A Phase 4 Study of Nivolumab in Combination With Ipilimumab in Patients With Previously Untreated Advanced Renal Cell Carcinoma and Intermediate-or Poor-risk Factors Conducted in India
Phase: PHASE4
Conditions: Kidney Neoplasms
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 4 Study of Nivolumab in Combination with Ipilimumab in Patients with Previously Untreated 
Advanced Renal Cell Carcinoma and Intermediate-or Poor-risk Factors Conducted in India 
 
NCT Number: NCT04513522 
Document Date (Date in which document was last revised): 10 November 2023 

Approved v 41.0 
930144776 4.0 
 
Page: 1 
Protocol Number: CA2097C9 
IND Number: Not applicable 
EX-US: Non-IND 
EUDRACT Number: Not applicable 
Date: 06-Feb-2020 
Revised Date: 10-Nov-2023 
CLINICAL PROTOCOL CA2097C9 
A Phase 4 Study of Nivolumab in Combination with Ipilimumab in Patients with Previously 
Untreated Advanced Renal Cell Carcinoma and Intermediate- or Poor-risk Factors 
Conducted in India 
(CheckMate 7C9: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 7C9) 
Short Title: 
A Phase 4 Study of Combination Nivolumab and Ipilimumab in Patients with Advanced Renal 
Cell Carcinoma in India 
Protocol Amendment Number 02 
Study Director 
Medical Monitor 
 
Bristol-Myers Squibb India Pvt. Ltd. 
The India Bulls Center 
6th floor, tower 1 
Senapati Bapat Marg 
Elphinstone (W) 
Mumbai-400013 
India 
Bristol-Myers Squibb India Pvt. Ltd The 
India Bulls Centre 
6th floor, tower 1 
Senapati Bapat Marg 
Elphinstone (W) 
Mumbai-400013 
India 
Telephone (office): 
Telephone (office): 
Fax: 
Fax: 
24-hr Emergency Telephone Number 
USA: 
International: 
 
Bristol-Myers Squibb Research and Development 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
Bristol-Myers Squibb India Pvt. Ltd 
The India Bulls Finance Centre 
Senapati Bapat Marg 
Elphinstone (W) 
Mumbai-400013 
India 
Avenue de Finlande 4 
B-1420 Braine-l’Alleud, Belgium 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
2 
Approved v 41.0 
930144776 4.0 
 
 
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
3 
Approved v 41.0 
930144776 4.0 
 
 
DOCUMENT HISTORY 
 
Document 
Date of Issue 
Summary of Changes 
Protocol 
Amendment 02 
10-Nov-2023 
This protocol amendment is being implemented to provide clarification of 
the statistical considerations and to achieve alignment of the definition of 
immune-mediated adverse events. 
Protocol 
Amendment 01 
10-Jan-2022 
This protocol amendment is being implemented to 
add guidance with regards 
to COVID-19. In addition, other minor editorial changes have been 
incorporated. 
Original Protocol 
06-Feb-2020 
Not applicable 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
4 
Approved v 41.0 
930144776 4.0 
 
 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: 
Protocol Amendment 02 includes clarifications to statistical methods and alignment of the 
definition of immune-mediated adverse events (IMAEs). 
Additional updates have been incorporated in order to improve alignment between protocol 
sections. 
Additional revisions, including to the sections of the Synopsis, have been made to align the 
protocol with respect to these changes. This protocol amendment applies to all participants. 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Synopsis 
Updated synopsis to align 
with changes to protocol 
Updated to align with changes to 
protocol 
Section 2: Schedule of 
Activities 
Table 2-4: Updated 
language for Efficacy 
Assessment, Body Imaging 
Updated to include withdrawal of 
consent, death, or 
investigator-assessed disease 
progression as conditions that could 
lead to cessation of body imaging 
collection 
Section 2: Schedule of 
Activities 
Section 4: Objectives and 
Endpoints 
Section 9.7.3: 
Exploratory 
Changed “efficacy” to 
“effectiveness” 
Corrected content for accuracy and 
consistency 
Biomarkers 
Section 5.1: Overall 
Design 
Updated language of 
adverse event (AE) 
collection 
Clarified duration of AE collection 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
5 
Approved v 41.0 
930144776 4.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 2: Schedule of 
Activities 
Section 3.1: Study 
Rationale 
Section 5.1: Overall 
Design 
Section 8.1.1: Nivolumab 
Treatment Beyond 
Disease Progression 
Updated language for 
tumor assessments and 
body imaging schedule 
Updated to include initiation of 
subsequent systemic cancer therapy, 
withdrawal of consent, death, or 
investigator assessed disease 
progression as conditions that could 
lead to cessation of tumor 
assessments or body imaging 
collection 
Section 9.1: 
Effectiveness 
Assessments 
 
 
 
 
 
 
 
 
Section 10.1: Sample 
Size Determination 
Updated language for 
sample size determination 
and added Table 10.1-1 
Clarified rationale for sample size 
determination 
Section 10.2: Populations 
for Analyses 
Updated language for 
analysis populations 
Clarified the analysis population to 
be used for time to response (TTR) 
and duration of response (DOR) 
analyses 
Section 10.3: Statistical 
Analyses 
Updated language for 
subgroups in participant 
population output report 
Removed race as a subgroup to be 
included in the participant 
population output report 
Section 10.3.1: Statistical 
Analyses 
Updated language for 
statistical analysis methods 
for effectiveness 
Updated TTR analysis method, time 
points for analyses of DOR and 
overall survival (OS), 
to be examined 
Section 10.3.2: Safety 
Analyses 
Updated language for 
statistical analysis methods 
for safety 
Clarified that IMAEs will be 
summarized by category only, 
aligned definition of IMAEs, and 
removed descriptive statistics of 
safety 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
6 
Approved v 41.0 
930144776 4.0 
 
 
TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
1 
DOCUMENT HISTORY.............................................................................................. 
3 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02 ............................. 
4 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02................ 
4 
TABLE OF CONTENTS.............................................................................................. 
6 
1 SYNOPSIS................................................................................................................. 
9 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
16 
3 INTRODUCTION ..................................................................................................... 
27 
3.1 Study Rationale ................................................................................................. 
27 
3.1.1 Research Hypothesis ................................................................................ 
29 
3.2 Background ....................................................................................................... 
29 
3.2.1 Indication Background............................................................................. 
29 
3.2.2 Nivolumab Mechanism of Action ............................................................. 
30 
3.2.3 Ipilimumab Mechanism of Action ............................................................ 
31 
3.2.4 Nivolumab in Renal Cell Carcinoma ....................................................... 
31 
3.2.5 Ipilimumab in Renal Cell Carcinoma ...................................................... 
33 
3.2.6 Nivolumab Combined with Ipilimumab Clinical Activity ........................ 
33 
3.2.7 Adverse Event Rates Associated with Nivolumab in Combination with 
Ipilimumab in Previously Untreated Advanced or Metastatic RCC........... 
34 
3.3 Benefit/Risk Assessment .................................................................................. 
37 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
38 
5 STUDY DESIGN....................................................................................................... 
39 
5.1 Overall Design .................................................................................................. 
39 
5.2 Data Monitoring Committee and Other External Committees ......................... 
44 
5.3 Number of Participants ..................................................................................... 
44 
5.4 End of Study Definition .................................................................................... 
45 
5.5 Scientific Rationale for Study Design............................................................... 
45 
5.6 Duration of Treatment with Nivolumab + Ipilimumab..................................... 
45 
5.7 Clinical Pharmacology Summary ..................................................................... 
45 
5.8 Justification for Combination Nivolumab and Ipilimumab Dose..................... 
47 
6 STUDY POPULATION ............................................................................................ 
48 
6.1 Inclusion Criteria .............................................................................................. 
48 
6.2 Exclusion Criteria ............................................................................................. 
50 
6.3 Lifestyle Restrictions ........................................................................................ 
52 
6.4 Screen Failures.................................................................................................. 
52 
6.4.1 Retesting During Screening or Lead-in Period ....................................... 
52 
7 TREATMENT ........................................................................................................... 
53 
7.1 Treatments Administered.................................................................................. 
56 
7.2 Method of Treatment Assignment .................................................................... 
57 
7.3 Blinding............................................................................................................. 
57 
7.4 Dosage Modification Criteria for Nivolumab and Ipilimumab ........................ 
57 
7.4.1 Dose Delay Criteria for Nivolumab and Ipilimumab .............................. 
57 
7.4.2 Criteria to Resume Treatment.................................................................. 
58 
7.4.3 Criteria for Treatment Discontinuation................................................... 
59 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
7 
Approved v 41.0 
930144776 4.0 
 
 
7.4.3.1 Nivolumab Dose Discontinuation ................................................... 
59 
7.4.3.2 Ipilimumab Dose Discontinuation .................................................. 
61 
7.4.4 Treatment of Related Infusion Reactions ................................................. 
62 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
64 
7.5.1 Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
64 
7.6 Treatment Compliance...................................................................................... 
64 
7.7 Concomitant Therapy........................................................................................ 
64 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
64 
7.7.2 Other Restrictions and Precautions......................................................... 
65 
7.7.2.1 Imaging Restriction and Precautions ............................................. 
65 
7.7.3 Permitted Therapy ................................................................................... 
65 
7.8 Post Study Drug Access.................................................................................... 
66 
8 DISCONTINUATION CRITERIA ........................................................................... 
66 
8.1 Discontinuation from Study Treatment ............................................................ 
66 
8.1.1 Nivolumab Treatment Beyond Disease Progression ............................... 
67 
8.1.2 Post-study Treatment Study Follow-up.................................................... 
68 
8.2 Discontinuation from the Study ........................................................................ 
69 
8.3 Loss to Follow-Up ............................................................................................ 
69 
9 STUDY ASSESSMENTS AND PROCEDURES..................................................... 
70 
9.1 Effectiveness Assessments................................................................................ 
70 
9.1.1 Imaging Assessment for the Study............................................................ 
71 
9.1.1.1 Methods of Measurement ................................................................ 
71 
9.1.2 Outcomes Research Assessments ............................................................. 
72 
9.1.2.1 Patient-reported Outcomes ............................................................. 
72 
9.1.2.2 Healthcare Resource Utilization..................................................... 
73 
9.2 Adverse Events ................................................................................................. 
73 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
74 
9.2.2 Method of Detecting AEs and SAEs......................................................... 
75 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
75 
9.2.4 Regulatory Reporting Requirements for SAEs......................................... 
76 
9.2.5 Pregnancy ................................................................................................ 
76 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
77 
9.2.7 Potential Drug-induced Liver Injury (DILI)............................................ 
77 
9.2.8 Other Safety Considerations .................................................................... 
78 
9.3 Overdose ........................................................................................................... 
78 
9.4 Clinical Safety................................................................................................... 
78 
9.4.1 Physical Examinations............................................................................. 
78 
9.4.2 Vital Signs ................................................................................................ 
78 
9.4.3 Electrocardiograms ................................................................................. 
78 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
78 
9.4.5 Imaging Safety Assessment ...................................................................... 
79 
9.5 Pharmacokinetics .............................................................................................. 
79 
9.6 Pharmacodynamics ........................................................................................... 
83 
9.7 Pharmacogenomics ........................................................................................... 
83 
9.7.1 Biomarkers ............................................................................................... 
83 
83 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
8 
Approved v 41.0 
930144776 4.0 
 
 
 
 
9.7.5 Immunogenicity Assessments ................................................................... 
10 STATISTICAL CONSIDERATIONS .................................................................... 
10.1 Sample Size Determination............................................................................. 
10.2 Populations for Analyses ................................................................................ 
10.3 Statistical Analyses ......................................................................................... 
10.3.1 Effectiveness Analyses ........................................................................... 
10.3.2 Safety Analyses....................................................................................... 
10.3.3 Pharmacokinetic Analysis...................................................................... 
10.3.4 Immunogenicity Analysis ....................................................................... 
10.3.5 Biomarker Analyses ............................................................................... 
10.3.6 Health Outcomes Assessment Analyses ................................................. 
10.3.7 Interim Analyses..................................................................................... 
11 REFERENCES ........................................................................................................ 
12 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERANCE CONSIDERATIONS .................................... 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW UP AND REPORTING......................................................................... 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION..................................................................... 
APPENDIX 5 INDIA PRESCRIBING INFORMATION FOR NIVOLUMAB AND 
IPILIMUMAB ........................................................................................................ 
APPENDIX 6 INTERNATIONAL METASTATIC RCC DATABASE 
CONSORTIUM (IMDC) PROGNOSTIC CRITERIA .......................................... 
APPENDIX 7 PERFORMANCE STATUS SCALES ................................................. 
APPENDIX 8 COUNTRY SPECIFIC REQUIREMENTS ......................................... 
APPENDIX 9 RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS ........................ 
84 
84 
85 
85 
85 
86 
86 
87 
87 
88 
89 
89 
89 
89 
90 
93 
94 
97 
 
104 
 
108 
111 
259 
260 
261 
262 
9.7.3 Exploratory 
Biomarkers ................................................ 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
9 
Approved v 41.0 
930144776 4.0 
 
 
 
1 
SYNOPSIS 
Protocol Title: A Phase 4 Study of Nivolumab in Combination with Ipilimumab in Patients with 
Previously Untreated Advanced Renal Cell Carcinoma and Intermediate- or Poor-risk Factors 
Conducted in India 
Short Title: 
A Phase 4 Study of Combination Nivolumab and Ipilimumab in Patients with Advanced Renal 
Cell Carcinoma in India 
Study Phase: 4 
Study Rationale: 
In intermediate- and poor-risk participants with previously untreated advanced renal cell 
carcinoma (RCC) or metastatic RCC (mRCC), this study aims to determine the safety and 
effectiveness of nivolumab combined with ipilimumab followed by nivolumab as a single-agent 
maintenance therapy as measured by the primary endpoint of incidence of high-grade (Common 
Terminology Criteria for Adverse Events [CTCAE] v4.0 Grade 3 to 4 and Grade 5) 
immune-mediated adverse events (IMAEs) with the characterization of outcome of all high-grade 
IMAEs and overall response rate (ORR), time to response (TTR), and duration of response (DOR) 
as key secondary endpoints. 
This first-line renal cell carcinoma (1L RCC) study is to be conducted in compliance with a 
condition of approval specified by the Health Authorities of India. 
Study Population: 
The study population includes male and female patients aged 18 or older with histologically 
confirmed, intermediate- or poor-risk, previously untreated, advanced (not amenable to curative 
surgery or radiation therapy) or mRCC. 
Key Inclusion Criteria 
• Histological confirmation of renal carcinoma with clear cell component including participants 
who may have sarcomatoid features. Advanced (not amenable to curative surgery or radiation 
therapy) RCC or mRCC with or without nephrectomy. 
• No prior systemic therapy for renal cell carcinoma (RCC) with the following exception: 
o One prior adjuvant or neoadjuvant therapy for completely resected RCC (see 
Exclusion 2b). These drugs must be discontinued ≥ 6 months prior to study entry. All 
AEs related to prior adjuvant or neoadjuvant therapy must have returned to baseline, 
and eligible patients must not have experienced severe or life-threatening irAEs except 
those that are unlikely to reoccur with standard countermeasures (eg, hormone 
replacement after adrenal crisis). 
• Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per 
RECIST 1.1 criteria. Radiated lesions cannot be used as measurable lesions unless there is 
clear evidence of progression. 
• Karnofsky Performance Status (KPS) of at least 70% (see Appendix 7). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
10 
Approved v 41.0 
930144776 4.0 
 
 
 
• Qualifies as intermediate or poor risk by meeting least 1 of the prognostic factors as per the 
International Metastatic RCC Database Consortium (IMDC) criteria. 
• Indian participants with Indian ethnicity living in India. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Participants must be intermediate or poor risk as per International Metastatic RCC Database 
Consortium (IMDC). 
 
