 
analysis is a futility analysis and that 
the threshold for positivity determines
continuation to Phase 3 study will be 
defined in the SAP. 
Clarification of the PFS interim analysis. 
Section 5.3, End of Study 
Definition
Revised to clarify the timing of the 
final analyses for the Phase 2 study, 
and the total duration of the assessment 
of PFS in thePhase 3 study.
Clarification on the PFS analysis timing. 
Section 7.3,Blinding
Specified when Sponsor and 
sites/participants will be unblinded 
to individual treatment 
assignments and to analysis results.

Specified that the analysis team 
reporting to the DMC is external to 
BMS.
Necessary with the inclusion of 
interim analyses for OS.
Clarification only.
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL03
Section Number & 
Title
Description of Change
Brief Rationale
Section 7.4, Dosage 
Modification
Added Table 7.4-1: AE Criteria for 
Delay, Resume, and Discontinuation of 
Treatment
Reorganized dose delay, resume, and 
discontinuation criteria for improved 
readability and to align with the 
current CTCAE version (v5).
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 7.4.2,Dose Delay 
Criteria; Section 7.4.3, 
Criteria to Resume 
Treatment; Section 8.1.1: 
Dose Discontinuation
Modified text to align criteria for dose 
delay, resume, and discontinuationof 
treatmentwith Table 7.4-1.
Updated dose delay, resume, and 
discontinuation criteria to align with the 
current CTCAE version (v5).
Section 9.3.1,Patient-
Reported Outcomes 
Language added to allow alternative 
collection methods. 
Permit alternative PRO collections should 
SARs-CoV-2 limit patient contact.
Section 9.1.3.2,FACT-M; 
Section 10.2.4.3 
Outcomes Research 
Addclarification regarding the use of 
GP-5in FACT-Mto assess burden due 
to treatment toxicities. 
Clarification only.
Section 9.2.1, Time 
Period and Frequency of 
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-19sequelaemay increase 
toxicity or impact interpretation of 
studyevents/results.
Remove inconsistent text to ensure 
alignment of this section with Table2-1.
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-19sequelaemay 
increase toxicity or impact interpretation 
of studyevents/results.
Section 9.4.4, Clinical 
Safety Assessments; 
Table 9.4.4-1 Clinical 
Laboratory Assessments
Added additional information regarding 
cardiac evaluation in the event of 
troponin elevations.
Clarification that troponin elevations will 
require cardiac evaluation in participants 
receiving ongoing treatment with 
relatlimab.
Section 9.5.1, 
Pharmacokinetics: 
Collection and 
Processing; Table 9.5.1-1 
PK and ADA Sampling 
Schedule for Relatlimab 
and Nivolumab
Updated footnotes to clarify End of 
Infusion (EOI) collection with respect 
to utilization of IV flush. 
Clarification for the sites regarding timing 
of EOI collection. 
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL03
Section Number & 
Title
Description of Change
Brief Rationale
Section 9.8.1.5, 
Circulating Tumor DNA 
Analysis (Plasma) 
Biomarkers
Updated to contain rationale for ctDNA 
and plasma samples. 
Clarification of rationale for collection. 
Section 10.1,Sample Size 
Determination
Added text on non-proportional hazards 
for sample size justification for Phase 2 
PFS estimation
Additional information added to provide 
clarity.
Section 10.2.2,Efficacy 
Analyses
Revised the Phase 3 secondary 
endpoints hierarchy (1. OS,2. ORR).
OS is a validated relevant endpoint in the 
current clinical landscape as described 
above. The testing strategy was changed 
to include an interim analysis of OS at the 
same time as a successful PFS analysis. 
This changes OS to be second in the 
hierarchy.
Provided more detail on the Phase 2 
Primary statistical methods.
Clarified Phase 2 PFS analysis.
Divided the “Testing Strategy” into 
separate sections for Phase 2 and Phase 
3.
Separation of Phase 2 and Phase 3 testing 
improves document clarity. 
Updated the Phase 3 Testing Strategy 
text to include overall alpha, and the 
plan and conditions for analysis of OS.
Provided potential subsequent analysis of 
OS secondary endpoint (if PFS is 
statistically significant), including alpha-
spending approach.
Updated the Phase 2 Testing Strategy 
text to include the stopping at Phase 2, 
and when the Sponsor would be 
unblinded in that case.
Clarified intention to unblindsponsor 
after 183 events if enrollment is stopped.
Appendix 2,Study 
Governance 
Consideration
Updated definition of “serious breach”;
provided additional criteria for the CSR 
Signatory Investigator; added 
publication policy.
Updated to most current definition in 
alignment with current standards.
Appendix 4, Women of 
Childbearing Potential 
Definitions and Methods 
of Contraception
Language regarding contraception 
for male participantswas removed 
from the appendix.
Updated the definition of end of 
relevant systemic exposure from 24 
weeks to 5 months.
Male 
contraception 
language 
removed due to no genotoxicity and 
no transmission of biologically 
relevant amount to WOCBP partner.
Updated relevant exposure duration 
for females to align with most recent 
IBfor nivolumab.
Appendix 9,Immuno-
oncology Agent 
Management Algorithms
Replaced IO agent management 
algorithms with those aligned with 
CTCAE v5.
Updated management algorithms for 
immune-mediated AEs to align with 
current CTCAE version (v5) and 
nivolumab IB.
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL03
Section Number & 
Title
Description of Change
Brief Rationale
All
Minor formatting and typographical 
corrections.
Minor, therefore have not been 
summarized.
References: 
1 Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J-J, et al.Five-year survival with combined nivolumab and 
ipilimumab in advanced melanoma. N Engl J Med.2019;381(16):1535-1546.
2 Ritchie G, Gasper H, Man J, et al.Defining the most appropriate primary end point in Phase 2 trials of immune 
checkpoint inhibitors for advanced solid cancers:a systematic review and meta-analysis. JAMA Oncol. 
2018;4(4):522-528.
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TABLE OF CONTENTS 
TITLE PAGE 
................................................................................................................ 
DOCUMENT HISTORY 
.............................................................................................. 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 03 
......................... 
TABLE OF CONTENTS 
............................................................................................. 
1 SYNOPSIS 
................................................................................................................. 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
3 INTRODUCTION 
..................................................................................................... 
3.1 Study Rationale 
................................................................................................ 
3.1.1 Research Hypothesis 
................................................................................ 
3.2 Background 
....................................................................................................... 
3.2.1 Indication Background 
............................................................................. 
3.2.2 Relatlimab Mechanism of Action 
............................................................. 
3.2.3 Nivolumab Mechanism of Action 
............................................................. 
3.3 Benefit/Risk Assessment .................................................................................. 
4 OBJECTIVES AND ENDPOINTS 
........................................................................... 
5 STUDY DESIGN....................................................................................................... 
5.1 Overall Design 
.................................................................................................. 
5.1.1 Data Monitoring Committee and Other External Committees 
................ 
5.2 Number of Participants 
..................................................................................... 
5.3 End of Study Definition 
.................................................................................... 
5.4 Scientific Rationale for Study Design............................................................... 
5.4.1 Rationale for Use of Fixed-Dose Combination Product.......................... 
5.4.2 Rationale for Blinding.............................................................................. 
5.4.3 Rationale for Stratification by M-Staging, BRAF, LAG-3, and PD-L1 
... 
5.4.4 Rationale for Progression-Free Survival as a Primary Endpoint 
........... 
5.4.5 Rationale for Inclusion of Adolescent Participants 
................................. 
5.4.6 Rationale for Evaluation of Predictive Biomarkers 
................................. 
5.5 Justification for Dose 
........................................................................................ 
5.5.1 Justification for Fixed-Dose Combination Dosing 
.................................. 
5.5.2 Justification for Nivolumab Monotherapy Dose 
...................................... 
5.5.3 Dose Rationale for Adolescents 
............................................................... 
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 or Lead-In Period 
....................................... 
7 TREATMENT 
........................................................................................................... 
7.1 Treatments Administered 
.................................................................................. 
7.1.1 BMS-986213 or Nivolumab Dosing 
......................................................... 
7.2 Method of Treatment Assignment 
.................................................................... 
7.3 Blinding............................................................................................................. 
7.4 Dosage Modification 
......................................................................................... 
7.4.1 Dose Modifications 
.................................................................................. 
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7.4.2 Dose Delay Criteria 
................................................................................. 
7.4.3 Criteria to Resume Treatment 
.................................................................. 
7.4.4 Management Algorithms for Immuno-Oncology Agents 
......................... 
7.5 Preparation/Handling/Storage/Accountability 
.................................................. 
7.5.1 Retained Samples for Bioavailability/Bioequivalence 
............................. 
7.6 Treatment Compliance 
...................................................................................... 
7.7 Concomitant Therapy........................................................................................ 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
7.7.1.1 Prohibited Treatments .................................................................... 
7.7.1.2 Imaging Restriction and Precautions 
............................................. 
7.7.2 Permitted Therapy ................................................................................... 
7.7.2.1 Palliative Therapy 
........................................................................... 
7.7.2.2 Surgical Resection Following Initial Response 
.............................. 
7.7.3 Treatment of Infusion-Related Reactions 
................................................. 
7.8 Treatment After the End of the Study 
............................................................... 
8 DISCONTINUATION CRITERIA 
........................................................................... 
8.1 Discontinuation from Study Treatment ............................................................ 
8.1.1 Dose Discontinuation............................................................................... 
8.1.2 Treatment Beyond Progression 
................................................................ 
8.1.2.1 Rationale 
......................................................................................... 
8.1.2.2 Criteria Required for Treatment Beyond Progression 
................... 
8.1.3 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............................................................ 
9.1.2 Methods of Measurement 
......................................................................... 
9.1.2.1 BICR Confirmation of Progression ................................................ 
9.1.3 Patient-Reported Outcomes 
..................................................................... 
9.1.3.1 EQ-5D-3L ....................................................................................... 
9.1.3.2 FACT-M 
.......................................................................................... 
9.1.3.3 WPAI:GH 
........................................................................................ 
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 
................................................................................................ 
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9.4.3 Electrocardiograms 
................................................................................. 
9.4.4 Clinical Safety Laboratory Assessments 
.................................................. 
9.4.5 Imaging Safety Assessment 
...................................................................... 
9.5 Pharmacokinetic and Immunogenicity Assessments 
........................................ 
9.5.1 Pharmacokinetics: Collection and Processing 
........................................ 
9.5.2 Pharmacokinetic Sample Analyses 
.......................................................... 
9.5.3 Immunogenicity 
........................................................................................ 
9.6 Pharmacodynamics 
..........................................
................................................. 
9.7 Pharmacogenomics 
..........................................
................................................. 
9.8 Biomarkers 
........................................................................................................ 
9.8.1 Peripheral Blood Markers 
....................................................................... 
9.8.1.1 Soluble Biomarkers 
......................................................................... 
9.8.1.2 Immunophenotyping 
........................................................................ 
9.8.1.3 T-Cell Repertoire Analysis 
.............................................................. 
9.8.1.4 Whole Blood for Germline DNA 
..................................................... 
9.8.1.5 Circulating Tumor DNA Analysis (Plasma) Biomarkers................ 
9.8.2 Tumor Samples......................................................................................... 
9.8.2.1 LAG-3 and PD-L1 Expression 
........................................................ 
9.8.2.2 Characterization of Tumor Infiltrating Lymphocytes (TILs) and 
Immune Biomarkers 
.............................................................................. 
9.8.2.3 Characterization of T-Cell Repertoire 
............................................ 
9.8.2.4 Gene Expression Profiling 
.............................................................. 
9.8.2.5 Tumor Genotyping, Mutational Analysis, and Tumor Antigen 
Profiling
 ................................................................................................
 
9.8.2.6 Tumor Sample Collection ............................................................... 
9.8.2.7 Additional Research Collection 
...................................................... 
9.9 Medical Resource Utilization and Health Economics 
...................................... 
10 STATISTICAL CONSIDERATIONS .................................................................... 
10.1 Sample Size Determination 
............................................................................. 
10.2 Statistical Analyses 
......................................................................................... 
10.2.1 Demographics and Baseline Characteristics......................................... 
10.2.2 Efficacy Analyses 
................................................................................... 
10.2.3 Safety Analyses....................................................................................... 
10.2.4 Other Analyses 
....................................................................................... 
10.2.4.1 Pharmacokinetic Analyses 
............................................................ 
10.2.4.2 Immunogenicity Analyses.............................................................. 
10.2.4.3 Outcomes Research 
....................................................................... 
10.2.5 Interim Analyses 
..................................................................................... 
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 
......................................................................... 
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APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION 
..................................................................... 
APPENDIX 5 RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS 
........................ 
APPENDIX 6 ECOG, KARNOFSKY, AND LANSKY PERFORMANCE STATUS 
SCALES 
.................................................................................................................. 
APPENDIX 7 AJCC MELANOMA STAGING (CANCER STAGING MANUAL 
8TH EDITION) 
....................................................................................................... 
APPENDIX 8 COUNTRY SPECIFIC REQUIREMENTS ......................................... 
APPENDIX 9 MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS 
................................................................................................................. 
APPENDIX 10 MUCOSAL MELANOMA STAGING 
.............................................. 
APPENDIX 11 REVISED PROTOCOL SUMMARY OF CHANGE HISTORY 
...... 
 
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1
SYNOPSIS
Protocol Title: A Randomized, Double-Blind Phase 2/3 Study of Relatlimab Combined with 
Nivolumab versus Nivolumab in Participants with Previously Untreated Metastatic or 
Unresectable Melanoma
Study Phase: 2/3
Rationale:
Individually targeting immune checkpoint receptors such as CTLA-4 and PD-1 has been clinically 
successful across multiple tumor types. It is possible, however, that combination therapies could 
potentially lead to greater depth of response and overall survival as has been noted with anti-PD-1 
and anti-CTLA-4 combination therapy in advanced melanoma patients. Targeting additional 
checkpoints, such as LAG-3, is considered a promising, novel approach. Blockage of LAG-3 in 
combination with anti-PD-1 has potential to improve efficacy in comparison with blocking 
anti-PD-1 alone without adding significant toxicity.
This study aims to demonstrate that treatment with BMS-986213 showsincreasedprogression-
free survival(PFS)compared with nivolumab monotherapy in participants with previously 
untreated, unresectable, or metastatic melanoma. Additional objectivesinclude the evaluation of 
OS, response rate and duration, characterization of safety and tolerability, pharmacokinetics, 
potential predictive biomarkers, and changes in patient-reported outcomes for quality-of-life 
assessments.
Study Population:
The study population includes adults and adolescents 12 years of age with unresectable or 
metastatic melanoma with no prior systemic anticancer therapy for their disease.
Key Inclusion Criteria:
Participants must havean ECOG performance status of 1/Lansky Performance Score ≥ 80% 
for minors (ages 12-17) ONLY
Participants must have histologically confirmed Stage III (unresectable) or Stage IV 
melanoma, per the AJCC staging system (8th edition)
Participants must be treatment-naïve (ie, no prior systemic anticancer therapy for unresectable 
or metastatic melanoma). 
Note that the following prior adjuvant or neoadjuvant melanoma therapies are allowedif 
all related adverse events have either returned to baseline or stabilized.
Anti-PD-1 or anti-CTLA-4 therapy with at least 6 months between the last dose and 
date of recurrence.
Interferon therapy with the last dose at least 6 weeks prior torandomization.
BRAF-or MEK-inhibitor-containing adjuvant therapy regimens with at least 6 months 
between the last dose and date of recurrence.
Participants must have measurable disease by CT or MRI per RECISTv1.1 criteria
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Tumor tissue froman unresectable or metastatic site of disease must be provided for biomarker 
analyses. In order to be randomized, a participant must be classified as PD-L1 positive or 
PD-L1 negative as well as LAG-3 positive or LAG-3 negative. 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 biomarker analyses.
Participants must have known BRAF V600 mutation status or consent to BRAF V600 mutation 
testing per local institutional standards during the screening period.
Prior radiotherapy must have been completed at least 2 weeks prior to study treatment 
administration.
Women must not bepregnant orbreastfeeding.
Key Exclusion Criteria:
Participants must not have active brain metastases or leptomeningeal metastases. Participants 
with brain metastases are eligible if these have been treated and there is no MRI evidence of 
progression for at least 4weeks after treatment is complete and within 28 days prior to first 
dose of study treatment administration. There must also be no requirement for 
immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) 
for at least 2 weeks prior to study treatment administration. Participants with brain disease 
treated with whole brain radiation are not eligible.
Participants must not haveuveal melanoma
Participants must not haveanactive, known, or suspected autoimmune disease. Participants 
may enroll with the following conditions:
type 1 diabetes mellitus
hypothyroidism only requiring hormone replacement
skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment
conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Participants must not havea condition requiring systemic treatment with either corticosteroids 
(>10mg daily prednisone equivalent) or other immunosuppressive medications within 
14days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid 
doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune 
disease.
Participants must not havea history of myocarditis
Participant must not havehad prior treatment with an anti-PD-1 (except if given as adjuvant 
or neoadjuvant therapy for melanoma), anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody 
(except if given as adjuvant or neoadjuvant therapy for melanoma), or any other antibody or 
drug specifically targeting T-cell costimulation or immune checkpoint pathways(except for 
interferon given as adjuvant or neoadjuvant therapy for melanoma). Prior treatment with 
relatlimab or any other with LAG-3 targeted agents.
Approved 5.0
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Objectives and Endpoints:
Objectives
Endpoints
Phase 3 Primary Objective
The Phase 3 primary objective is to compare 
PFS
of BMS-986213 to nivolumab 
monotherapy in participants with previously 
untreated, unresectable or metastatic 
melanoma.
PFS time as assessed by a Blinded 
Independent Central Review (BICR), 
using RECIST v1.1. PFS is defined as the 
time between the date of randomization 
and the first date of documented 
progression, or death due to any cause, 
whichever occurs first.
1. Phase 3 Safety Objective:
Toassesstheoverallsafetyandtolerability
of
BMS-986213 and of
nivolumab
monotherapy.
IncidenceofAEs,SAEs,AEsleadingto
discontinuation of treatment, deaths,
andlaboratoryabnormalities.
Phase 3 Secondary Objectives
The Phase 3 secondary objectives are:
To compare overall survival (OS) of 
BMS-986213 to nivolumab monotherapy in 
participants with previously untreated, 
unresectable or metastatic melanoma.
OS is defined as the time between the 
date of randomization and the date of 
death due to any cause.
To compare ORR of BMS-986213 to 
nivolumab monotherapy in participants with 
unresectable or metastatic melanoma.
ORR as assessed by a BICR. The ORR is 
defined as the number of subjects with a 
BOR of CR or PR divided by the number 
of randomized
subjects for each 
treatment group. The BOR is defined as 
the best response designation, recorded 
between the date of randomization and 
the date of objectively documented 
progression per RECIST v1.1 or the date 
of subsequent anti-cancer therapy, 
whichever occurs first.
Phase 2 Primary Objective
The Phase 2 primary objective is to compare 
PFS of BMS-986213 to nivolumab 
monotherapy in participants with previously 
untreated, unresectable, or metastatic 
melanoma.
PFS time as assessed by a Blinded 
Independent Central Review (BICR), 
using RECIST v1.1. PFS time is defined 
as the time between the date of 
randomization and the first date of 
documented progression, or death due to 
any cause, whichever occurs first.
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Objectives
Endpoints
2. Phase 2 Safety Objective:
Toassesstheoverallsafetyandtolerability
of
BMS-986213 and of
nivolumab
monotherapy.
IncidenceofAEs,SAEs,AEsleadingto
discontinuation of treatment, deaths,
andlaboratoryabnormalities.
Phase 2 Secondary Objectives
The Phase 2 secondary objectives are:
Toestimatethetreatmenteffect,measured
byORR, asdetermined byBICR using
RECISTv1.1 in all-comers and in subgroups 
based on combinations of LAG-3 expression 
(1% expression versus <1% expression)
and PD-L1status (1% tumor cell surface 
expression versus <1% tumor cell surface 
expression) among participants with 
unresectable or metastatic melanoma treated 
with BMS-986213 compared to those treated 
with nivolumab monotherapy.
ORR as assessed by a BICR.
To evaluateDOR and PFSratesatpre-
specifiedtimepoints(eg,24weeks)based
onBICRassessmentsusingRECISTv1.1 in 
the randomized population (for DOR) and in 
subgroups based on combinations of LAG-3 
expression (1% expression versus <1% 
expression and PD-L1status (1% tumor 
cell surface expression versus <1% tumor 
cell surface expression) among subjects with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
DOR
PFS time as assessed by a BICR using 
RECIST v1.1.
Toassessthe1-and2-yearOS rate in the 
randomized population and in subgroups 
based on combinations of LAG-3 expression 
(1% expression versus <1% expression)
and PD-L1status (1% tumor cell surface 
expression versus <1% tumor cell surface 
expression) 
among 
subjects 
with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
OS is defined as the time between the 
date of randomization and the date of 
death due to any cause. 
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Overall Design:
This is a Phase 2/3, randomized, double-blind study of BMS-986213 (fixed-dose combination 
relatlimab/nivolumab at a 1:3 ratio) versus nivolumab monotherapy in adult and adolescent 
participants (ages 12 to 17 years of age) with previously untreated, unresectable, or metastatic 
melanoma.
Depending on the treatment arm, the participant will receive BMS-986213 or nivolumab in a 
blinded manner. 
One cycle of treatment is defined as 4 weeks. Treatment beyond initial investigator-assessed 
RECIST v1.1-defined progression is permitted if the participant has investigator-assessed 
clinical benefit, is tolerating study treatment. Dose reductions will not be allowed.
On-study tumor assessments will begin12 weeks after randomization and will continue every 
8 weeks until Week 52 and every 12 weeks thereafter until BICR-confirmed disease 
progression or treatment discontinuation, whichever occurs later.
Number of Participants: 
The Phase 2 part of the study will enroll approximately 400 participants. An interim analysis of 
PFS will be performed when a minimum follow-up of 12 weeks is achieved for approximately 400 
randomized subjects or at least150PFSevents have been observed using BICR. If the interim 
analysis of PFS is positive (based on a pre-specified threshold as defined in the Statistical Analysis 
Plan (SAP) and the DMC Charter), then the study will continue to Phase 3 and remain blinded. If 
the interim analysis of PFS does not support continuing to the Phase 3 study, the study will allow 
the Phase 2 data to mature and then unblind the sponsor for analysis. If the latterscenario takes 
place, approximately 575 participants will need to be enrolled in order to randomize 400
participants assuming a screen failure rate of 30%.
If the study does continue to Phase 3, it is expected that approximately 1000 participants will need 
to be enrolled to randomize at least 700 participants, assuming a screen failure rate of 
approximately30%. 
Participants will be randomized 1:1 to one of two parallel treatment groups: 
BMS-986213 IV Q4W
nivolumab IV Q4W
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Treatment Arms and Duration:
Study Treatment: 
Study Treatments for CA224047
Medication 
Potency 
IP/Non-IP 
BMS-986213
(Relatlimab 160mg/
Nivolumab 480mg)
16 mg/mL
IP
Nivolumab 480 mg
10 mg/mL
IP
The study design schematic for adults and adolescents is presented below.
Figure 1-1:
Study Design Schematic
a Asafety lead-in evaluation will be performed on the first (up to) 18 participants.
b BMS-986213 is the fixed-dose combination relatlimab/nivolumab at a 1:3 ratio. For adults, dosing is relatlimab 
160 mg/nivolumab 480 mg. Adolescents ≥ 40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 
relatlimab 2 mg/kg/nivolumab 6 mg/kg.
c Nivolumab monotherapy dosing for adults is 480 mg. Adolescents ≥40 kg will receive adult dosing; for adolescents 
< 40 kg, dosing is 6 mg/kg. 
d The 700 subjects in Phase 3 will consist of the 400 from Phase 2 and an additional 300 from the Phase 3 part of the 
trial.
During the treatment phase, participants will receive the following treatments in a blinded manner:
BMS-986213 IV Q4W (for adolescent participants < 40 kg, the dose will be weight-based 
relatlimab 2 mg/kg Q4W, nivolumab 6 mg/kg Q4W) or, 
Previously untreated for 
unresectableor
 
metastatic melanoma
•Tissue available for 
b
iomarker
 analyses
Stratify by:
•PD-L1 status
•LAG-3 status
•BRAF status
•AJCC M
 stage
BMS-986213b
IV Q4W
Nivolumabc
IV Q4W
Randa
1:1
Enrollment 
Pause
Interim Analysis
Decision Point
BMS-986213b
IV Q4W
N
ivolumab
c
IV Q4W
Phase 2
N=400
Phase 3
N=700d
Screening Period
Stratification
Treatment 
Assignment
On Treatment
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CA224047
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Nivolumab 480 mg IV Q4W (for adolescent participants < 40 kg, the dose will be weight-
based; nivolumab 6 mg/kg Q4W)
Dose reductions are not permitted for either study treatment.
Doses of relatlimab and nivolumab should be delayed due to treatment-related adverse events as 
outlined in the protocol. Treatment may be discontinued due to unacceptable toxicity, withdrawal 
of consent, disease progression, or termination of the study, whichever occurs first. A DMC will 
provide independent oversight of safety, study conduct, and efficacy of the study treatments. The 
DMC will convene to assess the results of the interim analysis and provide its recommendations. 
Duration
An interim PFSanalysis will be performed when a minimum follow-up of 12 weeks is achieved 
for approximately 400 randomized subjects or at least150PFSevents have been observed using 
BICR. 
If the decision from the PFS interim is not to proceed to Phase 3, the study will stop enrollment 
and remain blinded until the final analysis of the Phase 2 study which will be performed with a 
minimum of 183 PFS events.
The total duration of the study for the Phase 3 primary endpoint of PFS will be determined by 
accrual of events.This is estimated to occur approximately 27 months after the first participant is 
randomized (which includes a potential 6-month delay in enrollment at the time of the interim 
analysis).
Additional follow-up for OS may be conducted up to approximately 5 years after the 
randomization of the last participant.
Approved 5.0
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2
SCHEDULE OF ACTIVITIES
Table 2-1:
Screening Procedural Outline (CA224047)
Procedure
ScreeningVisit
Notes
Eligibility Assessments
Informed Consent
X
Prior to any screening procedures.
Contact IRT 
X
For participant number assignment at time informed consent is obtained.
Inclusion/Exclusion Criteria
X
All inclusion/exclusion criteria should be assessed at screening.
Medical History
X
Including concomitant medications, disease state related to the study, AJCC M stage, 
and BRAF mutation status.
Tumor Tissue Samples
X
All participants must have tumor tissue available, either recent archival sample 
(obtained within 3 months of enrollment and with no intervening treatment between 
time of acquisition and enrollment) or a fresh pre-treatment biopsy obtained during 
the screening period. Tissue may be from a core biopsy, punch biopsy, excisional 
biopsy, or surgical specimen. Sufficient quantities must be available: a block or a 
minimum of 20 slides is requested. The analytical laboratory must provide IRT with 
related results prior to randomization.
In order to be randomized, a participant must have quantifiable PD-L1 expression (≥ 
1% or < 1% tumor cell membrane staining), and LAG-3 expression (≥ 1% or < 1%).
Please refer to Section 9.8.2for additional information.
BRAF Status
Results from a previous or new BRAF mutation test or a new sample must be 
processed per local institutional standard. Although this will be conducted on all 
participants, the results will be required for entry into IRT by the site prior to 
randomization.
NRAS and KIT Status
Results from a previous or new NRAS and KIT mutational test, if available, must be 
documented.
Safety Assessments
Physical Examination
X
Within 14 days prior to randomization.
Physical Measurements (including performance 
status)
X
Within 14 days prior to randomization.Height, weight, and ECOG Performance 
Status/Lansky Performance Score for minors ONLY (see Appendix 6).
Vital Signs 
X
Within 14 days prior to randomization.Including BP, heart rate, and temperature.
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Clinical Protocol
CA224047
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Table 2-1:
Screening Procedural Outline (CA224047)
Procedure
ScreeningVisit
Notes
Assessment of Signs and Symptoms
X
Within 14 days prior to randomization.
Concomitant Medication Use
X
Within 14 days prior to randomization.
Serious Adverse Events Assessment
X
Serious Adverse Events ongoing from time of consent.
Laboratory Tests
X
Hematology, Serum Chemistry, and Urinalysis as outlined inTable 9.4.4-1within 14 
days of randomization.
Serology as outlined inTable 9.4.4-1within 28 days of randomization.
For HIV: testing at sites where locally mandated, see Appendix 8.
Troponin
X
Within 14 days prior to randomization.
ECG
X
Within 14 days prior to randomization.
Pregnancy Test (WOCBP only)
X
Serum or urine (minimum sensitivity equivalent units 25IU/L or equivalent units of 
HCG).
Follicle-stimulating hormone (FSH)
X
If needed to document post-menopausal status as defined inTable 9.4.4-1.
Efficacy Assessments
Body Imaging
X
Contrast-enhanced CT of the chest, abdomen, pelvis, and all known sites of disease 
within 28 days prior to randomization.
SeeTable 9.1.2-1for preferred and alternative imaging methods.
Brain Imaging
X
MRI of the brain without and with contrast is required for ALL participants during 
screening to rule out brain metastases within 28 days prior to randomization. CT of 
the brain (without and with contrast) can be performed if MRI is contraindicated.
SeeTable 9.1.2-1for preferred and alternative imaging methods.
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Clinical Protocol
CA224047
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Table 2-2:
On-Study Assessments (CA224047)
Procedurea
Day 1 of each 
cycle 
(Cycle = 4 weeks)
Other Time 
Points Relative to 
Dosing Schedule
Notes
Safety Assessments
Inclusion/Exclusion Criteria
X
All inclusion/exclusion criteria should beconfirmed prior to randomization.
Targeted Physical Examination
X
To be performed only as clinically indicated within 3 calendar days prior to 
dosing.
Vital Signs 
X
Including BP, heart rate, and temperature within 3 calendar days prior to dosing.
Physical Measurements 
(including performance status)
X
Weight and ECOG Performance Status/Lansky Performance Score for minors 
ONLY (see Appendix 6) within 3 calendar days prior to dosing.
Adverse Events Assessment
Continuously
All AEs (SAEs or non-serious AEs), including those associated with SARS-
CoV-2 infection, must be collected continuously during the treatment period.
Concomitant Medication 
Assessment
Continuously
Laboratory Tests
X
Within 3 calendar days prior to dosing including Hematology, Serum 
Chemistry, Urinalysis as outlined inTable 9.4.4-1.
All labs should be checked prior to dosing.
Troponin 
X
C1D1 (predose)* and C1D14 (5days).
C2D1 (predose) and C2D14 (5days).
C3D1 (predose).
*  Only if not done at screening.
Predose:Within 3 calendar days prior to dosing. All labs should be checked 
prior to dosing.
Day 14 lab should be checked as soon as possible.In case of high troponin, 
perform cardiac imaging via echocardiography or cardiac MRI.
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Clinical Protocol
CA224047
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Table 2-2:
On-Study Assessments (CA224047)
Procedurea
Day 1 of each 
cycle 
(Cycle = 4 weeks)
Other Time 
Points Relative to 
Dosing Schedule
Notes
ECG
X
Within 3 calendar days prior to dosing; all ECGs should be checked prior to 
dosing.
Pregnancy Test (WOCBP only)
X
Serum or urine (minimum sensitivity equivalentunits 25IU/L or equivalent 
units of HCG) within 24 hours prior to administration of first dose of study 
treatment and then every 4 weeks (7 days) regardless of dosing schedule.
Home pregnancy test that meets the minimum sensitivity requirements can be 
used as necessary.
Efficacy Assessments
Body Imaging
X
FIRST tumor assessment should be performed at 12 weeks (1 week) relative 
to date of randomization.
SUBSEQUENT tumor assessments should occur every 8 weeks (1week) up 
to Week 52(relative to date of randomization) and then every 12 weeks (1 
week) (relative to date of randomization). Tumor assessments should continue 
until disease progression is confirmed by BICRor discontinuation of study 
treatment, whichever occurs later.
Contrast enhanced CT chest, CT (or MRI with and without contrast) abdomen, 
pelvis,and all known sites of disease. Use same imaging method as was used at 
screening/baseline. 
See Section 9.1.
Brain Imaging
X
Participants with a history of brain metastasis or symptoms should have a 
surveillance MRI (without and with contrast) study 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 
Section9.1. 
SeeTable 9.1.2-1for instructions on performance of scans in participants with 
contrast allergies.
Pharmacokinetic and Immunogenicity Assessments
PK and Immunogenicity blood 
sample
X
Refer toTable 9.5.1-1.
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Clinical Protocol
CA224047
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Table 2-2:
On-Study Assessments (CA224047)
Procedurea
Day 1 of each 
cycle 
(Cycle = 4 weeks)
Other Time 
Points Relative to 
Dosing Schedule
Notes
Exploratory Biomarkers
On treatment tumor biopsy
X
On-treatment tumor biopsy optional for all participants (see Table 9.8.2.6-1).
Biopsied lesions should be distinct from index lesion(s) being evaluated for 
radiological response, if clinically feasible.
Exploratory Serum & Plasma 
Biomarkers, Peripheral Blood 
Mononuclear Cells (PBMCs)
X
Refer toTable 9.8.2.6-1.
Whole Blood Sample (DNA)
X
The whole blood sample (DNA) is to be collected predose for the first dose only 
(only one time point).
SeeTable 9.8.2.6-1.
Additional Research 
Sampling
X
SeeSection9.8.2.7.
Patient-Reported Outcomes Assessments
EQ-5D-3L
X
Each assessment should be completed at the start of the clinic visitprior to 
dosing.
Pediatric participants (≥12 and <18 years of age) should only complete the EQ-
5D-3L and not the WPAI:GH or FACT-Massessments
FACT-M
X
WPAI:GH
X
Health Care Resource 
Utilization
X
Health care resource utilization data will be collected at each visit by study site 
staff using the CRF.
Clinical Drug Supplies
Administer Study Treatment
X
The first dose is to be administered within 3 calendar days following 
randomization.
Study treatments will be administered via a single IV bagin a single 1-hour 
infusion.
Treatment will continue until progression, unacceptable toxicity, or study ends.
a If a dose is delayed, the procedures scheduled for that same timepoint should also be delayed to coincide with when that timepoint’s dosing actually occurs, 
except for body imaging and pregnancy testing.
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Clinical Protocol
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BMS-986213
relatlimab-nivolumab fdc
Table 2-3:
Follow-Up Procedural Outline (CA224047)
Procedure
Follow-Upa
Visits 1and 2
Survival Follow-
Up Visitsb
Notes
Safety Assessments
Targeted Physical Examination
X
Weight, BP, heart rate, and temperature.Targeted physical examination 
to be performedonly as clinically indicated.
Serious Adverse Events Assessment/ 
Adverse Events Assessment
X
All SAEs and non-serious AEs should be collected continuously during 
the treatment period and for a minimum of 100 days following 
discontinuation of study treatment.
Participants will be followed for all SAEs, non-serious AEs of special 
interest (as defined in Section 9.2.3), 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.
Laboratory Tests
X
For Follow-Up Visit 1, onsite/local including Hematology, Serum 
Chemistry, and Urinalysis as outlined inTable 9.4.4-1.
Repeat at Follow-Up Visit 2 if study treatment related toxicity persists.
Pregnancy Test (WOCBP only)
X
Pregnancy testing is only required at FU Visits1 and 2 unless increased 
frequency and duration is required per local regulations.
Efficacy Assessments
Body Imaging
X
X
Only for participants withoutBICR-confirmed progression on study 
therapy. 
Tumor assessments subsequent to the first assessment should occur 
every 8 weeks (± 1 week) up to Week 52and then every 12 weeks (± 1 
week) until disease progression is documented or study treatment is 
discontinued, whichever occurs later
Contrast enhancedCT chest, CT (or MRI with and without contrast) 
abdomen, pelvis,and all known sites of disease. Use same imaging 
method as was used at screening/baseline. See Section 9.1.
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Table 2-3:
Follow-Up Procedural Outline (CA224047)
Procedure
Follow-Upa
Visits 1and 2
Survival Follow-
Up Visitsb
Notes
Brain Imaging
X
X
Only for participants withoutBICR-confirmed progression on study 
therapy. 
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.
SeeTable 9.1.2-1for instructions on performance of scans in 
participants with contrast allergies.
PFS2 Assessment
X
X
Following first progression, participants will continue to be followed 
during the safety and survival Follow-Up Visits. Time of second 
progression per investigator’s assessment will be documented.
Pharmacokinetic (PK) Assessments
PK and Immunogenicity blood sample
X
Refer toTable 9.5.1-1for details regarding specific sample timing.
Outcomes Research Assessments
EQ-5D-3L
X
X
For survival visits, questionnaire can be administered by phone.
Pediatric participants (≥12 and <18years of age) should only complete 
the EQ-5D-3L and not the WPAI:GH or FACT-Massessments
FACT-M
X
FACT-M melanoma subscale(MS)
X
For survival visits, MS questionnaire can be administered by phone.
WPAI:GH
X
Health Care Utilization
X
Health care resource utilization data will be collected by study site staff 
using the CRF.
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Clinical Protocol
CA224047
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relatlimab-nivolumab fdc
Table 2-3:
Follow-Up Procedural Outline (CA224047)
Procedure
Follow-Upa
Visits 1and 2
Survival Follow-
Up Visitsb
Notes
Exploratory Biomarker Testing
Tumor Tissue Biopsyand Biomarker 
Assessments
SeeTable 9.8.2.6-1.
a Follow-upvisits occur as follows:Follow-up Visit 1 = 30 days from the last dose (7 days) or coincide with the date of discontinuation (7 days) if date of 
discontinuation is greater than 42days after last dose.Follow-up Visit 2 = 100days (7 days) from last dose of study treatment. Participants must be followed 
for at least 100 days after last dose of study treatment.Both follow-up visits should be conducted in person.
bSurvival follow up visits may be conducted in clinic or by phone. Survival visits:first Survival Follow-up visit 3 months (14 Days) after FU 2, subsequent 
survival FU visits every 3 months (14 days). BMS may request that survival data be collected on all treated participants outside of the 3 month specified 
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.
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3
INTRODUCTION
Study CA224047is a Phase 2/3, randomized, double-blind study ofBMS-986213 (fixed-dose 
combination[FDC]relatlimab/nivolumab at a 1:3 ratio)versusnivolumabmonotherapy in 
participants with previously untreated, unresectable,or metastatic melanoma. Relatlimabis a fully 
human lymphocyte activation gene 3(LAG-3)-specific antibody that was isolated following 
immunization of transgenic mice expressing human immunoglobulin (Ig) genes. Relatlimabbinds 
to LAG-3 with high affinity and prevents binding of this receptor to cells bearing its ligand, major 
histocompatibility complex (MHC) Class II, the peptide antigen presentation molecule recognized 
by CD4+ T cells. Relatlimabbinding inhibits the negative regulatory function of LAG-3 in vitro. 
By blocking the normal downregulatory pathway, relatlimab enhances the anti-tumor immune 
response and, thus, has the potential to inhibit the growth of multiple malignancies when 
administered in combination with other therapeutic immuno-oncology (IO) monoclonal antibodies
(mAbs).
Nivolumab is a human mAb (IgG4-S228P) that targets the programmed death-1 (PD-1) cluster of 
differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory 
molecule expressed by activated T and B lymphocytes.
1 Binding of PD-1 to its ligands, 
programmed death-ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of lymphocyte 
activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses 
and antigen-specific T-cell responses to both foreign antigens as well as self-antigens.
BMS-986213is being developed for use in patients with advanced malignancies, including 
melanoma. This is the first randomizedstudy for BMS-986213and will allow for direct 
comparison of BMS-986213versusnivolumabmonotherapy in participants with unresectable or 
metastatic melanoma.
3.1
Study Rationale
Individually targeting immune checkpoint receptors such asCTLA-4 and PD-1 has been clinically 
successful across multiple tumor types.It is possible, however,that combination therapies could 
potentially lead to greater depth of response and overall survival(OS)as has been noted with the 
combination of anti-PD-1 and anti-CTLA-4 in advanced melanoma patients.2,3 Targeting 
additional checkpoints, such as by targetingLAG-3, is considered apromising novel approach.
The combination blockage of LAG-3 andanti-PD-1 has potential to improve efficacy without 
adding significant toxicity compared to blockinganti-PD-1 alone.
This study aims to demonstrate that treatment with BMS-986213shows increased progression-
free survival (PFS) compared with nivolumab monotherapy in participants with previously 
untreated, unresectable, or metastatic melanoma. Additional objectives of the study include
evaluation of OS, response rate and duration,characterization of safety and tolerability, 
pharmacokinetics, potential predictive biomarkers, and changes in patient -reported outcomes for 
quality-of-life assessments.
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3.1.1
Research Hypothesis
Treatment with BMS-986213will improve PFSwhen compared to nivolumabmonotherapy in 
previously untreated participants with unresectable or metastatic melanoma.
3.2
Background
3.2.1
Indication Background
Melanoma, the most serious form of skin cancer, accounts for approximately 1-2% of all cancer 
deaths and approximately 5% of all new cases of cancer in the United States (US) with a 5-year 
survival rate of 18% for late-stage disease.4
Prior to 2011, approved therapies for the treatment of metastatic melanoma were limited and 
included chemotherapy (DTIC) and immunotherapy (interleukin-2 [IL-2]). Since then,threenew 
therapeutic classes have been added to the treatment armamentarium and include sevennew drugs 
administered as monotherapy or in combination. These drugs include: 1) ipilimumab, an anti-
CTLA-4 blocking antibody, 2) drugs targeting the tyrosine kinase pathways including BRAF and 
MEK which include vemurafenib, dabrafenib, trametinib, and cobimetinib, and 3) monoclonal 
antibodies that bind to the PD-1 receptor, which include the recently approved nivolumaband 
pembrolizumab.Thoughmany of these therapies have demonstrated OS benefit in Phase 3 studies, 
there are still areas of high unmet medical need for this population. Many patients relapse within 
months of initiating treatment5,6,7or are not eligible for treatment due to tumor mutation status 
requirements (eg,BRAF V600 mutation is present in approximately 50% of melanoma tumors).8,9
Overall, despite advances in therapeutic options, patients with metastatic melanoma continue to 
experience poor long-term clinical outcomes, reflecting the aggressive nature and complex 
etiology of the disease, and highlighting the continued unmet medical need.
3.2.2
RelatlimabMechanism of Action
Relatlimabis a fully human antibody specific for human LAG-3 that was isolated from immunized 
transgenic mice expressing human immunoglobulin genes. It is expressed as an IgG4isotype 
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 (Kd,0.25-0.5nM) and 
specificity and potently blocks the interaction of LAG-3with its ligand, MHC class II (IC50, 
0.7nM). 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, relatlimabenhances activation of human T cells in superantigen stimulation 
assays when added alone or in combination with nivolumab (antiPD-1 antibody).
See also the Investigator’s Brochure (IB)for relatlimabSection4.1 (nonclinical pharmacology 
studies with relatlimab) and Section 4.2 (nonclinical pharmacokinetics with relatlimab).
3.2.3
NivolumabMechanism of Action
Cancer immunotherapy rests on the premise that tumors can be recognized as foreign rather than 
as self andcan be effectively attacked by an activated immune system. An effective immune 
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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 cancercell 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.
10,11,12
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).
13Collectively, 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, ICOS, and BTLA.14 PD-1 signaling has been shown to inhibit CD28-mediated 
upregulation of IL-2, IL-10, IL-13, interferon-γ (IFN-γ) and Bcl-xL. PD-1 expression 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.15These 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.
Nivolumab is a fully human, IgG4 (kappa) isotype, monoclonal antibodythat binds PD-1. 
Blockade of the PD-1pathway by nivolumab was studied using the mixed lymphocyte reaction 
(MLR). PD-1 blockade resulted in a reproducible enhancement of both proliferation and IFN-
release in the MLR.16The effect of nivolumab on antigen-specific recall response was investigated 
using a CMV-re-stimulation assay with human peripheral blood mononuclear cells (PBMCs), and 
was evaluated by ELISA. 
In vitro, nivolumab(BMS-936558) binds to PD-1 with high affinity (EC50 0.39-2.62 nM), and 
inhibits the binding of PD-1 to its ligands PD-L1 and PD-L2 (IC50 1 nM). Nivolumabbinds 
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 nivolumabresults in a reproducible enhancement 
of both proliferation andIFN-γ release in the MLR. Using a cytomegalovirus (CMV)
re-stimulation assay with human PBMC, the effect of nivolumabon antigen specific recall 
response indicates that nivolumabaugmented IFN-γ secretion from CMV specific memory T cells 
in a dose-dependent manner versus isotype-matched control. In vivo blockade of PD-1 by a murine 
analog of nivolumabenhances the anti-tumor immune response and result in tumor rejection in 
several immunocompetent mouse tumor models (MC38, SA1/N, and PAN02).17
3.3
Benefit/Risk Assessment
There continues to be a significant unmet need for patients with previously untreated, unresectable 
melanoma. BMS-986213has the potential for increased benefit compared to nivolumab
monotherapy, withan acceptable safety profile.
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Study CA224020 is aPhase 1 dose escalation and cohort expansion study of the safety, tolerability, 
and efficacy of relatlimab administered alone and in combination with nivolumab in advanced 
solid tumors. As of cut-off date of 07-Apr-17,preliminary proof-of-concept efficacy has been 
revealed in Part C in the combination treatment expansion cohort of advanced melanoma with 
prior treatment with anti-PD-1/PD-L1. All subjects were treated with relatlimab80 mg 
+nivolumab 240 mg every 2 weeks. The overall ORR was 11.5% (n=61 response evaluable) with 
a disease control rate of 49%. Biomarker analyses showed that patients whose tumor associated 
immune cells expressed more LAG-3 had a higher response rate, with a greater than 3-fold increase 
in ORR observed in patients with evidence of LAG-3 expression in at least 1% of nucleated cells 
within the tumor region, compared to less than 1% LAG-3 expression (ORRs of 18.2% [6/33] and 
5.0% [1/20], respectively). PD-L1 expression did not appear to enrich forresponse.
The treatment group had the following characteristics: 1) Most patients had M1C disease (69%), 
2) the cohort was heavily pretreated (76% with 2 or more prior therapies), 3) all patients had 
progressed while receiving anti-PD-1/PD-L1, and 4) progressive disease was the best response to 
prior anti-PD-1/PD-L1 in 40% of patients. Overall,relatlimabin combination with nivolumab 
demonstrated encouraging initial efficacy with a safety profile similar to nivolumab monotherapy.
In summary, relatlimabin combination with nivolumab hasshown the capacity to induce responses 
in heavily treated advanced solid tumors, with the added ability to trigger responses in tumors that 
have demonstrated resistance to nivolumab therapy.
Thisstudy involves investigational (relatlimab) and approved (nivolumab) drugs whose effects on 
pregnancy arenot yet known or fully defined.Contraception is therefore required for participants 
who are women of childbearing potential (WOCBP)or male, and for female partners of male 
participants who are WOCBP. Thesecontraception guidelines (see Appendix 4) were developed 
for the nivolumab development program and apply to all female participants and partners of male 
participants who could be exposed to the drug and who could become pregnant both during 
treatment andduring a defined period after study drug treatment.
Overall, based on preliminary data as of the clinical cutoff date of 15-Jun-2017, the safety profile 
of relatlimabin combination with nivolumab is manageable, with no maximum tolerated dose 
(MTD)reachedat the tested doses up to 160 mg relatlimaband 240 mg nivolumab (flat dose, every 
2 weeks [Q2W]), with evaluation of the 240mg relatlimab/240 mg nivolumab combination dose-
level ongoing. At the time of the clinical cutoff date (15-Jun-2017) onedose-limiting toxicity 
(DLT) of Grade 5myocarditis was observed at the 240 mg relatlimab/240 mg nivolumab 
combination dose level among fiveevaluable subjects. There was no dose relationship between 
the incidence, severity, or causality of adverse events (AEs)to combination therapy. In the nine
expansion cohorts, a total of 262 subjects were treated with 80 mg relatlimaband 240 mg 
nivolumab Q2W. Most AEs were low grade (Grade 1 to Grade 2) with a total of 26 subjects 
experiencing a drug-related serious adverse event (SAE). All AEs, except for oneGrade 5 
myocarditis and oneGrade 4 drug-induced liver injury(DILI), were reversible and manageable by 
withholding study drug administration providing standard medical care, and/or following immune-
related AE algorithms.In summary the safety profile of the combination of relatlimab and 
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nivolumab appears similar to nivolumab monotherapy in terms of both frequency and severity of 
AEs.
A pattern of immune-related adverse events has been defined for treatment with nivolumab
monotherapy and nivolumabin combination with other immune-targeting agents such as 
relatlimab. Management algorithms have been developed for these events and are provided in 
Appendix 9. Most high-grade events are manageable with the use of corticosteroids or hormone 
replacement therapy (endocrinopathies) as instructed in these algorithms.
Myocarditis has been observed with nivolumab monotherapy treatment (see nivolumab IBSection 
5.6.2). Given the grade 5 myocarditis event in the CA224020 study,and the known nonclinical 
mouse double LAG-3/PD-1 knockout myocarditisphenotype, increased cardiac surveillance with
troponin measurements were instituted.As of the clinical cutoff date of 15-Jun-2017 there have 
been four grade 1 myocarditis cases (asymptomatic troponin elevations with imaging correlate of 
myocardial inflammation but without evidence of cardiac dysfunction). Treatment was delayed in 
all cases, and precautionary steroid treatment was given without any of the participants developing 
evidence of cardiac dysfunction.
Additional details on the safety profiles of 
relatlimaband nivolumab, including 
guidance regarding 
myocarditis and other potential risks, as well as results from other clinical studies, are available in 
the relatlimaband nivolumab IBs.
Evaluating the combination of relatlimaband nivolumab will provide clinical data allowing 
clinicians to select the appropriate treatment for each patient based on the individual risk-benefit 
ratio. The promising clinical activity of relatlimabcombined with nivolumabin participants with 
advanced melanomaalongwith the manageable safety profile and the ongoing need for survival-
prolonging agents for a large segment of the previously untreated population,supports further 
development of this combination and initiation of this Phase 2/3 study.
This study will employ the FDC drug product BMS-986213 in which both drugs are formulated in 
the same vial. However, given a theoretical risk of infusion reactionsdue to the new formulation,
an acute toxicity safety lead-in with BMS-986213 will be completed.
4
OBJECTIVES AND ENDPOINTS
Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Phase 3 Primary Objective
The Phase 3 primary objective is to compare 
PFS of BMS-986213 to nivolumab 
monotherapy in participants with previously 
untreated, unresectable, or metastatic 
melanoma.
PFS time as assessed by a Blinded 
IndependentCentral Review (BICR), 
using RECIST v1.1. PFS is defined as the 
time between the date of randomization 
and the first date of documented 
progression, or death due to any cause, 
whichever occurs first.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Phase 3 Safety Objective:
To assess the overall safety and tolerability 
of BMS-986213 and of nivolumab 
monotherapy.
IncidenceofAEs,SAEs, AEsleadingto
discontinuation of treatment,deaths,
andlaboratoryabnormalities.
Phase 3 Secondary Objectives
The Phase 3 secondary objectives are:
To compare OS of BMS-986213 to 
nivolumab monotherapy in participants with 
previously untreated, unresectable or 
metastatic melanoma.
OS is defined as the time between the 
date of randomization and the date of 
death due to any cause.
To compare ORR of BMS-986213 to 
nivolumab monotherapy in participants with 
unresectable or metastatic melanoma
ORR as assessed by a BICR. The ORR is 
defined as the number of subjects with a 
best overall response (BOR)of complete 
response (CR)or partial response (PR)
divided by the number of randomized 
subjects for each treatment group. The 
BOR is defined as the best response 
designation, recorded between the date of 
randomization and the date of objectively 
documented progression per RECIST 
v1.1or the date of subsequent anti-cancer 
therapy, whichever occurs first.
Phase 3 Tertiary/Exploratory Objective
The Phase 3 tertiary/exploratory objectives are:
To evaluate duration of and time to objective 
response
Duration of response (DOR) is defined as 
the time between the date of first 
response to the date of first documented 
tumor progression (per RECIST v1.1) or 
death due to any cause. Time to objective 
response (TTR) is defined as the time 
from randomization to the date of the 
first documented CR or PR.
To evaluate PFS, ORR, DOR, and OS of 
BMS-986213 to nivolumab monotherapy in 
subgroups based on combinations of LAG-3 
expression (1% expression versus <1% 
expression)and PDL-1status (1% tumor 
cell surfaceexpression versus <1% tumor 
cell surface expression)among participants 
with unresectable or metastatic melanoma 
PFS time as assessed by a BICR using 
RECIST v1.1.
ORR as assessed by a BICR.
DOR.
TTR.
OS.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
treated with BMS-986213 compared to those 
treated with nivolumab monotherapy.
To evaluate the difference in symptom 
burden 
between 
participants 
with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
Time to meaningful 
symptomatic 
deterioration (TTSD) as measured by the 
Functional Assessment
of Cancer 
Therapy
– Melanoma 
(FACT-M) 
Melanoma Subscale (MS).
To characterize the pharmacokinetics(PK)
of relatlimab and nivolumab in subjects with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
PKparameters, influence of intrinsic and 
extrinsic covariates will be characterized 
using population PKmodels.
To 
characterize immunogenicity of
relatlimab and nivolumab in subjects with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
Incidence of anti-drug-antibody (ADA) 
to relatlimab and nivolumab when 
administered in combination with 
nivolumab. 
To explore potential exposure-response 
relationships in subjects treated with
BMS-986213.