Key Exclusion Criteria 
• Participants with active, untreated, symptomatic central nervous system (CNS) metastases. 
• Participants with type I diabetes mellitus, hypothyroidism only requiring hormone 
replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic 
treatment, or conditions not expected to recur in the absence of an external trigger are permitted 
to enroll. 
• Participants with an autoimmune disease, or any other condition, requiring systemic treatment 
with either corticosteroids within 14 days (> 10 mg daily prednisone equivalent) or other 
immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, 
and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in 
the absence of active autoimmune disease. 
• Patients with serious or uncontrolled medical disorders. 
• Active infection requiring systemic therapy within 14 days of first dose of study drug. 
• Patients with known human immunodeficiency virus (HIV) who have had an acquired 
immunodeficiency syndrome (AIDS) defining opportunistic infection within the last year, or 
a current CD4 count < 350 cells/µL. NOTE: Testing for HIV must be performed at sites where 
mandated locally (see Appendix 8). 
• Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study treatment. 
• Radiotherapy within 4 weeks except palliative radiation to bone lesions, which requires 
2 weeks of washout prior to the first dose of study treatment. 
• Patients with a concurrent malignancy requiring treatment. Patient with a previously treated 
malignancy are eligible if treatment was completed at least 2 years before registration and the 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
11 
Approved v 41.0 
930144776 4.0 
 
 
 
patient has no evidence of disease. Patients who have a concurrent malignancy that is clinically 
stable and does not require tumor-directed treatment are also eligible. 
• Presence of any toxicities attributed to prior anticancer therapy, other than alopecia, that have 
not resolved to Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse 
Events [NCI CTCAE] v4) or baseline before administration of study treatment. 
• Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of 
the investigator, would preclude the participant from adhering to the protocol or would increase 
the risk associated with study participation or study treatment administration or interfere with 
the interpretation of safety results (eg, a condition associated with diarrhea or acute 
diverticulitis). 
• Women who are pregnant or breastfeeding. 
• Any of the following laboratory test findings: 
o White blood cells < 2000/mm3 
o Neutrophils < 1500/mm3 
o Platelets < 100 × 103/mm3 
o Hemoglobin < 9.0 g/dL 
o Serum creatinine > 1.5× upper limit of normal (ULN) or creatinine clearance 
≥ 40 mL/min (using the Cockroft-Gault formula) 
Female CrCl = (140 - age in years) × weight in kg × 0.85 
72 × serum creatinine in mg/dL 
Male CrCl = (140 - age in years) × weight in kg × 1.00 
72 × serum creatinine in mg/dL 
o Aspartate aminotransferase/Alanine aminotransferase > 3× ULN 
o Total bilirubin (TBili) > 1.5× ULN (except participants with Gilbert syndrome, who 
must have TBili < 3.0× ULN) 
• Serologic evidence of chronic HBV infection with an HBV viral load above the limit of 
quantification. Patients with chronic HBV infection must be on concurrent viral suppressive 
therapy. 
• Serologic evidence of current HCV infection with an HCV viral load above the limit of 
quantification. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
12 
Approved v 41.0 
930144776 4.0 
 
 
Objectives and Endpoints: 
 
Objective 
Endpoint 
Primary 
• 
To assess the incidence of high-grade (CTCAE v4.0 
Grade 3 to 4 and Grade 5) IMAEs in intermediate- or 
poor-risk participants with previously untreated, 
advanced RCC who are treated with combination 
therapy of nivolumab 3 mg/kg administered 
intravenously over a period of 30 minutes every 
3 weeks for the first 4 doses in combination with 
intravenous ipilimumab 1 mg/kg over a period of 
30 minutes, followed by nivolumab 3 mg/kg every 
2 weeks administered intravenously over a period of 
30 minutes. 
• 
Incidence of high-grade (CTCAE v4.0 Grade 
3 to 4 and Grade 5) IMAEs 
Secondary 
• 
To characterize the outcome of all high-grade (CTCAE 
v4.0 Grade 3 to 4 and Grade 5) IMAEs in intermediate- 
or poor-risk participants with previously untreated, 
advanced RCC. 
• 
Characterization of outcome of all high grade 
(CTCAE v4.0 Grade 3 to 4 and Grade 5) 
IMAEs (eg, time to onset, time to resolution, 
percentage of patients who received immune- 
modulating medication) 
• 
To assess the effectiveness of nivolumab in 
combination with ipilimumab by measuring objective 
response rate (ORR), time to response (TTR), and 
duration of response (DOR), using RECIST 1.1. 
• 
ORR, TTR, DOR 
Exploratory 
• 
To assess the incidence of all treatment-related AEs in 
intermediate- or poor-risk participants with previously 
untreated, advanced RCC. 
• 
Incidence of all treatment related AEs 
• 
To assess the effectiveness of nivolumab in combination 
with ipilimumab by measuring progression-free survival 
(PFS) at time of initial progression and overall survival 
(OS) 1-year survival rates in intermediate- or poor-risk 
participants with previously untreated, advanced RCC. 
• 
PFS, OS 
• 
To assess the participant’s cancer-related symptoms 
and quality of life (QoL) 
• 
All total and subscale scores and post-baseline 
score changes for the FKSI-19 
• 
To evaluate the pharmacokinetics of nivolumab and 
ipilimumab when administered in combination and the 
PK of nivolumab as a single-agent maintenance 
therapy. To explore exposure-response relationships 
between select exposure measures, and safety and 
effectiveness endpoints, as appropriate. 
• 
Predose serum nivolumab and ipilimumab 
concentrations to be used for population 
pharmacokinetics (PPK) analysis to predict 
nivolumab pharmacokinetic parameters. 
Explore exposure-response relationships if 
data permit. 
• 
To characterize the immunogenicity of nivolumab and 
ipilimumab when administered in combination and the 
immunogenicity of nivolumab as a single-agent 
maintenance therapy. 
• 
Immunogenicity will be determined by 
measurement of anti-drug antibody (ADA) in 
serum and samples with positive ADA 
response may be analyzed for neutralizing 
ADA response to nivolumab and ipilimumab 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
13 
Approved v 41.0 
930144776 4.0 
 
 
 
Objective 
Endpoint 
• 
To assess the impact of SARS-CoV-2 serologic status 
on participants receiving nivolumab in combination 
with ipilimumab and previously untreated, advanced 
RCC and to support Health Authority requests 
• 
Exploratory measurements of SARS-CoV-2 
serology (anti-SARS-CoV-2 total or IgG), 
from serum samples collected at baseline (and 
additional time points, if applicable) and the 
potential association between these 
measurements and selected endpoints related 
to safety, effectiveness, and/or biomarkers 
Abbreviations: AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; FKSI-19 = 
Functional Assessment of Cancer Therapy - Kidney Symptom Index; IMAE = immune-mediated adverse event; 
NCI = National Cancer Institute; IgG = immunoglobulin G; 
; RCC = renal cell 
carcinoma; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2 
Note: All AEs to be assessed using NCI CTCAE v4. 
Overall Design: 
This is a Phase 4, open-label, single arm, multi-center, prospective study to be conducted in India 
in participants with intermediate or poor risk, previously untreated, advanced renal cell carcinoma 
or mRCC (N = 100 treated patients). Potential participants will undergo screening evaluations to 
determine eligibility within 28 days prior to first dose. Participants who meet the protocol-defined 
inclusion/exclusion criteria will be prospectively enrolled in a sequential manner. All enrolled 
participants will be treated with nivolumab 3 mg/kg administered intravenously over a period of 
30 minutes plus ipilimumab 1 mg/kg administered intravenously over a period of 30 minutes, 
every 3 weeks for 4 doses (combination phase), followed by nivolumab 3 mg/kg administered 
intravenously over a period of 30 minutes every 2 weeks (single-agent maintenance phase). 
Treatment will continue as long as clinical benefit is observed for a maximum of 52 weeks or until 
treatment is no longer tolerated by the participant or withdrawal of consent. 
The treatment period for this study is 52 weeks of treatment and 2 weeks of follow-up after the 
final on-study dose of nivolumab. Participants who are observed to continue to receive clinical 
benefit at follow-up will continue nivolumab treatment via commercial supply (provided by BMS 
India) as long as clinical benefit is observed or until treatment is no longer tolerated by the 
participant or withdrawal of consent. 
Any participant who discontinues treatment before 52 weeks on study treatment will be followed 
for safety at 30 days (Follow up Visit 1) and 100 days (Follow-up Visit 2) after discontinuation. 
In addition, for these patients, survival follow-up visits may be conducted in clinic or by phone 
3 months (±14 Days) after follow-up Visit 2 and subsequent survival follow-up visits every 
3 months (±14 days) until death, withdrawal of consent, loss to follow-up, or for a maximum of 
52 weeks from the date of the first on-study dose of nivolumab. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
14 
Approved v 41.0 
930144776 4.0 
 
 
Number of Participants: 
A total of 100 treated participants with intermediate or poor-risk, previously untreated, advanced 
or mRCC will be enrolled. 
Treatment Arms and Duration: 
All participants will receive the study drug as follows: 
Combination Phase 
• Nivolumab 3 mg/kg administered intravenously over a period of 30 minutes plus ipilimumab 
1 mg/kg administered intravenously over a period of 30 minutes, every 3 weeks for 4 doses. 
 
Single-agent Maintenance Phase 
• Nivolumab 3 mg/kg administered intravenously over a period of 30 minutes every 2 weeks for 
up to 52 weeks. 
 
The duration of treatment in the study for all participants is a maximum of 52 weeks. Participants 
who are observed to continue to receive clinical benefit from treatment at 52 weeks may continue 
nivolumab treatment via commercial supply (provided by BMS India) as long as clinical benefit 
is observed or until the participant no longer tolerates treatment. 
Study Drug: Includes Investigational [Medicinal] Products (IP/IMP) as Listed: 
 
Study Drug for CA2097C9 
Product Description / Class and Dosage Form 
Potency 
IP/non-IMP 
Nivolumab solution for infusion 
100 mg (10 mg/mL concentrate) 
IP 
Ipilimumab solution for infusion 
50 mg (5 mg/mL) 
IP 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
15 
Approved v 41.0 
930144776 4.0 
 
 
Study Design Schematic: 
 
Data Monitoring Committee: Not applicable. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
16 
Approved v41.0 
930144776 4.0 
 
 
2 
SCHEDULE OF ACTIVITIES 
Table 2-1: 
Screening Procedures and Assessments (CA2097C9) 
 
Procedure 
Screening 
Visita 
Notes 
(Screening visit will occur within 28 days before start of combination phase) 
Eligibility Assessments 
Informed Consent 
X 
The participant must sign the informed consent prior to any study-related assessment being 
performed. 
Interactive Voice Response System 
X 
An IRT will be used to assign participant numbers. 
Inclusion/Exclusion Criteria 
X 
All inclusion/exclusion criteria must be confirmed prior to treatment assignment. 
Medical History 
X 
IMDC Prognostic Score 
X 
See Appendix 6. 
Safety Assessments 
Full Physical Examination, 
Vital Signs, Performance Status 
X 
Height, weight, KPS (Appendix 7), BP, RR, heart rate, and temperature within 14 days of first 
dose, prior to study treatment initiation. 
Electrocardiogram 
X 
Within 14 days of first dose, prior to study treatment initiation. 
Assessment of Signs and Symptoms 
X 
Within 14 days of first dose, prior to study treatment initiation. 
Concomitant Medication Use 
X 
Within 14 days of first dose, prior to study treatment initiation. 
SAE Assessment 
X 
SAEs from time of consent. See Section 9.2. 
All AEs (SAEs or non-serious AEs) associated with SARS-CoV-2 infection collected from time of 
consent. 
Laboratory Tests 
X 
See Section 9.4.4 for additional details on tests required. To be completed locally at each site. Must 
be performed within 14 days prior to first dose (unless otherwise specified) per Table 9.4.4-1. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
17 
Approved v41.0 
930144776 4.0 
 
 
Table 2-1: 
Screening Procedures and Assessments (CA2097C9) 
 
Procedure 
Screening 
Visita 
Notes 
(Screening visit will occur within 28 days before start of combination phase) 
• CBC with differential and chemistry panel (AST, ALT, TBili, ALP, LDH, creatinine, BUN or 
serum urea level, glucose, albumin, Na, K, Cl, Ca [also Ca corrected], P, Mg) 
• Thyroid panel (includes TSH with free T3 and free T4) 
• Hepatitis B/C (HBVsAg, HCV antibody, or HCV RNA) 
• HIV if mandated locally (see Appendix 8) 
Pregnancy Test (WOCBP only) 
X 
Serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) to be 
done at screening visit and within 24 hours of first dose of study treatment. 
Biomarker Samples 
SARS-CoV-2 Serology 
Serum collected to be used for potential future measurements of anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total 
or IgG [see Section 9.7.1]) 
Effectiveness Assessments 
Body Imaging 
Contrast enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known and/or suspected sites of 
disease, within 28 days prior to first dose. See Section 9.1.1 for further details. 
Brain Imaging 
MRI of the brain (without and with contrast) is required for ALL participants during screening to rule out brain 
metastases. CT of the brain (without and with contrast) can be performed if MRI is contraindicated. See Section 9.1.1 
for further details. 
Abbreviations: AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase, AST = aspartate aminotransferase; BP = blood pressure; 
BUN = blood urea nitrogen; CBC = complete blood count; CT = computed tomography; eCRF = electronic case report form; 
; HBVsAg = hepatitis B virus surface antigen; HCG = human chorionic gonadotrophin; HIV = human immunodeficiency virus; IMDC = International 
Metastatic RCC Database Consortium; IU = international unit; IRT = Interactive response technology; KPS = Karnofsky's index of performance status; 
LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; RNA = ribonucleic acid; RR = respiratory rate; SAE = serious adverse event; 
T3 = triiodothyronine, T4 = thyroxine; Tbili = total bilirubin; TSH = thyroid-stimulating hormone, WOCBP = women of childbearing potential 
a 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 2-2: 
On-treatment Procedural Outline Cycles 1 through 4 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
18 
Approved v41.0 
930144776 4.0 
 
 
 
 
Procedurea 
Cycles 1 through 4 
(1 cycle = 3 weeks) 
Dosing Q3W for 4 Dosesb 
Notes 
Day 1 
Cycle 1 
Day 1 
Cycle 2 
Day 1 
Cycle 3 
Day 1 
Cycle 4 
Safety Assessments 
Targeted Physical Examination, Vital 
Signs, Performance Status 
X 
X 
X 
X 
Weight, BP, RR, heart rate, temperature, and KPS (Appendix 7) to be 
performed within 72 hours prior to dosing. 
Assessment of Signs and Symptoms 
X 
X 
X 
X 
AE and SAE Assessment 
Continuously 
Record at each visit. Participants will be followed for drug-related toxicities 
until these toxicities resolve, return to baseline, or are deemed irreversible. 
(Appendix 3). 
The collection of non-serious AE information, including that associated with 
SARS-CoV-2 infection, must begin at initiation of study treatment until the 
follow-up contact. 
All SAEs, including those associated with SARS-CoV-2 infection, that occur 
during the screening period, during treatment, and within 100 days of 
discontinuation or a maximum of 52 weeks of treatment plus 2 weeks of 
follow-up, whichever is earliest, must be collected. (Appendix 3). 
Concomitant Medication Use 
X 
X 
X 
X 
Laboratory Tests 
X 
X 
X 
X 
See Section 9.4.4 for additional details on tests required. Laboratory tests 
do not need to be repeated at C1D1 if performed within 14 days prior to 
the first dose unless repeat of tests for eligibility prior to C1D1 dosing is 
clinically indicated. After C1D1, within 72 hours prior to re-dosing to 
include: 
CBC with differential and chemistry panel at every cycle (includes AST, 
ALT, TBili, ALP, LDH, creatinine, BUN or serum urea, glucose, Na, K, 
Cl, Ca, P, Mg) 
Thyroid panel (includes TSH with reflexive fT3 and fT4 if TSH is 
abnormal) at every cycle 
Pregnancy Test (WOCBP Only) 
X 
X 
X 
X 
Within 24 hours prior to administration of study drug. Serum or urine. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 2-2: 
On-treatment Procedural Outline Cycles 1 through 4 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
19 
Approved v41.0 
930144776 4.0 
 
 
 
 
Procedurea 
Cycles 1 through 4 
(1 cycle = 3 weeks) 
Dosing Q3W for 4 Dosesb 
Notes 
Day 1 
Cycle 1 
Day 1 
Cycle 2 
Day 1 
Cycle 3 
Day 1 
Cycle 4 
Pharmacokinetic Samples 
Pharmacokinetic Samples 
For details on sampling time points, see Table 9.5-1. 
Immunogenicity Blood Sample 
For details on sampling time points, see Table 9.5-1. 
Exploratory Biomarker Testing - See Section 9.7.1 
SARS-CoV-2 Serologyc 
For details on sampling time points, see Table 9.7.1-1. 
Study Treatment 
IRT 
X 
X 
X 
X 
Administer Nivolumab (3 mg/kg) and 
Ipilimumab (1 mg/kg) 
X 
X 
X 
X 
First dose is to be administered within 28 days after signing the ICF. 
Subjects may be dosed up to 3 days after the scheduled date if necessary. 
Outcomes Research Assessments 
FKSI-19 
X 
X 
X 
X 
This assessment should be completed at the start of the clinic visit prior to 
dosing and/or other study assessments. See Section 9.1.2.1. 
Healthcare Resource Utilization 
X 
X 
X 
X 
Healthcare resource utilization data will be collected at each visit by study 
site staff using the CRF. See Section 9.1.2.2. 
Abbreviations: AE = adverse event; ALP = alkaline phosphatase; ALT = alkaline alanine aminotransferase; AST = aspartate aminotransferase; BP = blood 
pressure; BUN = blood urea nitrogen; C1D1 = Cycle 1 Day 1; CBC = complete blood count; CRF = case report form; eCRF = electronic case report form; 
FKSI-19 = Functional Assessment of Cancer Therapy - Kidney Symptom Index; ICF = informed consent form; IgG = immunoglobulin G; IRT = Interactive 
response technology; KPS = Karnofsky's index of performance status; LDH = lactate dehydrogenase; PK = pharmacokinetics; Q3W = every 3 weeks; 
RR = respiratory rate;  SARS-CoV-2 =  severe acute respiratory  syndrome  coronavirus  2;  SAE = serious adverse  event;  T3 = triiodothyronine, 
T4 = thyroxine; Tbili = total bilirubin; TSH = thyroid-stimulating hormone, WOCBP = women of childbearing potential 
a 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
20 
Approved v41.0 
930144776 4.0 
 
 
b If a dose is delayed, the procedures scheduled for that same time point should also be delayed to coincide with when that time point’s dosing actually occurs. 
c Serum collected approximately every 6 months during study treatment to be used for potential future measurements of anti-SARS-CoV-2 serology (anti-SARS- 
CoV-2 total or IgG). Serum should also be collected approximately 4 weeks after a documented or suspected SARS-CoV-2 infection (see Section 9.7.1). If a 
documented or suspected SARS-CoV-2 infection occurs within 4 weeks of the 6-month sampling time point, a single serum sample will be collected to satisfy 
the requirements for both the every 6 month and approximately 4 weeks after infection time points. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 2-3: 
On-study Assessments Cycle 5 and Beyond 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
21 
Approved v41.0 
930144776 4.0 
 
 
 
 
Procedure 
Cycle 5 and beyond, up to 
52 weeks of treatment 
(1 cycle = 2 weeks)a 
Notes 
Day 1 
Safety Assessments 
Targeted Physical Examination, 
Vital Signs, Performance Status 
X 
Weight, BP, heart rate, RR, temperature, and KPS (Appendix 7). Performance Status to 
be performed within 72 hours prior to dosing. 
Assessment of Signs and Symptoms 
X 
AE and SAE Assessment 
Continuously 
Record at each visit. Participants will be followed for drug-related toxicities until these 
toxicities resolve, return to baseline, or are deemed irreversible. (Appendix 3). 
The collection of non-serious AE information, including that associated with SARS-CoV-2 
infection, must begin at initiation of study treatment until the follow-up contact. 
All SAEs, including those associated with SARS-CoV-2 infection, that occur during the 
screening period, during treatment, and within 100 days of discontinuation or a maximum of 
52 weeks of treatment plus 2 weeks of follow-up, whichever is earliest, must be collected. 
(Appendix 3). 
Concomitant Medications Use 
X 
Laboratory Tests 
X 
See Section 9.4.4 for additional details on tests required. 
Within 72 hours prior to dosing to include: 
CBC with differential and chemistry panel at every cycle (includes AST, ALT, TBili, 
ALP, LDH, creatinine, BUN or serum urea, glucose, Na, K, Cl, Ca, P, Mg) 
Thyroid panel (includes TSH with reflexive fT3 and fT4 if TSH is abnormal) at every 
cycle 
Pregnancy Test (WOCBP Only) 
X 
Within 24 hours prior to administration of study drug. Serum or Urine. 
Pharmacokinetic Samples 
Pharmacokinetic Samples 
For details on sampling time points, see Table 9.5-1 
Immunogenicity Blood Sample 
For details on sampling time points, see Table 9.5-1 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 2-3: 
On-study Assessments Cycle 5 and Beyond 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
22 
Approved v41.0 
930144776 4.0 
 
 
 
 
Procedure 
Cycle 5 and beyond, up to 
52 weeks of treatment 
(1 cycle = 2 weeks)a 
Notes 
Day 1 
Biomarker Samples 
SARS-CoV-2 Serologyb 
For details on sampling time points, see Table 9.7.1-1. 
Effectiveness Assessments 
Body Imaging 
Contrast enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known and/or suspected sites of 
disease should occur at Week 12 (±7 days) following the first dose, then every 8 weeks (± 7 days) until 52 weeks of 
treatment plus 2 weeks of follow-up or initiation of subsequent systemic cancer therapy, whichever occurs first. These time 
points are independent of dosing. See Section 9.1.1 for further details. 
Brain Imaging 
Participants with a history of brain metastasis or symptoms should have surveillance MRIs per standard of care 
(approximately every 12 weeks) or sooner if clinically indicated. CT of the brain without and with contrast can be 
performed if MRI is contraindicated. See Section 9.1.1 for further details. 
Clinical Drug Supplies 
IRT 
X 
Administer Nivolumab (3 mg/kg) 
X 
Subsequent doses may be administered within 3 days after the scheduled date if 
necessary. 
Outcomes Research Assessments 
FKSI-19 
X 
Starting with Cycle 5, assessments should occur every other cycle 
(eg, Cycles 5, 7, 9, etc). Prior to dosing and other study assessments. 
Healthcare Resource Utilization 
X 
Starting with Cycle 5, Healthcare Resource Utilization should be collected every other 
cycle (eg, Cycles 5, 7, 9, etc). Healthcare resource utilization data will be collected at 
each visit by study site staff using the CRF. See Section 9.1.2.2. 
Abbreviations: AE = adverse event; ALP = alkaline phosphatase; ALT = alkaline alanine aminotransferase; AST = aspartate aminotransferase; BP = blood 
pressure; BUN = blood urea nitrogen; CBC = complete blood count; CRF = care report form; CT = computed tomography; FKSI-19 = Functional Assessment of 
Cancer Therapy - Kidney Symptom Index; IgG = immunoglobulin G; IRT = Interactive response technology; KPS = Karnofsky's index of performance status; 
LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; PK = pharmacokinetics; RR = respiratory rate; SARS-CoV-2 = severe acute respiratory 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
23 
Approved v41.0 
930144776 4.0 
 
 
syndrome coronavirus 2; SAE = serious adverse event; T3 = triiodothyronine, T4 = thyroxine; Tbili = total bilirubin; TSH = thyroid-stimulating hormone, 
WOCBP = women of childbearing potential 
a If a dose is delayed, the procedures scheduled for that same time point should also be delayed to coincide with when that time point’s dosing actually occurs. 
b Serum collected approximately every 6 months during study treatment to be used for potential future measurements of anti-SARS-CoV-2 serology (anti-SARS- 
CoV-2 total or IgG). Serum should also be collected approximately 4 weeks after a documented or suspected SARS-CoV-2 infection (see Section 9.7.1). If a 
documented or suspected SARS-CoV-2 infection occurs within 4 weeks of the 6-month sampling time point, a single serum sample will be collected to satisfy 
the requirements for both the every 6 month and approximately 4 weeks after infection time points. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 2-4: 
Follow-up Procedural Outline 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
24 
Approved v41.0 
930144776 4.0 
 
 
 
 
Procedure 
Follow-up 
Visit 1a, b 
Follow-up 
Visit 2b 
Survival 
Follow-up 
Visitc 
Notes 
Safety Assessments 
Targeted Physical Examination, 
Vital Signs, Performance Status 
X 
X 
Weight, BP, heart rate, RR, temperature, and KPS (Appendix 7). 
Assessment of Signs and 
Symptoms 
X 
AE and SAE Assessment 
X 
X 
X 
Record at each visit. Participants will be followed for drug-related toxicities until 
these toxicities resolve, return to baseline, or are deemed irreversible 
(Appendix 3). 
The collection of non-serious AE information must begin at initiation of study 
treatment until the follow-up contact. 
All SAEs that occur during the screening period, during treatment, and within 
100 days of discontinuation or a maximum of 52 weeks of treatment plus 2 weeks 
of follow-up, whichever is earliest, must be collected (Appendix 3). 
Participants will be followed for all SAEs 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 
X 
See Section 9.4.4 for additional details on tests required. 
CBC with differential and chemistry panel (includes AST, ALT, TBili, ALP, 
LDH, creatinine, BUN or serum urea, glucose, Na, K, Cl, Ca, P, Mg) 
Thyroid panel (includes TSH with reflexive fT3 and fT4 if TSH is abnormal) 
Pregnancy Test (WOCBP Only) 
X 
X 
Within 24 hours prior to administration of study drug. Serum or urine. 
Concomitant Medication Use 
X 
X 
Electrocardiogram 
X 
X 
Pharmacokinetic Samples 
Pharmacokinetic Samples 
X 
X 
For details on sampling time points, see Table 9.5-1 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 2-4: 
Follow-up Procedural Outline 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
25 
Approved v41.0 
930144776 4.0 
 
 
 
 
Procedure 
Follow-up 
Visit 1a, b 
Follow-up 
Visit 2b 
Survival 
Follow-up 
Visitc 
Notes 
Immunogenicity Blood Sample 
X 
X 
For details on sampling time points, see Table 9.5-1 
Exploratory Biomarker Testing 
SARS-CoV-2 Serologyd 
For details on sampling time points, see Table 9.7.1-1. 
Effectiveness Assessments 
Body Imaging 
Contrast enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known and/or suspected sites of disease 
should occur beginning at Week 12 (±7 days) from the date of first dose and continuing every 8 weeks (± 7 days) until 
Week 52, initiation of subsequent systemic cancer therapy, withdrawal of consent, death, or investigator-assessed disease 
progression, whichever occurs first. These time points are independent of dosing. See Section 9.1.1 for further details. 
Brain Imaging 
Participants with a history of brain metastasis or symptoms should have surveillance MRIs per standard of care 
(approximately every 12 weeks) or sooner if clinically indicated. CT of the brain without and with contrast can be performed 
if MRI is contraindicated. See Section 9.1.1 for further details. 
Survival Status 
Participant Status 
X 
X 
X 
During safety follow-up and every 3 months (clinic visit or by telephone) during 
survival phase. Include documentation of subsequent lines of therapy. 
Outcomes Research Assessments 
FKSI-19 
X 
X 
Administered prior to any procedures on that day 
Healthcare Resource Utilization 
X 
X 
Healthcare resource utilization data will be collected at each visit by study site 
staff using the CRF. See Section 9.1.2.2. 
Abbreviations: AE = adverse event; ALP = alkaline phosphatase; ALT = alkaline alanine aminotransferase; AST = aspartate aminotransferase; BP = blood 
pressure; BUN = blood urea nitrogen; CBC = complete blood count; CRF = case report form; CT = computed tomography; FKSI-19 = Functional Assessment of 
Cancer Therapy - Kidney Symptom Index; IgG = immunoglobulin G; KPS = Karnofsky's index of performance status; LDH = lactate dehydrogenase; 
MRI = magnetic resonance imaging; PK = pharmacokinetics; RR = respiratory rate; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; 
SAE = serious adverse event; T3 = triiodothyronine, T4 = thyroxine; Tbili = total bilirubin; TSH = thyroid-stimulating hormone, WOCBP = women of 
childbearing potential 
a For patients who complete 52 weeks of treatment: Follow-up Visit 1 = 2 weeks (+5 days) after last dose of on-study treatment. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
26 
Approved v41.0 
930144776 4.0 
 
 
b For patients who discontinue early (prior to 52 weeks of treatment): Follow-up Visit 1 = 30 days from the last dose (±7 days) or coincides with the date of 
discontinuation (±7 days) if date of discontinuation is greater than 42 days after the last dose. Follow-up Visit 2 = 100 days (±7 days) from the last dose of study 
treatment. Both follow-up visits should be conducted in person. Participants must be followed for at least 100 days after the last dose of study treatment or for a 
maximum of 52 weeks from the date of the first on-study dose of nivolumab, whichever occurs earliest. 
c For patients who discontinue early only (prior to 52 weeks of treatment): Survival follow-up visits may be conducted in clinic or by phone. Survival visits: first 
survival follow-up Visit 3 months (±14 days) after follow-up Visit 2 and subsequent survival follow-up visits every 3 months (±14 days) until death, withdrawal 
of consent, loss to follow-up, or for a maximum of 52 weeks from the date of the first on-study dose of nivolumab. 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 contact. 
d Serum collected to be used for potential future measurements of anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total or IgG [see Section 9.7.1]). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
27 
Approved v 41.0 
930144776 4.0 
 
 
3 
INTRODUCTION 
In India, the incidence of RCC is 1.2/100,000 in males and 0.5/100,000 in females, annually.1 
Approximately 20% to 30% of patients present with metastatic disease at diagnosis, and about 
one-third of patients undergoing nephrectomy for localized disease will develop metastases.2,3 
However, there is no satisfactory treatment for advanced RCC.4 The 5-year overall survival (OS) 
for patients with metastatic disease at presentation remains less than 20%.5,6 
RCC remains a disease with significant burden and unmet medical need. New agents that have 
meaningful clinical efficacy in RCC are needed.6 
The CA209214 study was a Phase 3 study of nivolumab in combination of ipilimumab compared 
with sunitnib in previously untreated patients with locally advanced RCC or metastatic renal cell 
carcinoma (mRCC). The study has demonstrated a favorable benefit/risk profile for the 
combination of nivolumab and ipilimumab over current standard of care sunitinib in International 
Metastatic RCC Database Consortium (IMDC) intermediate/poor risk patients as shown by the 
unprecedented OS benefit in this population. It also showed superior objective response rate 
(ORR), higher rate of complete response (CR) as well as a clinically meaningful increase in 
progression-free survival (PFS) compared to sunitinib. 
The combination of nivolumab and ipilimumab is approved by the United States (US) Food and 
Drug Administration for the treatment of intermediate- and poor-risk, previously untreated patients 
with advanced RCC, and it is incorporated into the European Association of Urology guidelines. 
In India, nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor antibody, is 
approved for the treatment of advanced renal cell carcinoma after treatment with antiangiogenic 
therapy, second line renal cell carcinoma (2L RCC) treatment based on an overall survival benefit.7 
Ipilimumab is an anti-cytotoxic T-lymphocyte-associated antigen 4 antibody. Although 
ipilimumab at a dose of 3 mg per kilogram of body weight was associated in 1 trial with an 
objective response rate of 13% among patients with metastatic renal cell carcinoma, its toxic 
effects precluded further development as a single-agent therapy for this disease. 7 
Clinical data from a comprehensive set of early clinical studies (CA209009, CA209010, 
CA209004, CA209003, and CA209016) provided early evidence of the activity of both nivolumab 
and ipilimumab as monotherapies in RCC and melanoma, which supported the incremental benefit 
of the combination and led to the study design of Study CA209214. 
The combination of nivolumab and ipilimumab has not been approved in India. 
3.1 
Study Rationale 
This is a Phase 4 study in India to establish the safety and effectiveness of the combination of 
nivolumab with ipilimumab followed by nivolumab as a single-agent maintenance therapy as 
first-line renal cell carcinoma (1L RCC) treatment in patients with intermediate- or poor-risk, 
previously untreated, advanced RCC, to be conducted in compliance with a condition of approval 
specified by the Health Authorities of India. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
28 
Approved v 41.0 
930144776 4.0 
 
 
Approval in India has been granted for the use of nivolumab (1) as a single agent for the treatment 
of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy; 
(2) as a single agent for the treatment of patients with advanced RCC after prior therapy in adults; 
(3) as monotherapy for the treatment of recurrent or metastatic squamous cell carcinoma of the 
head and neck (SCCHN) after platinum-based therapy; (4) as a single agent for the treatment of 
patients with BRAF V600 wildtype unresectable or metastatic melanoma; (5) for the treatment of 
adult patients with classical Hodgkin lymphoma that has relapsed or progressed after autologous 
hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or 3 or more lines of 
systemic therapy that includes autologous HSCT; (6) for the treatment of patients with 
hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; (7) for the 
treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease 
progression during or following platinum-containing chemotherapy or have disease progression 
within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; 
and (8) for the treatment of adult and pediatric (12 years and older) patients with microsatellite 
instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer that 
has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. 
This will be the first indication (1L RCC) for which ipilimumab in combination with nivolumab 
is approved in India. 
As a condition of approval for the indication of 1L RCC, Bristol-Myers Squibb (BMS) is required 
to conduct a Phase 4 clinical trial to provide effectiveness and safety data. Adverse reactions 
related to treatment will be reported to the Health Authorities in India and subsequently, any 
regulatory action resulting from the review of reported adverse reactions should be complied with 
by the Sponsor. This Phase 4 clinical trial is to be conducted in addition to the Periodic Safety 
Update Report, which must be submitted to the health authorities in India every 6 months for the 
first 2 years after approval, and annually for subsequent 2 years. 
Safety will be evaluated throughout the treatment period and during the follow-up of participants 
who discontinue treatment before 52 weeks by assessing the incidence of high-grade 
immune-mediated adverse events (IMAEs) in patients who are treated. 
The evaluation of patient-reported outcomes (PROs) 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. 
 
 
 
Effectiveness will be evaluated throughout the treatment period by tumor assessments (computed 
tomography [CT]/magnetic resonance imaging (MRI) of the chest, abdomen, pelvis, and all other 
known and/or suspected sites of disease) at screening, and then at Week 12 (± 7 days) following 
first dose; subsequent tumor assessments will occur every 8 weeks (±7 days) until 52 weeks of 
treatment plus 2 weeks of follow-up or initiation of subsequent systemic cancer therapy, 
withdrawal of consent, death, or investigator-assessed disease progression, whichever occurs first 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
29 
Approved v 41.0 
930144776 4.0 
 
 
These time points are independent of dosing. See Section 9.1.1 for further details. Endpoint 
analysis of PFS, ORR, time to response (TTR), and duration of response (DOR) will be done based 
on these assessments. 
 
Collecting immunogenicity/pharmacokinetic (PK) data on the India population will allow 
comparison between the India population and the global population. 
3.1.1 
Research Hypothesis 
There is an unmet medical need in India in the setting of advanced or mRCC. Combination therapy 
of nivolumab and ipilimumab as first-line treatment for patients with clear-cell RCC has been 
evaluated in the CA209214 clinical trial. The present study will aim to evaluate a combination 
dosing regimen of nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks (Q3W) followed by 
a single-dose agent of nivolumab 3 mg/kg every 2 weeks (Q2W) for a maximum of 52 weeks or 
until treatment is no longer tolerated by the participant or withdrawal of consent. 
The research hypothesis is that this dosing regimen will result in a comparable safety profile as 
assessed by the incidence of high-grade (Common Terminology Criteria for Adverse Events 
[CTCAE] v4.0 Grade 3 to 4 and Grade 5) IMAEs observed in patients with advanced or mRCC in 
India with clear-cell histology who are treated in the first-line setting, when compared to Study 
CA209214 safety data in this patient population. 
3.2 
Background 
3.2.1 
Indication Background 
Renal Cell Carcinoma Background and Standard Treatments 
According to the GLOBOCAN estimates, 403,262 new cases of kidney cancer were diagnosed in 
2018 worldwide accounting for 2.2% of all adult cancers.8 In India, 15,454 new cases of kidney 
cancer were diagnosed in 2018, with an age‑standardized incidence rate of 1.3%.9 Renal cell 
carcinoma (RCC) is the most common form of kidney cancer (90% of cases). It is nearly twice as 
common in men as in women, with a median age at diagnosis of 64 years. Clear cell tumors are 
the most common pathological subtype of RCC (80% of cases); some other less common subtypes 
include papillary, chromophobe, and collecting duct tumors. Smoking, obesity, and hypertension 
are well‑known risk factors for RCC. It primarily metastasizes to the lung, bone, liver, lymph 
nodes, adrenal gland, and brain.10 Although the 5‑year OS of early-stage RCC is as high as 66%, 
metastatic or advanced stage disease is only 8% to 10%. Moreover, local recurrence or distant 
metastasis develops in up to 30% to 40% of patients treated for localized stage disease. Metastatic 
RCC responds very poorly to conventional chemotherapy. Cytokine therapy is associated with 
modest response rates of 15% to 20% but at the cost of significant toxicities. 10 
Multiple scoring systems are available to characterize prognosis in treatment-naive RCC. Two of 
the most commonly used are the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
30 
Approved v 41.0 
930144776 4.0 
 