Potential exposure response relationship 
(PDeffect, efficacy,and select safety) 
will be evaluated using integrated 
analysis.
To explore potential biomarkers associated 
with clinical efficacy (ORR, PFS,and OS) 
by analyzing biomarker measures within the 
tumor microenvironment and periphery (eg, 
tumor, serum and PBMCs) as related to
clinical outcomes.
Association 
measures 
of select 
biomarkers and key efficacy endpoints 
(eg,ORR, PFS, and OS)
To characterize changes in cancer-related 
symptoms and quality of life for participants 
with unresectable or metastatic melanoma 
treated with BMS-986213 and those treated 
with nivolumab monotherapy 
Summary measures of FACT-M total 
and subscale scores (and changes) 
following treatment.
To characterize participant perceptions of the 
bothersomeness of symptomatic AEs, based 
on FACIT GP5 item as found in the FACT-
M.
Summary changes and frequency of 
responsesin FACIT GP5 item measuring 
bother due to side effects of treatment.
To characterize changes in overall health 
status and health utility for participants with 
unresectable or metastatic melanoma treated 
Summary measures of EQ-5D-3L visual 
analog scale (VAS) and utility index 
scores.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
with BMS-986213 and those treated with 
nivolumab monotherapy.
To characterize changes in work productivity 
and activity impairment for participants with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy  
Summary 
measures 
of 
Work 
Productivity and Activity Impairment 
General Health
(WPAI:GH)
work 
productivity loss, activity impairment, 
presenteeism, and absenteeism scores.
To evaluate PFS, PFS after next line of 
treatment (PFS2),ORR, and DOR of BMS-
986213 to nivolumab monotherapy in 
participants with previously untreated, 
unresectable, or metastatic melanoma
PFSand PFS2 timeasassessedby
investigatorusingRECISTv1.1.
ORR as assessed by investigator.
DOR.
To evaluate treatment-free interval (TFI) 
defined as time from last dose of study 
treatment to the start of subsequent systemic 
therapy or the last known date alive (for 
those who never received subsequent cancer 
therapy)
TFI
Phase 2 Primary Objective
The Phase 2 primary objective is to compare 
PFS of BMS-986213 to nivolumab 
monotherapy in participants with previously 
untreated, unresectable, or metastatic 
melanoma.
PFS time as assessed by BICR, using 
RECIST v1.1. PFS time is defined as the 
time between the date of randomization 
and the first date of documented 
progression, or death due to any cause, 
whichever occurs first.
Phase 2 SafetyObjective:
To assess safetyandtolerabilityamong 
participants with unresectable or metastatic 
melanoma treated with BMS-986213 
compared to those treated withnivolumab 
monotherapy.
IncidenceofAEs,SAEs, AEsleadingto
discontinuation of treatment,deaths,
andlaboratoryabnormalities.
Phase 2 Secondary Objectives
The Phase 2 secondary objectives are:
To estimate the treatment effect, measured 
by ORR, as determined by BICR using 
RECIST v1.1 in all-comers and in subgroups 
based on combinations of LAG-3 expression 
(≥ 1% expression versus <1% expression)
and PDL-1 status (≥ 1% tumor cell surface 
ORR as assessed by a BICR.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
expression versus <1% tumor cell surface 
expression) among participants with 
unresectable or metastatic melanoma treated 
with BMS-986213 compared to those treated 
with nivolumab monotherapy.
To evaluateDOR and PFSratesatpre-
specifiedtimepoints(eg,24weeks)based
onBICRassessmentsusingRECISTv1.1 in 
the randomized population (for DOR) and in 
subgroups based on combinations of LAG-3 
expression (1% expression versus <1% 
expression and PDL-1status (1% tumor 
cell surface expression versus <1% tumor 
cell surface expression) among subjects with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
DOR.
PFS time as assessed by a BICR using 
RECIST v1.1.
Toassessthe1-and2-year OS rate in the 
randomized population and in subgroups 
based on combinations of LAG-3 expression 
(1% expression versus <1% expression)
and PDL-1status (1% tumor cell surface 
expression versus <1% tumor cell surface 
expression) 
among 
subjects 
with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
OS is defined as the time between the 
date of randomization and the date of 
death due to any cause.
Phase 2 Exploratory Objectives
Phase 2 exploratory objectives are:
To characterize the PK of relatlimab and 
nivolumab in subjects with unresectable or 
metastatic 
melanoma 
treated with 
BMS-986213 and those treated with 
nivolumab monotherapy.
Summary measures of PK parameters 
based on population PK models 
including influence of intrinsic and 
extrinsic covariates 
To characterize the immunogenicity of
relatlimab and nivolumab in subjects with 
unresectable ormetastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
Incidence of ADA to relatlimab and 
ADA of nivolumab when administered in 
combination with relatlimab
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
ToassessthePDeffectsofBMS-986213 
based on select biomarkersin the peripheral 
blood and tumor biopsyspecimens.
Summary measures of change (or % 
change) from baseline in various 
biomarkers.
To characterize T-cell function during 
treatment of BMS-986213.
Summary ofpre-treatmentlevelsand of 
changes in T cells levels observed on-
treatment.
To explore potential exposure-response 
relationships (eg, with efficacy, receptor 
occupancy, pharmacodynamic effects) in 
subjects treated withBMS-986213.
Measures of Potential PK exposure 
response 
relationship  
(with 
pharmacodynamic effects, efficacy and 
select safety) 
ToevaluateORR,DOR,PFS,and PFS2 rates
atpre-specifiedtime points(eg,24weeks)
based on investigatorassessments using 
RECISTin the randomized population and in 
subgroups based on combinations of LAG-3 
expression (1% expression versus <1% 
expression)and PDL-1status (1% tumor 
cell surface expression versus <1% tumor 
cell surface expression)among subjects with 
unresectable or metastatic melanoma treated 
with BMS-986213 and those treated with 
nivolumab monotherapy.
ORR.
DOR.
TTR.
PFS and PFS2 time using RECIST v1.1.
5
STUDY DESIGN
5.1
Overall Design
This is a Phase2/3, randomized, double-blind study of BMS-986213(FDCrelatlimab/nivolumab
at a 1:3 ratio)versus nivolumabmonotherapy in adult andadolescent participants (≥ 12 years of 
age) with previously untreated, unresectable,or metastatic melanoma. Participants must have 
unresectable Stage III or Stage IV melanoma, per the 8th edition of the American Joint Committee 
on Cancer (AJCC) staging system18(see Appendix 7),and must not have received prior systemic 
therapy for the treatment of unresectable or metastatic melanoma. 
The study design schematic is presented inFigure 5.1-1. 
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Figure 5.1-1:
Study Design Schematic
a A safety lead-in evaluation will be performed on the first (up to) 18 participants.
b BMS-986213 is the fixed-dose combination relatlimab/nivolumab at a 1:3 ratio. For adults, dosing is relatlimab 160 mg/nivolumab 480 mg. Adolescents ≥40 
kg will receive adult dosing; for adolescents < 40 kg, dosing is relatlimab 2 mg/kg/nivolumab 6 mg/kg.
c Nivolumab monotherapy dosing for adults is 480 mg. Adolescents ≥40 kg will receive adult dosing; for adolescents < 40 kg, dosing is 6 mg/kg. 
d The 700 subjects in Phase 3 will consist of the 400 from Phase 2 and an additional 300 from the Phase 3 part of the trial.
Previously untreated for
 
unresectableor
 
metastatic 
melanoma
•Tissue available for
 
biomarker
 analyses
Strat
ify by:
•PD-L1 status
•LAG-3 status
•BRAF status
•AJCC M stage
BMS-986213b
IV Q4W
Nivolumabc
IV Q4W
Randa
1:1
Enrollment 
Pause
Interim 
Analysis
Decision Point
BMS-986213b
IV Q4W
N
ivolumab
c
IV Q4W
Phase 2
N=400
Phase 3
N=700d
Screening Period
Stratification
Treatment 
Assignment
On Treatment
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A pre-treatment tumor sample to determine PD-L1 and LAG-3 status is required to be submitted 
from all participantsprior to randomization. The sample must be obtained within 3 months prior 
to enrollment from a metastatic tumor lesion or from an unresectable primary tumor lesion that
has not been previously irradiated; no intervening treatment may have been administered between 
the time of biopsy/surgeryand study entry. The tumor sample will be submitted as either a 
formalin-fixed paraffin-embedded(FFPE)block (preferred) or minimum of 20 slides requested, 
obtained fromcore biopsy, punch biopsy, excisional biopsy,or surgical specimen. If sufficient 
tissue is not available from within 3 months prior to enrollment, then a fresh biopsy will be required 
during the screening period. Sampleswill be submitted to the analytical laboratoryfor PD-L1and 
LAG-3testing. The analytical laboratorymust provide the interactive response technology (IRT)
withthe related results prior to randomization. 
Participants must have a documented BRAF status prior to randomization. Those participants 
enrolling in this study without documented results must have testing performed locally and result 
(wild type or mutant) be available prior to randomization. 
Depending on the treatment arm, the participantwill receive BMS-986213or nivolumabuntil 
disease progression, treatment discontinuation, withdrawal of consent,or the study ends. 
One cycle of treatment isdefined as 4weeks. 
Dose reductions will be not be allowed.
On-study tumor assessments will begin 12weeks from randomizationand will continue every 
8weeks up to Week 52and every 12 weeks thereafter. Tumor assessments should continueuntil 
disease progressionconfirmed by the BICR or treatment discontinuation, whichever occurs later. 
Treatment beyond initial investigator-assessed RECIST v1.1-defined progression (see 
Appendix5) is permitted if the participanthas investigator-assessed clinical benefitandis 
tolerating study treatment(Section 8.1.2andSection8.1.2.2).
The decision on whether to complete the Phase 3 enrollment (N=700) or stop at the Phase 2 
enrollment (N=400) will be recommended by the Data Monitoring Committee (DMC) based upon 
the interim analysis of PFS, which is for futility. If the Phase 2 enrollment is complete before a 
decision on completing the Phase 3 enrollment has been made, enrollment to the study will pause. 
Given estimates of accrual, this pause may be up 
to 5 to 6 months but could be shorter if enrollment 
is slower than anticipated. If the interim PFS analysis meets the pre-specified threshold and the 
study proceeds to Phase 3, the final PFS analysis will be performed when approximately365 PFS 
events have occurred per BICR (see Section 10.2.2).
Safety Lead-In
Given atheoretical risk of infusion reactions with the administration of BMS-986213, a safety 
lead-in will be employed for the first (up to) 18subjects randomized.
The lead-in will follow a 6+6+6design to monitor forGrade 3 or 4 infusion reactions. Sixsubjects 
will be treated in each sequential set. There will be no time interval restrictions for patients to 
begin treatment within aset of 6.
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The infusion reactionobservation period will be 48 hours. Completion of the observation 
period for all patients in each set must be completed prior to any randomization to the next set.
Rules:
If 1 of the first 6participantsexperiences a Grade 3 or 4 infusion reaction then the second 
set 
of 
6 
will 
be 
randomized.
If 2 of the first 6 participants experience a Grade 3 or 4 infusion reaction then 
randomization will be held until further evaluations can be performed.
If ≤2 of 12participantsexperience a Grade 3 or 4 infusion reaction the third set of 6 will 
be 
randomized.
If ≥3 of 12 participants experience a Grade 3 or 4 infusion reaction then randomization 
will be held until further evaluations can be performed.
If ≤2of 18, experience aGrade 3 or 4 reaction, randomization will be continued.
If ≥3 of 18subjects experience Grade 3 or 4 infusion reactions then randomizationwill be 
held until further evaluations can be performed.
For the management of infusion reactions, please refer to the treatment guidelines outlined 
under Section 7.7.3.
5.1.1
Data Monitoring Committee and Other External Committees
When required, adjudicated events will be submitted to the DMC and Health Authorities for review 
on a specified timeframe in accordance with the adjudication documentation.
A DMCwill be established to provide oversight ofsafety andefficacy considerations and to 
provide advice to the Sponsor regarding actions the committee deems necessary for the continued
protection of participants enrolled in the study. The DMC will be charged with assessing such 
actions in light of an acceptable benefit/risk profile for relatlimaband nivolumab. The DMC will 
act in an advisory capacity to BMS and will monitor participantsafety and evaluate the available 
efficacy data for the study. The oncology therapeutic area of BMS has primary responsibility for 
design and conduct of the study. 
The DMC will convene to assess the results of the interim analyses(see Section 10.2.5and provide 
its recommendations. Additional details concerning DMC oversight are provided in the DMC 
charter.
In addition, a BICR will be utilized in this study for determination of BICR-assessed endpoints. 
The BICR will review all available tumor assessment scans for all treated participants. Details of 
BICR responsibilities and procedures will be specified in the BICR charter.
5.2
Number of Participants
The Phase 2 part of the study will enroll approximately 400 participants. An interim analysis will 
be performed when a minimum follow-up of 12 weeks is achieved for approximately 
400randomized subjects or at least150PFSevents have been observed using BICR.The interim 
PFS analysis is a futility analysis.If the interim PFS analysis is positive (based on thepre-specified
thresholdas defined in theStatistical Analysis Plan [SAP]), then the study will continue to Phase 
3 and remain blinded. If the interimPFSanalysis does not support continuing to the Phase 3 study, 
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the study will allow the Phase 2datato mature and then unblind the sponsor for analysis. If the 
latterscenario takes place, approximately 575 participants will need to be enrolled in order to
randomize 400 participants assuming a screen failure rate of 30%.
If the study does continue to Phase 3, it is expected that approximately 1000 participants will need 
to be enrolled to randomize at least 700 participants, assuming a screen failure rate of
approximately 30%.
Participants will be randomized 1:1 to one of two parallel treatment groups: 
BMS-986213by intravenous (IV) infusion every 4 weeks (Q4W)
nivolumab IV Q4W
See Section10.1for sample size determination.
5.3
End of Study Definition
The start of the studyis defined as the first visit for the first participant screened. End-of-studyfor 
the primary endpoint is defined as the last visit or scheduled procedure shown in the Schedule of 
Activities 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.
An interim PFS analysis will be performed when a minimum follow-up of 12 weeks is achieved 
for approximately 400 randomized subjects or at least150PFSevents have been observed using 
BICR. If the decision from the interim analysis is not to proceed to Phase 3, the study will stop 
enrollment and remain blinded until the final analysis 
ofthe Phase 2 study 
which will be performed 
witha minimum of 183 PFS events.
The total duration of the study for the Phase 3 primary endpoint of PFSwill be determined by 
accrual of events.This is estimated to occur approximately 27 months after the first participant is 
randomized (which includes a potential 6-month delay in enrollment at the time of the interim 
analysis, see Section 10.1).
Additional follow-up for OS may be conducted up to approximately 5 years after the 
randomization of the last participant.
5.4
Scientific Rationale for Study Design
5.4.1
Rationale for Useof Fixed-DoseCombination Product 
BMS-986213, a FDC product,contains relatlimab and nivolumab in protein-mass ratio 1:3 in a 
single vial. The FDCwill be administered via IV infusionoverapproximately1 hour. Key 
advantages of a FDCare as follows:
Patients benefit from reduced infusion time and less time in the clinic and/or doctor’s office
Increased ease of administration
Pharmacists require less time in preparation of the intravenous solution to be administered to 
the patient
Reduces potential for medication preparation and administration error.
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5.4.2
Rationale for Blinding
The study will be double-blinded in order to:
minimize bias
limit thresholds for classification of progression between the arms(which could subsequently 
affect treatment duration between the arms and have an impact on the primary endpointof 
PFS)
curtail bias in reporting, classification, and management of adverse events.
As participants who progress will not require knowledge of which treatment arm they were 
assigned to for selection of subsequent therapies, blinding will be maintained even after disease 
progression.The Sponsor’s central protocol team (including but not limited to clinical, statistics, 
and data management) will remain blinded to treatment assignmentthroughout the duration of the 
study until the primary endpoint of PFS has been reached.
5.4.3
Rationale for Stratification by M-Staging, BRAF, LAG-3,and PD-L1 
In order to minimize the potential for imbalances across treatment arms, there will be four
stratification factors utilized in this trial: AJCC M stage (M0/M1any[0] versusM1any[1]), BRAF 
mutation (mutation positive versuswild type), LAG-3 status(1% expression versus <1% 
expression)and PD-L1expression(1% tumor cell surface expression versus<1% tumor cell 
surface expression). Prognostic implications of M staging are well established.
19BRAF mutations 
have likewise been associated with adverse clinical outcomes in melanoma patients.
20Preliminary 
data from the CA224020 study have shown that LAG-3 expression may be a strong predictor of 
efficacy in tumors that have become resistant to anti-PD-1 therapy.
21With regard to PD-L1 
expression, previous clinical studieswith nivolumab monotherapy have shown patients with PD-
L1 positive tumorsmayhave higher response rates than those with indeterminate expression.22
Participants in the current trial will therefore be stratified by PD-L1 status as the effect of PD-L1 
expression on response to PD-1 and anti-LAG-3combination therapies is not yet known. 
5.4.4
Rationale for Progression-Free Survival as a Primary Endpoint
Treatment options that are clinically active (eg, ipilimumab, vemurafenib, dabrafenib, trametinib) 
are increasingly available in patients with unresectable or metastatic melanomaand their use after 
disease progression on the current study may confound an OS endpoint. PFS is not confounded by 
post-study treatmenttherapies and has been demonstrated to correlate with overall survival in a 
meta-analysis of randomized, dacarbazine-controlled trials in metastatic melanoma.23In addition, 
PFS hasbeen recognizedas an acceptable regulatory endpoint. For example, dabrafenib and 
trametinib as monotherapy and in combination wereapproved by the FDA for treatment of
unresectable or metastatic melanoma based on Phase 3 clinical trials where the primary endpoint 
was PFS.
24,25,26Radiographic images will be collectedand should be submitted on a rolling basis 
to an Imaging Core lab,for BICR tumor assessment.
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5.4.5
Rationale for Inclusion of Adolescent Participants
Patients under 18 years of age have often been excluded from adult oncology trials because of 
safety or regulatory concerns; a practice that leads to delays in pediatric studies. Separate adult 
and pediatric cancer centers, distinct cooperative research groups, and oncologists specializing in 
different populations do not often conduct unified adult–pediatric clinical trials or -drug 
developmentprograms.27
Although rare, the incidence of childhood and adolescent melanoma in the United States has been 
increasing in the past 35 years. This trend is most prominent in the adolescent age range, 
specifically those 15 to 19 years of age. Single-center and industry-sponsored trials often exclude 
advanced melanoma adolescent patients for historical or empiric reasons. A recent genomic 
analysis of pediatric melanoma demonstrates that conventional melanoma in children and 
adolescents shares many of the genomic features that have been described in adult melanoma, 
including BRAF mutations. The abstract of this genomic analysis advocated for the opportunity 
for pediatric patients to be enrolled in pharmaceutically sponsored trials that incorporate novel 
agents. Many pediatric subjects who are diagnosed with melanoma get referred to and treated by 
medical oncologists versus pediatric oncologists, due to divergent expertise in the field.
28
Individual countries and sites have the option of opting out of adolescent eligibility.
5.4.6
Rationale for Evaluation of Predictive Biomarkers
Despite striking advances in patient survival drivenby immunotherapy, the majority of patients 
have not yet realized benefit from these treatments.Identification of biomarkers that predict 
clinical benefit or that are associated with resistance to therapy are critical needs.To date, PD-L1 
expression within the tumor microenvironment has been associatedwith response to treatment of 
melanoma with nivolumab as monotherapy or in combination with ipilimumab. Similarly, 
preliminary data suggest that expression of LAG-3on immune cells was associated with response 
to treatment of melanoma with relatlimabin combination with nivolumab. Additional biomarkers 
of response to immunotherapy include tumor mutation burden and gene signatures of tumor 
inflammation (IFNg signature). In the current trial, PD-L1 and LAG-3 levels, tumor mutation 
burden, and gene expression signatures will all be evaluated for predictive value of response to 
nivolumab monotherapy and BMS-986213. Serum, plasma, and peripheral blood immune cell 
analysis will be assessed in samples collected pretreatment and at time points during treatment. 
These analyses will allow identification of predictive biomarkers and allow discrimination 
between factors predictive of monotherapy versus combination therapy. Additional analysis of 
pretreatment versus on treatment tumor biopsies will be performed in order to identify additional 
pathways contributing to therapeutic resistance.
5.5
Justification for Dose
5.5.1
Justification for Fixed-Dose CombinationDosing
In this study, BMS-986213Q4W will be administered as an IVinfusion over approximately 
1hour. The dosing regimen for this study was selected after considering model predicted PK, 
peripheral receptor occupancy (RO), efficacy,and safety profile observed in adult population from 
Study CA224020,and extensive nivolumab monotherapy clinical experience.
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The predicted steady-state exposure and corresponding peripheral RO of relatlimab 160 mg Q4W 
is expected to be similar to the 80 mg Q2W dose, that is shown to provide meaningful efficacy 
when administered in combination with nivolumab in various tumor types. The relatlimab steady-
state average concentration and corresponding RO comparing the Q2W and Q4W regimen is 
provided inTable 5.5.1-1.
Table 5.5.1-1: 
Comparison of Relatlimab Model Predicted Steady-State Exposure 
and Corresponding RO between Q2W and Q4W Regimen
Parameter
80 mg Q2W
(Geo.Mean)
160 mg Q4W
(Geo.Mean)
% Difference
Cavg,ss (µg/mL)
19.1
19.3
1.05
RO (%)
94.4
94.4
0.00
Similarly, nivolumab 480 mg Q4W iscurrently under investigation in several monotherapy and 
combination oncology studies.The nivolumab dosing regimen wasselected using population PK
(PPK)and exposure-response analyses modeling and simulation approaches such that they are 
predicted to provide approximately equivalent exposures (Cavg,ss) following administration of 
nivolumab 3mg/kg Q2W. The model predicted that following administration of nivolumab 480 
mg Q4W, Cavg,ss is expected to be similar to those following nivolumab 3 mg/kg or 240 mg 
Q2W, thoughCmin,ss is predicted to be approximately 16% lower, respectively, and are not 
considered to be clinically relevant. Following nivolumab 480 mg Q4W, Cmax,ss ispredicted to 
be approximately 43% greater, relative to that following nivolumab 3 mg/kg Q2W dosing; 
however, the range of nivolumab exposures (median and 90% prediction intervals) following 
administration of 480 mg Q4W regimen across the 35 to 160 kg weight range arepredicted to be 
maintained well below the corresponding exposures observed with the well-tolerated 10 mg/kg 
nivolumab Q2W dosing regimen, and arenot considered to put participants at increased risk.
Relatlimab as a single agent has had an acceptable safety profile at all tested doses: 20, 80, 240, 
and 800 mg, flat dose. The MTD was not reached up to 800 mg relatlimab Q2W. The combination 
therapy of relatlimab and nivolumab when administered sequentially (nivolumab 30-minute IV 
infusion followed by relatlimab 1-hour IV infusion) has an acceptable safety profile ofall dose 
combinations that have completed safety testing, up to relatlimab160mg/nivolumab 240 mg 
Q2W. In addition, safety evaluation with alternative less frequent regimen (Q4W) dose escalation 
cohorts are currently under investigation in Study CA224020. The less frequent dosing regimens 
of relatlimab are designed to afford more convenience to the target patient population and allow 
combination with less frequent nivolumab dosing regimens. To date, the sequential administration 
of relatlimab 160 mg/nivolumab 480 mg Q4W has been shown safe (1DLT out of six evaluable 
subject) to move to the next cohort of relatlimab 240 mg/nivolumab 480 mg Q4W. 
Robust safety data (N=304) in patients treated with sequential administration (nivolumab 240 mg 
IV over 30 minutes followed by relatlimab 80 mg IV over 1 hour Q2W) has shown small risk 
(5.9%, all Grade 1 or 2) of infusion reactions. The overall safety as well as PK profile of 
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BMS-986213 is not expected to be different to that of the sequential administration. The 
comparative safety and PK assessment between sequential, co-administration and FDC is ongoing 
under Part D of study CA224020. This will make possible a shorter infusion time for patients with 
FDC product (infusion duration of 1 hour) thansequential infusion (total infusion duration of 
approximately 2.5 hours). 
Relatlimab 80 mg/nivolumab 240 mg Q2W has shown the capacity to induce responses in 
previously heavily treated advanced solid tumors, with the added ability to trigger responses in 
tumors that have demonstrated resistance to nivolumab therapy. As of the cutoff date of 
15-Jun-2017 for Part B of Study CA224020, in subjects treated with relatlimab/nivolumab 
combination therapy, partial responses were seen in subjects with melanoma, cervical cancer, non-
small cell lungcancer (NSCLC), and squamous cell carcinoma of the head and neck (SCCHN). 
There is limited data to summarize efficacy for relatlimab 160 mg/nivolumab 480 Q4W regimen. 
However, exposure-response profile of relatlimab 160 mg/nivolumab 480 mg Q4W is not expected 
to be different to the relatlimab 80 mg/nivolumab 240 mg Q2W.
5.5.2
Justification for Nivolumab Monotherapy Dose
The nivolumab dose of 480mg Q4W was selected for this study based on clinical data and 
modeling and simulation approaches using PPK and exposure-response (ER) analyses examining 
relationships between nivolumabexposures and efficacy (eg,OS, OR) and safety responses, using 
data from studies in multiple tumor types (melanoma, NSCLC, and renal cell carcinoma [RCC]) 
with body weight-normalized dosing (mg/kg). A flat doseis expected to reduce prescription dosing 
errors, shorten pharmacy preparation time, and improve ease of administration. Extending the 
dosing interval to 4 weeks provides numerous benefits to patients as they would have increased 
flexibility between clinical visits. The PPK analyses have shown that exposure to nivolumab
increased dose proportionally over the dose rangeof 0.1 to 10mg/kg administered Q2W, and no 
clinically meaningful differences in PK across ethnicities and tumor types were observed. 
Nivolumabclearance and volume of distribution were found to increase as body weight increases 
but less than proportionally with increasing weight, indicating that milligram-per-kilogram dosing 
represents an over-adjustment for the effect of body weight on nivolumabPK. 
Using the PPK and ER models, nivolumabexposures and probabilities of efficacy responses and 
risks of AEs were predicted following nivolumab480 mg Q4W and were comparable to those 
following nivolumab3 mg/kg Q2W. The overall distributions of average nivolumabsteady-state 
exposures (Cavg,ss) were comparable following administration with either nivolumab3mg/kg 
Q2W or nivolumab480mg Q4W over a wide range of body weight ranges.Nivolumab480mg 
Q4W is predicted to result in approximately 43% greater steady statepeak concentrations 
(Cmax,ss) compared to nivolumab3mg/kg Q2W; however, these exposures are predicted to be 
lower than the exposure ranges observed at doses up to nivolumab10mg/kg Q2W used in the 
nivolumabclinical program. Although the Cmax,ss of nivolumabis expected to be greater 
following nivolumab480 mg Q4W compared to nivolumab3 mg/kg Q2W, the predicted Cmax,ss 
following nivolumab 480 mg Q4W is well below the median Cmax,ss achieved following 
administration of nivolumab10 mg/kg Q2W, a safe and tolerable dose level. 