 
scoring system and the IMDC prognostic scoring system.11,12 Each of these systems categorizes 
patients as favorable, intermediate, or poor-risk based on how many adverse prognostic factors are 
present (0: favorable risk, 1 to 2: intermediate risk, 3 or more: poor-risk). The 6 parameters of 
importance for IDMC prognostic score classification are Karnofsky Performance Status (KPS), 
time from diagnosis to treatment, hemoglobin value, corrected calcium concentration, absolute 
neutrophil count, and platelet count. The 5 parameters included in the MSKCC prognostic score 
are KPS, nephrectomy status, hemoglobin value, lactate dehydrogenase (LDH), and corrected 
calcium concentration. Time from diagnosis to treatment is often used in place of nephrectomy 
status. With each system, total number of adverse prognostic factors present has been shown to 
correlate with OS. 
Approximately 25% of patients are in the favorable-risk group, 50% are in the intermediate-risk 
group, and 25% are in the poor-risk group (median OS: ~ 9 months). In an analysis of 
1,028 patients scored using the IMDC system, median OS for favorable-, intermediate-, and 
poor-risk patients is 43.2, 22.5, and 7.8 months, respectively.13 
Until recently, the cytokines interleukin-2 and interferon-α were the only active treatments for 
advanced or metastatic RCC. However, due to each of these agent’s limited clinical benefit and 
substantial toxicity profile, newer targeted agents have largely replaced cytokines in the treatment 
of advanced or mRCC.14,15,16,17 The recognition of the importance of hypoxia inducible factor 
alpha (HIFα) signaling in the pathogenesis of clear-cell RCC has led to widespread study of 
2 classes of targeted therapies: anti-angiogenic agents and mammalian target of rapamycin 
(mTOR) inhibitors.18 Targeting of angiogenesis is rational because constitutive HIFα activation 
leads to the upregulation or activation of several proteins including vascular endothelial growth 
factor (VEGF), which can subsequently lead to tumor proliferation and neovasculature formation. 
Targeting of the mTOR pathway is important because activation of the upstream PI3K/Akt/mTOR 
signaling pathway is one method by which constitutive HIFα activation or upregulation occurs. 
There are 7 agents for the treatment of RCC in the US and European Union (EU): 5 that target 
angiogenesis (ie, the VEGF-receptor tyrosine kinase inhibitors sorafenib, sunitinib, pazopanib, 
axitinib, and the VEGF-binding monoclonal antibody bevacizumab) and 2 that target the mTOR 
pathway (ie, everolimus and temsirolimus). Among these approved agents, none has demonstrated 
a statistically significant improvement in OS except for temsirolimus in poor-risk patients. 
According to National Comprehensive Cancer Network (NCCN) guidelines, sunitinib, 
temsirolimus (poor-risk only), bevacizumab plus interferon, and pazopanib are Category 1 
recommendations for first-line therapy of mRCC.19 
According to ESMO guidelines, sunitinib, bevacizumab plus interferon, and pazopanib are all 
standard treatment options for favorable- and intermediate-risk patients, but sunitinib is the only 
one also considered an alternative to temsirolimus for the treatment of poor-risk patients.20 
3.2.2 
Nivolumab Mechanism of Action 
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human monoclonal 
antibody (immunoglobulin G4 [IgG4]-S228P) that targets the PD-1 cluster of differentiation 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
31 
Approved v 41.0 
930144776 4.0 
 
 
(CD) 279 cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by 
activated T and B lymphocytes.21 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. Nivolumab is expressed in Chinese 
hamster  ovary  cells  and  is  produced  using  standard  mammalian  cell  cultivation  and 
chromatographic purification technologies. The clinical study product is a sterile solution for 
parenteral administration. 
Nivolumab (OPDIVO) is approved for the treatment of several types of cancer in multiple 
regions including the US (Dec-2014), the EU (Jun-2015), and Japan (Jul-2014). 
A detailed description of the chemistry, pharmacology, effectiveness, and safety of nivolumab is 
provided in the India prescribing information for nivolumab (Appendix 5). 
3.2.3 
Ipilimumab Mechanism of Action 
Ipilimumab (BMS-734016, MDX010, MDX-CTLA4) is a fully human monoclonal 
immunoglobulin G1 kappa specific for human cytotoxic T-lymphocyte antigen 4 (CTLA-4, 
CD152), which is expressed on a subset of activated T cells. CTLA-4 is a negative regulator of 
T-cell activity. Ipilimumab is a monoclonal antibody that binds to CTLA-4 and blocks the 
interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to 
augment T-cell activation and proliferation, including the activation and proliferation of tumor- 
infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell 
(Treg) function, which may contribute to a general increase in T-cell responsiveness, including the 
anti-tumor response. 
A detailed description of the chemistry, pharmacology, effectiveness, and safety of ipilimumab is 
provided in the India prescribing information for ipilimumab (Appendix 5). 
3.2.4 
Nivolumab in Renal Cell Carcinoma 
Nivolumab monotherapy has been studied in participants with RCC in several BMS-sponsored 
studies, with the largest amount of data coming from 3 studies in participants with mRCC: 
CA209010, CA209009, and CA209025. In Study CA209010, 168 participants who received at 
least 1 prior anti-angiogenic therapy were randomized to receive nivolumab 0.3 mg/kg (n = 60), 
2 mg/kg (n = 54), and 10 mg/kg (n = 54).22 Median PFS was 2.7, 4.0, and 4.2 months at 0.3, 2, 
and 10 mg/kg, respectively. The ORR ranged from 20% to 22% across dose levels. Median OS 
was 18.2 months at 0.3 mg/kg, but was not yet reached at the 2 highest dose levels. CA209009 
enrolled a similar population to Study CA209010, but also included 24 participants with treatment- 
naive RCC. Among treatment-naive participants, all of whom received nivolumab 10 mg/kg Q3W, 
the ORR was 13% (3/23). 
Study CA209010 includes the largest safety database for nivolumab monotherapy in mRCC. All 
treated participants (n = 167) were included in the safety analyses. Drug-related AEs of any grade 
occurred in 74.6%, 66.7%, and 77.8% of participants treated at 0.3, 2, and 10 mg/kg, respectively. 
The most common (≥ 10% in any group) drug-related AEs included fatigue, dry skin, rash, 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
32 
Approved v 41.0 
930144776 4.0 
 
 
pruritus, arthralgia, nausea, diarrhea, decreased appetite, dry mouth, and hypersensitivity. Grade 3 
drug-related AEs occurred in 5.1%, 16.7%, and 13% of participants treated at 0.3, 2, and 10 mg/kg, 
respectively. Related Grade 3 events in at least 2 patients across dose levels included nausea, 
aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increased, and anemia. No 
drug-related Grade 4 or Grade 5 events occurred. No dose-toxicity relationship was identified 
except for hypersensitivity/infusion reaction, which occurred most frequently in the 10 mg/kg 
treatment group. 
Based on the clinical activity of nivolumab observed in these Phase 1 and 2 studies, a large Phase 
3 trial (CA209025) was conducted in 821 participants with advanced RCC previously treated with 
1 or 2 anti-angiogenic therapies who were randomized to receive nivolumab 3 mg/kg Q2W or 
everolimus 10 mg daily. A planned interim analysis, after a minimum follow-up of 14 months, 
demonstrated a statistically significant and clinically meaningful improvement in OS of nivolumab 
monotherapy versus everolimus (median OS, 25.0 months vs 19.6 months, respectively; hazard 
ratio [HR] 0.73 [98.5% confidence interval (CI): 0.57 to 0.93, P = 0.002]). ORR was 25% for 
nivolumab versus 5% for everolimus. Among 756 participants with quantifiable PD-L1 tumor 
expression in pre-treatment samples, 24% had PD-L1 expression ≥ 1%. Among participants with 
PD-L1 expression ≥ 1%, median OS was 21.8 months in the nivolumab group and 18.8 months in 
the everolimus group (HR 0.79 [95% CI: 0.53 to 1.17]). Among participants with PD-L1 
expression < 1%, the median OS was 27.4 months in the nivolumab group and 21.2 months in the 
everolimus group (HR, 0.77 [95% CI: 0.60 to 0.97]). No new safety concerns were identified, and 
nivolumab monotherapy showed a favorable safety profile as compared to everolimus, evidenced 
by the lower rates of drug-related AEs (all grades, 79% vs 88%; Grade 3 to 4, 19% vs 37%, 
respectively) and drug-related AEs leading to discontinuation (all grades, 8% vs 13%, 
respectively) in the nivolumab group. These results were the basis for regulatory approval of 
nivolumab monotherapy in advanced RCC. 
Based on the limited data from Studies CA209009 and CA209010, when Study CA209214 was 
initiated in 2014, the observed preliminary anti-tumor activity was not considered to be sufficient 
to test against sunitinib, the standard of care in 1L RCC. As the treatment of RCC landscape 
continues to evolve, accumulative evidence showed a single-agent activity for anti-PD-1 or anti- 
PD-L1 monotherapy in the 1L treatment of advanced RCC. In a Phase 2, nonrandomized, 
noncomparative study (Keynote-427),23 pembrolizumab was studied as monotherapy in 110 
patients with advanced clear cell RCC who had not received prior systemic therapy, including 41 
IMDC favorable-risk patients. The interim data showed single-agent activity with an overall 
response rate of 38.2% including a CR rate of 2.7%. Responses lasting for 6 months or more were 
observed in 74.8% of patients. The median PFS was 8.7 months (95% CI: 6.7 to 12.2 months) and 
the 6-month PFS rate was 60.2%. In an analysis based on PD-L1 status, patients whose tumors 
expressed PD-L1 (combined positive score [CPS] ≥ 1) (n = 46) had an ORR of 50.0% (95% CI: 
34.9 to 65.1), with a CR rate of 6.5%. In patients whose tumors did not express PD-L1 (CPS < 1) 
(n = 53), ORR was 26.4% (95% CI: 15.3 to 40.3) (all responses were PRs). 
Atezolizumab was evaluated in the IMmotion 150 study, a randomized Phase 2 study comparing 
the combination of atezolizumab with bevacizumab (a VEGF-targeted antibody) and atezolizumab 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
33 
Approved v 41.0 
930144776 4.0 
 
 
monotherapy versus sunitinib, as a 1L treatment for previously untreated RCC.24 In the 
atezolizumab monotherapy arm (n = 103 patients), an ORR of 25%, including 11% of CR, was 
reported. Among 54% of PD-L1 positive patients treated with atezolizumab monotherapy, an ORR 
of 28%, with 15% of CR, was observed. The median PFS for atezolizumab was 5.4 months, which 
was not statistical significant compared with sunitinib (HR 1.03 [95% CI: 0.63 to 1.67, P = 0.917]). 
Taken together, agents targeting PD-1/PD-L1 pathway demonstrated initial anticancer activities. 
However, the role of single agents of PD-1 and PD-L1 inhibitors versus those agents in 
combination with other agents with different targeted pathways, such as anti-CTLA-4 or anti- 
VEGF agents, remains to be defined. 
3.2.5 
Ipilimumab in Renal Cell Carcinoma 
Ipilimumab monotherapy for the treatment of mRCC was studied in the Phase 2 clinical trial 
MDX010-11.25 Two sequential cohorts were studied, each with a loading dose of 3 mg/kg 
followed by 3 doses of either 1 mg/kg (group 3-1; n = 21) or 3 mg/kg (group 3-3; n = 40). 
Participants with stable disease or partial response (PR) or CR were allowed additional treatment. 
In group 3-1 (n = 21), 1 participant (5%) had a PR.26 In group 3-3 (n = 40), 5 participants (12.5%) 
had a PR. Among 14 treatment-naive participants in group 3-3, 3 participants (21%) had a PR. 
In the ipilimumab monotherapy Phase 2 clinical trial MDX010-11, the major toxicities were colitis 
(all Grade 3/4: 14% in group 3-1, 33% in group 3-3) and hypophisitis (1 grade 3/4, 1 grade 1/2 in 
group 3-3; none in group 3-1). Most reported AEs were Grade 1/2 (57% in group 3-1, 35% in 
group 3-3) or Grade 3 (38% in group 3-1, 48 % in group 3-3).27 Most reported AEs were Grade 
1/2 (57% in group 3-1, 35% in group 3-3) or Grade 3 (38% in group 3-1, 48% in group 3-3). There 
were 6 participants (15%) with Grade 4 AEs in group 3-3. The most common treatment-related 
AEs in group 3-1 (total 81%) and group 3-3 (total 93%) were diarrhea (38% and 40%, respectively) 
and fatigue (33% and 38%, respectively). Most AEs were manageable with appropriate treatment, 
including high dose corticosteroids and hormone replacement. 
3.2.6 
Nivolumab Combined with Ipilimumab Clinical Activity 
Multiple clinical studies have evaluated nivolumab combined with ipilimumab at different doses 
and schedules. The following information describes the results of initial early phase clinical studies 
that were the basis for the nivolumab plus ipilimumab combination regimens that have been 
explored in late phase clinical development. 
Based on the safety data from the completed and ongoing advanced RCC studies, the safety profile 
of nivolumab in combination with ipilimumab, and nivolumab monotherapy using the acceptable 
dosing regimens, in the context of the observed clinical activity, are manageable using well- 
established guidelines and present a favorable benefit/risk profile in patients with advanced RCC. 
The indication for which there is clear benefit are as follows: Nivolumab in combination with 
ipilimumab in previously untreated, advanced RCC based on Study CA209214: nivolumab 
3 mg/kg combined with ipilimumab 1 mg/kg Q3W administered as an intravenous (IV) infusion 
for 4 doses followed by nivolumab 3 mg/kg Q2W. Treatment was to continue until disease 
progression or unacceptable toxicity. This is the first Phase 3 trial to demonstrate improved OS in 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
34 
Approved v 41.0 
930144776 4.0 
 
 
this population compared to the current standard of care sunitinib. The nivolumab + ipilimumab 
combination also demonstrated a significantly higher IRRC-assessed ORR compared to sunitinib 
(41.6% vs 26.5%), with objective responses that were deeper, including 9.4% of subjects achieving 
a CR, and more durable, with a median DOR not reached at the time of database lock. Clinically 
meaningful improvement in PFS was also demonstrated with the nivolumab + ipilimumab 
combination vs sunitinib. In Study CA209214, the overall safety profile observed in the nivolumab 
+ ipilimumab group (using nivolumab 3 mg/kg combined with ipilimumab 1 mg/kg) was 
consistent with the known and well-characterized safety profile of nivolumab monotherapy (using 
nivolumab 3 mg/kg) and more tolerable than the nivolumab + ipilimumab combination (using 
nivolumab 1 mg/kg combined with ipilimumab 3 mg/kg) in melanoma. There were no new safety 
signals relative to combination therapy in melanoma (nivolumab 1 mg/kg combined with 
ipilimumab 3 mg/kg) as well as nivolumab monotherapy (using nivolumab 3 mg/kg), and it was 
well tolerated with 23.4% of patients remaining on therapy at the time of analysis. Overall, the 
benefit-risk profile of nivolumab + ipilimumab is favorable relative to sunitinib. The clinically 
meaningful benefit, including significant improvement in OS, and acceptable safety profile in 
Study CA209214 provide evidence for a new standard of care for nivolumab 3 mg/kg in 
combination with ipilimumab 1 mg/kg in treatment-naive patients with advanced RCC with an 
intermediate/poor-risk prognosis. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of nivolumab and 
ipilimumab is provided in the India prescribing information for nivolumab and ipilimumab 
(Appendix 5). 
3.2.7 
Adverse Event Rates Associated with Nivolumab in Combination with 
Ipilimumab in Previously Untreated Advanced or Metastatic RCC 
In Study CA209214, the dataset of nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg 
in RCC (n = 547), with a minimum follow-up of 17.5 months, the most frequent adverse reactions 
(≥ 10%) were fatigue (48%), rash (34%), pruritus (28%), diarrhea (27%), nausea (20%), 
hypothyroidism (16%), musculoskeletal pain (15%), arthralgia (14%), decreased appetite (14%), 
pyrexia (14%), vomiting (11%), and hyperthyroidism (11%). The majority of adverse reactions 
were mild to moderate (Grade 1 or 2).28 
Among the patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in 
Study CA209214, 169/547 (31%) had the first onset of Grade 3 or 4 adverse reactions during the 
initial combination phase. Among the 382 patients in this group who continued treatment in the 
single-agent phase, 144 (38%) experienced at least 1 Grade 3 or 4 adverse reaction during the 
single-agent phase. 28 
The treatment-related AEs and SAEs, and discontinuations due to treatment-related AEs in the 
Checkmate 214 study are presented in Table 3.2.7-1. These reactions are presented by system 
organ class and by frequency. Frequencies are defined as: very common (≥ 1/10); common 
(≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); and very 
rare (< 1/10,000). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
35 
Approved v 41.0 
930144776 4.0 
 
 
Table 3.2.7-1: 
Adverse Reactions in Patients Receiving Nivolumab Plus Ipilimumab 
(Checkmate-214) 
 
Nivolumab 3 mg/kg in Combination with 
Ipilimumab 1 mg/kg in RCCa 
Infections and infestations 
Common 
pneumonia, upper respiratory tract infection 
Uncommon 
bronchitis, aseptic meningitis 
Blood and lymphatic system disorders 
Common 
NA 
Uncommon 
eosinophilia 
Immune system disorders 
Common 
infusion-related reaction, hypersensitivity 
Uncommon 
NA 
Endocrine disorders 
Very common 
hypothyroidism, hyperthyroidism 
Common 
adrenal insufficiencyb, hypophysitisb, thyroiditis, diabetes 
mellitusb 
Uncommon 
diabetic ketoacidosisb, hypopituitarism 
Metabolism and nutrition disorders 
Very common 
decreased appetite 
Common 
dehydration 
Uncommon 
metabolic acidosis 
Hepatobiliary disorders 
Common 
hepatitisb 
Nervous system disorders 
Very common 
NA 
Common 
headache, peripheral neuropathy, dizziness 
Uncommon 
polyneuropathy, autoimmune neuropathy (including facial and 
abducens nerve paresis), myasthenia gravisb 
Eye disorders 
Common 
blurred vision 
Uncommon 
uveitis 
Cardiac disorders 
Common 
tachycardia 
Uncommon 
arrhythmia (including ventricular arrhythmia), myocarditisb 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
36 
Approved v 41.0 
930144776 4.0 
 
 
Table 3.2.7-1: 
Adverse Reactions in Patients Receiving Nivolumab Plus Ipilimumab 
(Checkmate-214) 
 
Nivolumab 3 mg/kg in Combination with 
Ipilimumab 1 mg/kg in RCCa 
Vascular disorders 
Common 
hypertension 
Uncommon 
NA 
Respiratory, thoracic and mediastinal disorders 
Very common 
NA 
Common 
pneumonitis, dyspnoea, pleural effusion, cough 
Uncommon 
NA 
Gastrointestinal disorders 
Very common 
diarrhoea, vomiting, nausea 
Common 
colitis, stomatitis, pancreatitis, abdominal pain, 
constipation, dry mouth 
Uncommon 
gastritis 
Skin and subcutaneous tissue disorders 
Very common 
rashc, pruritus 
Common 
dry skin, erythema, urticaria 
Uncommon 
Stevens-Johnson syndrome, vitiligo, erythema multiforme, 
alopecia, psoriasis 
Musculoskeletal and connective tissue disorders 
Very common 
musculoskeletal paind, arthralgia 
Common 
arthritis, muscle spasms, muscular weakness 
Uncommon 
polymyalgia rheumatica, myositis (including polymyositis), 
rhabdomyolysis 
Common 
renal failure (including acute kidney injury)b 
Uncommon 
tubulointerstitial nephritis 
General disorders and administration site conditions 
Very common 
fatigue, pyrexia 
Common 
oedema (including peripheral oedema), pain, chest pain, 
chills 
Uncommon 
NA 
Investigationsb 
Common 
weight decreased 
Abbreviations: CTLA-4 = cytotoxic T-lymphocyte antigen 4; NA = not applicable; RCC = renal cell carcinoma 
a Nivolumab in combination with ipilimumab for the first 4 doses followed by nivolumab as a single-agent 
maintenance therapy in RCC. 
b Life-threatening cases have been reported in completed or ongoing clinical studies. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
37 
Approved v 41.0 
930144776 4.0 
 
 
c Rash is a composite term that includes maculopapular rash, rash erythematous, rash pruritic, rash follicular, rash 
macular, rash morbilliform, rash papular, rash pustular, rash papulosquamous, rash vesicular, rash generalised, 
exfoliative rash, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis bullous, 
dermatitis exfoliative, dermatitis psoriasiform, drug eruption, and pemphigoid. 
d Musculoskeletal pain is a composite term that includes back pain, bone pain, musculoskeletal chest pain, 
musculoskeletal discomfort, myalgia, neck pain, pain in extremity, and spinal pain. 
 
3.3 
Benefit/Risk Assessment 
Extensive details on the safety profile of nivolumab are available in the India prescribing 
information for nivolumab (Appendix 5) and will not be repeated herein. 
Overall, the safety profile of nivolumab as a single-agent therapy, as well as in combination with 
ipilimumab, is manageable and generally consistent across completed and ongoing clinical trials, 
with no maximum tolerated dose reached at any dose tested up to 10 mg/kg. Most AEs were low- 
grade (Grade 1 to 2) with relatively few related high-grade (Grade 3 to 4) AEs. There was no 
pattern in the incidence, severity, or causality of AEs with respect to nivolumab dose level. 
A pattern of immune-related AEs has been defined; these are provided in the India prescribing 
information for nivolumab (Appendix 5). Most high-grade events were manageable with the use 
of corticosteroids or hormone replacement therapy (endocrinopathies) as instructed in these 
algorithms. 
Additional details on the safety profile of nivolumab, including results from other clinical studies, 
are also available in the India prescribing information for nivolumab. 
Patients with mRCC have multiple treatment options available to them, but none of the available 
targeted agents have been able to demonstrate a significant improvement in OS when compared to 
each other. Median OS remains less than 4 years for treatment-naive patients with the most 
favorable prognosis and is substantially shorter for patients who possess adverse prognostic 
factors. Therefore, new therapeutic options with the potential to provide greater survival across 
risk groups are needed. 
Nivolumab 3 mg/kg combined with ipilimumab 1 mg/kg has demonstrated substantial clinical 
activity, as measured by ORR, while still exhibiting an acceptable safety profile in the 
Checkmate-214 study, and the magnitude of OS benefit from the combination is unprecedented in 
studies of mRCC for intermediate- and poor-risk participants. 
More detailed information about the known and expected benefits and risks and reasonably 
anticipated AEs of nivolumab and ipilimumab may be found in the India prescribing information 
for nivolumab and ipilimumab. 
Non-live coronavirus disease 2019 (COVID-19) vaccination is considered a simple concomitant 
medication within the study. However, the efficacy and safety of non-live vaccines (including non- 
live COVID-19 vaccines) in participants receiving investigational agents is unknown. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
38 
Approved v 41.0 
930144776 4.0 
 
 
4 
OBJECTIVES AND ENDPOINTS 
Table 4-1: 
Objectives and Endpoints 
 
Objective 
Endpoint 
Primary 
• 
To assess the incidence of high-grade (CTCAE v4.0 
Grade 3 to 4 and Grade 5) IMAEs in intermediate- 
or poor-risk participants with previously untreated, 
advanced RCC who are treated with combination 
therapy of nivolumab 3 mg/kg administered 
intravenously over a period of 30 minutes Q3W for 
the first 4 doses in combination with intravenous 
ipilimumab 1 mg/kg over a period of 30 minutes, 
followed by nivolumab 3 mg/kg Q2W administered 
IV over a period of 30 minutes. 
• 
Incidence of high-grade (CTCAE v4.0 Grade 3 to 
4 and Grade 5) IMAEs 
Secondary 
• 
To characterize the outcome of all high grade 
(CTCAE v4.0 Grade 3 to 4 and Grade 5) IMAEs 
in intermediate or poor risk participants with 
previously untreated, advanced RCC. 
• 
Characterization of outcome of all high grade 
(CTCAE v4.0 Grade 3 to Grade 5) IMAEs 
(eg, time to onset, time to resolution, percentage of 
patients who received immune modulating 
medication) 
• 
To assess the effectiveness of nivolumab in 
combination with ipilimumab by measuring ORR, 
TTR, and DOR, using RECIST 1.1. 
• 
ORR, TTR, DOR 
Exploratory 
• 
To assess the incidence of all treatment-related 
AEs in intermediate or poor risk participants with 
previously untreated, advanced RCC. 
• 
Incidence of all treatment related AEs 
• 
To assess the effectiveness of nivolumab in 
combination with ipilimumab by measuring PFS 
(at time of initial progression) and OS 1-year 
survival rates in intermediate- or poor-risk 
participants with previously untreated, advanced 
RCC. 
• 
PFS, OS 
• 
To assess the participant’s cancer-related 
symptoms and QoL. 
• 
All total and subscale scores and post-baseline 
score changes for the FKSI-19 
• 
To evaluate the PK of nivolumab and ipilimumab 
when administered in combination and the PK of 
nivolumab as a single-agent maintenance therapy. 
To explore the exposure-response relationships 
between select exposure measures, and safety and 
effectiveness endpoints, as appropriate. 
• 
Predose serum nivolumab and ipilimumab 
concentrations to be used for PPK analysis to 
predict nivolumab PK parameters. Explore 
exposure-response relationships if data permit. 
• 
To characterize the immunogenicity of nivolumab 
and ipilimumab when administered in combination 
and the immunogenicity of nivolumab as a single- 
agent maintenance therapy. 
• 
Immunogenicity will be determined by 
measurement of ADA in serum and samples with 
positive ADA response may be analyzed for 
neutralizing ADA response to nivolumab and 
ipilimumab 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
39 
Approved v 41.0 
930144776 4.0 
 
 
Table 4-1: 
Objectives and Endpoints 
 
Objective 
Endpoint 
 
 
 
 
• 
To assess the impact of SARS-CoV-2 serologic 
status on participants receiving nivolumab in 
combination with ipilimumab and previously 
untreated, advanced RCC and to support Health 
Authority requests 
• 
Exploratory measurements of SARS-CoV-2 
serology (anti-SARS-CoV-2 total or IgG) from 
serum samples collected at baseline (and additional 
time points if applicable) and the potential 
association between these measurements and 
selected endpoints related to safety, effectiveness, 
and/or biomarkers 
Abbreviations: ADA = antidrug antibody; AE = adverse event; CTCAE = Common Terminology Criteria for Adverse 
Events; DOR = duration of response; FKSI-19 = Functional Assessment of Cancer Therapy - Kidney Symptom Index; 
IgG = immunoglobulin G; IMAE = immune-mediated adverse event; IV = intravenous(ly); NCI = National Cancer 
Institute; ORR = objective response rate; OS = overall survival; 
; PFS = 
progression-free survival; PK = pharmacokinetics; PPK = population pharmacokinetics; Q2W = every 2 weeks; 
Q3W = every 3 weeks; QoL = quality of life; RCC = renal cell carcinoma; RECIST = Response Evaluation Criteria 
in Solid Tumors; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TTR = time to response 
Note: All AEs to be assessed using NCI CTCAE v4.0. 
 
 
5 
STUDY DESIGN 
5.1 
Overall Design 
This is a Phase 4, open-label, single-arm, multi-center, prospective study of nivolumab 3 mg/kg 
Q2W combined with ipilimumab 1 mg/kg Q3W for 4 doses followed by nivolumab 3 mg/kg for 
up to 52 weeks. The study is to be conducted in India and will enroll intermediate- or poor-risk 
participants with previously untreated, advanced RCC or mRCC (N = 100). 
Potential participants will undergo screening evaluations to determine eligibility within 28 days 
prior to first dose. Participants who meet the protocol-defined inclusion/exclusion criteria will be 
prospectively enrolled in a sequential manner. 
The study treatment will continue until participants experienced disease progression per Response 
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, unacceptable toxicity, withdrawal of 
consent, or a maximum 1 year of study treatment of nivolumab. There are a maximum 4 doses of 
ipilimumab. 
Participants who are observed to continue to receive clinical benefit at follow-up will continue 
nivolumab treatment via commercial supply (provided by BMS India) as long as clinical benefit 
is observed or until treatment is no longer tolerated by the participant. 
For drug-related toxicities, dosing of both drugs can be delayed and resumed after resolution per 
protocol-specified criteria (Section 7.4.1). No dose increases or reductions are allowed for either 
drug. Management of the drug-related toxicities, including the use of corticosteroids and other 
immunomodulating agents, is provided in the India prescribing information (Appendix 5). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
40 
Approved v 41.0 
930144776 4.0 
 
 
Participants should have baseline CT/MRI with measurable disease lesion(s) per RECIST 1.1 and 
first post-baseline tumor assessment at Week 12 followed by subsequent tumor assessments every 
8 weeks in the first 52 weeks (Section 9.1.1 for more details). The tumor assessment schedule will 
continue until a maximum of 52 weeks of treatment plus 2 weeks of follow-up or initiation of 
subsequent systemic cancer therapy, withdrawal of consent, death, or investigator-assessed disease 
progression, whichever occurs first. These time points are independent of dosing. See Section 9.1.1 
for further details. The scans will be submitted to the blinded independent central review (BICR)- 
designated imaging laboratory. 
AE should be collected throughout the study until 100 days after the last dose or for a maximum 
of 52 weeks from the date of the first on-study dose of nivolumab, whichever occurs earlier. Safety 
laboratory including complete blood count (CBC) and chemistry will be obtained at each 
scheduled visit and unscheduled visit as indicated. PK and biomarker samples should be collected 
per protocol-specified schedule (see Table 9.5-1 and Table 9.7.1-1, respectively). PROs will be 
completed by the participant per the protocol-specified Schedule of Activities in Section 2. 
Participants who discontinue the study treatment will be followed for safety at 30 days (Follow-up 
Visit 1) and 100 days (Follow-up Visit 2) of the last dose, thereafter for survival until death, 
withdrawal of consent, loss to follow-up, or for a maximum of 52 weeks from the date of the first 
on-study dose of nivolumab. Tumor assessments schedule will continue in the follow-up period 
per schedule until a maximum of 52 weeks of treatment plus 2 weeks of follow-up or initiation of 
subsequent systemic cancer therapy, withdrawal of consent, death, or investigator-assessed disease 
progression, whichever occurs first. These time points are independent of dosing. See Section 9.1.1 
for further details. 
The study design schematic is presented in Figure 5.1-1. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
41 
Approved v 41.0 
930144776 4.0 
 
 
Figure 5.1-1: 
Study Design Schematic 
 
This study will consist of 3 phases: screening, treatment, and follow-up. 
Screening Phase: 
• Begins by establishing the subject’s initial eligibility and signing of the informed consent form 
(ICF). 
• Subject is enrolled using Interactive Response Technology (IRT). 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
42 
Approved v 41.0 
930144776 4.0 
 
 
 
 
 
• Participants will be assessed for complete study eligibility prior to treatment assignment as 
specified in Table 2-1. 
• The Screening stage ends with either confirmation of full eligibility or with the confirmation 
that the participant is a screen failure. 
• This study permits the re-enrollment of a participant who discontinued the study as a 
pre-treatment failure prior to the treatment phase. If re-enrolled, the participant must be 
re-consented. A new participant identification number will be assigned by IRT at the time of 
re-enrollment. 
 
Treatment Phase: 
• Each visit begins with a call to the IRT system. 
• The first dose is to be administered within 28 days of signing informed consent. 
• For the first 4 cycles (cycle = 3 weeks): 
− Nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV Q3W will be administered 
for 4 doses (12 weeks total). 
• Starting with Cycle 5 (cycle = 2 weeks): 
− Nivolumab 3 mg/kg IV will be administered Q2W. 
• Nivolumab and ipilimumab to be continued until disease progression or unacceptable toxicity, 
with maximum nivolumab treatment of 52 weeks from the first dose in Cycle 1. 
• See Table 7.1-1 for the dosing schedule and Section 5.6 for dose and timing justification. Study 
treatments may be delayed for toxicity (see Section 7.4.1). Treatment may be continued 
beyond investigator-assessed progression if the investigator confirms that the participant meets 
the criteria specified in Section 7.4.2. 
• A negative pregnancy test must be documented within 24 hours prior to the start of 
investigational product. 
• PRO instruments must be completed according to the Schedule of Activities in Section 2. 
• Potential participants will undergo screening evaluations to determine eligibility within 
28 days prior to first dose. Participants who meet the protocol-defined inclusion/exclusion 
criteria will be prospectively enrolled in a sequential manner. 
• On-study laboratory assessments (Cycle 2 and beyond) should be drawn within 72 hours prior 
to dosing. 
• AE assessments should be documented at each clinic visit. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
43 
Approved v 41.0 
930144776 4.0 
 
 
• WOCB must have a pregnancy test within 24 hours prior to administration of study drug. 
• PK samples and immunogenicity samples will be collected according to the schedule in 
Table 9.5-1 and biomarkers according to Section 9.7.1. 
• Study drug dosing may be delayed for toxicity. 
 
For all subjects: 
• Treated subjects will be evaluated for response by the investigator according to the RECIST 
1.1 guidelines beginning at Week 12 (± 7days) following the first dose, then every 8 weeks 
(± 7 days) until Week 52, then until a maximum of 52 weeks of treatment plus 2 weeks of 
follow-up or initiation of subsequent systemic cancer therapy, withdrawal of consent, death, 
or investigator-assessed disease progression, whichever occurs first. These time points are 
independent of dosing. See Section 9.1.1 for further details. 
• Patients treated beyond progression with nivolumab will continue to have tumor assessments 
beginning 12 weeks (±7 days) after the first dose and continuing every 8 weeks (±7 days) until 
Week 52, then until a maximum of 52 weeks of treatment plus 2 weeks of follow-up or 
initiation of subsequent systemic cancer therapy, withdrawal of consent, death, or 
investigator-assessed disease progression, whichever occurs first. These time points are 
independent of dosing. See Section 9.1.1 for further details. 
 
Follow-up Phase 
The follow-up stage begins when the decision to discontinue a participant from study therapy is 
made or the participant completes treatment (no further study treatment). 
• For patients who complete 52 weeks of study treatment: 
− Follow-up Visit 1 will be conducted 2 weeks (+5 days) after the final dose of study 
treatment. 
− PRO instruments must be completed according to the Schedule of Activities in Section 2. 
• For patients who discontinue early (prior to 52 weeks of treatment): 
− Follow-up Visit 1 = 30 days from the last dose (±7 days) or coincides with the date of 
discontinuation (±7 days) if date of discontinuation is greater than 42 days after the last 
dose. 
− Follow-up Visit 2 = 100 days (±7 days) from the last dose of study treatment. 
− Both follow-up visits should be conducted in person. 
− Participants must be followed for at least 100 days after the last dose of study treatment or 
for a maximum of 52 weeks from the date of the first on-study dose of nivolumab, 
whichever occurs earlier. 
− All AEs (not only those deemed to be treatment-related) should be collected continuously 
during the treatment period and for a minimum of 100 days following the last dose or for 
a maximum of 52 weeks from the date of the first on-study dose of nivolumab, whichever 
occurs earlier. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
44 
Approved v 41.0 
930144776 4.0 
 
 
− Events with an "Outcome" of death, regardless of the type of event or relationship 
(ie, including study drug toxicity) are required to be also reported as Grade 5 events. 
− All SAEs after 52 weeks of study duration and 2 weeks of follow-up for participants on 
commercial nivolumab supply will be reported to India Health Authority as part of 
spontaneous reporting. 
− Subjects will be followed for drug-related toxicities until these toxicities resolve, return to 
baseline, or are deemed irreversible. 
− The 2 follow-up visits include collection of PK/immunogenicity samples. 
− After follow-up, patients who discontinue early (prior to 52 weeks of treatment) will be 
followed for OS status every 3 months (±14 days) after follow-up Visit 2, and subsequent 
survival follow-up visits every 3 months (±14 days) until death, withdrawal of consent, 
loss to follow-up, or for a maximum of 52 weeks from the date of the first on-study dose 
of nivolumab. 
− If new anti-tumor therapy is initiated for either progression or a secondary malignancy at 
any time during this period, this and all other pertinent data obtained should be recorded 
on the appropriate case report form (CRF). 
− PRO instruments will be completed according to the Schedule of Activities in Section 2. 
 