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Exposure-safety analysis demonstrated that the exposure margins for safety are maintained 
following nivolumab480 mg Q4W, and the predictedrisks of discontinuations due to AEs or 
death, AE Grade 3+, and immune-mediated AEs (IMAEs)Grade 2+, are predicted to be similar 
following nivolumab480 mg Q4W relative to nivolumab3 mg/kg Q2W across tumor types. Safety 
analyses using available data following nivolumab3mg/kg Q2W and 10 mg/kg Q2W 
administration indicated there were no differences in AE profiles across body weight groups. 
Finally, initial evidence demonstrates that, following administration of nivolumab480 mg Q4W, 
nivolumabhas been well tolerated.
Nivolumab 480mg Q4W is predicted to have approximately 16% lower steady-state trough 
concentrations (Cmin,ss) compared to nivolumab 3mg/kg Q2W. Thoughthese exposures are 
predicted to be lower, they are on the flat part of the exposure-response curves and are not predicted 
to affect efficacyexposure-efficacy analyses of multiple PK measures and efficacy endpoints 
(eg,OS, OR) indicated that, following administration of nivolumab480 mg Q4W, efficacy is 
predicted to be similar to that following administration of nivolumab3 mg/kg Q2W across multiple 
tumor types. Based on these data, nivolumab480mg Q4W is expected to have similar efficacy 
and safety profiles to nivolumab240mg Q2W or nivolumab3mg/kg Q2W.
5.5.3
Dose Rationale for Adolescents
The PKof drugs and many therapeutics proteins has been shown to be similar between adolescent 
and adults once the effect of body size on PKis taken into consideration.29,30Therefore, in general,
adult doses would expected to achieve similar systemic exposures in adolescents. In study 
CA224020,relatlimab in combination with nivolumab was administered as a flat dosing in adults, 
therefore, a minimum body weight threshold in adolescents (≥40 kg) is defined to receive the 
same adult flat dose to prevent exceeding target adult exposures. Adolescent participants<40-kg 
body weight will be given a weight-based dose that is equivalent to the adult dose(typical subject 
of 80-kg body weight). 
Adolescents ≥ 40 kg will be administered relatlimab 160 mg in combination with 480 mg 
nivolumab Q4W. Adolescents < 40 kg will be administered body weight adjusted relatlimab dose 
2 mg/kg and nivolumab 6 mg/kg Q4Wof relatlimab/nivolumab combination or 6mg/kg Q4W IV 
infusion over approximately1 hour. 
6 
STUDY POPULATION
6.1
Inclusion Criteria
For entry into the study, the following criteria MUST be met.
1) Signed Written Informed Consent
a) Participants must have signed and dated an IRB/IEC approved written informed consent 
form 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 
patient care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory testing, and other requirements of the study.
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2) Type of Participant and Target Disease Characteristics
a) Participants must havean Eastern Cooperative Oncology Group (ECOG) performance 
status of 1/Lansky Performance Score ≥ 80% for minors(ages 12-17)ONLY (for details, 
see Appendix 6).
b) Participants must have histologically confirmed Stage III (unresectable) or Stage IV 
melanoma, per the AJCC staging system(for details, see Appendix 7).
c) Participants must not have had prior systemic anticancer therapy for unresectable or 
metastatic melanoma. 
i) Note that the following prior adjuvant or neoadjuvant melanoma therapies are allowed
if all related adverse events have either returned to baseline or stabilized.
(1)Anti-PD-1 or anti-CTLA-4 therapy withat least6 months between the last dose and 
date of recurrence.
(2)Interferon therapy with thelast dose at least 6 weeks prior torandomization.
(3)BRAF-or MEK-inhibitor-containing regimenswith at least 6 months between the 
last dose and date of recurrence.
d) Participants must have measurable disease by CT or MRI per RECIST v1.1criteria (for 
details, see Appendix 5).
e) Tumor tissue from an unresectable or metastatic site of disease must be provided for 
biomarker analyses. Either a recent archival sample obtained within 3 months prior to 
enrollment (with no intervening treatment between time of acquisition and enrollment) or 
a fresh pre-treatment biopsy is to be submitted as a FFPE tissue block or unstained tumor 
tissue sections, to the analytical laboratory for inclusion. In order to be randomized, a 
participant must be classified as PD-L1 positive or PD-L1 negative, as well asLAG-3 
positive or LAG-3 negative. Participants with indeterminate or unevaluable PD-L1 or 
LAG-3 status results will not be permitted to randomize to a treatment arm. 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 ofbiomarker analyses.
The biopsy should be a core biopsy, a punch biopsy, an excisional biopsy, or a surgical 
specimen. Fine needle aspiration is unacceptable for submission.The analytical laboratory 
must provide IRT with the related results prior to randomization.
f) Participants must have known BRAF V600 mutation status or consentto BRAF V600 
mutation testing per local institutional standards during the screening period.
g) Prior radiotherapy must have completed at least 2 weeks prior to study treatment 
administration.
h) Participant Re-enrollment: This study permits the re-enrollment of a participant that has
discontinued the study as a pre-treatment failure (ie, participant has not been randomized). 
If re-enrolled, the participant must re-consent.
3) Age and Reproductive Status
a) Male and femaleparticipants must be≥ 12 years at the time of informed consent if local 
regulations and/or institutional policies allow for participants < 18 years of age (pediatric 
population). If pediatric population is not allowed to participate, then ≥ 18 years applies.
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b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L 
or equivalent units of HCG) within 24 hours prior to the start of study treatment.
c) Women must not be pregnant orbreastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception (see Appendix 
4) for the duration of treatment with study treatment(s) plus 24 weeksafter 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).
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception (see Appendix 4) for the duration of treatment with study 
treatment(s) plus 33 weeksafter the last dose of the study treatment (ie, 90 days [duration 
of sperm turnover] plus the time required for nivolumaband relatlimabto undergo 
approximately 5 half-lives). In addition, male participants must be willing to refrain from 
sperm donation during this time. 
f) WOCBP who are continuously not heterosexually active are exempt from contraceptive 
requirements, and still must undergo pregnancy testing as described in this section.
Investigators shall counsel WOCBP, and male participants whoare sexually active with WOCBP,
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective methods of contraception (Appendix 4) 
which have a failure rate of < 1% when used consistently and correctly. 
6.2
Exclusion Criteria
1) Medical Conditions
a) Participants must not have active brain metastases or leptomeningeal metastases. 
Participants with brain metastases are eligible if these have been treated and there is no 
MRI evidence of progression for at least 4weeks after treatment is complete and within 28 
days prior to first dose of study treatment administration. There must also be no 
requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day 
prednisoneequivalents) for at least 2 weeks prior to study treatment administration.
Participants with brain disease treated withwhole brain radiation are not eligible.
b) Participants must not haveuveal melanoma.
c) Participants must not haveanactive, known or suspected autoimmune disease. Participants 
may enroll with the following conditions:
i) with type 1diabetes mellitus
ii)hypothyroidism only requiring hormone replacement
iii)skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment
iv)conditions not expected to recur in the absence of an external trigger are permitted to 
enroll.
d) Participants must not have a condition requiring systemic treatment with either 
corticosteroids (>10mg daily prednisone equivalent) or other immunosuppressive 
medications within 14days of start of study treatment.Inhaled or topical steroids, and 
adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in 
the absence of active autoimmune disease.
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e) Participants must not havea historyof myocarditis.
f) Participants must not haveany serious or uncontrolled medical disorder that, in the opinion 
of the investigator, may increase the risk associated with study participation or study 
treatment administration, impair the ability of the participant to receive protocol therapy, 
or interfere with the interpretation of study results.
g) Participants must not havehad a 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.
2) Prior/Concomitant Therapy
a) Participants must not havehad prior treatment with an anti-PD-1(except if given as 
adjuvant or neoadjuvant therapy for melanoma), anti-PD-L1, anti-PD-L2, anti-CTLA-4 
antibody(except if given as adjuvant or neoadjuvant therapy for melanoma), or any other 
antibody or drug specifically targeting T-cell costimulation or immune checkpoint 
pathways(except for interferon given as adjuvant or neoadjuvant therapy for melanoma).
b) Participantsmust not have a history of life-threatening toxicity related to prior immune 
therapy (eg,anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug 
specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those 
that are unlikely to re-occur with standard countermeasures (eg,hormone replacement after 
adrenal crisis).
c) Participants must not havehad prior treatment withrelatlimabor any otherLAG-3 targeted 
agent.
d) Participants must not havetreatment 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. Refer to Section 7.7.1for 
prohibited therapies.
e) Participants must not have received a live / attenuated vaccine within 30 days of first 
treatment(inactivated vaccines are permitted).
3) Physical and Laboratory Test Findings
The following lab criteriamust be met:
a) WBC < 2000/L
b) Neutrophils < 1500/L
c) Platelets < 100*103/L
d) Hemoglobin < 9.0 g/dL
e) Serum creatinine > 1.5x ULN or calculated creatinine clearance < 40 mL/min (using the 
Cockcroft-Gault formula):
Female CrCl = (140-age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl = (140-age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL
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f) AST/ALT > 3.0x ULN
g) Total bilirubin > 1.5x ULN (except participants with Gilbert Syndrome who must have a 
total bilirubin level of < 3.0x ULN)
h) Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Between > 1 to 2 × ULN will be 
permitted if a repeat assessment remains ≤2×ULN and patient undergoes a cardiac 
evaluation.
i) Participants must not have any positive test result for hepatitis B virus or hepatitis C virus 
indicating presence of virus, eg, Hepatitis B surface antigen (HBsAg, Australia antigen) 
positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
j) Participants must not have a known history of a 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.
k) Participants must not have a positive pregnancy test at enrollment or prior to administration 
of study medication
4) Allergies and Adverse Drug Reaction
a) Participants must not havea history of allergy or hypersensitivity to study treatment 
components.
5) Other Exclusion Criteria
a) Participants must not beprisoners or involuntarily incarcerated. (Note: Under certain 
specific circumstances,a person who has been imprisoned may be included or permitted 
to continue as a participant. Strict conditions apply and BMSapproval is required.)
b) Participants must not becompulsorily 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
LifestyleRestrictions
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 are 
not subsequently randomized.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, 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 or Lead-In Period
Participant Re-enrollment: This study permits the re-enrollment of a participantwho has 
discontinuedthe study as a pre-treatment failure (ie, participanthas not been randomized). If re-
enrolled, the participantmust re-consent.
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Retesting of laboratory parameters and/or other assessments within any single Screening or Lead-
In 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 inTable 2-1, Screening Procedural 
Outline(CA224047),may be repeated in an effort to find all possiblewell-qualified participants. 
Consultation with the BMS Medical Monitor/designeemay be needed to identify whether repeat 
testing of any particular parameter is clinically relevant.
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:
BMS-986213
Nivolumab
An investigational product (IP;also known as investigational medicinal product in some regions)
is defined asa 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 preventive, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-
investigational products.
Investigational products used in this trial are provided inTable 7-1. There are no non-
investigational products in thisstudy.
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Table 7-1:
Study Treatments for CA224047 
Product Description / 
Class and Dosage Form
Potency
Primary Packaging 
(Volume)/Label Type
Secondary Packaging 
(Qty)/Label Type
Appearance
Storage Conditions
(per label)
BMS-986213
(Relatlimab80mg/
Nivolumab240mg)vial
16mg/mL 
20mL vial/open label
2 vials/carton
Colorless to pale yellow 
liquid, clear to slightly 
opalescent, light (few) 
particulates (consistent 
in appearance to protein 
particulates) may be 
present
Refer to the label on 
container and/or 
pharmacy manual
Nivolumab 100mg/vial
10mg/mL 
10mL vial/open label
4vials/carton/open 
label
Clear to opalescent, 
colorless to pale yellow
liquid,light (few) 
particulates may be 
present
Refer to the label on 
container and/or 
pharmacy manual
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7.1
Treatments Administered
Theselection and timing of dose for each participant is presented inTable 7.1-1.
Study treatment will be dispensed at the study visits as listed in Schedule of Activities (Section2). 
Table 7.1-1: 
Selection and Timing of Dose
Study 
Treatment
Patient 
Age/Weight
Unit dose 
strength(s)/Dosage 
level(s)
Dosage 
formulation/
Frequency of 
Administration
Route of Administration
BMS-986213
Adults
and adolescents
40 kg
Relatlimab 160 mg/
Nivolumab 480 mg
Total: 640 mg
Solution for 
injection/
every 4 weeks
IV
Adolescents
<40 kg
Relatlimab 2mg/kg/
Nivolumab 6 mg/kg
Total:8mg/kg
Solution for 
injection/
every 4 weeks
Nivolumab
Adults
and adolescents
40 kg
480 mg
Solution for 
injection/
every 4 weeks
IV
Adolescents
<40 kg
6mg/kg
Solution for 
injection/
every 4 weeks
For mg/kg dosing, the dosing calculations should be based on the body weight assessed at 
screening. It is not necessary to re-calculate subsequent doses if the subject weight is within 10% 
of the weight used to calculate the previous dose. All doses should be rounded to the nearest 
milligram. For an adolescent < 40kg becoming an adult, the dose calculation should continue to 
be based on the body weight and not switched to flat dosing.
7.1.1
BMS-986213 or Nivolumab Dosing
BMS-986213(prepared in normal saline for relatlimab 160mg/nivolumab 480 mg)or nivolumab 
480 mg dosing is to be administered as an IV infusion through a 0.2-micron to 1.2-micron pore-
size, low-protein binding in-line filter at the protocol-specified doses. It is not to be administered 
as an IV push or bolus injection. Instructions for dilution and infusion of relatlimab/nivolumab or 
nivolumab injection will be provided in the pharmacy binder. Care must be taken to assure sterility 
of the prepared solution as the product does not contain any antimicrobial preservative or 
bacteriostatic agent.
Participants should receive BMS-986213or nivolumabas a 1-hourinfusion on Day 1 of each 
treatment cycle until progression, unacceptable toxicity, withdrawal of consent, or thestudy ends, 
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whichever occurs first. Participants should begin study treatment within 3 calendar days of 
randomization.
The sponsor, participants, 
investigator,and site staff will be blinded to the study drug administered. 
Each investigative site must assign an unblinded pharmacist/designee.
There will be no dose escalations or reductions of any study treatmentallowed. Participants may 
be dosed within a 3 day window(ie,participants may be dosed no less than 25 days and no more 
than 31 days between doses). Premedication is not recommended for the first dose of either 
treatment.
Participants should be carefully monitored for infusion reactions during administration. If anacute 
infusion reaction is noted, participants should be managed according to Section 7.7.3.
Doses may be interrupted, delayed, or discontinued depending on how well the participant tolerates 
the treatment. Dosing visits must not be skipped, only delayed.
Infusions are compatible with polyvinyl chloride (PVC) or polyolefin containers and infusion sets, 
and glass bottles.
Care must be taken to assure sterility of the prepared solution as the product does not contain any 
antimicrobial preservative or bacteriostatic agent. 
For details on prepared drug storage, preparation, and administration, please refer to the IBs and/or 
pharmacy binder. 
The selection and timing of dose for each participant is provided inTable 7.1-1.
7.2
Method of Treatment Assignment
All participants will be centrally randomized using IRT. Before the study is initiated, each user 
will receive log-in information and directions on how to access the IRT. After the participant’s 
informed consent 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 participant who signs 
the informed consent form 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. The following information is required for enrollment:
Date that informed consent was obtained
Yearof birth
Gender at birth
After enrollmentin theIRT, participants who have met all eligibility criteria will be randomized 
through the IRT. The following information is required for participant randomization:
Participant number 
Yearof birth 
PD-L1 status(positive or negative)provided by the central lab directly to the IRT system
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LAG-3 IHC status (positive or negative)provided by the central lab directly to the IRT system
BRAF V600 mutational status(positive or wild type)
AJCC M stageat screening (M0/M1any[0] vs M1any[1]),
Participants will be randomized in a 1:1ratio as described in Section5.1and stratified by PDL-1 
status, LAG-3 status, BRAF status, and AJCC M stage as described below:
LAG-3 status
LAG-3 positive (1% expression) or
LAG-3negative (< 1% expression)
PD-L1 Status
PD-L1 positive (1% expression)or
PD-L1negative(<1% expression)
BRAF status
BRAF V600 mutation positive or
BRAF V600 wildtype
AJCC M stage at screening (see Appendix 7)
M0/M1any(0)
M1any(1)
The randomization procedures will be carried out via permuted blocks within each stratum, 
defined 
by combination ofLAG-3 status (positive ornegative),PD-L1 status(positive ornegative),BRAF 
V600 mutational status (positiveorwild type), and M Stage (M0/M1any[0] or M1any[1]). The 
exact procedures for using the IRT will be detailed in the IRT manual.
7.3
Blinding
The sponsor, participants, investigator,and site staff will be blinded to the study therapy 
administered.
Each investigative site must assign an unblinded pharmacist/designee.
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual participant in which knowledge of the 
investigational product is critical to the participant’s management, the blind for that participant 
may be broken by the investigator. The participant’s safety takes priority over any other 
considerations in determining if a treatment assignment should be unblinded.
Before breaking the blind of an individual participant
's treatment, the investigator should 
determine that the unblinded information is necessary, ie, that it will alter the participant
's 
immediate management. In many cases, particularly when the emergency is clearly not related to 
the investigational product, the problem may be properly managed by assuming that the participant 
is receiving active product. It is highly desirable that the decision to unblind treatment assignment 
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be discussed with the BMS Medical Monitor/designee, but the investigator always has ultimate 
authority for the decision to unblind. The actual TASK of unblinding can be delegated by the 
investigator to a designee assigned the task on the Delegation of Authority. The principal 
investigator or appointed designee should only call in for emergency unblinding AFTER the 
decision to discontinue the participant has beenmade.
For this study, the method of unblinding for emergency purposes isavailable in the IRT manual.
Any request to unblind a participant’s treatment assignment for non-emergency purposes should 
be discussed with the BMS Medical Monitor/designee.
In cases of accidental unblinding, contact the BMS Medical Monitor/designeeand ensure every 
attempt is made to preserve the blind.
The DMC will assess safety and risk benefit on an ongoing basis, and will have access to unblinded 
treatment codes for individual subjects. An external analysis team(external to BMS),including a 
reporting statistician and programming support, who are notinvolved with the conduct of the 
study, will provide analyses to the DMC. The procedures to be respected and the reasons for 
unblinding of the DMC are discussed in the DMC charter.
Ifthe interim PFSanalysis meetsthepre-specifiedthresholdandthestudyproceedstoPhase3,
thefinalPFSanalysiswillbeperformedwhenapproximately 365PFSeventshaveoccurredper
BICR.The sponsorwillbeunblindedto individual treatment assignments at the time of the final 
PFSanalysis.If the final PFS analysis is statistically significant, participants,investigator,andsite
staffwillremain blindedto individual treatment assignments untilaninterimOSresultis 
statistically significantoruntilfinalanalysisoftheOSendpoint,whichevercomesfirst.
At the time of the final PFS analysis, if the results are statisticallysignificant, there will be an 
interim analysis of OS (OS IA1). If the OS IA1 is not statistically significant, the second interim 
analysis of OS (OS IA2) will be performed when a minimum of 90% (270/300) of the expected 
deaths have occurred.If OS IA2 is not statistically significant, the final OS analysis will be 
performed when approximately300 deaths have occurred. 
Designated staff of BMS Research & Development may be unblinded prior to final PFS results to 
facilitate the bioanalytical analysis of pharmacokinetic, immunogenicity, and pharmacodynamic 
samples.
A bioanalytical scientist in the Bioanalytical Sciences department of BMS Research & 
Development (or a designee in the external central bioanalytical laboratory) will be unblinded to 
the randomized treatment assignments in order to minimize unnecessary bioanalytical analysis of 
samples.
To further minimize potential bias, the participants and the investigative clinical site staff are 
blinded to results from PD-L1 and LAG-3 analysis. 
7.4
Dosage Modification
AE criteria for delaying, resuming, and discontinuing of study treatment is provided in Table 7.4-
1.
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Table 7.4-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Treatment
Drug-Related Adverse Event 
(AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and Resume 
Criteria
Gastrointestinal
Colitis or Diarrhea
Grade 2 
Delay dose
Dosing may resume when AE resolves to 
baseline.
Grade 3 
Delay dose
Dosing may resume when AE resolves to 
baseline.
Grade 4 
Permanently discontinue
Renal
Serum Creatinine Increased
Grade 2 or 3 
Delay dose
Dosing may resume when AE resolves to Grade 
≤1 or baseline value.
Grade 4 
Permanently discontinue
Pulmonary
Pneumonitis
Grade 2 
Delay dose
Dosing may resume after pneumonitis has 
resolved to ≤ Grade 1.
Grade 3 or 4 
Permanently discontinue
Hepatic
Aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), or total 
bilirubin (T.bili) increased
AST or ALT > 3×and ≤5×
upper limit of normal 
(ULN) or T.Bili >1.5×and 
≤3×ULN, regardless of 
baseline value
Delay dose
Dosing may resume when laboratory values 
return to baseline.
AST or ALT > 5×ULN or 
T. bili > 3×ULN, 
regardless of baseline value
Permanently discontinue 
In most cases of AST or ALT > 5×ULN, study 
treatment will be permanently discontinued. If the 
investigator determines a possible favorable 
benefit/risk ratio that warrants continuation of 
study treatment, a discussion between the 
investigator and the Medical Monitor/ designee 
must occur and approval from Medical Monitor 
prior to resuming therapy.
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Table 7.4-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Treatment
Drug-Related Adverse Event 
(AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and Resume 
Criteria
Concurrent AST or ALT > 
3×ULN and T.bili > 2×
ULN, regardless of 
baseline value
Permanently discontinue 
Endocrinopathy
Adrenal Insufficiency
Grade 2 adrenal 
insufficiency
Delay dose
Dosing may resume after adequately controlled 
with hormone replacement.
Grade 3 or 4 adrenal 
insufficiency or adrenal 
crisis
Delay dose or permanently 
discontinue
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming 
therapy. If adrenal insufficiency resolves or is 
adequately controlled with physiologic hormone 
replacement, participant may not require 
discontinuation of study drug.
Hyperglycemia
Hyperglycemia requiring 
initiation or change in daily 
management (Grade 2 or 3)
Delay dose
Dosing may resume if hyperglycemia resolves to 
Grade ≤1 or baseline value, or is adequately 
controlled with glucose-controlling agents.
Grade 4
Delay dose or permanently 
discontinue
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming 
therapy. If hyperglycemia resolves, or is 
adequately controlled with glucose-controlling 
agents, participant may not require 
discontinuation of study drug.
Hypophysitis/Hypopituitarism
Symptomatic Grade 1-3 
that is also associated with 
corresponding abnormal 
lab and/or pituitary scan
Delay dose 
Dosing may resume if endocrinopathy resolves to 
be asymptomatic, or is adequately controlled with 
only physiologic hormone replacement.
Grade 4
Delay dose or permanently 
discontinue
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming 
therapy. If endocrinopathy resolves or is 
adequately controlled with physiologic hormone 
replacement, participant may notrequire 
discontinuation of study drug.
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Table 7.4-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Treatment
Drug-Related Adverse Event 
(AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and Resume 
Criteria
Hyperthyroidism or Hypothyroidism
Grade 2 or 3
Delay dose
Dosing may resume if endocrinopathy resolves to 
be asymptomatic, or is adequately controlled with 
only physiologic hormone replacement or other 
medical management.
Grade 4
Delay dose or permanently 
discontinue
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming 
therapy. If endocrinopathy resolves or is 
adequately controlled with physiologic hormone 
replacement or other medical management, 
participant may not require discontinuation of 
study drug.
Skin
Rash
Grade 2 rash covering 
>30% body surface area or 
Grade 3 rash 
Delay dose 
Dosing may resume when rash reduces to ≤10% 
body surface area.
Suspected Stevens-Johnson 
syndrome (SJS), toxic 
epidermal necrolysis 
(TEN) or drug reaction 
with eosinophilia and 
systemic symptoms 
(DRESS)
Delay dose
Dosing may resume if SJS, TEN, or DRESS is 
ruled out and rash reduces to is ≤10% body 
surface area.
Grade 4 rash or confirmed 
SJS,TEN, or DRESS
Permanently discontinue
Neurological
Guillain-Barre Syndrome (GBS)
Any Grade
Permanently discontinue
Myasthenia Gravis (MG)
Any Grade
Permanently discontinue
Encephalitis
Any Grade encephalitis
Delay dose 
After workupfor differential diagnosis, (ie,
infection, tumor-related), if encephalitis is not 
drug related, then dosing may resume when AE 
resolves.
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Table 7.4-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Treatment
Drug-Related Adverse Event 
(AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and Resume 
Criteria
Any Grade drug-related 
encephalitis 
Permanently discontinue
Myelitis
Any Grade myelitis
Delay dose
Afterworkup for differential diagnosis, (i.e. 
infection, tumor-related), if myelitis is not drug 
related, then dosing may resume when AE 
resolves.
Any Grade drug-related 
myelitis
Permanently discontinue
Neurological (other than GBS, MG, 
encephalitis, or myelitis)
Grade 2
Delay dose
Dosing may resume when AE resolves to 
baseline.
Grade 3 or 4
Permanently discontinue
Cardiovascular
Myocarditis
Symptoms induced from 
mild to moderate activity 
or exertion
Delay dose
Dosing may resume after myocarditis has 
resolved.
Severe or life threatening, 
with symptoms at rest or 
with minimal activity or 
exertion, and/or where 
intervention indicated.
Permanently discontinue
Cardiac Troponin I or Troponin T 
Increased
Asymptomatic
Delay dose
All troponin elevations (including asymptomatic 
elevations) will require a dose delay in order for 
the participant to undergo a cardiac evaluation 
(viaprompt cardiology consult) and a 
confirmatory repeat within 24 hours. If troponin 
elevation is not confirmed within 24 hours in an 
asymptomatic participant, the dose delay may not 
be needed provided that the cardiac evaluation is 
completed and a cardiologist has made the 
recommendation to proceed with treatment. 
Otherwise, if troponin elevation is confirmed, 
dosing may resume when AE resolves to baseline.
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Table 7.4-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Treatment
Drug-Related Adverse Event 
(AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and Resume 
Criteria
Other Clinical AE
Pancreatitis: Amylase or Lipase 
increased
Grade 3 with symptoms
Delay dose
Note: Grade 3 increased amylase or lipase 
without signs or symptoms of pancreatitis does 
not require dose delay. 
Dosing may resume when patient becomes 
asymptomatic.
Grade 4
Permanently discontinue
Uveitis 
Grade 2 uveitis
Delay dose
Dosing may resume if uveitis responds to topical 
therapy (eye drops) and after uveitis resolves to 
Grade ≤ 1 or baseline. If patient requires oral 
steroids for uveitis, then permanently discontinue 
study drug. 