The total duration of the study from enrollment to final analysis is expected to be 36 months 
(52 weeks of patients treatment + 24 months for patient accrual), assuming a fixed accrual rate of 
approximately 5 subjects per month. 
Safety will be evaluated throughout treatment and during the follow-up of participants who 
discontinue treatment before 52 weeks by physical examinations including vital signs, AE/SAE 
monitoring, laboratory evaluations, and recording of concomitant medications. 
Data analyses will be conducted only on the safety data collected within the maximum of the 
52 weeks of treatment and 2-week follow-up study period, which will include safety collected 
during the follow-up of participants who discontinue treatment before 52 weeks. 
All SAEs for patients who continue on commercial nivolumab supply after the 52 weeks of 
treatment and 2-week follow-up study duration will be reported to India Health Authority as part 
of spontaneous reporting. 
Physical examinations, vital sign measurements, and clinical laboratory evaluations will be 
performed at selected times throughout the dosing interval and during follow-up for those 
participants who discontinue treatment before the end of the treatment period (52 weeks). 
Participants will be closely monitored for AEs throughout the study. 
5.2 
Data Monitoring Committee and Other External Committees 
Not applicable. 
5.3 
Number of Participants 
A total of 100 treated participants with intermediate- or poor-risk, previously untreated, advanced 
RCC will be enrolled. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
45 
Approved v 41.0 
930144776 4.0 
 
 
The sample size calculation is presented in Section 10.1. 
5.4 
End of Study Definition 
The start of the trial is defined as the first visit of the first participant screened. End of trial is 
defined as the last visit or scheduled procedure shown in the Schedule of Activities in Section 2 
for the last participant. Study completion is defined as the final date on which data for the primary 
endpoint are expected to be collected, if this is not the same. 
In this trial, the study will be completed on the date on which safety data (primary endpoint) are 
collected for the last participant on study. 
5.5 
Scientific Rationale for Study Design 
This is a Phase 4 study in India to establish the safety and effectiveness of the combination of 
nivolumab with ipilimumab followed by nivolumab as a single-agent maintenance therapy in 
patients with intermediate- or poor-risk, previously untreated, advanced RCC. 
This Phase 4 clinical trial is to be conducted in addition to the Periodic Safety Update Report, 
which must be submitted to the health authorities in India every 6 months for the first 2 years after 
approval and annually for the subsequent 2 years. 
The results of this study of nivolumab in combination with ipilimumab followed by nivolumab as 
a single-agent maintenance therapy for the treatment of intermediate- or poor-risk, previously 
untreated, advanced RCC in a limited number of participants in India will be submitted in 
accordance with the requirements of the health authorities in India. 
5.6 
Duration of Treatment with Nivolumab + Ipilimumab 
The study treatment will continue until participants experience disease progression per Response 
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, unacceptable toxicity, withdrawal of 
consent, or a maximum of 1 year of study treatment of nivolumab. There is a maximum of 4 doses 
of ipilimumab. 
At the conclusion of the study, participants who continue to benefit clinically from nivolumab at 
52 weeks will continue treatment via commercial supply (provided by BMS) as long as clinical 
benefit is observed or until treatment is no longer tolerated by the participant. AEs/SAEs for 
participants receiving commercial supply will be reported via spontaneous reporting. 
5.7 
Clinical Pharmacology Summary 
Nivolumab PK was assessed using a population PK approach for both single-agent nivolumab and 
nivolumab with ipilimumab. 
Nivolumab as a single agent: The PK of single-agent nivolumab was studied in patients over a 
dose range of 0.1 to 20 mg/kg administered as a single dose or as multiple doses of nivolumab as 
a 60-minute IV infusion every 2 or 3 weeks. Nivolumab clearance (CL) decreased over time, with 
a mean maximal reduction (percent coefficient of variation [CV%]) from baseline values of 24.5% 
(47.6%) resulting in a geometric mean steady-state clearance (CLss) (CV%) of 8.2 mL/h (53.9%) 
in patients with metastatic tumors; the decrease in CLss was not considered clinically relevant. 
Nivolumab CL does not decrease over time in patients with completely resected melanoma, as the 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
46 
Approved v 41.0 
930144776 4.0 
 
 
geometric mean population CL is 24% lower in this patient population compared with patients 
with metastatic melanoma at steady state. The geometric mean volume of distribution at steady 
state (Vss) (CV%) is 6.8 L (27.3%), and geometric mean elimination half-life is 25 days (77.5%). 
Steady-state concentrations of nivolumab were reached by 12 weeks when administered at 3 mg/kg 
Q2W, and systemic accumulation was 3.7-fold. The exposure to nivolumab increases dose 
proportionally over the dose range of 0.1 to 10 mg/kg administered Q2W. The predicted exposure 
(average concentration and maximum observed concentration) of nivolumab after a 30-minute 
infusion is comparable to that observed with a 60-minute infusion. 
Nivolumab with ipilimumab: When nivolumab 1 mg/kg was administered in combination with 
ipilimumab 3 mg/kg, the CL of nivolumab was increased by 29%, and the CL of ipilimumab was 
unchanged compared to nivolumab administered alone. When nivolumab 3 mg/kg was 
administered in combination with ipilimumab 1 mg/kg, the CL of nivolumab and ipilimumab were 
unchanged. When nivolumab was administered in combination with ipilimumab, the presence of 
anti-nivolumab antibodies increased the CL of nivolumab by 20% and the CL of ipilimumab was 
unchanged in presence of anti-ipilimumab antibodies. 
Specific Populations: The population PK analysis suggested that the following factors had no 
clinically important effect on the CL of nivolumab: age (29 years to 87 years), weight (35 kg to 
160 kg), gender, race, baseline LDH, PD-L1 expression, solid tumor type, tumor size, renal 
impairment, and mild hepatic impairment. 
Renal Impairment: The effect of renal impairment on the CL of nivolumab was evaluated by a 
population PK analysis in patients with mild (estimated glomerular filtration rate [eGFR] 60 to 
89 mL/min/1.73 m2), moderate (eGFR 30 to 59 mL/min/1.73 m2), or severe (eGFR 15 to 
29 mL/min/1.73 m2) renal impairment. No clinically important differences in the CL of nivolumab 
were found between patients with renal impairment and patients with normal renal function. 
Hepatic Impairment: The effect of hepatic impairment on the CL of nivolumab was evaluated by 
population PK analyses in patients with HCC and in patients with other tumors with mild hepatic 
impairment (total bilirubin [TBili] less than or equal to the upper limit of normal [ULN] and AST 
greater than ULN or TBili greater than 1 to 1.5× ULN and any AST) and in HCC patients with 
moderate hepatic impairment (Tbili greater than 1.5 to 3×ULN and any AST). No clinically 
important differences in the CL of nivolumab were found between patients with mild/moderate 
hepatic impairment. 
Full details on the clinical pharmacology aspects of nivolumab can be found in the India 
prescribing information for nivolumab and ipilimumab (Appendix 5). 
Nivolumab 3 mg/kg is approved in the following indications in India: 
1) As a single agent for the treatment of locally advanced or metastatic NSCLC after prior 
chemotherapy 
2) As a single agent for the treatment of patients with advanced RCC after prior therapy in adults 
3) As monotherapy for the treatment of recurrent or metastatic SCCHN after platinum-based 
therapy 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
47 
Approved v 41.0 
930144776 4.0 
 
 
4) As a single agent for the treatment of patients with BRAF V600 wild-type unresectable or 
metastatic melanoma 
5) For the treatment of adult patients with classical Hodgkin lymphoma that has relapsed or 
progressed after autologous HSCT and brentuximab vedotin, or 3 or more lines of systemic 
therapy that includes autologous HSCT 
6) For the treatment of patients with HCC who have been previously treated with sorafenib 
7) For the treatment of patients with locally advanced or metastatic urothelial carcinoma who 
have disease progression during or following platinum-containing chemotherapy or have 
disease progression within 12 months of neoadjuvant or adjuvant treatment with 
platinum-containing chemotherapy 
8) For the treatment of adult and pediatric (12 years and older) patients with MSI-H or dMMR 
metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, 
oxaliplatin, and irinotecan. Nivolumab 3mg/kg will be used in this study. 
 
Nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg Q3W for 4 cycles followed by 
nivolumab 3 mg/kg Q2W is approved in India and will be used in this study. 
5.8 
Justification for Combination Nivolumab and Ipilimumab Dose 
Nivolumab 3 mg/kg Q3W IV for 30 minutes will be combined with ipilimumab 1 mg/kg Q3W IV 
for 30 minutes for 4 cycles and then switched to nivolumab 3 mg/kg Q2W IV for 30 minutes 
during the maintenance phase, 3 weeks after the last combination dose. 
Data in support of the nivolumab 3 mg/kg Q3W and ipilimumab 1 mg/kg Q3W regimen in RCC 
come from a Phase 2 clinical study (CA209016) and a Phase 3 clinical study (CA209214). 
Data from Study CA209016 demonstrated a level of clinical activity, as measured by ORR, for the 
combination of nivolumab 3 mg/kg Q3W combined with ipilimumab 1 mg/kg Q3W for 4 cycles, 
followed by nivolumab 3 mg/kg Q2W that was substantially greater with an ORR (95% CI) of 
40.4% (26.4 to 55.7) than that observed in a previous phase 3 clinical study (CA209-025) 
evaluating nivolumab 3 mg/kg Q2W with an ORR (95% CI) of 25.1% (21.0 to 29.6). The 
combination dosing regimen of nivolumab 3 mg/kg Q3W combined with ipilimumab 1 mg/kg 
Q3W for 4 cycles, followed by nivolumab monotherapy was chosen because it exhibited a similar 
ORR and a more favorable safety profile than that of nivolumab 1 mg/kg Q3W combined with 
ipilimumab 3 mg/kg Q3W for 4 cycles, followed by nivolumab monotherapy. 
In the Phase 3 clinical study (CA209214), the clinical benefit of OS was demonstrated in the 
intermediate- or poor-risk population (HR 0.63 [99.8% CI: 0.44 to 0.89]) for the nivolumab 
3 mg/kg Q3W combined with ipilimumab 1 mg/kg Q3W regimen dosed for 4 cycles followed by 
nivolumab 3 mg/kg Q2W maintenance compared to sunitinib in 1L RCC. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
48 
Approved v 41.0 
930144776 4.0 
 
 
6 
STUDY POPULATION 
For entry into the study, the following criteria MUST be met. 
6.1 
Inclusion Criteria 
1) Signed Written Informed Consent 
a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC)-approved written ICF in accordance with regulatory and 
institutional guidelines. This must be obtained before the performance of any protocol- 
related procedures that are not part of normal participant care. 
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory tests, biomarker and PK testing, and other requirements of the study. 
2) Type of Participant and Target Disease Characteristics 
a) Histological confirmation of renal cell carcinoma with clear cell component including 
participants who may have sarcomatoid features. Advanced (not amenable to curative 
surgery or radiation therapy) RCC or mRCC with or without prior nephrectomy. 
b) No prior systemic therapy for RCC with the following exception: 
i) One prior adjuvant or neoadjuvant therapy for completely resected RCC (see Exclusion 
2b). These drugs must be discontinued ≥ 6 months prior to study entry. All AEs related 
to prior adjuvant or neoadjuvant therapy must have returned to baseline, and eligible 
patients must not have experienced severe or life-threatening immune-related AEs 
except those that are unlikely to reoccur with standard countermeasures (e.g., hormone 
replacement after adrenal crisis). 
c) Measurable disease lesion by CT or MRI per RECIST 1.1 criteria. Radiated lesions cannot 
be used as measurable lesions unless there is clear evidence of progression. 
d) KPS of at least 70% (see Appendix 7). 
e) Qualifies as intermediate or poor risk by meeting least 1 of the following prognostic factors 
as per the IMDC criteria: 
i) KPS less than 80 
ii) Less than 1 year from diagnosis including original localized disease (if applicable) to 
study enrollment 
iii) Hemoglobin less than the lower limit of normal 
iv) Corrected calcium concentration greater than 10 mg/dL 
v) Absolute neutrophil count greater than the ULN 
vi) Platelet count greater than the ULN 
3) Age and Reproductive Status 
a) Male and female participants must be 18 years or older at the time of informed consent 
(ICF) 
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic 
gonadotropin [HCG]) within 24 hours prior to the start of study treatment. 
c) Women must not be breastfeeding. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
49 
Approved v 41.0 
930144776 4.0 
 
 
d) WOCBP must agree to follow instructions for method(s) of contraception (Appendix 4) for 
the duration of study treatment plus 5 half-lives of study treatment plus 30 days (duration 
of ovulatory cycle) for a total of 5 months after the last dose of study treatment. 
e) No Longer Applicable per Protocol Amendment 01: Males who are sexually active with 
WOCBP must agree to follow instructions for method(s) of contraception and fetal 
protection (Appendix 4) for the duration of treatment with nivolumab and ipilimumab plus 
7 months after the last dose of study treatment. In addition, male participants must be 
willing to refrain from sperm donation during this time. 
f) WOCBP who are continuously not heterosexually active are also exempt from 
contraceptive requirements, and still must undergo pregnancy testing as described in this 
section. 
g) No Longer Applicable per Protocol Amendment 01: Azoospermic males are exempt from 
contraceptive requirements unless the potential exists for fetal toxicity due to study drug 
being present in seminal fluid, even if the participant has undergone a successful vasectomy 
or if the partner is pregnant. 
 
Investigators will counsel WOCBP on the importance of pregnancy prevention and the 
implications of an unexpected pregnancy and when applicable, the potential of fetal toxicity 
occurring due to transmission of study drug, present in seminal fluid, to a developing fetus, even 
if the participant has undergone a successful vasectomy or if the partner is pregnant. Investigators 
will advise on the use of highly effective methods of contraception (Appendix 4) that have a failure 
rate of < 1% when used consistently and correctly. 
4) Other Inclusion Criteria 
a) Indian participants with Indian ethnicity living in India. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
50 
Approved v 41.0 
930144776 4.0 
 
 
6.2 
Exclusion Criteria 
1) Medical History and Concurrent Diseases 
a) Favorable risk as per IMDC classification defined as having none of the 6 risk factors used 
to evaluate IMDC risk score. 
b) Untreated, symptomatic central nervous system (CNS) metastases. Patients are eligible if 
CNS metastases are asymptomatic and do not require immediate treatment, or have been 
treated and patients have neurologically returned to baseline (except for residual signs or 
symptoms related to the CNS treatment). In addition, patients must have been either off 
corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or 
equivalent) for at least 2 weeks prior to enrollment. 
c) Participants with an autoimmune disease, or any other condition, requiring systemic 
treatment with either corticosteroids within 14 days (> 10 mg daily prednisone equivalent) 
or other immunosuppressive medications within 30 days of randomization. Inhaled or 
topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone 
equivalent, are permitted in the absence of active autoimmune disease. 
d) Participants with type I diabetes mellitus, hypothyroidism only requiring hormone 
replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic 
treatment, or conditions not expected to recur in the absence of an external trigger are 
permitted to enroll. 
e) Patients with serious or uncontrolled medical disorder. Previous SARS-CoV-2 infection 
(either suspected or confirmed) within 4 weeks prior to screening. Additionally, in the case 
of prior SARS-CoV-2 infection, acute symptoms must have resolved and based on 
investigator assessment in consultation with the Medical Monitor, there are no sequelae 
that would place the participant at a higher risk of receiving investigational treatment. 
f) Active infection requiring systemic therapy within 14 days of first dose of study drug. 
g) Patients with known human immunodeficiency virus (HIV) who have had an acquired 
immunodeficiency syndrome (AIDS) defining opportunistic infection within the last year, 
or a current CD4 count < 350 cells/µL. NOTE: Testing for HIV must be performed at sites 
where mandated locally (see Appendix 8). Patients enrolled with known HIV need 
monitoring of CD4 counts and viral load during the study and ART therapy administered 
as clinically indicated. 
h) Major surgery (e.g., nephrectomy) less than 28 days prior to the first dose of study 
treatment. 
i) Radiotherapy within 4 weeks except palliative radiation to bone lesions which requires 
2 weeks of washout prior to the first dose of study treatment. 
j) Patients with a concurrent malignancy requiring treatment. Patient with a previously 
treated malignancy are eligible if treatment was completed at least 2 years before 
registration and the patient has no evidence of disease. Patients who have a concurrent 
malignancy that is clinically stable and does not require tumor-directed treatment are also 
eligible. 
k) Presence of any toxicities attributed to prior anti-cancer therapy, other than alopecia, that 
have not resolved to Grade 1 (National Cancer Institute [NCI] CTCAE v4.0) or baseline 
before administration of study treatment. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
51 
Approved v 41.0 
930144776 4.0 
 
 
l) Any condition including medical, emotional, psychiatric, or logistical that, in the opinion 
of the investigator, would preclude the participant from adhering to the protocol or would 
increase the risk associated with study participation or study treatment administration or 
interfere with the interpretation of safety results (e.g., a condition associated with diarrhea 
or acute diverticulitis). 
m) Women who are pregnant or breastfeeding. 
2) Prior/Concomitant Therapy 
a) Use of an investigational agent or an investigational device within 28 days before 
administration of first dose of study treatment 
b) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or 
any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint 
pathways 
c) Prior treatment with a VEGF-targeted agent except when used as a neoadjuvant or adjuvant 
therapy and discontinued ≥ 6 months prior to study entry. 
d) Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese 
medicines) to treat the disease under study within 2 weeks prior to treatment. Refer to 
Section 7.7.1 for prohibited therapies. 
e) Participants who have received a live/attenuated vaccine within 30 days of first treatment. 
f) The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on 
study without restriction. 
g) Participants currently in other interventional trials, including those for COVID-19, may not 
participate in BMS clinical trials until the protocol-specific washout period is achieved. If 
a study participant has received an investigational COVID-19 vaccine or other 
investigational product designed to treat or prevent COVID-19 prior to screening, 
enrollment must be delayed until the biologic impact of the vaccine or investigational 
product is stabilized, as determined by discussion between the Investigator and the Medical 
Monitor. 
3) Physical and Laboratory Test Findings 
a) White blood cells < 2000/mm3 
b) Neutrophils < 1500/mm3 
c) Platelets < 100 × 103/mm3 
d) Hemoglobin < 9.0 g/dL 
e) Serum creatinine > 1.5× ULN, unless calculated creatinine clearance (CrCl) ≥ 40 mL/min 
(using the Cockcroft-Gault formula): 
Female CrCl =  (140 - age in years) × weight in kg × 0.85 
72 × serum creatinine in mg/dL 
Male CrCl =  (140 - age in years) × weight in kg × 1.00 
72 × serum creatinine in mg/dL 
f) AST/ALT: > 3.0× ULN 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
52 
Approved v 41.0 
930144776 4.0 
 
 
g) Tbili > 1.5× ULN (except participants with Gilbert Syndrome who must have a Tbili level 
of < 3.0× ULN) 
h) Serologic evidence of chronic hepatitis B virus (HBV) infection with an HBV viral load 
above the limit of quantification. Patients with chronic HBV infection must be on 
concurrent viral suppressive therapy. 
i) Serologic evidence of current hepatitis C virus (HCV) infection with an HCV viral load 
above the limit of quantification. 
4) Allergies and Adverse Drug Reaction 
a) History of allergy or hypersensitivity to study drug components. 
b) Known history of severe hypersensitivity reaction to any monoclonal antibody. 
5) Other Exclusion Criteria 
a) Prisoners or participants who are 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 BMS approval is required). 
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness. 
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria. 
6.3 
Lifestyle Restrictions 
Not applicable. No restrictions are required. 
6.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, 
to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, as 
applicable, and to respond to queries from regulatory authorities. Minimal information includes 
date of consent, demography, screen failure details, eligibility criteria, and any SAEs. 
6.4.1 
Retesting During Screening or Lead-in Period 
Participant Re-enrollment: This study permits the re-enrollment of a participant who has 
discontinued the study as a pre-treatment failure (ie, participant has not been enrolled / has not 
been treated). If re-enrolled, the participant must be re-consented and assigned a new participant 
number in the IRT. 
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 enrollment is the value by which study inclusion will be assessed, 
as it represents the participant’s most current, clinical state. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
53 
Approved v 41.0 
930144776 4.0 
 