Grade 3 or 4 uveitis
Permanently discontinue
OtherDrug-Related AE (not listed 
above)
Grade 2 non-skin AE, 
except fatigue
Delay dose
Dosing may resume when AE resolves to Grade ≤ 
1 or baseline value.
Grade 3 AE -First 
occurrence lasting ≤ 7 days
Delay dose
Dosing may resume when AE resolves to Grade ≤ 
1 or baseline value.
Grade 3 AE-First 
occurrence lasting > 7 days
Permanently discontinue
Recurrence of Grade 3 AE 
of any duration
Permanently discontinue
Grade 4 or Life-threatening 
adverse reaction
Permanently discontinue
Other Lab abnormalities 
OtherDrug-Related lab abnormality (not 
listed above)
Grade 3
Delay dose
Exceptions:
No delay required for:  Grade 3 lymphopenia 
Permanent Discontinuation for: Grade 3 
thrombocytopenia > 7 days or associated with 
bleeding. 
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Table 7.4-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Treatment
Drug-Related Adverse Event 
(AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and Resume 
Criteria
Grade 4
Permanently discontinue
Exceptions: The following events do not require 
discontinuation of study drug: 
Grade 4 neutropenia ≤ 7 days
Grade 4 lymphopenia or leukopenia
Grade 4 isolated electrolyte 
imbalances/abnormalities that are not associated 
with clinical sequelae and are responding to 
supplementation/appropriate management 
within 72 hours of their onset.
Infusion Reactions (manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other 
allergic-like reactions.)
Hypersensitivity reaction or infusion 
reaction
Grade 3 or 4
Permanently discontinue
Refer to Section 7.7.3on Treatment of Related 
Infusion Reactions.
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7.4.1
Dose Modifications
No dose modifications for either treatment arepermitted.
7.4.2
Dose DelayCriteria
Dose delay criteria apply for all drug-related AEs. Delay treatment administration if any of the 
delay criteria in Table 7.4-1are met. Delay dosing for any adverse event, laboratory abnormality, 
or intercurrent illness which, 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 study drug, re-evaluate weekly,or more frequently,if 
clinically indicated and resume treatmentwhen retreatment criteria are met (see Section 7.4.3). 
Continue tumor assessments per protocol even if dosing is delayed.
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7.4.3
Criteria to Resume Treatment 
Participants mayresume treatment with study drugif they have completed AE management (ie,
corticosteroid taper) or are on ≤ 10mg prednisone or equivalent, and meet the requirements per 
Table 7.4-1.
Prior to re-initiating treatment in a participant with a dosing delay lasting > 8weeks, the Medical 
Monitor (or Clinical Scientist) must be consulted. Continue tumor assessments per protocol even 
if dosing is delayed. Continueperiodic study visits to assess safety and laboratory studies weekly
or more frequently if clinically indicated during such dosing delays.
In the event of treatment delay due to SARS-CoV-2 infection (confirmed or suspected), 
participants with 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 haspassed 
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;and4) 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.
7.4.4
Management Algorithms for Immuno-Oncology Agents
Immuno-oncology (IO) agents are associated with AEs thatcan differ in severity and duration than 
AEs caused by other therapeutic classes. Relatlimaband nivolumabare considered as immuno-
oncology agentsin this protocol. Early recognition and management of AEs associated with IO
agents may mitigate severe toxicity. Management algorithms have been developed to assist 
investigators in assessing and managing the following groups of AEs:
Gastrointestinal
Renal
Pulmonary(notefor participantswithdyspnea, CBC should be measured)
Hepatic
Endocrinopathy
Skin
Neurological
Myocarditis
The above algorithms are found in the Appendix 9of this protocol.
7.5
Preparation/Handling/Storage/Accountability
For nivolumab, refer to the current version of the IB and/or Pharmacy Manual for complete 
storage, handling, dispensing, and infusion information.
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Similarly, for BMS-986213, refer to the current version of the IB and/or Pharmacy Manual for 
complete storage, handling, and dispensing information.
The investigational products should be stored in asecure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational products are only dispensed to 
study participants. The investigational products must be dispensed only from official study sites 
by authorized personnel according to local regulations.
The product storage manager should ensure that the study treatments are 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 treatments arise, do not dispense the 
study treatment and contact BMS immediately.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
Investigational product 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)
Further guidance and information for final disposition of unused study treatmentsare provided in 
Appendix 2.
The unblinded pharmacist will obtain treatment assignment by IRTand prepare blinded drug.
7.5.1
Retained Samples for Bioavailability/Bioequivalence
Not applicable.
7.6
Treatment Compliance
Treatment compliance for all study treatmentswill be monitored by drug accountability, medical 
record, and electronic Case Report Form (eCRF). Drug accountability should be reviewed by the 
study-site 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 eCRF. 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 eCRF.
7.7.1
Prohibited and/orRestricted Treatments
Prohibited and/or restricted medications taken prior to and during study treatment administration 
in the study are described below. Medications taken within 2 weeks prior to study treatment 
administration must be recorded on the CRF.
7.7.1.1
Prohibited Treatments
The following medications are prohibited during the study:
LAG-3 targetingagents. 
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Any botanical preparation (eg,herbal supplements or traditional Chinese medicines) intended 
to treat the disease under study or provide supportive care. Use of marijuana and its derivatives 
for treatment of symptoms related to cancer or cancer treatment are permitted if obtained by 
medical prescription or if its use (even without a medical prescription) has been legalized 
locally.
Immunosuppressive agents (except used to treat a drug-related AE).
Immunosuppressive doses of systemic corticosteroids (except as stated in Section7.7.2).
Any concurrent anti-neoplastic therapy (ie, chemotherapy, hormonal therapy, immunotherapy, 
extensive, non-palliative radiation therapy, or standard or investigational agents for treatment 
of malignancy)
Any live / attenuated vaccine (eg,varicella, zoster, yellow fever, rotavirus, oral polio and 
measles, mumps, rubella [MMR]) during treatment and until 100 days afterlast dose.
Inactivated vaccines are permitted.
7.7.1.2
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 for each participant. Imaging contraindications and contrast risks should be considered in 
this assessment. Participants with renal insufficiency should be assessed as to whether or not they 
should receive contrast and if so, what type and dose of contrastis appropriate. Specific to MRI, 
participants with severe renal insufficiency (ie, estimated glomerular filtration rate [eGFR]
<30mL/min/1.73 m2) are at increased risk of nephrogenic systemic fibrosis. MRI contrast should 
not be given to this participant population. In addition, participants are excluded from MRI if they 
have tattoos, metallic implants, pacemakers, etc.
The ultimate decision to perform MRI in an individual participant in this study rests with the site 
radiologist, the investigator,and the standard set by the local Ethics Committee.
7.7.2
Permitted Therapy
Participants are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses > 10mg 
daily prednisoneequivalentare 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.
7.7.2.1
Palliative Therapy
Palliative (limited-field) radiation therapy and palliative surgical resection are permitted 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 (Section8.1.2.2).
The case is discussed with the BMS Medical Monitor/designee. Palliative therapy must be 
clearly documented as such in the study record.
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Participants should not receive study treatment during radiation as the potential for overlapping 
toxicities with radiotherapy and BMS-986213or with radiotherapy and nivolumabis currently not 
known. Anecdotal data suggest that radiotherapy administered to participants while receiving 
nivolumabtherapy is tolerable. However, because concurrent radiotherapy and immunotherapies 
in cancer have not been formally evaluated, in cases where palliative radiotherapy is required for 
a tumor lesion, then all study treatmentsshould be withheld for at least 1 week before, during, and 
1 week after radiation. Participants should be closely monitored for any potential toxicity during 
and after receivingradiotherapy, and AEs related to radiotherapy should resolve to Grade 1 prior 
to resuming study treatment.
7.7.2.2
Surgical Resection Following Initial Response
Investigators may choose to resect solitary lesions in participantswith unresectable or metastatic 
melanoma and render the participantfree of macroscopic disease. Participants enrolled in this 
study may have lesions surgically resected only following consultation with the BMS Medical 
Monitor/designeeand following the Week 20efficacy assessments. If tumor shrinkage of the 
solitary lesion is noted on the re-staging assessment (eg, Week 20), it is highly encouraged that 
surgical resection be delayed until subsequent scans fail to demonstrate further shrinkage. 
Participants with a PR who go on to have surgical resection of remaining disease will be considered 
a PR. Tumor tissue of any resected solitary lesion should be submitted to BMS (see Section9.8.2).
Detailed instructions onthe obtaining, processing, labeling, handling, storage,and shipment of 
these specimens will be provided in a separate procedure manual at the time of study initiation.
7.7.3
Treatment of Infusion-Related Reactions 
Because both relatlimab andnivolumab contain only human immunoglobulin 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 fever, chills, rigors, headache, rash, pruritus, 
arthralgias, hypotension, hypertension, bronchospasm, or other allergic-like reactions. All Grade 
3 or 4 infusion reactions should be reported within 24 hours to the BMS Medical Monitor/designee
andreported as an SAE if it meets the criteria. Infusion reactions should be graded according to 
NCI CTCAE (Version 5.0) guidelines.
Treatment recommendations are provided below and may be modified based on local treatment 
standards and guidelines, as appropriate:
For Grade 1 symptoms: (mild reaction; infusion interruption not indicated; intervention not 
indicated):
Remain at bedside and monitor participant until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg at least 30 minutes before 
additional nivolumab administrations
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For Grade 2 symptoms:(moderate reaction required therapy or infusion interruption but responds 
promptlyto symptomatic treatment (eg, antihistamines, non-steroidal anti-inflammatory drugs, 
narcotics, corticosteroids, bronchodilators, IV fluids); prophylactic medications indicated for 24 
hours):
Stop the study treatment infusion, begin an IV infusion of normal saline, and treat the 
participant 
with 
diphenhydramine 
50 
mg 
IV (or equivalent) 
and/or 
acetaminophen/paracetamol 325 to 1000 mg; remain at bedside and monitor participant until 
resolution of symptoms. Corticosteroid and/or bronchodilator therapy may also be 
administered as appropriate. If the infusion is interrupted, then restart the infusion at 50% of 
the original infusion rate when symptoms resolve; if no further complications ensue after 
30minutes, the rate may be increased to 100% of the original infusion rate. Monitor participant 
closely. If symptoms recur, then no further study treatment will be administered at that visit.
For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/oracetaminophen/paracetamol 325 to 1000 mg 
should be administered at least 30 minutes before infusion. If necessary, corticosteroids (up to 
25 mg of hydrocortisone or equivalent) may be used.
For Grade 3 or 4 symptoms: (severe reaction, Grade 3: prolonged [ie, not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following 
initial improvement; hospitalization indicated for other clinical sequelae [eg, renal impairment, 
pulmonary infiltrates];Grade 4: Life-threatening; pressor or ventilatory support indicated):
Immediately discontinue infusion of study treatment. Begin an IV infusion of normal saline 
and treat the participant as follows:Recommend bronchodilators, epinephrine 0.2 to 1 mg of a 
1:1000 solution for subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution 
injected slowly for IV administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed. Participant should be monitored 
until the investigator iscomfortable that the symptoms will not recur. Study treatment will be 
permanently discontinued. Investigators should follow their institutional guidelines for the 
treatment of anaphylaxis. Remain at bedside and monitor participant until recovery of the 
symptoms.
In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine or corticosteroids).
7.8
TreatmentAfter 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 treatmentfor the maximum treatment durationspecified 
in Section5.3. Study treatmentwill 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 treatmentifany of the following occur: a)the study is terminated due to safety concerns; b)
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the development of relatlimabis terminated for other reasons, including but not limited to lack of 
efficacy and/or not meeting the study objectives; c) the participantcan 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 investigational product (and non-investigational 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, a participant who has been imprisoned may be permitted to continue 
as a participant. Strict conditions apply and BMS approval is required.)
Additional protocol-specified reasons for discontinuation(Section 8.1.1)
In the case of pregnancy, the investigator must immediately,within 24 hours of awareness of the 
pregnancy, notify the BMS medical monitor or designee 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). Refer to Section 9.2.5, Pregnancy. 
Refer to the 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.
All participants who discontinue study treatmentshould comply with protocol specified follow-up 
procedures as outlined in Section2.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 treatmentis 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 eCRFpage.
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8.1.1
Dose Discontinuation
If a participant in any of the nivolumab/relatlimab combination arms meets criteria for 
discontinuation in Table 7.4-1, the participant must discontinue both nivolumab and relatlimab 
and be taken off the treatment phase of the study.
Nivolumab and relatlimab treatment must be permanently discontinued per criteria in Table 7.4-1
in Section7.4(Dosage Modification). Discontinue from study treatment 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 or relatlimab dosing.
Study treatment must also be permanently discontinued for the following:
Any event that leads to delay in dosing lasting > 8weeks from the previous dose requires 
discontinuation, with the following exceptions:
Dosing delays to allow for prolonged steroid tapers to manage drug-related AEs are allowed. 
Dosing delays lasting > 8weeks from the previous dose that occur for non-drug-related reasons 
may be allowed if approved by the BMS Medical Monitor (or Clinical Scientist). 
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 6weeks or more 
frequently if clinically indicated during such dosing delays.
8.1.2
Treatment Beyond Progression
8.1.2.1
Rationale
Accumulating clinical evidence indicates some participants treated with immune system 
stimulating agents may develop progression of disease (by conventional response criteria) before 
demonstrating clinical objective responses and/or stable disease.31This phenomenon was observed 
in approximately 10% of participants in the Phase 1 study of nivolumaband also with ipilimumab 
monotherapy. Two hypotheses have been put forth to explain this phenomenon. First, enhanced 
inflammation within tumors could lead to an increase in tumor size which would appear as 
enlarged index lesions and as newly visible small non-index lesions. Over time, both the malignant 
and inflammatory portions of the mass may then decrease leading to overt signs of clinical 
improvement. Alternatively, in some individuals, the kinetics of tumor growth may initially 
outpace anti-tumor immune activity. With sufficient time, the anti-tumor activity will dominate 
and become clinically apparent. Therefore, participants will be allowed to continue study therapy 
after initial investigator-assessed RECIST v1.1defined progression (See Appendix 5) if they are 
assessed to be deriving clinical benefit and tolerating study treatment (Section8.1.2.2). Such 
participants must discontinue study therapy upon evidence of further progression.
8.1.2.2
Criteria Required for Treatment Beyond Progression
Participants will be permitted to continue studytreatment beyond initial RECIST v1.1 defined PD
(see Appendix5), assessed by the investigator, as long as they meet the following criteria:
Investigator-assessed clinical benefit
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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 studytreatment.All 
other elements of the main consent including description of reasonably foreseeable risks or 
discomforts, or other alternative treatment options will still apply.
A follow-up scan should be performed at the next scheduled imaging evaluation 8 weeks later (but 
no sooner than 4 weeks) of initial investigator-assessed progression to determine whether there 
has been a decrease in the tumor size or continued PD. The assessment of clinical benefit should 
be balanced by clinical judgment as to whether the participant is clinically deteriorating and 
unlikely to receive any benefit from continued studytreatment.
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 the Schedule of Activities(Section2).
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 PD. 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 PD. All studytreatment should 
be discontinued permanently upon documentation of further progression.
New lesions are considered measurable 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
15mm). Any new lesion considered non-measurable at the time of initial progression may become 
measurable 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 15mm). 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
Post-Study Treatment Study Follow-Up
In this study, overall survivalis a key endpoint. 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 for collection of outcome and/or survival 
follow-up data as required and in line with Section2until 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 (Table 2-3). At the time of this request, each participant will be 
contacted to determine their survival status unless the participant has withdrawn consent for all 
contact or is lost to follow-up.
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8.2
Discontinuation from the Study
Participants who request to discontinue study treatmentwill 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 withdrawsconsent for any further contact with him/her or persons 
previously authorized by participantto 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 treatmentonly 
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 locallaw.
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 participantto one 
registered mail letter. All attempts should be documented in the participant’s medical records.
If it is determined that the participanthas died, the site will usepermissible local methods to 
obtain date and cause of death.
If investigator’s use of 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 
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 the Schedule of Activities. 
Protocol waivers or exemptions are not allowed.
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All immediate safety concerns must be discussed with the sponsorimmediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment.
Adherence to the study design requirements, including those specified in theSchedule 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 the 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 on site/local 
labs until all study treatment-related toxicities resolve, return to baseline, or are deemed 
irreversible.
If a participant shows pulmonary-related signs (hypoxia, fever) or symptoms (eg. dyspnea, cough, 
and fever) consistent with possible pulmonary adverse events, the participant should be 
immediately evaluated to rule out pulmonary toxicity, according to the suspected pulmonary 
toxicity management algorithm in the nivolumabIB.
For those subjects receiving on-going treatment, troponin elevations will requirethe subject to 
undergo a cardiac evaluation. Following this evaluation, determination of further treatment will be 
based on the discussion with the BMS Medical Monitor/designee.
Some of the assessments referred to in this section may not be captured as data in the eCRF. 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.
This study will consist of three phases: screening, treatment, and follow-up.
Screening Phase:
Begins by establishing the participant’s initial eligibility and signing the informed consent 
form (ICF).
TreatmentPhase:
Begins with the randomization call to the IRT. The participant is randomly assigned to either 
the BMS-986213arm or the nivolumab monotherapy arm.
Ends when the participantis discontinued from study therapy. For a complete list of reasons 
for treatment discontinuation, see Section8.1.
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Follow-Up Phase
Begins when the decision to discontinue a participantfrom study therapy is made (no further 
treatment with study therapy)and ends when survival data have been collected forall 
participants(Section8.1.3).
9.1
Efficacy Assessments
Study evaluations will take place in accordance with the Schedule of Activities in Section2. 
Baseline assessments should be performed within 28 days prior to randomization by contrast 
enhanced CT chest, CT (or MRI with and without contrast) abdomen, pelvis,and all known or 
suspected sites of disease.MRI of brain (without and with contrast) should be acquired as outlined 
in Schedule of Activities (Section 2). CT of the Brain (without and with contrast) can be performed 
if MRI is contraindicated.
Subsequent assessments should include chest, abdomen, and pelvis, and all known or suspected 
sites of disease and should use the same imaging method as was used at baseline beginning at 
12weeks (1 week) after randomizationand continuing every 8weeks (1 week) up to Week52
and then every 12 weeks (1 week).Assessments should continue until disease progression is
confirmedby a BICRor treatment is discontinued, whichever occurs later.Participants with a 
history of brain metastasis or symptoms should have a surveillance MRI (without and with 
contrast) study 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. 
SeeTable 9.1.2-1for instructions on performance of scans in participants with contrast allergies.
Tumor imaging assessments for ongoing study treatment decisions will be completed by the 
investigator using RECIST v1.1 criteria, see Appendix 5.
A BICR will be utilized in this study for determination of BICR-assessed endpoints. The BICR 
will review all available tumor assessment scans for all treated participants. Details of BICR 
responsibilities and procedures will be specified in the BICR charter.
9.1.1
Imaging Assessment for the Study
Images should be submitted on a rolling basis to the imaging core lab. Sites should be trained prior 
to scanning the first study participant. Image acquisition guidelines and submission process will 
be outlined in the Imaging Manual tobe provided by the core lab.
9.1.2
Methods of Measurement
Acceptable imaging methods per anatomical area are detailed inTable 9.1.2-1.
Tumor assessment with contrast-enhanced CT scans acquired on dedicated CT equipment is 
preferred for this study. Contrast-enhanced CT of thechest, abdomen, pelvis, and other 
known/suspected sites of disease should be performed for tumor assessments.Baseline 
assessment must occur prior to dosing.
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Should a participant have a contraindication for CT IV contrast, a non-contrast CT of the chest 
and a contrast-enhanced MRI of the abdomen and pelvis and otherknown/suspectedsites of 
disease may be obtained. 
Should a participant have contraindication for both MR and CT IVcontrasts, a non-contrast 
CT of the chest and a non-contrast MRI of the abdomen, pelvis, and other known/suspected 
sites of disease should be obtained.
PET alone will not be considered for the disease assessment. Complementary CT and/or MRI must 
be performed in such cases. Note: Use of CT component of a PET/CT scanner: Combined modality 
scanning, such as with FDG-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 FDG-PET/CT are of limited use 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 RECISTv1.1(see Appendix 5) measurements. However, if a site 
can document that the CT performed as part of a FDG PET/CT is of identicaldiagnostic quality to 
a diagnostic CT (with IV and oral contrast), then the CT portion of the FDG-PET/CT can be used 
for RECIST v1.1 measurements. Note, however, that the FDG-PET portion of the CT introduces 
additional data which may bias an investigator if it is not routinely or serially performed. 
Table 9.1.2-1:
Acceptable Imaging Assessment Methods for Different Anatomical 
Areas
Anatomic Region
Preferred Method
Alternative Methods
Chest, abdomen, 
and pelvis
Note: Scan must 
cover lung apices to 
diaphragm, 
diaphragm through 
entire liver, and to 
below the pubic 
symphysis
CT with IV contrast
For chest:
CT without contrast can be used only if the 
participant has a clinical contraindication for 
iodine-based IV contrast (eg, hypersensitivity, 
renal insufficiency)
For abdomen and pelvis:
MRI with gadolinium-based IV contrast is the 
first alternative method if the participant has a 
clinical contraindication for iodine-based IV 
contrast
CT without contrast can be used as the second 
alternative method only if the participant has a 
clinical contraindication for both contrast-
enhanced CT and MRI.
Brain
MRI with IV contrast
CT with IV contrast is the first alternative 
method if IV gadolinium is clinically 
contraindicated. 
MRI without contrast can be used as asecond 
alternative method if a participant has clinical 
contraindications for both contrast-enhanced CT 
and MRI
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Notes:
CT/MRIscans must be performed with slices thickness of 5 mm. The reconstruction interval 
should be equal to slice thickness to avoid gap. 
The same modality for a given anatomical coverage and the same scanning procedure (most 
importantly: reconstruction slice thickness, anatomic coverage, use of IV contrast) should be 
consistent between baseline and all subsequent follow-up scanning.If possible, the same 
scanner or an equivalent scanners should be used throughout the study. 
For abdomen and pelvis CT scans,oral contrast is recommendedper institutional standards. 
MRI should include T1 and T2-weighted sequences with T1-weighted at both pre-and post-
contrast. 
All scans generated should be exportable in electronic format (DICOM) to enable secure and 
rapid electronic transmission to the designated central imaging laboratory
. 
9.1.2.1
BICR Confirmation of Progression
Sites should submit all scans to the imaging core lab on a rolling basis, preferably within 7 days 
of scan acquisition throughout the duration of the study. BICR will review scans on a rolling basis 
and must be blinded to treatment arm and investigator assessment of submitted scans. When 
progression per RECIST v1.1 criteria is assessed by the investigator, the site will inform the 
imaging core lab, so that the BICR assessment of progression can be performed. The BICR review 
will be completed and the results provided to the site within approximately 5 days of receipt of the 
scans, provided there are no pending imaging queries to the site. 
Participants whose progression is not confirmed by the BICR will be required to continue tumor 
assessments (if clinically feasible) according to the protocol-specified schedule or sooner if 
clinically indicated. Also, if participants discontinue treatment without radiographic progression, 
tumor assessments will continue according to the protocol specified schedule, as noted in 
Section2, until progression has been confirmed by BICR.
All study treatment decisions will be based on the investigator’s assessment of tumor images and 
not on the BICR assessment. 
9.1.3
Patient-Reported Outcomes
The evaluation of patient-reported outcomes is an increasingly important aspect of clinical efficacy 
in oncology trials. Such data provide an understanding of the impact of treatment from the 
participant’s perspective and offer insights into patient experience that may not be captured 
through physician reporting. Additionally, generic health-related quality of life measures provide 
data needed for calculating utility values to inform health economic models.
Participants will be asked to complete the Functional Assessment of Cancer Therapy-Melanoma 
(FACT-M), 3-level version of the EuroQol Group’s EQ-5D (EQ-5D-3L), and Work Productivity 
and Activity Impairment: General Health(WPAI:GH)questionnaires after randomization but prior 
to first dose, at on-study clinic visits while on treatment, and at Follow-Up Visits 1 and 2. Whereas 
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all participants will complete the EQ-5D-3L, only those ≥18 years of age at baseline will be asked 
to complete the FACT-M and WPAI:GH.All questionnaires will be provided in the participant’s 
preferred language when available.
In addition, the EQ-5D-3L and the 16-items comprising the Melanoma Subscale (MS) of the 
FACT-M will be administered by telephone at designated time points during the survival follow-up 
phase. There exist standardized guides that can be used to facilitate telephone administration of 
the EQ-5D-3L though a similar guide does not exist for the MS. Participants will be provided with 
a hard copy of the latter questionnaire to take home and use as a visual aid during telephone 
interviews. 
If exceptional circumstances preclude the continued administration of measures using planned 
modalities, then alternate administration methods may be required.Table 2-2andTable 2-3
provide information regarding the timing of patient-reported outcomes assessments. 
9.1.3.1
EQ-5D-3L
The EQ-5D-3L is a standardized instrument used to measure self-reports of health status and 
functioning. The instrument’s descriptive system consists of 5 dimensions: mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression. Eachdimension has 3 levels, reflecting 
“no health problems,” “moderate health problems,” and “extreme health problems.” A dimension 
for which there are no problems is said to be at level 1, whereasa dimension for which there are 
extreme problems is said to be at level 3. Thus, the vectors 11111 and 33333 represent the best 
health state and the worst health state, respectively, as described by the EQ-5D-3L. Altogether, the 
instrument describes 35= 243 health states. 
Empirically-derived weights can be appliedto an individual’s responses to the EQ-5D-3L 
descriptive system to generate an index measuring the value to society of his or her current health. 
Such preference-weighting systems have been developed for the UK, US, Spain, Germany, and 
numerous other populations. Utility index values range from a 1 (full health) to 0 (dead) with 
negative values indicating a state considered worse than being dead. In addition, the EQ-5D-3L 
includes a VAS that allows respondents to rate their own current health on a 101-point scale 
ranging from “best imaginable” to “worst imaginable” health.
A change from baseline of 0.08 for the EQ-5D-3L utility score and of 7 for the EQ-5D-3L VAS 
are considered minimally important differences for the EQ-5D-3L.32The EQ-5D-3L uses a recall 
period of “today.”
9.1.3.2
FACT-M 
The FACT-M questionnaire will be used to assess the effects of disease symptoms on functioning 
and well-being. As a generic cancer-related core, the FACT-M includes the 27-item FACT General 
(FACT-G) to assess physical well-being (PWB; seven items), social/family well-being (SWB; 
seven items), emotional well-being (EWB; six items), and functional well-being (FWB; seven 
items). In addition, the FACT-M includes a 16-item disease-specific Melanoma Subscale (MS).A 
single item from the FACT-M (ie, GP5) will be used to assess the extent of perceived bother due 
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to symptomatic AEs. Evidence exists for the validity of this item and its usefulness as an overall 
summary measure of burden due to symptomatic treatment toxicities.