 
Laboratory parameters and/or assessments that are included in the Schedule of Activities in 
Section 2 may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant. 
Testing for asymptomatic SARS-CoV-2 infection, for example by reverse transcription 
polymerase chain reaction (RT-PCR) or viral antigen is not required. However, some participants 
may develop suspected or confirmed symptomatic SARS-CoV-2 infection, or be discovered to 
have asymptomatic SARS-CoV-2 infection during the screening period. In such cases, participants 
may be considered eligible for the study after meeting all inclusion/exclusion criteria related to 
active infection, and after meeting the following criteria: 
• At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive RT-PCR of viral antigen test result, and 
• At least 24 hours have passed since last fever without the use of fever-reducing 
medications, and 
• Acute symptoms (e.g. cough, shortness of breath) have resolved and 
• In the opinion of the investigator, there are no COVID-19-related sequelae that may place 
the participant at a higher risk of receiving investigational treatment, and 
• Negative follow-up SARS-CoV-2 RT-PCR or viral antigen test based on institutional, local 
or regional guidelines. 
 
 
7 
TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device intended to be administered to a study participant according to the study treatment 
allocation. 
Study treatment includes both investigational product (IP)/investigational medicinal product 
(IMP) and non-IP/non-IMP and can consist of the following: 
• Nivolumab concentrate for solution for infusion 
• Ipilimumab concentrate for solution for infusion 
 
An investigational product, also known as investigational medicinal product in some regions, is 
defined as a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form. 
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-IPs. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
54 
Approved v 41.0 
930144776 4.0 
 
 
Medications used to treat BMS-936558 (nivolumab)- and BMS-734016 (ipilimumab)-related 
infusion reactions are (eg, diphenhydramine, acetaminophen/paracetamol, and corticosteroids) 
considered non-IPs and will not be provided by the sponsor. These will be obtained by the 
investigational sites as marketed product, which should be stored in accordance to the package 
insert. For further details related to these medications and nivolumab-related infusion reactions, 
see Section 7.4.3.1. 
Study treatments are listed in Table 7-1. 

 
Clinical Protocol 
CA2097C9 
BMS-936558 
nivolumab 
 
 
Table 7-1: 
Study Treatments for Study CA2097C9 
 
Product Description / 
Class and Dosage Form 
Potency 
IP/ 
Non-IMP 
Blinded or 
Open Label 
Packaging / Appearance 
Storage Conditions 
(per label) 
Nivolumab 
Solution for infusiona,b 
100 mg 
(10 mg/mL concentrate) 
IP 
Open label 
Vial 
(1 or more vials per carton) 
Store at 2°C to 8°C 
Protect from light and freezing 
Ipilimumab 
Solution for infusionb 
50 mg 
(5 mg/mL concentrate) 
IP 
Open label 
Vial 
(1 or more vials per carton) 
Store at 2°C to 8°C 
Protect from light and freezing 
Abbreviations: IP = investigational product; IMP = investigational medicinal product; SmPC = summary of product characteristics 
a May be labeled as “BMS-936558-01” or “nivolumab.” 
b These products may be obtained by the investigational sites as local commercial product in certain countries if allowed by local regulations. In these cases, 
products may be a different pack size/potency than listed in the table. These products should be prepared/stored/administered in accordance with the package 
insert or SmPC. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
55 
Approved v41.0 
930144776 4.0 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
56 
Approved v 41.0 
930144776 4.0 
 
 
7.1 
Treatments Administered 
Participants will receive a combination dosing regimen of nivolumab 3 mg/kg as a 30-minute IV 
infusion + ipilimumab 1 mg/kg as a 30-minute IV infusion Q3W followed by a single-dose agent 
of nivolumab 3 mg/kg Q2W for a maximum of 52 weeks or until treatment is no longer tolerated 
by the participant or withdrawal of consent. The first dose is to be administered within 28 days 
after signing the ICF. Subjects may be dosed up to 3 days after the scheduled date if necessary. 
Dosing calculations should be based on the body weight assessed at baseline. It is not necessary to 
re-calculate subsequent doses if the participant weight is within 10% of the weight used to calculate 
the previous dose. All doses should be rounded up or to the nearest milligram per institutional 
standard. 
There will be no dose escalations or reductions of nivolumab allowed. 
During the combination phase, participants may be dosed no less than 19 days between doses 
during Q3W cycles. During the single agent-maintenance phase, subjects may be dosed no less 
than 12 days from the previous dose during Q2W cycles. 
If dosing is delayed, both nivolumab and ipilimumab must be delayed together. If dosing is 
resumed after a delay, both nivolumab and ipilimumab should be resumed on the same day. 
Subjects may be dosed up to 3 days after the scheduled date if necessary. Subsequent dosing should 
be based on the actual date of administration of the previous dose of drug. 
Premedications are not recommended for the first dose of nivolumab. 
Participants should be carefully monitored for infusion reactions during study treatment 
administration. If an acute infusion reaction is noted, participants should be managed according to 
Section 7.4.3.1. 
Study treatments may be interrupted, delayed, or discontinued depending on how well the 
participant tolerates the treatment. Dosing visits are not skipped, only delayed. 
Please refer to the current India prescribing information (Appendix 5) for further details regarding 
storage, preparation, and administration of nivolumab and/or ipilimumab. 
Separate infusion bags and filters should be used when administering nivolumab and ipilimumab 
on the same day. 
Care must be taken to assure sterility of the prepared solutions, as the drug product does not contain 
any antimicrobial preservatives or bacteriostatic agents. 
The selection and timing of dose for each participant are described in Table 7.1-1. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
57 
Approved v 41.0 
930144776 4.0 
 
 
Table 7.1-1: 
Selection and Timing of Dose 
 
Study Treatment 
Unit Dose 
Strength(s)/Dosage 
Level(s) 
Dosage Formulation 
Frequency of Administration 
Route of 
Administration 
Nivolumab 
3 mg/kg 
Q3W (Cycles 1 to 4) 
Q2W (Cycle 5 onward) 
IV 
Ipilimumab 
1 mg/kg 
Q3W (Cycles 1 to 4) 
IV 
Abbreviations: IV = intravenous; Q2W = every 2 weeks; Q3W = every 3 weeks 
 
 
7.2 
Method of Treatment Assignment 
An IRT will be used to assign participant numbers. 
All participants will be centrally assigned to treatment using the IRT system. Before the study is 
initiated, each user will receive log-in information and directions on how to access the IRT. 
Study treatment will be dispensed at the study visits as listed in Schedule of Activities in Section 2. 
Enrolled participants, including those not dosed, will be assigned sequential participant numbers 
. Those enrolled participants meeting 
inclusion and exclusion criteria will be eligible to be dosed. 
7.3 
Blinding 
This is an open-label study; blinding procedures are not applicable. 
7.4 
Dosage Modification Criteria for Nivolumab and Ipilimumab 
I-O agents are associated with AEs that can differ in type, severity, and duration than AEs caused 
by other therapeutic classes. Nivolumab and ipilimumab are considered I-O agents in this protocol. 
Early recognition and management of AEs associated with I-O agents may mitigate severe toxicity. 
The safety profile of nivolumab and in combination of ipilimumab is described in the India 
prescribing information for nivolumab and ipilimumab. Management of drug-related AE includes 
dose modification and medical interventions, and supportive care should be carefully considered. 
The recommended management algorithms for IMAEs are outlined in the India prescribing 
information (Appendix 5) in the following groups: Gastrointestinal, Renal, Pulmonary, Hepatic, 
Endocrinopathy, Skin, Neurological, and Myocarditis. In general, both nivolumab and ipilimumab 
have similar safety profiles and overlapping IMAEs. The management algorithms and criteria for 
dose delay, resumption, or discontinuation should be applicable for both drugs. Both drugs should 
be delayed, resumed, or discontinued when the criteria are met. 
Dose reductions or dose increases of nivolumab or ipilimumab are not permitted. 
7.4.1 
Dose Delay Criteria for Nivolumab and Ipilimumab 
Nivolumab and ipilimumab administration should be delayed for the following: 
• Grade 2 nonskin, drug-related AE, with the exception of fatigue 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
58 
Approved v 41.0 
930144776 4.0 
 
 
• Grade 2 drug-related creatinine, AST, ALT and/or TBili abnormalities 
• Grade 3 skin, drug-related AE 
• Grade 3 drug-related laboratory abnormality, with the following exceptions: 
− Grade 3 lymphopenia or asymptomatic amylase or lipase does not require 
dose delay 
− Grade ≥ 3 AST, ALT, and TBili will require dose discontinuation (see Section 
7.4.3) 
• Any AE, laboratory abnormality, or intercurrent illness that, in the judgment of the 
investigator, warrants delaying the dose of study medication. 
• SARS-CoV-2 infection, either confirmed or suspected 
 
 
During Cycles 1 through 4, both nivolumab and ipilimumab must be delayed at the same time. 
Participants who require delay of study treatment should be re-evaluated weekly or more frequently 
if clinically indicated and resume study treatment dosing when re-treatment criteria are met. Tumor 
assessments should continue as per protocol even if dosing is delayed. 
The algorithms recommended for utilization in CA2097C9 are included in the India prescribing 
information in Appendix 5. 
7.4.2 
Criteria to Resume Treatment 
Prior to re-initiating treatment in a participant with a dosing delay lasting > 10 weeks for 
nivolumab and > 8 weeks for ipilimumab, the BMS Medical Monitor (or designee) must be 
consulted. Tumor assessments should continue as per protocol even if dosing is delayed. Periodic 
study visits to assess safety and laboratory studies should also continue every 6 weeks or more 
frequently if clinically indicated during such dosing delays. 
Delayed doses of study treatment should be administered as soon as the participant meets criteria 
to resume treatment. If a dose has been delayed, the participant should not wait until the next 
scheduled dosing date. 
Participants may resume treatment with study treatment when the drug-related AE(s) resolve to 
Grade ≤ 1 or baseline value, with the following exceptions: 
• Participants may resume treatment in the presence of Grade 2 fatigue 
• Participants who have not experienced a Grade 3 drug-related skin AE may resume treatment 
in the presence of Grade 2 skin toxicity 
• For participants with Grade 2 AST, ALT and/or Tbili abnormalities, dosing may resume when 
laboratory values return to baseline and management with corticosteroids, if needed, is 
complete. 
• Drug-related pulmonary toxicity, diarrhea, or colitis must have resolved to baseline before 
treatment is resumed. Participants with persistent Grade 1 pneumonitis after completion of a 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
59 
Approved v 41.0 
930144776 4.0 
 
 
steroid taper over at least 1 month may be eligible for re-treatment if discussed with and 
approved by the BMS Medical Monitor (or designee). 
 
Participants with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement may resume treatment after consultation with the BMS Medical Monitor (or 
designee). 
Participants with SARS-CoV-2 infection (either confirmed or suspected) may resume treatment 
after all of the following: 
• at least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive test result (e.g. RT-PCR or viral antigen), 
• resolution of acute symptoms (including at least 24 hours has passed since last fever without 
fever reducing medications), 
• evaluation by the Investigator with confirmation that there are no sequelae that would place 
the participant at a higher risk of receiving investigational treatment, and 
• 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. 
 
7.4.3 
Criteria for Treatment Discontinuation 
The assessment for discontinuation of nivolumab should be made separately from the assessment 
made for discontinuation of ipilimumab. Although there is overlap among the discontinuation 
criteria, if discontinuation criteria are met for ipilimumab but not for nivolumab, treatment with 
nivolumab may continue if ipilimumab is discontinued. 
If a participant in any of the nivolumab/ipilimumab combination arms meets criteria for 
discontinuation and the investigator is unable to determine whether the event is related to both or 
one study drug, the participant should discontinue both nivolumab and ipilimumab and be taken off 
the treatment phase of the study. 
Please refer to Section 7.4.3.1 for discontinuation criteria for nivolumab and Section 7.4.3.1 
for discontinuation criteria for ipilimumab. 
 
7.4.3.1 
Nivolumab Dose Discontinuation 
Nivolumab treatment should be permanently discontinued for the following: 
• Any Grade 2 drug-related uveitis, eye pain, or blurred vision that does not respond to topical 
therapy and does not improve to Grade 1 severity within the re-treatment period OR requires 
systemic treatment 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
60 
Approved v 41.0 
930144776 4.0 
 
 
• Any Grade 3 non-skin, drug-related AE lasting > 7 days, or recurs with the following 
exceptions for laboratory abnormalities, neurologic toxicity, drug-related uveitis, pneumonitis, 
bronchospasm, hypersensitivity reactions, infusion reactions, and endocrinopathies: 
− Grade 3 drug-related uveitis, pneumonitis, bronchospasm, neurologic toxicity, 
myocarditis, hypersensitivity reaction, or infusion reaction of any duration requires 
discontinuation. 
− Grade 3 drug-related endocrinopathies, adequately controlled with only physiologic 
hormone replacement, do not require discontinuation. Adrenal insufficiency requires 
discontinuation regardless of control with hormone replacement. 
− Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation 
except: 
♦ Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding requires 
discontinuation 
♦ Any drug-related liver function test (LFT) abnormality that meets the following criteria 
require discontinuation: 
o Grade ≥ 3 drug-related AST, ALT or Tbili requires discontinuation* 
o Concurrent AST or ALT > 3 x ULN and Tbili > 2 x ULN 
*In most cases of Grade 3 AST or ALT elevation, 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 BMS Medical 
Monitor (or designee) must occur. 
• Any Grade 4 drug-related AE or laboratory abnormality (including but not limited to 
creatinine, AST, ALT, or Tbili), except for the following events, which do not require 
discontinuation: 
− Grade 4 neutropenia ≤ 7 days 
− Grade 4 lymphopenia or leukopenia or asymptomatic amylase or lipase 
− Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 72 hours 
of their onset 
− Grade 4 drug-related endocrinopathy AEs, such as, hyper- or hypothyroidism, or glucose 
intolerance, which resolve or are adequately controlled with physiologic hormone 
replacement (corticosteroids, thyroid hormones) or glucose-controlling agents, 
respectively, may not require discontinuation after discussion with and approval from the 
BMS Medical Monitor. 
• Any event that leads to delay in dosing lasting > 10 weeks 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 > 10 weeks from the previous dose that occur for non-drug-related 
reasons may be allowed if approved by the BMS Medical Monitor (or designee). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
61 
Approved v 41.0 
930144776 4.0 
 
 
• Any AE, laboratory abnormality, or intercurrent illness, which, in the judgment of the 
Investigator, presents a substantial clinical risk to the participant with continued nivolumab 
dosing. 
 
Prior to re-initiating treatment in a participant with a dosing delay lasting > 10 weeks, the BMS 
Medical Monitor (or designee) must be consulted. Tumor assessments should continue as per 
protocol even if dosing is delayed. Periodic study visits to assess safety and laboratory studies 
should also continue Q3W during induction, Q2W during maintenance, or more frequently if 
clinically indicated during such dosing delays. 
7.4.3.2 
Ipilimumab Dose Discontinuation 
Ipilimumab treatment should be permanently discontinued for the following: 
• Any Grade 2 drug-related uveitis, eye pain, or blurred vision that does not respond to topical 
therapy and does not improve to Grade 1 severity within the re-treatment period OR requires 
systemic treatment 
• Any Grade 3 non-skin, drug-related AE lasting > 7 days, or recurs, with the following 
exceptions for laboratory abnormalities, diarrhea, colitis, neurologic toxicity, drug-related 
uveitis, pneumonitis, bronchospasm, hypersensitivity reactions, infusion reactions, and 
endocrinopathies: 
− Grade 3 drug-related diarrhea, colitis, neurologic toxicity, uveitis, pneumonitis, 
bronchospasm, myocarditis, hypersensitivity reaction, or infusion reaction of any duration 
requires discontinuation. 
− Grade 3 drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement do not require discontinuation. Adrenal insufficiency requires 
discontinuation regardless of control with hormone replacement. 
− Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation 
except: 
♦ Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding requires 
discontinuation 
♦ Any drug related LFT abnormality that meets the following criteria requires 
discontinuation: 
o Grade ≥ 3 drug-related AST, ALT, or TBili requires discontinuation* 
o Concurrent AST or ALT > 3 x ULN and TBili > 2 x ULN 
*In most cases of Grade 3 AST or ALT elevation, 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 BMS Medical Monitor (or 
designee) must occur. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
62 
Approved v 41.0 
930144776 4.0 
 
 
• Any Grade 4 drug-related AE or laboratory abnormality (including but not limited to 
creatinine, AST, ALT, and TBili), except for the following events, which do not require 
discontinuation: 
− Grade 4 neutropenia ≤ 7 days 
− Grade 4 lymphopenia or leukopenia or asymptomatic amylase or lipase 
− Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 72 hours 
of their onset 
− Grade 4 drug-related endocrinopathy AEs, such as hyper- or hypothyroidism or glucose 
intolerance, which resolve or are adequately controlled with physiologic hormone 
replacement (eg, corticosteroids, thyroid hormones) or glucose- controlling agents, 
respectively, may not require discontinuation after discussion with and approval from the 
BMS Medical Monitor (or designee). 
• Any event that leads to delay in dosing lasting > 8 weeks 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 > 8 weeks from the previous dose that occur for non-drug- related 
reasons may be allowed if approved by the BMS Medical Monitor (or designee). 
• Any AE, laboratory abnormality, or intercurrent illness that, in the judgment of the investigator, 
presents a substantial clinical risk to the participant with continued ipilimumab dosing. 
 