33
Each FACT-M item is rated on a 5-point scale ranging from 0 (not at all) to 4 (very much). Scores 
for the PWB, FWB, SWB, and EWB subscales can be combined to produce a FACT-G total score, 
which provides an overall indicant of generic quality of life, while the FACT-G and MS scores 
can be combined to produce a total score for the FACT-M, which provides a composite measure 
of general and targeted quality of life. 
A variant of the total score that is often more sensitive to physical and functional outcomes, the 
Trial Outcome Index (TOI), can be derived by summing the PWB, FWB, and MS scores. All 
scores are scaled so that higher values indicate better functioning as well as lower symptom burden.
For any given scale, the minimally important difference (MID)represents the smallest difference 
in score that informed patients might perceive as important and that would warrant consideration 
of a change in management. With regard to the MS, the minimally important difference has been 
estimated as a change of 2-4 points.34For this trial, we will use the midpoint of the range (ie, a 
change ≥3 points) to define a minimally important change in MS score. This interpretation has 
been applied in previous investigations.35
The FACT-M uses a 7-day recall period.
9.1.3.3
WPAI:GH
TheWPAI:GH is a 6-item measure of impairment in work productivity and usual activities. 
Responses to the questionnaire’s items are used to derive ascore measuring the amount of 
absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job 
effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), 
and daily activity impairment attributable to general health. Outcomes are expressed as impairment 
percentages with higher numbers indicating greater impairment or less productivity. 
TheWPAI:GHuses a 7-day recall period.
9.2
Adverse Events
The definitions of an AE or SAE can be found in Appendix3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
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 
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autoimmunity. Information supporting the assessment will be collected on the participant’s case 
report form.
Contacts for SAE reporting are 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 pointsspecified 
in the Schedule of Activities (Section2). Non-serious AE information should also be collected 
from the start of a placebo lead-in period or other observational period intended to establish a 
baseline status for the participants.
Following the participant’s written consent to participate in the study, all SAEs, whether related 
ornot related to study treatment, must be collected, including those thought to be associated with 
protocol-specified procedures.
All SAEs must be collected that occur during the screening period and within 100 daysof the last 
dose of study treatment, 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. For participants 
randomized/assigned to treatment and never treated with study treatment, SAEs should be 
collected for 30 days from the date ofrandomization.If applicable, SAEs must be collected that 
relate to any later protocol-specified procedure (eg, a follow-up skin biopsy).
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study treatment or protocol-specified procedure.
Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF section.
All SAEs will be recorded and reported to sponsoror designee within 24 hours, as indicated in 
Appendix 3. 
The investigatorwill submit any updated SAE data to the sponsor within 24 hours of this 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.
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 100 days 
following discontinuation of dosing.
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9.2.2
Method of Detecting AEs and SAEs
Adverse events 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 AE and/or SAEs. Inquiry about specific AEs should be guided by clinical judgement in 
the context of known adverse events, when appropriate for the program or protocol.
Every adverse event 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 case report form.
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 duringthe 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, and non-serious AEs of special interest (as defined in 
Section9.2), 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, 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 sponsorof 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 sponsorwill file it along with 
the IBand will notify the IRB/IEC, if appropriate according to local requirements.
Sponsor or designeewill be reporting adverse events 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 
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.
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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 
5half-livesafter product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form 
to 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/designee must occur. If, for whatever reason, the pregnancy has ended, 
confirmed by negative serum pregnancy test, treatment may be resumed (at least 3 weeks and not 
greater than 6 weeks after the pregnancy has ended), following approvals of participant /sponsor 
/IRB/EC, as applicable.
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.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
sponsor or designee.In order for sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an informed consent form for 
disclosure of this information. Information on this pregnancy will be collected on the Pregnancy 
Surveillance Form.
In cases where a study drug can be present in seminal fluid, at exposures sufficient to potentially 
cause fetal toxicity, and if any sexual activity (e.g. vaginal, anal, oral) has occurred between a male 
participant and a pregnant WOCBP partner(s), the information should be reported to the Sponsor 
or designee, even if the male participant has undergone a successful vasectomy. In order for 
Sponsor or designee to collect any pregnancy surveillance information from the female partner, 
the female partner(s) must sign an informed consent form for disclosure of this information. 
Information on the pregnancy will be collected 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 participantto have study treatment
discontinued or interrupted
Any laboratory test result abnormality that required the participantto receive specific 
corrective therapy
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It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus 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 event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section9.2and Appendix 3 for reporting 
details).
Potential drug induced liver injury
 is defined as: 
1) ALT or AST elevation > 3x ULN
AND 
2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase), 
AND 
3) No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, preexisting chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
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 or serious AE, as appropriate, and reported accordingly.
9.3
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important.
All occurrences of overdose must be reported as SAEs (see Appendix 3).
In the event of an overdose the investigator/treating physician should:
1) Contact the BMS Medical Monitor/designeeimmediately
2) Closely monitor the participant for AEs/SAEs and laboratory abnormalities
3) Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the BMS Medical Monitor/designeebased on the clinical evaluation of the 
participant.
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9.4
Safety
Planned time points for all safety assessments are listed in the 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 the Schedule of Activities.
9.4.1
Physical Examinations
Refer to Schedule of Activities, Section2.
9.4.2
Vital Signs
Refer to Schedule of Activities, Section 2.
9.4.3
Electrocardiograms
Refer to Schedule of Activities, Section 2.
9.4.4
Clinical Safety Laboratory Assessments
Laboratory assessments are listed inTable 9.4.4-1.
Investigators must document their review of each laboratory safety report.
All clinical safety laboratory assessments will be performed locally per the Schedule of 
Activities (Section 2)
Table 9.4.4-1:
Laboratory Assessment Panels
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Serum Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Alkaline phosphatase
Gamma-glutamyl transferase only when alkaline 
phosphatase is Grade 2
Creatinine
Blood urea nitrogen (BUN) or serum urea level
Glucose 
Lactate dehydrogenase (LDH)
Uric acid
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
TSH, free T3 and free T4 -screeningonly
TSH, with reflexive free T3 and free T4 if TSH is 
abnormal -ontreatment
Creatinine clearance (CrCl) -screening only
FSH (if needed to document postmenopausal status as 
defined in Appendix 4)-screening only
Troponin (local standard to be used/allowed),Cardiac Troponin T (cTnt),or I (cTnI): For those participants 
receiving ongoing treatment with relatlimab, troponin elevations will require the participant to undergo a cardiac 
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Table 9.4.4-1:
Laboratory Assessment Panels
evaluation. Following this evaluation, determination of further treatment will be based on the discretion of the 
Investigator.
Urinalysis 
Protein
Glucose
Blood
Leukocyte esteraseor leukocyte
Specific gravity
pH
Serology(at screening)
Serum for hepatitis C antibody (if Hepatitis C antibody 
is positive reflex to hepatitis C RNA) or hepatitis C 
RNA, hepatitis B surface antigen,HIV-1 andHIV-2 
antibodies. (Testing for HIV-1 and HIV-2 must be 
performed at sites where mandated by local 
requirements, see Appendix 8)
Other Analyses
Pregnancy test (WOCBP only, Section2).
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 investigatorper standard 
medical/clinical judgment. 
9.5
Pharmacokineticand Immunogenicity Assessments
Serum samples for relatlimaband nivolumab PK and ADA assessments will be collected for all 
subjects. 
9.5.1
Pharmacokinetics: Collection and Processing
A detailed schedule of PK and ADA evaluations is provided inTable 9.5.1-1. All time points are 
relative to the start of study drug administration. Pre-dose samples should be taken within 
30minutes before the start of dose administration. If samples are drawn but study drug(s) is not 
administered on the same day, samples will be retained and analyzed as planned. There is no need to 
collect another sample when dosingis resumed. End-of-infusion samples should be taken just prior 
to the end of infusion (preferably within 2 minutes). Further details of sample collection, 
processing, and shipment will be provided in the laboratory procedures manual. On treatment PK 
samples are intended to be drawn relative to actual dosing days, if a dose occurs on a different day 
withinthe cycle due to delays or minor schedule adjustments, PK samples should be adjusted 
accordingly.
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Table 9.5.1-1: 
PK and ADA Sampling Schedule for Relatlimab and 
Nivolumab
Study Day of 
Sample Collection
(1 Cycle = 4 
Weeks)
Event
(Relative to 
Study Treatment 
Dosing)
Time(hour:min)
(Relative to 
Start ofDose 
Administration)
Pharmacokinetics
(2 Distinct 
Samples)
Anti-Drug 
Antibodies
(2 Distinct 
Samples)
Cycle 1 Day 1
Predosea
X
X
Cycle 1 Day 1
End of infusionb
01:00b
X
Cycle 2 Day 1
Predosea
X
X
Cycle 6 Day 1
Predosea
X
X
Cycle 6 Day 1
End of infusionb
01:00b
X
Every 4th Dose 
After Cycle 6
Day 1
Predosea
X
X
End of Treatment 
and Follow-Up 
Period
Follow-Up Visit 1
X
X
Follow-Up Visit 2
X
X
a Take all predose samples for nivolumab prior to the start of nivolumab infusion.
b Since the end of infusion-PK (EOI-PK) sample is drawn with the intent of accurately estimating the maximum 
concentration (Cmax) of the drug, draw the EOI-PK when all the study drug has been infused. If the site infuses 
drug without a flush, then collect the EOI-PK sample within approximately 5 minutes after end of infusion. If a 
flush is administered to clear the IV lines of the drug and to ensure delivery of the entire drug dose, then draw the 
EOI-PK sample within approximately 5 minutes after end of the flush. Do not draw EOI samples from the same IV 
access that the drug was administered.
9.5.2
Pharmacokinetic Sample Analyses
The serum samples will be analyzed for relatlimaband nivolumab by a validated immunoassay. 
Samples collected from a participant in the nivolumab monotherapy group may not be analyzed 
for relatlimab concentrations. In addition, selected serum samples may be analyzed by an 
exploratory orthogonal method (eg, liquid chromatography [LC]-mass spectrometry [MS]/MS) 
that measures total relatlimaband/or nivolumab, but the generated data will not be reported. Only 
results generated from the validated immunoassay method will be reported. Potential results 
generated from any orthogonal method are intended as informational for technology exploration 
purposes and will not be reported.
For adolescent participants, local standards for volumes of blood based on body weight that may 
be drawn within a specific time period should be followed. In order to obtain the samples required 
for safety, PK, and PDevaluations specified at a time point, blood volumes for safety laboratory 
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analysisshould be minimized through the use of pediatric sample tubes, if possible. If, despite the 
use of these measures, the blood volumes required in the Schedule of Activities for a time point 
will exceed those recommended for the participant, the sponsor should be contacted for 
instructions on which blood tests can be omitted or modified to meet volume requirements. These 
omitted/modified tests will likely to pharmacodynamic and/or pharmacokinetic assessments, since 
all required safety assessments must be performed.
9.5.3
Immunogenicity
Serum samples for analysis of development of ADAs will be collected in conjunction with analysis 
of relatlimab and nivolumab serum concentrations and will be collected from all participants as 
indicated in Table 9.5.1-1. These serum samples will be analyzed for relatlimab and nivolumab 
ADAs by a validated immunoassay; samples may also be analyzed for neutralizing antibodies by 
validated methods. Samples collected from a participant in the nivolumab monotherapy group may 
not be analyzed for relatlimab ADAs. Selected serum samples may be analyzed by an exploratory 
orthogonal method that measures anti-relatlimab or anti-nivolumab antibodies. Potential results 
generated from any orthogonal method are intended as informational for technology exploration 
purposes and will not be reported. In addition, serum samples designated for PK or biomarker 
assessments may also be used for immunogenicity analysis if required (eg, insufficient volume for 
complete immunogenicity assessment or to follow up on suspected immunogenicity related AE). 
Further details of blood collection and processing will be provided to the site in the procedure 
manual.
9.6
Pharmacodynamics
PDanalysis will be performed on serum, plasma, peripheral blood RNA, and/or peripheral blood 
mononuclear samples collected at time points specified inTable 9.8.2.6-1.The purpose of these 
exploratory analyses will be to identify PD markers changing with treatment, including changes 
that are associated with clinical benefit.
9.7
Pharmacogenomics
Pharmacogenomics assessments include, gene expression profiling,and mutational analyses as 
described in further detail in Section 9.8.
9.8
Biomarkers
Peripheral blood and tumor tissue will be collected prior to therapy. Peripheral blood samples will 
also be collected at selected timepoints on treatment. If a biopsy or surgical resection is performed 
at the time of progression or suspected progression, tumor sample (block or slides) should be 
submitted for analysis. If biomarker samples are drawn but study drug(s) is not administered, 
samples will be retained. A detailed description of each assay system is described below and a 
schedule of pharmacodynamic evaluations is provided inTable 9.8.2.6-1. All biomarker sampling 
at timepoints when study drug is not administered are optional.
9.8.1
Peripheral Blood Markers
A variety offactors that may impact the immunomodulatory properties and efficacy of relatlimab
in combination with nivolumab will be investigated in peripheral blood specimens taken from all 
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subjects prior to or during treatment. Data from these investigations will be evaluated for 
associations with response, survival, and/or safety (AE) data. Several analyses will be completed 
and are described briefly below.
9.8.1.1
Soluble Biomarkers
Soluble factors, such as cytokines, chemokines, soluble receptors, and antibodies to tumor antigens 
will be characterized and quantified by immunoassays in serum. Analyses may include, but not 
necessarily be limited to, soluble LAG-3, CXCL-9 and IL2Ralpha. Collected serum samples may 
also be used for the assessment of tumorantigen-specific responses elicited following treatment 
with monotherapy and combination therapy to explore which antitumor antibodies are most 
associated with clinical response. Antibody levels to cancer test antigens may be assessed by 
multiplex assays and enzyme-linked immunosorbent assay (ELISA).
9.8.1.2
Immunophenotyping
The proportion of specific lymphocyte subsets and expression levels of T cell co-stimulatory 
markers in peripheral blood mononuclear cell (PBMC) preparations will be quantified by flow 
cytometry. Analyses may include, but not necessarily be limited to, the proportion of T, B, and 
NK cells, granulocytes, the proportion of memory and effector T cell subsets, and expression levels 
of PD-1, PD-L1, other B7 family members, ICOS, and Ki67.
9.8.1.3
T-Cell Repertoire Analysis
Low diversity of the peripheral T-cell compartment has been shown to correlate with poor overall 
survival in metastatic breast cancer. A standing theory in immuno-oncology suggests a diverse and 
activated immune environment is better adept at eradicating tumor compared to a skewed 
repertoire of naïve and tolerized T cells. In order to explore whether a diverse T-cell repertoire is 
predictive of response to therapy, 
DNA/RNAsequencing will be performed on DNA/RNAisolated 
from peripheral blood and tumor tissue(Section 9.8.2.3)to quantitate the composition of the T-
cell repertoire prior to and during therapy.
9.8.1.4
Whole Blood for Germline DNA
Whole blood will be collected from all subjects prior to treatment to generate genomic DNA for 
geneticanalyses and to serve as a reference for tumor genomic testing. These analyses will focus 
on, but are not limited to,genetic variations within genes associated with PD1 and other 
immunoregulatory signaling pathways to determine if natural variation within those genes is 
associated with response to nivolumab and/or with adverse events during treatment.
9.8.1.5
Circulating Tumor DNA Analysis (Plasma) Biomarkers
The presence of cell-free DNA in circulating blood is a well-documented phenomenon. Fragments 
of DNA are shed into the blood stream from dividing cells during cell proliferation or cell death. 
In patients with cancer, a fraction of this DNA is tumor-derived and is termed circulating tumor 
DNA (ctDNA). Albeit small, fragments of DNA average between 180 to 200 bpand specific 
genomic regions can be amplified with PCR. ctDNA may be a surrogate of disease burden and/or 
may be used for the assessment of cancer-related gene mutations that may be associated with 
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response to immunotherapy. Plasma samples may also be used to assess any of the soluble factors 
described above.
9.8.2
Tumor Samples
Tumor biopsy specimens will be obtained from consenting subjects prior to treatment to 
characterize immune cell populations and expression of selected tumor markers. A fresh biopsy 
must be available for submission prior to randomization. Biopsies of bone lesions that do not have 
a soft tissue component are also unacceptable for submission. On-treatment biopsy samples are 
optional.Biopsied lesions should be distinct from index lesion(s) being evaluated for radiological 
response, if clinically feasible.
9.8.2.1
LAG-3and PD-L1 Expression
Entry to this study is limited to subjects assessed for LAG-3and PD-L1 expression in tumor 
specimens. LAG-3and PD-L1 expression on immune cells will be measured using an analytically 
validated immunohistochemical assay. LAG-3 and PD-L1 status, as determined using a 1% 
threshold, will be stratification criteria for randomization.
9.8.2.2
Characterization of Tumor Infiltrating Lymphocytes(TILs) and Immune 
Biomarkers
Immunohistochemistry (IHC) or other technologies will also be used to assess the number and 
composition of immune infiltrates in order to define the immune cell subsets present within FFPE 
tumor tissue before and after exposure to therapy. These IHC analyses will include, but not 
necessarily be limited to, the following markers: CD8, MHC-I, MHC-II, and PD-L1.
9.8.2.3
Characterization of T-Cell Repertoire
DNA or RNA sequencing may be performed on pre-and post-treatment tumor tissue to assess the 
composition of the T-cell repertoire. DNA/RNAwill be isolated from either the FFPE tumor block 
or equivalent preparations.
9.8.2.4
Gene Expression Profiling
Tumor biopsies may be examined for mRNA gene expression by RNAseq, EdgeSeq and/or 
equivalent technology platforms to measure the tumor transcriptome, including genes or gene 
signatures of interest. These include expression of LAG-3, PD1,and PD-L2 as well as 
inflammation gene signatures.
9.8.2.5
Tumor Genotyping, Mutational Analysis, and Tumor Antigen Profiling
DNA from tumor samples will be analyzed using whole-exome and transcriptome sequencing to 
determine the number of mutations found within a given sample relative to a normal host tissue, 
such as adjacent non-transformed cells, whole blood or PBMC. Mutations that are detected will 
be analyzed for their ability to bind the MHC I and MHC II proteins using prediction algorithms, 
such as NetMHC. Evaluating the ability of tumor mutations to bind MHC molecules will provide 
evidence that these mutations are serving as antigens that are recognized the immune system and 
are potential rejection antigens.
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9.8.2.6
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.Biopsied lesions should be distinct from index lesion(s) being evaluated for 
radiological response, if clinically feasible.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 subject.
Detailed instructions of the obtaining, processing, labeling, handling, storage and shipment of 
specimens will be provided in a separate Procedure Manual at the time of study initiation
Table 9.8.2.6-1:
CA224047 Biomarker Sampling Schedule (All subjects)a
Collection Timing
Serum
Plasma
Whole Blood
PBMC
Tumor
Screening
--
--
--
--
Xc
Cycle 1 Day 1
X
X
X
X
Cycle 2Day 1
X
X
--
X
Xe
Cycle 3Day 1
X
--
--
--
--
Upon Progressiond
X
X
--
--
Xe
a Biomarker sampling occurs prior to dosing of study drug and can occur 5 days from the scheduled time.
b Original footnote b has been deleted.
c Tumor biopsy prior to therapy is mandatory. If a recent archived biopsy,as defined by protocol,is not available at 
screening, a fresh biopsy will be taken at any point prior to treatment. 
d Samples from subjects that have confirmed progression are optional.
e Optional biopsies on-treatment and upon progression and may be taken at the discretion ofthe investigator.
9.8.2.7
Additional Research Collection
This protocol will include residual sample storage for additional research.
For All US Sites
Additional research participation is required for all investigational sites in the U.S.
For All Non-US Sites
Additional research 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 additional research is intended to expandthe translational 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
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patients. This may also include genetic/genomic exploration aimed at exploring disease pathways,
progression and response to treatment etc.
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse
committee of the study sponsor’s senior leaders in Research and Development (or designee) to
ensure the research supports appropriate and well-defined scientific research activities.
PK, residual tumor, plasma, serum, whole blood DNA, whole blood RNA, and PBMC(seeTable 
9.8.2.6-1) will be retained for additional research purposes.
Samples kept for future research will be stored at the BMS Biorepository 
or an independent, BMS-approved storage vendor.
The manager of these samples will ensure they are properly used throughout their usable life and
willdestroy the samples at the end of the scheduled storage period, no longer than 15years after 
the end of the study or the maximum time 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.
Further details of sample collection and processing will be provided to the site in the procedure
manual.
Table 9.8.2.7-1:
Residual Sample Retention for Additional Research Schedule
Sample Type 
Time points for which residual samples will be retained
PK 
All
Tumor biopsy 
All
Plasma 
All
Serum 
All
Whole blood DNA 
All
Whole blood RNA 
All
PBMC
All
9.9
Medical Resource Utilization and Health Economics
Health care resource utilization data will be collected for all randomized participants using an 
internal CRF developed for use in previous trials. The form, which is completed by study staff, 
records information about hospital admissions, including number of days spent in various wards 
and discharge diagnosis, as well as non-protocol specified visits related to study therapy, including 
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date of visit, reason for visit, and type of visit. The health care resource utilization data will be 
used to support subsequent economic evaluations.
10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination
The sample size for the study is based ona primary endpoint of PFS usingBICR for either a Phase 
2 or a Phase 3 study. The sample size for the Phase 2 study as justified below is approximately 400 
randomized participants. The sample size for the Phase 3 study as justified below is 700 
randomized participants, comprised of the Phase 2 population and an additional 300 participants. 
The overall alpha for the Phase 3 study is 0.05 (two-sided) with detailed alpha-spending strategy 
described in Section 10.2.2.
Sample Size Justification for Phase 2 PFS Estimation
The primary objective of the Phase 2 portion of the study is to demonstrate preliminary clinical 
evidence of the treatment effect, measured by PFS, as determined by BICR using RECIST v1.1 in 
randomized participants with unresectable or metastatic melanoma treated with BMS-986213 
compared to those treated with nivolumab monotherapy.The number of events is based on results 
from study CA209067with a median PFS of 6.9 months for nivolumab monotherapy and 11.8 
months for nivolumab with relatlimab.With 183 events,therewill beapproximately 80% power 
to detect ahazard ratio (HR)=0.73 with a type 1 error of 0.1 (1-sided).The cure rates were 
assumed to be 30% in the nivolumab arm and 40% in the nivolumab with relatlimab arm. The 
power is also affected by non-proportional hazards, since it is driven by the number of events, not 
the number of study participants, and some fraction of the participants in each arm are assumed 
will remain event-free for the duration of the study. Approximately 400 participants will be 
randomized to the Phase 2 study to ensure enough power to analyze the biomarker subgroups (see 
section below on the secondary endpointof ORRin subgroup).
Based on an anticipated screen failure rate of 30%, approximately 575participants will need to be 
screened in order to randomize approximately 400 participants who fit the eligibility criteria.
Sample Size Justification for Phase 3 PFS Comparison
The sample size is calculated in order to compare PFS amongparticipants randomized to receive 
BMS-986213 versusnivolumab. The number of events required is simulated based on results from 
study CA209067, with a median PFS of 6.9 months for nivolumab monotherapy and 11.8 months 
for nivolumab with relatlimab, incorporating 35% of subjects with durable response in the 
combined groups, and a piecewisehazard ratio resulting in an effective hazard ratio of 
approximately 0.73.
Based on these assumptions, the study requires 365 PFS events to ensure approximately 85% 
power to detect a hazard ratio of 0.73 with an overall type I error of 0.05. Approximately 700 
participants will be randomized to the two treatment arms in a 1:1 ratio. ThefinalPFSanalysisis
plannedtooccurwhen365participantshavehadaPFSeventperBICR.Totalenrollmentwilltake
approximately27months(includingapotential6-monthpauseduetotheinterim PFSanalysis).
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Based on an anticipated screen failure rate of 30%, approximately 1000 participants will need to 
be screened in order to randomize 700 participantswho meet the eligibility criteria.
Sample Size Justification for Secondary Objective of Overall Survival Comparison in 
Phase 3Trial
The sample size is calculated in order to compare OSamong participants randomized to receive 
BMS-986213 versus nivolumab. The number of OS events (deaths) required isbased on results 
from study CA209067, with a median PFS of 36.9 months for nivolumab monotherapy and 49.2
months for nivolumab with relatlimab, resulting in an effective hazard ratio of approximately 0.75.
With 300 deaths the power will be approximately 69% with a type I error rate of 0.05.
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Sample Size Justification for Secondary Objective of Subgroup Comparison inPhase 2 
Trial
Iftheinterim PFS analysisdoesnotsupportcontinuingtoaPhase3study,thestudywillcomplete
asaPhase 2trial.TheprimaryobjectiveofthePhase2studyusingpatientswithpreviously
untreated,unresectableormetastaticmelanomaistoassesspreliminaryclinicalevidenceofthe
treatment effectmeasured byPFSasdeterminedbyBICR thatmayrepresentsubstantial
improvementover availabletherapies.As asecondaryobjective,thePhase2will examine
ORRinformationinbiomarkersubgroupsbasedonLAG-3expression(1%expressionversus
<1%expression)andPDL-1status(1%tumorcellsurfaceexpressionversus<1%tumorcell
surfaceexpression).ORRinformationandbiomarkerprevalencerates(forLAG-3positiveand
negativeexpression, andforPDL-1positiveandnegativestatus)usedinthesamplesize
calculationswere basedon informationfromstudyCA209067andinteriminformationfrom
studyCA224020.Table 10.1-1showsthepowerforvaryingORRsandvaryingprevalencerates
forsubgroups,assumingaType1errorrateof0.1(one-sided)andanoverallNof400subjects.
TheBenjamini-HochbergprocedurewillbeusedtocontroltheFalseDiscoveryRate(FDR)when
testingmultiple subgroups.
Table 10.1-1:
Power for Subgroups with Different N and Prevalence
Overall N for
Phase 2Study
Subgroup N
SubgroupORR
Subgroup
Prevalence
Power (one-sided alpha .1and 20% 
delta)
400
200
0.7
0.5
0.991
140
0.7
0.35
0.962
50
0.5
0.125
0.576
80
0.5
0.2
0.72
50
0.33
0.125
0.57
80
0.33
0.2
0.713
100
0.23
0.25
0.815
120
.23
0.3
0.865
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Enrolled Participants
All participants who sign informed consent and were registered 
into IRT
Randomized
All participants who are randomized to any treatment group. 
Treated
All participants who received at least one dose of double-blind 
study medication.
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Population
Description
Safety
All randomized participants who take at least 1 dose of double 
blind study treatment. Data in this data set will be analyzed based 
on randomized treatment, except in the following cases:
If a participant received the same incorrect treatment 
throughout the study, then the participant will be analyzed 
based on the treatment received.
If a participant received study drug from more than one 
treatment group, and none of the administrations were 
consistent with the assigned randomized treatment group, then 
the participant will be analyzed based on the first treatment 
received.
PK
All randomized participants with available serum time-
concentration data.
Immunogenicity
All randomized participants with available ADA data.
Biomarker
All randomized participants with available biomarker data.
10.2
Statistical Analyses
10.2.1
Demographics and Baseline Characteristics
Frequency distributions of gender, race, ethnicity, and other categorical baseline characteristics 
will be tabulated. Baseline body mass index (BMI) will be derived from measurements of baseline 
body weight and height. Summary statistics for age, body weight, height, and BMI will be 
tabulated. Baseline disease characteristics will be summarized for expansion cohorts for different 
disease cohorts separately, as appropriate.
10.2.2
EfficacyAnalyses
Below is a summary of planned statistical analyses of the primary and secondary efficacy 
endpoints.
Endpoint
Statistical Analysis Methods
Phase 3 Primary
PFS time, as assessed by a BICR, using 
RECIST v1.1. PFS is defined as the time 
between the date of randomization and 
the first date of documented 
progression, or death due to any cause, 
whichever occurs first.
Two-sidedlog-rankteststratifiedbyLAG-3 expression 
(1%vs<1%),(PD-L1status(1%vs<1%),
BRAFstatus,andAJCC (8thedition)M Stagein
randomized participantstocompare thePFS of
relatlimab+nivolumabarm(BMS-986213)andthe
nivolumab alone arm. Hazard ratios and
corresponding2-sided95%CI will beestimated
using a Cox proportional hazards model, with
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Endpoint
Statistical Analysis Methods
treatmentgroupasasinglecovariate, stratified by 
the above factors.
PFS curves, PFS medians with 95% CIs, and PFS
ratesat6and12months with95%CIswill be
estimated using Kaplan-Meier methodology.
Phase 3 Secondary
OStimeis defined as the time between 
the date of randomization and the date 
of death due to any cause.
This test will only be interpreted if the primary 
analysis is significantly superior. Two-sided log-rank 
test stratified by LAG-3 expression (≥1% vs <1%), 
PD-L1 status (≥1% vs <1%), BRAF status, and 
AJCC (8th edition) M Stage will be used to compare 
the relatlimab + nivolumab arm (BMS-986213) and 
the nivolumab arm. Hazard ratio and corresponding 
two-sided 95% CI will be estimated using a Cox 
proportional hazards model, with treatment group as 
a single covariate, stratified by the above factors. 
Additionally, OS curves, OS medians with 95% CIs, 
and OS rates at 12 months with 95% CIs will be 
estimated using Kaplan-Meier methodology. 
ORR as assessed by BICR. The ORR is 
defined as the number of subjects with a 
BOR of CR or PR divided by the 
number of randomized subjects for each 
treatment group. The BOR is defined as 
the best response designation, recorded 
between the date of randomization and 
the date of objectively documented 
progression per RECIST v1.1 or the 
date of subsequent anti-cancer therapy, 
whichever occurs first.
This test will only be interpreted if the primary (PFS) 
and first secondary (OS) analyses aresignificantly 
superior. Two-sided Cochran-Mantel-Haenszel 
(CMH) test stratified by LAG-3 expression (≥1% vs 
< 1%), (PD-L1 status (≥1% vs < 1%), BRAF status, 
and AJCC (8th edition) M Stage to compare the 
BMS-986213 arm and the nivolumab monotherapy 
arm. Associated odds ratios and 95% CIs will be 
calculated. Additionally, ORRs and corresponding 
95% exact CIs will be calculated using the Clopper 
Pearson method.
Phase 3 Exploratory
Will be described in the Statistical Analysis Plan 
(SAP)finalizedbeforedatabase lock
Phase 2 Primary
PFS time, as assessed by BICR, using 
RECIST v1.1. PFS time is defined as the 
time between the date of randomization 
and the first date of documented 
Two-sided log-rank test stratified by LAG-3 
expression (≥1% vs < 1%), (PD-L1 status (≥1% vs 
< 1%), BRAF status, and AJCC (8th edition) M Stage 
in randomized participants to compare the PFS of 
relatlimab + nivolumab arm (BMS-986213) and the 
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Endpoint
Statistical Analysis Methods
progression, or death due to any cause, 
whichever occurs first.
nivolumab alone arm. Hazard ratios and 
corresponding 2-sided 95% CI will be estimated 
using a Cox proportional hazards model, with 
treatment group as a single covariate, stratified by the 
above factors.
PFS curves, PFS medians with 95% CIs, and PFS 
rates at 6 and 12 months with 95% CIs will be 
estimated using Kaplan-Meier methodology.
Phase 2 Secondary
ORR as assessed by BICR. 
Summary of ORR with corresponding 2-sided 95% 
CI in each arm and for the difference between arms, 
along with each category of BOR. Multiple 
comparisons in population subgroups will be handled 
using the Benjamini-Hochberg method to control the 
False Discovery Rate (FDR) at 0.05. 
DOR is defined as the time between the 
date of first response to the date of first 
documented tumor progression (per 
RECIST v1.1) or death due to any 
cause. TTR is defined as the time from 
randomization to the date of the first 
documented CR or PR.
Summary of DOR with median (95% CI) and range 
(min, max) by K-M method. Summary of median 
Time to Response (mTTR) (95% CI)
PFS time and PFS rate as assessed by 
BICR, using RECIST v1.1 for 
subgroups
Summary of PFS with median (95% CI) by Kaplan-
Meier method and PFS rate
OS is defined as the time between the 
date of randomization and the date of 
death due to any cause.
OS with median (95% CI) and range (min, max) by 
Kaplan-Meier method
Phase 2 Exploratory
Will
bedescribed inthe SAP finalizedbefore
database lock
PFS is defined as the time between the date of randomization and the first date of documented 
progression, or death due to any cause, whichever occurs first. Participants who die without a 
reported progression will be considered to have progressed on the date of their death. Participants 
who did not progress or die will be censored on the date of their last evaluable tumor assessment. 
Participants who did not have any on study tumor assessments and did not die will be censored on 
their date of randomization. Participants who started anti-cancer therapy without a prior reported 
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progression will be censored on the date of their last evaluable tumor assessment prior to the 
initiation of subsequent anti-cancer therapy.
Phase 3 Testing Strategy
ThePhase2partofthestudywillenrollapproximately400participants.Aninterimanalysisof
PFSwillbeperformedwhenaminimumfollow-upof12weeksisachievedforapproximately
400randomizedsubjectsoratleast150PFSeventshavebeenobservedusingBICR.
If the interim PFSanalysis achievesthepre-specified threshold (as definedin the SAPand the 
DMC Charter), thenthestudywillcontinuetoPhase3andremainblinded.
Ifinterim PFSanalysis doesnotachievethepre-specifiedthreshold(asdefinedinthe
SAPandDMC Charter)thestudywillnotopenenrollmenttoPhase3.ThePhase2data
willbeallowedtomatureandthenthesponsorwillunblindforanalysis.Ifthatscenario
takesplace, approximately575participantswillneedtobeenrolledinordertorandomize
400participantsassumingascreenfailurerateof30%.
The overall alpha for the Phase 3 study is 0.05 (two-sided). 
ForthePhase3study,typeIerrorcontrolacrossendpointswillbeperformedhierarchically.The
primaryanalysisisforPFS.Ifthatanalysisissignificantlysuperior,thenthesecondaryendpoints
maybetestedintheorderofOSfollowedbyORR.Thatis,iftheresultscomparingPFSbetween
treatmentgroupsaresignificantattheapplicablealphalevel,thenresultscomparingOSbetween
treatmentgroupswillbeinterpreted.IftheresultscomparingOSbetweentreatmentgroupsare
significant,thenresultscomparingORR betweentreatmentgroupswill beinterpreted.Other
endpointswillnotbetestedformally.
An administrative alpha penalty of 0.001 will be used for the interim PFS analysis. If the interim 
PFS analysis meets the pre-specified threshold and proceeds to Phase 3, the final PFS analysis will 
be performed when approximately365 PFS events have occurred per BICR and will use all 
remaining unspent alpha. If the pre-specified efficacy boundary is achieved at PFS final analysis, 
all remaining alpha will be passed to OS in a hierarchical fashion as described above, and 
participants will continue to be followed for OS.
Assuming the PFS result is significantly superior (at the final PFSanalysis), there will be interim 
analyses of OS. The interim OS analyses will use an O’Brien-Fleming boundary based on the 
actual number of deaths observed. The first interim analysis of OS (OS IA1) will take place at the 
same time as final PFS. If OS IA1 does not achieve statisticalsignificance, the second interim 
analysis of OS (OS IA2) will be performed when a minimum of 90% (270/300) of the expected 
deaths have occurred. If OS IA2 is not statistically significant, the final OS analysis will be 
performed when approximately300 deaths have occurred.
IfPFSandOSare each significantly superior, then ORRwillbeformallytested.
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Phase 2 Testing Strategy
If the interim PFS analysis indicates the study will stop at Phase 2 the study will not enroll any 
additional participants, and the study will remain blinded until the data are sufficiently mature (183 
PFS events and aminimum 6 months of follow-up). The final Phase 2 analysis includes multiple 
subgroups of interest. The Benjamini-Hochberg method will be used to account for multiplicity by 
controlling the False Discovery Rate (FDR) when making comparisons in multiple subgroups.
10.2.3
Safety Analyses
All safety analyses will be performed on the Safety Population.
Endpoint
Statistical Analysis Methods
The Safety and tolerability objective 
(whether for Phase 2 or Phase3) will be 
measured by the incidence of adverse events 
(AEs), serious adverse events (SAEs), 
adverse events leading to discontinuation, 
deaths, and laboratory abnormalities in each 
arm.
Safety analyseswill be performed in all
treatedparticipants.Descriptive statisticsof
safetywillbepresentedusingNationalCancer
Institute(NCI)CommonTerminologyCriteria
forAdverse Events(CTCAE)version5.0by
treatment group.Allon-studyAEs, treatment-
related AEs, SAEs, and treatment-related
SAEswillbetabulatedusingworstgradeper
NCI CTCAEv5.0criteriabysystemorgan
class and preferred term. On-study lab
parametersincludinghematology,chemistry,
liverfunction,andrenalfunction will be
summarizedusingworst gradeNCICTCAE
v5.0criteria.
10.2.4
Other Analyses 
PK and biomarker exploratory analyses will be described in the SAP finalized before database 
lock.
10.2.4.1 Pharmacokinetic Analyses
Trough concentrations of relatlimab will be plotted versus study day and cycle. Nivolumab end-
of-infusion and trough (Ctrough) concentrations will be tabulated using summary statistics. 
These data may also be pooled with other datasets for population PK analysis which will be 
presented in a separate report.
10.2.4.2 Immunogenicity Analyses
A listing will be provided for all available immunogenicity data. Baseline ADA positive subject 
is defined as a subject with positive seroconversion detected in the last sample before initiation 
of treatment. ADA-positive subject is a subject with at least oneADA-positive sample relative to 
baseline after initiation of the treatment. For each drug, frequency distribution of baseline ADA 
positive subjects and ADA positive subjects after initiation of the treatment will be summarized. 
To examine the potential relationship between immunogenicity and safety, a table summarizing 
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the frequency and type of AEs of special interest may be explored by immunogenicity status. In 
addition, potential relationships between immunogenicity and efficacy and/or PK may also be 
explored.
10.2.4.3 Outcomes Research
Analyses of EQ-5D-3L, FACT-M(and GP5 item alone), and WPAI:GH scores will be performed 
in all randomized participants who have an assessment at baseline (Day 1, assessment prior to 
administration of drug on day of first dose) and at least 1 subsequent assessment while on 
treatment. Questionnaire completion rate, defined as the proportion of questionnaires actually 
received out of the expected number, will be calculated and summarized at each assessment point.
EQ-5D-3L data collected during on-study clinic visits, at Follow-up Visits 1 and 2, and during the 
survival follow-up phase, will be described by treatment group as randomized in the following 
ways:
EQ-5D-3L index scores and post-baseline changes in scores will be summarized at each 
assessment time point using descriptive statistics (ie, N, mean with SD and 95% CI, median, 
first and third quartiles, minimum, maximum). In the base case, scores will be calculated using 
the UK preference-weighting algorithm.
EQ-5D-3L VAS scores and post-baseline changes in scores will be summarized at each 
assessment time point using descriptive statistics (ie, N, mean with SD and 95% CI, median, 
first and third quartiles, minimum, maximum).
The proportion (N) of participants reporting no, moderate, or extreme problems will be 
presented for each of the 5 EQ-5D-3L dimensions at each assessment time point. 
A by-participant listing of the level of problems in each dimension, corresponding EQ-5D-3L 
health state (ie, 5-digit vector), EQ-5D-3L index score, and EQ-5D-3L VAS score will be 
provided.
FACT-M data collected during on-study clinic visits, at Follow-up Visits 1 and 2, and during the 
survival follow-up phase will be described by treatment group as randomized in the following 
ways:
Scores and post-baseline changes in scores for the FACT-M total scale and subscales, and the 
GP5will be summarized at each assessment time point using descriptive statistics (ie, N, mean 
with SD and 95% CI, median, first and third quartiles, minimum, maximum
, andfrequency of 
responsesfor GP5 item).
The proportion (N) of participants with symptomatic deterioration, defined as a clinically 
meaningful decline in FACT-M MS score (worsening from baseline ≥34 points) or death, will 
be summarized at each assessment time point (on-study visits only).
WPAI:GH data collected at baseline, on-treatment visits, and at follow-up Visits 1 and 2 will be 
described by treatment group as randomized in the following ways:
Employment status (Q1, Yes/No) will be summarized at each assessment time point using 
frequency counts and percentages.
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Hours actually worked during the past 7 days (Q4) will be summarized at each assessment time 
point as a categorical variable (> 0 hour/0 hour) using frequency counts and percentages.
Absenteeism,presenteeism, work productivity loss, and activity impairment scores and post-
baseline changes in scores will be summarized at each assessment time point using descriptive 
statistics (ie, N, mean with SD and 95% CI, median, first and third quartiles, minimum, 
maximum). Absenteeism and work productivity loss scores will be summarized for 
participants who were employed (Q1=Yes). Presenteeism will be summarized for participants 
who actually worked during the past 7 days (Q4 > 0 hour). Activity impairment will be 
summarized for all participants.
10.2.5
InterimAnalyses 
The DMC will perform 1interimanalysis of PFS, andup to 2 interim analyses of OS(See Section 
10.2.2).
The DMC Statistical Analysis Plan will further describe the planned interim analyses.
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REFERENCES
1 Sharpe AH, Wherry EJ, Ahmed R, et al. The function of programmed cell death 1 and its 
ligands in regulating autoimmunity and infection. Nat Immunol 2007;8(3):239-45.
2 Wolchok JD, Kluger HM, Callahan MK, et al. Safety and clinical activity of nivolumab 
(anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with 
advanced melanoma (MEL). ASCO Annual Meeting Proceedings; 2013.
3 Sznol M, Kluger HM, Callahan MK, et al. Survival, response duration, and activity by BRAF
mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and 
ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). ASCO Annual Meeting; 
June 2014; Chicago, IL.
4 Cancer Facts and Figures 2017. American Cancer Society. Atlanta, GA. 2017.
5 Hodi SF, O
'Day SJ, McDermott DF, et al. Improved Survival with Ipilimumab in Patients with 
Metastatic Melanoma. N Engl J Med. 2010;363:711-23.
6 Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously 
untreated metastatic melanoma. N Engl J Med. 2011;354:2517-26.
7 McArthur G, Chapman P, Robert C, et al. Safety and efficacy of vemaurafenib in BRAF 
V600E and BRAF V600K mutation-positive melanoma (BRIM-3): extended follow-up of a 
Phase 3, randomised, open-label study. Lancet Oncol. 2014;15:323-32.
8 Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemuafenib in melanoma 
with BRAF V600E mutation. N Engl J Med. 2011;364:2507-16.
9 Hauschild A, Grob JJ, Demidov LV, et al. Debrafenib in BRAF mutated metastatic melanoma: 
a multicentre, open-label, Phase 3 randomised controlled trial. Lancet. 2012;380:358-65.
10 Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev Immunol. 
2003;21:807-39.
11 Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection 
and immunosubversion. Nat Rev Immunol. 2006;6(10):715-27.
12 Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to 
tumor escape. Nat Immunol. 2002;3(11):991-8.
13 Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 
2005;23:515-48.
14 Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a 
novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 
2000; 192(7): 1027-34.
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15 Sharpe AH, Wherry EJ, Ahmed R, et al. The function of programmed cell death 1 and its 
ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8(3):239-45.
16 Alegre ML, Noel PJ, Eisfelder BJ, et al. Regulation of surface and intracellular expression of 
CTLA4 on mouse T cells. J Immunol 1996;157:4762-70.
17 Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity 
in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-20.
18 AJCC Cancer Staging Manual,  8th Edition Staging Rules. Amin MB, Edge S, Greene F, Byrd 
DR, Brookland RK, Washington MK, et al. editors. Springer International Publishing. 2017.
19 Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. final 
Version of 2-009 AJCC Melanoma Staging and Classification. J Clin Oncol. 2009;27:6199-
6206.
20 Thomas NE, Edmiston SN, Alexander A, Groben PA, Parrish E, Kricker A, et al. Association 
Between NRAS and BRAF Mutational Status and Melanoma-Specific Survival Among 
Patients with Higher-Risk Primary Melanoma. JAMA Oncol. 2015;1:359-68.
21 Ascierto PA, Bono P, Bhatia S, et al. LBA18 -Efficacy of BMS-986016, a monoclonal 
antibody that targets lymphocyte activation gene-3 (LAG-3), in combination with nivolumab 
in pts with melanoma who progressed during prior anti–PD-1/PD-L1 therapy (mel prior IO) in 
all-comer and biomarker-enriched populations. Annal Oncol 2017;28(suppl_5):v605-v649.
22 Robert C, Long GV, Brady B, Dutriaux C, Maio M, et al. Nivolumab in Previously Untreated 
Melanoma without BRAF Mutation. N Engl J Med. 2015;372:320-330.
23 Flaherty, K.T. et al. Surrogate endpoints for overall survival in metastatic melanoma: a meta-
analysis of randomised controlled trials. Lancet Oncol.2014;15:297-304.
24 Long, G.V. et al, COMBI-d: A randomized, double-blinded, Phase III study comparing the 
combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line 
therapy in patients (pts) with unresectable or metastatic BRAFV600E/Kmutation-positive 
cutaneous melanoma. Journal of Clinical Oncology 2014 ASCO Annual Meeting Abstracts; 
32:9011.
25 Hauschild, A. et al, Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-
label, phase 3 randomised controlled trial. Lancet. 2012;380:358-65. 
26 Flaherty, K.T., Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl 
J Med 2012;367:107-14.
27 Julia A. Beaver, M.D., Gwynn Ison, M.D., and Richard Pazdur, M.D. N Engl J Med 2017; 
376:1504-1505April 20, 2017DOI: 10.1056/NEJMp1615879.
28 Wong J, Harris J, Rodrigues-Galindo C, Johnson K. Incidence of childhood and adolescent 
melanoma in the united states: 1973-2009. Pediatrics 2013;131:846-854
29 Xu Z, Davis HM, Zhou H. Rational development and utilization of antibody-based therapeutic 
proteins in pediatrics. Pharmacol Ther 2013;137:225–47
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30 Zhang Y, Wei X, Bajaj G, Barrett JS, Meibohm B, Joshi A, et al. Challenges and considerations 
for development of therapeutic proteins in pediatric patients. J Clin Pharmacol 2015;55 Suppl 
3:S103–15.
31 Wolchok JD, Hoos A, O’Day S, et al. Guidelines for 
the evaluation of immune therapy activity 
in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-20.
32 Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D 
utility and VAS scores in cancer. Health Qual Life Outcomes 2007;5:70.
33 Pearman TP, Beaumont JL, Mroczek D, et al. Validity and Usefulness of a Single-Item 
Measure of Patient-Reported Bother From Side Effects of Cancer Therapy. Cancer. 
2018;124(5):991-997.
34 Askew RL et al. Value in Health. 2009 Nov-Dec; 12(8): 1144-50.
35 Robinson DW et al. Melanoma Research. 2012 Feb; 22(1): 54-62.
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
ADA
anti-drug antibody
AEs
adverse events
AIDS
acquired immunodeficiency syndrome
AJCC
American Joint Committee on Cancer
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BICR
Blinded Independent Central Review
BMI
body mass index
BOR
best overall response
CBC
complete blood count
CD279
cluster of differentiation 279
CI
confidence interval
CMV
cytomegalovirus
CNS
central nervous system
CONSORT
Consolidated Standards of Reporting Trials
CR
complete response
CrCl
creatinine clearance
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DCR
Disease control rate
DILI
drug-induced liver injury
DLT
dose-limiting toxicity
DMC
Data Monitoring Committee
DOR
Duration of response
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic Case Report Form
eGFR
estimated glomerular filtration rate
ELISA
enzyme-linked immunosorbent assay
EQ-5D-3L 
3-level version of the EuroQol Group’s EQ-5D
ER
exposure-response
EWB
emotional well-being
FACT-M 
Functional Assessment of Cancer Therapy –Melanoma
FACT-M MS
FACT-M Melanoma Subscale
FDC
fixed-dose combination
FDR
False Discovery Rate
FFPE
formalin-fixed paraffin-embedded
FWB
functional well-being
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HR
hazard ratio
IA1, IA2
interim analysis 1, interim analysis 2
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Term
Definition
IB
Investigator’s Brochure
ICF
informed consent form
Ig
immunoglobulin
IHC
Immunohistochemistry
IMAEs
immune-mediated AEs
IO
immuno-oncology
IP
investigational product
IRB/IEC
Institutional Review Board/Independent Ethics Committee
IRT
interactive response technology
IV
intravenous
LAG-3
lymphocyte activation gene 3
LC
liquid chromatography
mAbs
monoclonal antibodies
MHC
major histocompatibility complex
MID
minimally important difference
MLR
mixed lymphocyte reaction
MRI
magnetic resonance imaging
MS
mass spectrometry
MTD
maximum tolerated dose
mTTR
median Time to Response
NCI
National Cancer Institute
NSCLC
non-small cell lung cancer
ORR
overall response rate
OS
overall survival
PBMC
peripheral blood mononuclear cells
PD
pharmacodynamics
PD-1
programmed death-1
PD-L1 
programmed death-ligand 1
PD-L2
programmed death-ligand 2
PET
positron emission tomography
PFS
progression-free survival
PK
pharmacokinetics
PPK
population PK
PR
partial response
PVC
polyvinyl chloride
PWB
physical well-being
Q2W
every 2 weeks
Q4W
every 4 weeks
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors
RO
receptor occupancy
SAE
serious adverse event
SAP
statistical analysis plan
SCCHN
squamous cell carcinoma of the head and neck
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Term
Definition
SD
stable disease
SUSAR
suspected, unexpected serious adverse reaction
SWB
social/family well-being
TCR
T-cell receptor
TnI
troponin I
TnT
troponin T
TOI
Trial Outcome Index
TTR
Time to objective response
TTSD
Time to meaningful symptomatic deterioration
ULN
upper limit of normal
US
United States
VAS
visual analog scale
WBC
white blood cells
WOCBP
women of childbearing potential
WPAI:GH
Work Productivity and Activity Impairment: General Health
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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 eCRF 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 GuidelinesGood 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 participantinformed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulationsprior to initiation of the study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach isdefined 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 REVIEWBOARD/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/participantsand 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 for 
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/participantscurrently 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/participantsprior 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 yearafter completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that subjects/participantsare 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 to 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 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. 
For minors, according to local legislation, one or both parents or a legally acceptable representative 
must be informed of the study procedures and must sign the informed consent form approved for 
the study prior to clinical study participation. The explicit wish of a minor, who is capable of 
forming an opinion and assessing this information to refuse participation in, or to be withdrawn 
from, the clinical study at any time should be considered by the investigator. 
Minors who are judged to be of an age of reason must also give their written assent.
The rights, safety, and well-being of the study subjects/participantsare the most important 
considerations and should prevail over interests of science and society.
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SOURCE DOCUMENTS
The Investigator is responsible for ensuring that the source data areaccurate, 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. 
Suchsystems 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 treatmentintegrity 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 (e.g., 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 recordall 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 thediscrepancies 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 designeeelectronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
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be reported on the electronic SAE formand Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
Sponsor or designee.
The confidentiality of records that could identify subjects/participantsmust 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 subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task.For electronic CRFs, review and approval/signature is completed electronically through the 
BMS electronic data capture tool.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 designeetraining 
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
Sponsor or designeerepresentatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records. 
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 recordsand 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 Sponsoror designeeinternal 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 BMSpromptly 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.
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BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, anotherinvestigator, 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) 
It is the investigator’s or designee’s 
responsibility to dispose of all containers
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. 
Foreach CSR related tothis protocol, the following criteria will be used to select the signatory 
investigator:
External Principal Investigator designated at protocol development
National Coordinating Investigator 
Study Steering Committee chair or their designee
Participant recruitment (eg, among the top quartile of enrollers)
Involvement in trial design
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 (CTA) 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 CTA.
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 
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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. 
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 participantadministered 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-druginteraction.
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 NOTMeeting 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 participantwas 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 participantor 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 9.2.7for the definition of potential DILI.) 
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Pregnancy and potential drug induced liverinjury (DILI) must follow the same transmission timing 
and processes to BMS as used for SAEs (see section 9.2.5 for reporting pregnancies).
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 mustdocument 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 treatmentor 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 preferred method for SAE data reporting collection is through the eCRF.
The paper SAEReport Formis 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 forms are to be 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 
45years 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 
>40mIU/mL to confirm menopause.
CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILD BEARING 
POTENTIAL
One of the highly effective methods of contraception listed below is required during study duration 
and until the end of relevant systemic exposure, defined as 5 monthsafter the end of study 
treatment.*
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 ovulationb 
oral 
intravaginal 
transdermal 
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Progestogen-only hormonal contraception associated with inhibition of ovulationb 
oral 
injectable 
Highly EffectiveMethods That Are User Independent
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationb
Intrauterine hormone-releasing system (IUS)
c
Intrauterine device (IUD)
c
Bilateral tubal occlusion
Vasectomizedpartner 
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 drug. 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.
It is not necessaryto use any other method of contraception when complete abstinence is 
elected. 
WOCBP participantswho 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 participantschooses to forego complete abstinence 
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 drug, 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 devices and 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
Unacceptable Methods of Contraception*
Male or female condom with or without spermicide.  Male and female condoms cannot be 
used simultaneously
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Diaphragm with spermicide
Cervical cap with spermicide
Vaginal Sponge with spermicide
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal (coitus interruptus).
Spermicide only
Lactation amenorrhea method (LAM)
* Local laws and regulations may require use of alternative and/or additional contraception 
methods.
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S)OF 
CHILD BEARING POTENTIAL.
No contraceptive requirements for male participants. 
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
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 InSolid Tumors version 1.1 
(RECIST1.1)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/MRIscan (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/MRIscan (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 
15mm by CT/MRIscan. 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 20mm 
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 
<10mm 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 notconsidered 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 identifiablesofttissuecomponents, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the softtissuecomponentmeets 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 identifiedas 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) forall 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 furthercharacterize 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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2
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, eachnode 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 
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small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 
default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm.
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 (<10mm 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 
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disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 
if all lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the change 
in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in 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 thisis 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 itrepresents 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:
Negative FDG-PET at baseline,with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion.
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No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 
CT scans are needed to determine if there is truly progression occurring at that site (if so, the 
date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET 
at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD.
2.3
Response Assessment
2.3.1
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
disease progression or the last response recorded, taking into account any requirement for 
confirmationand censoring rules regarding subsequent therapy. 
The patient’s best overall response
assignment will depend on the findings of both target and non-target disease and will also take into 
consideration the appearance of new lesions. Furthermore, depending on the nature of the study 
and the protocol requirements, it may also require confirmatory measurement.
2.3.2
Time Point Response
At each protocol specified time point, a response assessment occurs. Table 2.3.2-1provides 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 2.3.2-2is 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
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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
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
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 canbe measured is not advised.
2.3.3
Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point of 
4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as in 
Table 2.3.3-1. When SD is believed to be best response, it must meet the protocol specified 
minimum time from the date of first treatment or randomization date.
For example, if the first scheduled follow-up imaging visit is Week 6 (7 days) for a particular 
protocol, a Best Response of SD can only be made after the subject is on-study for a minimum of 
6 weeks (42 days) minus 7 days, for an absolute minimum time on-study of 35 days from the 
reference start date (reference date is considered Day 1 on study).  If the subject is not on-study 
for at least this amount of time, any tumor assessment indicating stable disease before this time 
period will have a Best Response of NE unless PD is identified.
Special note on response assessment:When nodal disease is included in the sum of target lesions 
and the nodes decrease to ‘normal’ size (< 10 mm), they may still have a measurement reported 
on scans. This measurement should be recorded even though the nodes are normal in order not to 
overstate progression should it be based on increase in size of the nodes. As noted earlier, this 
means that patients with CR may not have a total sum of ‘zero’ on the case report form (CRF).
Table 2.3.3-1:
Best Overall Response (Confirmation of CRand PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
BestOverall Response
CR
CR
CR
CR
PR
SD, PD OR PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
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Table 2.3.3-1:
Best Overall Response (Confirmation of CRand PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
BestOverall Response
CR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
PR
NE
SD provided minimum criteria for SD durationmet, otherwise, 
NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and 
NE=inevaluable
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR.
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 subsequentrepeat assessments that should be performed no 
less than 28days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of apreviously identified CR even with an intervening NE or PR
(eg,CR NE CRor CR PR CR).Subsequent documentation of a PR may provide confirmation of 
apreviously 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/CRsfor 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, thenthe subject is considered to not have 
progressive disease.
REFERENCES
1Eisenhauer 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 6
ECOG, KARNOFSKY,AND LANSKY PERFORMANCE STATUS 
SCALES
PERFORMANCE STATUS CRITERIA: ECOG Score 
ECOG (Zubrod) 
Score 
Description
0
Fully active; able to carry on all pre-disease performance without
restriction
1
Restricted in physically strenuous activitybut ambulatory and able to carry out work of alight 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.
PERFORMANCE STATUS CRITERIA: Karnofsky and Lansky
Score
Karnofsky Description
Lansky Description
100
Normal; no complaints; no evidence of disease
Fully active, normal
90
Able to carry on normal activity; minor signs or 
symptoms of disease.
Minor restrictions in physically strenuous 
activity
80
Normal activity with effort; some signs or symptoms of 
disease.
Active, but tires more quickly
70
Cares for self; unable to carry on normal activity or to do 
active work.
Substantial restriction of, and less time 
spent, in play activity
60
Requires occasional assistance, butis able to care for 
most of their personal needs.
Out of bed, but minimal active play; keeps 
busy with quiet activities
50
Requires considerable assistance and frequent medical 
care.
Gets dressed, but inactive much of day; no 
active play, able to participate in quiet play
40
Disabled; requires special care and assistance.
Mostly in bed; participates in some quiet 
activities
30
Severely disabled; hospital admission is indicated 
although death not imminent.
In bed; needs assistance even for quiet play
20
Very sick; hospital admission necessary; active 
supportive treatment necessary.
Often sleeping; play limited to passive 
activities
10
Moribund; fatal processes progressing rapidly.
No play; does not get out of bed
0
Dead
Unresponsive
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APPENDIX 7
AJCC MELANOMA STAGING (CANCER STAGING MANUAL 
8TH EDITION)
[From AJCC Cancer Staging Manual, 8th Edition.Amin MB, Edge S, Greene F, Byrd DR, 
Brookland RK, Washington MK, et al. editors. Springer International Publishing. 2017(pages 577 
& 578)]
Definition of Primary Tumor (T)
T Category
Thickness
Ulceration Status
TX:primary tumor thickness cannot be 
assessed (e.g., diagnosis by curettage)
Not applicable 
Not applicable
T0:no evidence of primary tumor (e.g., 
unknown primary or completely 
regressed melanoma)
Not applicable
Not applicable
Tis(melanoma in situ)
Not applicable 
Not applicable
T1
1.0 mm
Unknown or unspecified
T1a
<0.8 mm
Without ulceration
T1b
<0.8 mm
With ulceration
0.8-1.0 mm
With or without ulceration
T2
>1.0-2.0 mm
Unknown or unspecified
T2a
>1.0-2.0 mm
Without ulceration
T2b
>1.0-2.0 mm
With ulceration
T3
>2.0-4.0 mm
Unknown or unspecified
T3a
>2.0-4.0 mm
Without ulceration
T3b
>2.0-4.0 mm
With ulceration
T4
>4.0 mm
Unknown or unspecified
T4a
>4.0 mm
Without ulceration
T4b
>4.0 mm
With ulceration
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Definition of Distant Metastasis (M)
M Category
Anatomic site
LDH level
M0
No evidence of distant metastasis
Not applicable
M1
Evidence of distant metastasis
See below
M1a
Distant metastasis to skin, soft tissue 
including muscle, and/or non-regional 
lymph node
Not recorded or unspecified
M1a(0)
Not elevated
M1a(1)
Elevated
M1b
Distant metastasis to lung with or without 
M1a sites of disease
Not recorded or unspecified
M1b(0)
Not elevated
M1b(1)
Elevated
M1c
Distant metastasis to non-CNS visceral 
sites with or without M1a or M1b sites of 
disease
Not recorded or unspecified
M1c(0)
Not elevated
M1c(1)
Elevated
M1d
Distant metastasis to CNS with or without 
M1a, M1b, or M1c sites of disease
Not recorded or unspecified
M1d(0)
Not elevated
M1d(1)
Elevated
Suffixes for M category: (0) LDH not elevated; (1) LDH elevated. No suffix is used if LDH is not recorded or is 
unspecified.
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Definition of Regional Lymph Node (N)
N 
Category
Number of tumor-involved regional 
lymph nodes
Presence of in-transit, 
satellite, or microsatellite 
metastases
NX
Regional nodes not assessed (e.g., SLN biopsy not 
performed, regional nodes previously removed for another 
reason)
Exception: pathological N category is not required for T1 
melanomas, use cN
No
N0
No regional metastases detected
No
N1
One tumor-involved node or in-transit, satellite, and/or 
microsatellite metastases with no tumor-involved nodes
N1a
One clinically occult (i.e., detected by SLN biopsy)
No
N1b
One clinically detected
No
N1c
No regional lymph node disease
Yes
N2
Two or three tumor-involved nodes or in-transit, satellite, 
and/or microsatellite metastases withone tumor-involved 
node
N2a
Two or three clinically occult (i.e., detected by SLN biopsy)
No
N2b
Two or three, at least one of which was clinically detected
No
N2c
One clinically occult or clinically detected
Yes
N3
Four or more tumor-involved nodes or in-transit, satellite, or 
microsatellite metastases with two or more tumor-involved 
nodes, or any number of matted nodes with or without in-
transit, satellite, and/or microsatellite metastases
N3a
Four or more clinically occult (i.e., detected by SLN biopsy)
No
N3b
Four or more, at least one of which was clinically detected, 
or presence any number of matted nodes
No
N3c
Two or more clinically occult or clinically detected, and/or 
presence any number of matted nodes
Yes
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AJCC Prognostic Stage Groups
Clinical (cTNM)
Clinical stage includes microstaging of the primary melanoma and clinical/radiologic/biopsy 
evaluation for metastases. By convention, clinical staging should be used after biopsy of the 
primary melanoma, with clinical assessment for regional and distant metastases. Note that 
pathological assessment of the primary melanoma is used for both clinical and pathological 
classification. Diagnostic biopsies to evaluate possible regional and/or distant metastasis also are 
included. Note there is only one stage group for clinical Stage III melanoma.
When T is....
And N is.....
And M is....
The clinical stage is...
Tis
N0
M0
0
T1a
N0
M0
IA
T1b
N0
M0
IB
T2a
N0
M0
IB
T2b
N0
M0
IIA
T3a
N0
M0
IIA
T3b
N0
M0
IIB
T4a
N0
M0
IIB
T4b
N0
M0
IIC
Any T, Tis
≥N1
M0
III
Any T
Any N
M1
IV
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PATHOLOGICAL (pTNM)
Pathological stagingincludes microstaging of the primary melanoma,including any additional 
staging information from the wide excision (surgical) specimen that constitutes primary tumor 
surgical treatment and pathological information about the regional lymph nodes after SLN biopsy 
or therapeutic lymph node dissection for clinically evident regional lymph node disease.
When T is....
And N is.....
And M is....
The pathological stage 
is...
Tis
N0
M0
0
T1a
N0
M0
IA
T1b
N0
M0
IA
T2a
N0
M0
IB
T2b
N0
M0
IIA
T3a
N0
M0
IIA
T3b
N0
M0
IIB
T4a
N0
M0
IIB
T4b
N0
M0
IIC
T0
N1b,N1c
M0
IIIB
T0
N2b, N2c, N3bor N3c M0
IIIC
T1a/b-T2a
N1a-N2a
M0
IIIA
T1a/b-T2a
N1b/c or N2b
M0
IIIB
T2b/T3a
N1a-N2b
M0
IIIB
T1a-T3a
N2c or N3a/b/c
M0
IIIC
T3b/T4a
Any N >N1
M0
IIIC
T4b
N1a-N2c
M0
IIIC
T4b
N3a/b/c
M0
IIID
Ant T, Tis
Any N
M1
IV
Pathological Stage 0 (melanoma in situ) and T1 do not require pathological evaluation of lymph nodes 
to complete pathological staging; use cN information to assign their pathological stage.
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APPENDIX 8 
COUNTRY SPECIFIC REQUIREMENTS
Argentina, Czech Republic, Germany, Peru and Any Other Countries Where Exclusion of 
HIV Positive Participants Is Locally Mandated
Country-specific language
Section2FlowChart/TimeandEvents
Schedule,Table2-1: Screening
Assessments-LaboratoryTests
Add“HIV”to the list of laboratory tests
Section6.2 Exclusion
Criteria,Exclusioncriterion3j
“Knownhistoryoftestingpositiveforhumanimmunodeficiencyvirus
(HIV)orknownacquiredimmunodeficiencysyndrome(AIDS)”to be 
replacedwith“PositivetestforHIV”.
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APPENDIX 9
MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens.
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated.
Corticosteroidsare a primary therapy for immuno-oncology drug-related adverse events. The oral 
equivalent of the recommended IV doses may be considered for ambulatory patients with 
low-grade toxicity. The lower bioavailability of oral corticosteroids should be taken into account 
when switching to the equivalent dose of oral corticosteroids.
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended.
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used.
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Relatlimab Myocarditis Adverse EventManagement Algorithm
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APPENDIX 10
MUCOSAL MELANOMA STAGING
Classification of Malignant Melanoma of Upper Aero-digestive Tract (7th edition of the 
UICC) (2009)a
Tumour
Characteristics
T3
Epithelium/submucosa (mucosal disease)
T4a
Deep soft tissue, cartilage, bone, or overlying skin
T4b
Brain, dura, skull base, lower cranial nerves, masticator space, carotid artery, 
prevertebral space, mediastinal structures, cartilage, skeletal muscle, or bone
Staging group
Tumour
Node
Metastases
III
T3
N0
M0
IVA
T3-T4a
N1
M0
IVB
T4b
Any N
M0
IVC
Any T
Any N
M1
a Ascierto PA, Accorona R, Botti G, et al. Mucosal melanoma of the head and neck. Crit Rev Oncol Hematol. 2017 
Apr;112:136-152.
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APPENDIX 11
REVISED PROTOCOL SUMMARY OF CHANGE HISTORY 
Overall Rationale for the Revised Protocol 02, 22-Feb-2019
PFS2 has been added as exploratory objective.
Pregnancy tests, incorrectly removed in the revised protocol 01, have been added back during 
follow-up visits.
In addition, minor changes were made to clarify timing of procedures and to improve clarity as 
noted in the table below.
Summary of Key Changes For Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Synopsis, Rationale
Updated study aim from ORR and 
PFS to just PFS.
To correct a discrepancy and to be aligned 
with the body text of the protocol.
Synopsis, Objectives and 
Endpoints
Added Phase 2 and Phase 3 safety 
objectives.
To define safety objectives.
Synopsis, Overall Design
Changing on-study tumor 
assessments to through Week 52 
instead of Week 49.
Clarified timing.
Section 2, Table 2-1: 
Screening Procedural 
Outline
Added BRAF, NRAS, and KIT 
mutation testing.
Added to support sites referencing Table 2-
1.
Section 2, Table 2-2: On-
Study Assessments
Added procedures for elevated 
troponin levels.
Added timing window for ECG.
Added for sites guidance.
Added to bring clarity.
Section 2, Table 2-3: 
Follow-Up Procedural 
Outline
Added pregnancy testing for 
Follow-Up Visits 1 and 2.
Were incorrectly removed in the previous 
revision.
Section 2, Table 2-3: 
Follow-Up Procedural 
Outline
Added PFS2 assessments.
Added to match the additional exploratory 
objective
Section 2, Table 2-3: 
Follow-Up Procedural 
Outline
Removed note regarding survival 
visit phone follow-up for FACT-M 
questionnaire.
This scale is not administered during 
survival follow-up, only Follow-Up Visits 1 
and 2.
Section 2, Table 2-3: 
Follow-Up Procedural 
Outline
Clarified the FACT-M subscale is 
the melanoma subscale (MS).
Clarified for sites.
Section 4, Objectives and 
Endpoints
Moved safety and tolerability 
objective from exploratory to a 
separate “Safety” objective for 
both Phase 2 and Phase 3.
Clarified safety into its own objective.
Section 4, Objectives and 
Endpoints
Added a Phase 3 exploratory 
objective to include PFS, PFS2, 
ORR, and, DOR for combo 
treatment versus nivolumab 
monotherapy.
Added additional exploratory objectives of 
clinical relevance to the melanoma field.
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Summary of Key Changes For Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Added PFS2 to the Phase 2 
exploratory objectives.
Section 6.2, Exclusion 
Criteria, 2), e)
Section 7.7.1.1 Prohibited 
Treatments
Added criteria to exclude receiving 
live/attenuated vaccine with 30 
days of study treatment, during 
treatment, and until 100 days after 
last dose.
Added to provide better guidance to the 
sites.
Section 5.1, Overall Design
Changed description of decision 
point to refer to interim analysis.
Simplified for consistency.
Section 9.1.3, Patient-
Reported Outcomes
Clarified timing of the PRO items.
Clarified for sites.
Section 9.1.3.1, EQ-5D-3L
Clarified change from baseline 
assessment and added reference.
Clarified for sites.
Section 9.4.4, Table 9.4.4-1:  
Laboratory Assessment 
Panels
Added option for leukocyte 
esterase or leukocyte.
Clarified for sites.
Section 9.5.1, 
Pharmacokinetics:  
Collection and Processing
Added clarification for sampling if 
study drug is not administered.
Clarified for sites.
Section 10.2.2, Efficacy 
Analyses
Moved ORR analysis to aboveOS.
Under Testing Strategy, changed 
OS to ORR.
Revised.
Section 10.2.3, Safety 
Analyses
Summarized safety endpoints into 
one.
Revised.
Section 11, References
Updated citation 21.
Updated for ease of reference.
Section 5.1.1, Data 
Monitoring Committee and 
Other External Committees
Section 7, Treatment
Section 7.3, Blinding
Section 8.1, Discontinuation 
from Study Treatment
Section 9.2.2, Method of 
Detecting AEs and SAEs
Section 9.2.5, Pregnancy
Section 10.2.5, Interim 
Analyses
Added clarifying language tobring 
in line with required language 
across all BMS protocols.
Additional required language for all BMS 
protocols.
Appendix 3, Adverse 
Events and Serious Adverse 
Events: Definitions and 
Procedures for Recording, 
Evaluating, Follow Up and 
Reporting
Updated AE definitions, clarified 
SAE definitions, revised 
assessment of causality, and 
updated reporting requirements.
Added updated required language for AEs.
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Summary of Key Changes For Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Appendix 9, Management 
Algorithms for Immuno-
oncology Agents
Updated algorithms to include 
version date.
Updated per program requirements.
Appendix 10, Mucosal 
Melanoma Staging
Added new appendix.
To support classification of mucosal 
melanoma.
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Overall Rationale for the Revised Protocol 01, 15-Aug-2018
Change of Endpoints
The primary endpoint for Phase 2 and the interim analysis endpoint were both changed to PFS 
instead of ORR. The changes were based on simulations performed by resampling data from 1L 
Melanoma study CA209067 with the assumption that the CA224047 study will perform similar to 
067. The simulation results indicated that PFS is the better predictor of final trial success (final 
Phase 3 PFS p-value < 0.049 with a penalty for the interim analysis) compared to ORR, DCR 
(disease control rate), or a combination of ORR and DCR. 
In addition, minor changes were made to clarify timing of procedures and to improve clarity as 
noted in the table below.
Summary of Key Changes For Revised Protocol 01
Section Number & Title 
Description of Change
Brief Rationale
Section 2, Schedule of 
Activities
Table 2-1: Screening 
Procedural Outline 
(CA224047)
Physical Measurements and 
Assessments of Signs and 
Symptoms were updated to note 
they should be performed 
within 14 days of 
randomization.
Brain Imaging note was 
updated.
Updated to specify timing of procedures.
Clarified use of MRI with and without 
contrast as applicable to all participants.
Section 2, Schedule of 
Activities
Table 2-2: On-Study 
Assessments (CA224047)
Table 2-3: Follow-Up 
Procedural Outline 
(CA224047)
Brain Imaging note was 
updated.
Troponin note was update to 
include predose timing.
Clarified use of MRI with and without 
contrast as applicable to all participants 
as well as updated timing of procedure.
Updated to specify timing of procedure.
Section 2, Schedule of 
Activities
Table 2-3: Follow-Up 
Procedural Outline 
(CA224047)
Pregnancy Testing was 
removed.
Brain Imaging note was 
updated.
PK and Immunogenicity blood 
sample timing was adjust from 
Survival Follow-Up to Follow-
Up Visits 1 and 2.
FACT-M Subscale was added 
to Survival Follow-Up Visit.
Added “Biomarker 
Assessments” to Tumor Tissue 
Biopsy.
No longer required during follow-up.
Clarified use of MRI with and without 
contrast as applicable to all participants 
as well as updated timing of procedure.
Samples corrected to correspond with in-
clinic visits.
Added to collect more detailed outcomes 
data.
Added for clarity.
Section 3.1.1, Research 
Hypothesis
Updated endpoints from ORR 
to PFS.
PFS is the better predictor of final trial 
success
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Summary of Key Changes For Revised Protocol 01
Section Number & Title 
Description of Change
Brief Rationale
Section 4, Objectives and 
Endpoints
Phase 3 
Tertiary/Exploratory 
Objective
Added parameters for LAG-3 
expressions (1% expression 
versus <1% expression) and 
PDL01 status (1% tumor cell 
surface expression versus <1% 
tumor cell surface expression)
Revised Endpoints language 
throughout forclarity. 
Added/revised for clarity.
Section 4, Objectives and 
Endpoints
Phase 2 Primary Objective
Updated endpoints from ORR 
to PFS and updated endpoints 
to PFS.
PFS is the better predictor of final trial 
success
Section 4, Objectives and 
Endpoints
Phase 2 Secondary 
Objectives
Added parameters for LAG-3 
expressions (1% expression 
versus <1% expression) and 
PDL01 status (1% tumor cell 
surface expression versus <1% 
tumor cell surface expression) 
throughout
Revised Endpoints language 
throughout for clarity. 
Added/revised for clarity.
Section 4, Objectives and 
Endpoints
Phase 2 Secondary 
Objectives
Added parameters for LAG-3 
expressions (1% expression 
versus <1% expression) and 
PDL01 status (1% tumor cell 
surface expression versus <1% 
tumor cell surface expression) 
throughout
Revised Endpoints language 
throughout for clarity.
Combined receptor occupancy 
objective with exposure-
response objective.
Removed tumor growth 
dynamic survival model 
objective.
Added/revised for clarity.
Section 5.1, Overall Design
Figure 5.1-1: Study Design 
Schematic
Removed line indicating split of 
Phase 2 population into interim 
and post-interim review 
populations.
Updated footnotes b and c for 
adolescent weight lower-bound 
Added footnote d to Phase 3 
population.
No longer needed.
Weight was previous > 40 kg, should be 
40 kg.
Footnote clarifies that the total 
population combines Phase 2 
participants with additional Phase 3 
participants.
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Summary of Key Changes For Revised Protocol 01
Section Number & Title 
Description of Change
Brief Rationale
Section 5.1, Overall Design
Updated tumor assessments 
from Week 49 to 52.
Updated to specify timing of procedures.
Section 5.2, Number of 
Participants
Section 5.3, End of Study 
Definition
Section 7.3, Blinding
Updated interim analysis to 
include all 400 participants 
from Phase 2 and clarified 
results of the interim analysis.
Clarified procedures based on interim 
analysis results.
Section 5.4.2, Rationale for 
Blinding
Updated endpoints from ORR 
to PFS and updated endpoints 
to PFS.
PFS is the better predictor of final trial 
success
Section 6.1, Inclusion 
Criteria
2), c), (3)
Added additional prior adjuvant 
or neoadjuvant therapy 
parameters for BRAF-or MEK-
inhibitor-containing regimens 
with at least 6 months between 
the last dose and date of 
recurrence
Adds clarification for possible other 
therapies.
Section 6.1, Inclusion 
Criteria
3), f)
Removed statement exempting 
azoospermic males from 
contraceptive requirements.
Azoospermic males are not exempt.
Section 6.2, Exclusion 
Criteria, 1), a)
Changed MRI progression 
timing from 8 weeks to 4.
Added participants with brain 
disease treated with whole brain 
radiation are ineligible.
Updated timing.
Excludes participants with whole brain 
radiation treatment.
Section 6.2, Exclusion 
Criteria, 1), b)
Change ocular melanoma to 
uveal melanoma.
Changed for better specificity.
Section 6.2, Exclusion 
Criteria, 3), h)
Revised troponin criteria 
language.
Changed to simplify testing procedure.
Section 7.1, Treatments 
Administered
Added language to regarding 
weight-based dosing 
adjustments.
Added for additional clarity on dosing.
Section 7.4.2, Dose Delay 
Criteria
Removed language regarding 
dose delays due to extenuating 
circumstances
Added to simply procedures.
Section 7.4.3, Criteria to 
Resume Treatment
Added Grade 3 qualifier for 
adrenal insufficiency.
Added for more specificity.
Section 7.4.4 Management 
Algorithms for Immuno-
Oncology Agents
Appendix 9
Added myocarditis.
Added for additional management 
information.
Section 7.7.1.2, Restricted 
Treatments
Removed entire section.
No longer allow for corticosteroid 
exception.
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Summary of Key Changes For Revised Protocol 01
Section Number & Title 
Description of Change
Brief Rationale
Section 7.7.2.2, Surgical 
Resection Following Initial 
Response
Updated timing from Week 21 
to Week 20.
Corrected per study visits.
Section 9.1, Efficacy 
Assessments
Updated brain imaging 
requirements and timing.
Updated for clarity and timing.
Section 9.4.4, Clinical 
Safety Laboratory 
Assessments
Table 9.4.4-1: Laboratory 
Assessment Panel
Removed direct bilirubin and 
HPV status.
Not needed.
Section 9.5.2, 
Pharmacokinetic Sample 
Analysis
Added language clarifying 
blinded analyses.
Added for clarity.
Section 9.5.3, 
Immunogenicity
Moved up to be included in PK 
section.
Moved for better placement in 
document.
Section 9.8.1.3, T-Cell 
Repertoire Analysis
Section 9.8.1.4, Whole 
Blood for Germline DNA
Section 9.8.1.5, Circulating 
Tumor DNA Analysis 
(Plasma) Biomarkers
Section 9.8.2.3, 
Characterization of T-Cell 
Repertoire
Clarified procedures.
Updated for clarity.
Section 9.8.2.1, LAG-3 and 
PD-L1 Expression
Updated to add PD-L1
Added for clarity.
Section 9.8.2.6, Tumor 
Sample Collection Details
Removed details regarding 
fresh biopsy.
Removed to provide more flexibility for 
sites.
Section 9.8.2.6, Tumor 
Sample Collection Details
Table 9.8.2.6-1:  CA224047 
Biomarker Sampling 
Schedule (All subjects)
Removed footnote b.
Biomarker samples are not optional.
Section 10.1, Sample Size 
Determination
Section 10.2.2, Efficacy 
Analyses
Updated endpoints and analyses 
from ORR to PFS.
PFS is the better predictor of final trial 
success
Section 10.2.5,Interim 
Analysis
Updated interim analysis to 
include all 400 participants 
from Phase 2 and clarified 
results of the interim analysis.
Clarified procedures based on interim 
analysis results.
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Summary of Key Changes For Revised Protocol 01
Section Number & Title 
Description of Change
Brief Rationale
Appendix 4, Women of 
Childbearing Potential 
Definitions and Methods of 
Contraception
Removed “hormonal methods 
of contraception including oral 
contraceptive pills containing a 
combination of estrogen and 
progesterone,vaginal ring, 
injectables, implantshormonal 
methods of contraception from 
“User Independent” category.
Such methods are not user independent. 
Appendix 8, Country 
Specific Requirements
Removed France, Italy, and 
Spain.
Requirements do not apply in those 
countries.
Appendix 9, Management 
Algorithms for Immuno-
Oncology Agents
Updated all algorithms with 
current data.
Added myocarditis algorithm
Updated for current requirements.
Added for additional requirements.
NCI CTCAE
Updated from version 4.0 to 5.0
Updated throughout.
All
Minor formatting and 
typographical corrections
Minor, therefore have not been summarized
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