Prior to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks, the BMS 
Medical Monitor (or designee) must be consulted. Tumor and other assessments should continue 
per protocol even if dosing is delayed. Periodic study visits to assess safety and laboratory studies 
should also continue Q3W during induction, Q2W during maintenance, or more frequently if 
clinically indicated during such dosing delays. 
7.4.4 
Treatment of Related Infusion Reactions 
Because nivolumab and ipilimumab contain only human immunoglobulin protein sequences, it is 
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 or hypertension, bronchospasm, or other allergic-like reactions. All Grade 
3 or 4 infusion reactions should be reported within 24 hours to the study Medical Monitor, or 
designee, and reported as an SAE if it meets the criteria. Infusion reactions should be graded 
according to NCI CTCAE 4.0 guidelines. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
63 
Approved v 41.0 
930144776 4.0 
 
 
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. 
For Grade 2 symptoms (therapy or infusion interruption indicated but responds promptly to 
symptomatic treatment [eg, antihistamines, non-steroidal anti-inflammatory drugs, narcotics, 
IV fluids]; prophylactic medications indicated for ≤ 24 hours). 
• Stop the study drug infusion, begin an IV infusion of normal saline, and treat the participant 
with diphenhydramine 50 mg IV (or equivalent) and/or acetaminophen/paracetamol 325 mg 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 30 minutes, the rate may be 
increased to 100% of the original infusion rate. Monitor participant closely. If symptoms recur, 
then no further study medication will be administered at that visit. 
• For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg 
should be administered at least 30 minutes before nivolumab and/or ipilimumab infusions. If 
necessary, corticosteroids (up to 25 mg of hydrocortisone or equivalent) may be used. 
 
For Grade 3 or Grade 4 symptoms (severe reaction, Grade 3: Prolonged [eg, not rapidly 
responsive to symptomatic medication and/or brief interruption of infusion], recurrence of 
symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4: 
Life-threatening consequences; pressor or ventilatory support indicated). 
• Immediately discontinue infusion of study drug. 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 is comfortable that the symptoms will not recur. Study drug 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). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
64 
Approved v 41.0 
930144776 4.0 
 
 
7.5 
Preparation/Handling/Storage/Accountability 
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study participants. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations. 
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and BMS should be contacted 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 and administration sets). 
Infusion-related supplies (eg, IV bags, in-line filters, and 0.9% sodium chloride solution) will not 
be supplied by the sponsor and should be purchased locally if permitted by local regulations. 
Please refer to the India prescribing information (Appendix 5) for nivolumab or ipilimumab for 
complete storage, handling, dispensing, and infusion information. 
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations. 
Further guidance and information for final disposition of unused study treatment are provided in 
Appendix 2. 
7.5.1 
Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
Not applicable. 
7.6 
Treatment Compliance 
Not applicable because treatment is injected and/or infused. 
7.7 
Concomitant Therapy 
7.7.1 
Prohibited and/or Restricted Treatments 
The following medications are prohibited during the study (unless utilized to treat a drug-related 
AE): 
• Immunosuppressive agents 
• Immunosuppressive doses of systemic corticosteroids (except as stated in Section 7.4.3.1) 
• Any concurrent anti-neoplastic therapy (ie, chemotherapy, hormonal therapy, immunotherapy, 
extensive, non-palliative radiation therapy, or standard or investigational agents for treatment 
of RCC) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
65 
Approved v 41.0 
930144776 4.0 
 
 
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) 
intended to treat the disease under study. Such medications are allowed if they are used as 
supportive care. 
• Any live/attenuated vaccine (eg, varicella, zoster, yellow fever, rotavirus, oral polio, and 
measles, mumps, rubella) during treatment and until 100 days after the last dose. 
 
Antiemetic premedications should not be routinely administered prior to dosing of drugs. See 
Section 7.4.3.1 for premedication recommendations following a nivolumab- or ipilimumab-related 
infusion reaction. 
7.7.2 
Other Restrictions and Precautions 
Participants with a condition requiring systemic treatment with either corticosteroids within 
14 days (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 
30 days of treatment initiation are excluded. Inhaled or topical steroids, and adrenal replacement 
steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active 
autoimmune disease. 
Palliative (limited-field) radiation therapy and palliative surgical resection are permitted, if the 
following criteria are met: 
• The subject will be considered to have progressed at the time of palliative therapy and must 
meet criteria to continue with treatment beyond progression (Section 8.1.1). 
• The case is discussed with the BMS Medical Monitor or Study Director. 
 
7.7.2.1 
Imaging Restriction and Precautions 
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history, and renal status), the appropriate imaging modality and 
contrast regimen per imaging study. Imaging contraindications and contrast risks are to be 
considered in this assessment. Participants with renal insufficiency are to be assessed as to whether 
or not they should receive contrast and if so, which contrast agent and dose is appropriate. Specific 
to MRI, participants with severe renal insufficiency (ie, eGFR < 30 mL/min/1.73 m2) are at 
increased risk of nephrogenic systemic fibrosis, therefore MRI contrast is contraindicated. In 
addition, participants may be excluded from MRI if they have tattoos, metallic implants, 
pacemakers, etc. This will be outlined in the image manual. 
Gentle hydration before and after IV contrast should follow local standard of care. The ultimate 
decision to perform MRI in an individual participant in this study rests with the site radiologist, 
the investigator, and standards set by the local ethics committee. 
7.7.3 
Permitted Therapy 
Concomitant medications are recorded at baseline and throughout the treatment phase of the study 
in the appropriate section of the CRF. All medications (prescriptions or over the counter 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
66 
Approved v 41.0 
930144776 4.0 
 
 
medications) continued at the start of the study or started during the study and different from the 
study drug must be documented in the concomitant therapy section of the CRF. 
Participants are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses > 10 mg 
daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for 
prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions 
(eg, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted. 
7.8 
Post Study Drug Access 
At the conclusion of the study, participants who continue to demonstrate clinical benefit will be 
eligible to receive BMS-supplied study treatment at the duration specified in Section 7.1. Study 
treatment will be provided via an extension of the study, a rollover study requiring approval by 
responsible health authority and ethics committee or through another mechanism at the discretion 
of BMS. In this study, participants who are observed to continue to receive clinical benefit from 
treatment with nivolumab at the end of 52 weeks plus 2 weeks of follow-up, may continue 
treatment via commercial supply, with nivolumab supplied by BMS. 
BMS reserves the right to terminate access to BMS-supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of the treatment 
regimen is terminated for other reasons, including, but not limited to, lack of effectiveness and/or 
not meeting the study objectives; c) the participant can obtain medication from a government- 
sponsored or private health program. In all cases BMS will follow local regulations. 
8 
DISCONTINUATION CRITERIA 
8.1 
Discontinuation from Study Treatment 
The assessment for discontinuation of nivolumab should be made separately from the assessment 
made for discontinuation of ipilimumab. Although there is overlap among the discontinuation 
criteria, if discontinuation criteria are met for ipilimumab but not for nivolumab, treatment with 
nivolumab may continue if ipilimumab is discontinued. 
If a participant in any of the nivolumab/ipilimumab combination arms meets criteria for 
discontinuation and the investigator is unable to determine whether the event is related to both or 
one study drug, the participant should discontinue both nivolumab and ipilimumab and be taken 
off the treatment phase of the study. 
Please refer to Section 7.4.3 for discontinuation criteria for nivolumab and ipilimumab. 
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 the participant 
to provide this information. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
67 
Approved v 41.0 
930144776 4.0 
 
 
• 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 
or compulsory detainment for treatment of either a psychiatric or physical illness 
(eg, infectious disease). (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.) 
− Criteria listed in Section 7.4.2 
• Disease progression of RCC or occurrence of a secondary malignancy that requires systemic 
therapy for treatment. 
• Additional criteria for the discontinuation of nivolumab and ipilimumab as recommended in 
the India prescribing information for nivolumab and ipilimumab (Appendix 5). 
 
Refer to the Schedule of Activities in Section 2 for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that can be completed. 
In the case of pregnancy in a participant, 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). Please call the BMS Medical Monitor within 24 hours 
of awareness of the pregnancy. If the investigator determines a possible favorable benefit/risk ratio 
that warrants continuation or re-initiation of study treatment, a discussion between the investigator 
and the BMS Medical Monitor (or designee) must occur. Refer to Section 9.2.5. 
All participants who discontinue study treatment should comply with protocol specified follow-up 
procedures as outlined in Section 2. 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 through imprisonment or involuntarily incarceration or compulsory 
detainment for the treatment of either a psychiatric or physical illness. 
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page. 
8.1.1 
Nivolumab Treatment Beyond Disease Progression 
Accumulating evidence indicates a minority of participants treated with immunotherapy may 
derive clinical benefit despite initial evidence of progressive disease.29 
Participants will be permitted to continue study treatment beyond initial RECIST 1.1-defined 
(Appendix 9) progressive disease, assessed by the Investigator up to a maximum of 52 weeks from 
date of first dose in Cycle 1 as long as they meet the following criteria: 
• Investigator-assessed clinical benefit. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
68 
Approved v 41.0 
930144776 4.0 
 
 
• 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 nivolumab 
treatment. All other elements of the main consent including description of reasonably 
foreseeable risks or discomforts, or other alternative treatment options will still apply. 
 
If the investigator feels that the participant continues to achieve clinical benefit by continuing 
treatment, the participant should remain on the trial and continue to receive monitoring according 
to Section 2. Radiographic assessment/scan(s) should continue in accordance with the Schedule of 
Activities in Section 2 for the duration of the treatment beyond progression and until a maximum 
of 52 weeks of treatment plus 2 weeks of follow-up or initiation of subsequent systemic cancer 
therapy, withdrawal of consent, death, or investigator-assessed disease progression, whichever 
occurs first. Radiographic assessment/scan(s) should be submitted to the central imaging vendor. 
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 treatment 
with nivolumab. 
For the participants who continue nivolumab study therapy beyond progression, further 
progression is defined as an additional 10% increase in tumor burden with a minimum 5-mm 
absolute increase from time of initial progressive disease. This includes an increase in the sum of 
diameters of all target lesions and/or the diameters of new measurable lesions compared to the 
time of initial progressive disease. It is recommended that study treatment 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 
least15 mm). 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 
15 mm). In situations where the relative increase in total tumor burden by 10% is solely due to 
inclusion of new lesions that become measurable, these new lesions must demonstrate an absolute 
increase of at least 5 mm. 
8.1.2 
Post-study Treatment Study Follow-up 
In this study, incidence of high-grade (CTCAE v4.0 Grade 3 to 4 and Grade 5) IMAEs is a key 
endpoint of the study. Post-study follow-up is of critical importance and is essential to preserving 
participant safety and the integrity of the study. Participants who discontinue study treatment must 
continue to be followed for collection of outcome and/or survival follow-up data as required and 
in line with Section 8 until death or the conclusion of the study. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
69 
Approved v 41.0 
930144776 4.0 
 
 
BMS may request that survival data be collected on all treated participants outside of the 
protocol-defined window (see the Schedule of Activities in Section 2). At the time of this request, 
each participant will be contacted to determine their survival status unless the participant has 
withdrawn consent for all contacts or is lost to follow-up. 
8.2 
Discontinuation from the Study 
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol-specified follow-up procedures. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by the participant to provide this information. 
• Participants should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible. 
• The withdrawal of consent should be explained in detail in the medical records by the 
investigator, as to whether the withdrawal is from further treatment with study treatment only 
or also from study procedures and/or post-treatment study follow-up, and entered on the 
appropriate CRF page. 
• In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law. 
• If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
 
8.3 
Loss 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 
3 documented phone calls, faxes, or emails, as well as lack of response by participant to 
1 registered mail letter. All attempts should be documented in the participant’s medical 
records. 
• If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death. 
• If investigator’s use of 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
70 
Approved v 41.0 
930144776 4.0 
 
 
9 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and timing are summarized in the Schedule of Activities. 
• Protocol waivers or exemptions are not allowed. 
• All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment. 
• Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before enrollment. 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 
laboratories until all study drug-related toxicities resolve, return to baseline, or are deemed 
irreversible. 
If a participant shows pulmonary-related signs (hypoxia or fever) or symptoms (eg, dyspnea, 
cough, or fever) consistent with possible pulmonary AEs, the participant should be immediately 
evaluated to rule out pulmonary toxicity, according to the suspected pulmonary toxicity 
management algorithm in the India prescribing information for nivolumab and ipilimumab 
(Appendix 5). 
Some of the assessments referred to in this section may not be captured as data in the electronic 
case report form (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. 
9.1 
Effectiveness Assessments 
Study evaluations will take place in accordance with the Schedule of Activities (Section 2). 
Baseline assessments should be performed within 28 days prior to the patient receiving the first 
dose, utilizing CT or MRI. In addition to chest, abdomen, pelvis, and brain, all known sites of 
disease should be assessed at baseline. Subjects who cannot receive IV contrast at the start of study 
should be imaged by MRI of abdomen/pelvis with IV contrast and CT of chest without contrast. 
Subsequent assessments should include chest, abdomen, and pelvis, and all known sites of disease 
and should use the same imaging method as was used at baseline. Patients initially imaged with 
CT of chest, abdomen, and pelvis with IV contrast who can no longer receive contrast can be 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
71 
Approved v 41.0 
930144776 4.0 
 
 
monitored by CT of chest, abdomen, and pelvis without IV contrast. Subjects will be evaluated for 
tumor response beginning 12 weeks (±7 days) from dosing and continuing every 8 weeks (±7 days) 
until a maximum of 52 weeks of treatment plus 2 weeks of follow-up or initiation of subsequent 
systemic cancer therapy, withdrawal of consent, death, or investigator-assessed disease 
progression, whichever occurs first. These time points are independent of dosing. Tumor 
assessments for ongoing study treatment decisions will be completed by the investigator using 
RECIST 1.1 criteria. 
9.1.1 
Imaging Assessment for the Study 
Images will be submitted to a central imaging vendor and may undergo BICR at any time during 
the study. Prior to scanning the first participant, sites should be qualified and understand the image 
acquisition guidelines and submission process as outlined in the Imaging Manual provided by the 
central imaging vendor. 
Screening and on-study images should be acquired as outlined in the Schedule of Activities 
(Section 2). 
Any additional imaging that may demonstrate tumor response or progression (including scans 
performed at unscheduled timepoints and/or at an outside institution) should be collected for tumor 
assessment and submitted to the BICR. Tumor assessments at other time points may be performed 
if clinically indicated and should be submitted to the central imaging vendor as soon as possible. 
Unscheduled CT/MRI should be submitted to the central imaging vendor. X-rays and bone scans 
that clearly demonstrate interval progressive disease, for example most commonly as unequivocal 
lesions that are unmistakably new since the prior CT/MRI, should be submitted to the central 
imaging vendor. Otherwise, they do not need to be submitted centrally. 
Consider including brain imaging at baseline if the disease under study is known for developing 
brain metastasis. 
9.1.1.1 
Methods of Measurement 
Contrast-enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known and/or 
suspected sites of disease should be performed for tumor assessments within 28 days prior to first 
dose. Images should be acquired with slice thickness of 5 mm or less with no intervening gap 
(contiguous). Every attempt should be made to image each participant using an identical 
acquisition protocol on the same scanner for all imaging time points. Tumor measurements should 
be made by the same investigator or radiologist for each assessment, whenever possible. Changes 
in tumor measurements and tumor responses to guide ongoing study treatment decisions will be 
assessed by the same investigator, if possible, using the RECIST 1.1 criteria. 
If a participant has a contraindication for CT IV contrast, then a non-contrast CT of the chest and 
a contrast-enhanced MRI of the abdomen, pelvis, and other known/suspected sites of disease 
should be obtained. 
If a participant has a contraindication for both MRI and CT IV contrasts, then 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
72 
Approved v 41.0 
930144776 4.0 
 
 
If a participant has a contraindication for MRI (eg, incompatible pacemaker) in addition to 
contraindication to CT IV contrast, then a non-contrast CT of the chest, abdomen, pelvis, and other 
known/suspected sites of disease is acceptable. 
Use of the CT component of a positron-emission tomography (PET)-CT scanner: Combined 
modality scanning, such as with PET-CT, is increasingly used in clinical care and is a 
modality/technology that is in rapid evolution; therefore, the recommendations outlined here may 
change rather quickly with time. At present, low-dose or attenuation correction CT portions of a 
combined PET-CT are of limited use in anatomically based efficacy assessments, and it is therefore 
suggested that they should not be substituted for dedicated diagnostic contrast-enhanced CT scans 
for anatomically based RECIST 1.1 measurements. However, if a site can document that the CT 
performed as part of a PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and 
oral contrast), then the CT portion of the PET-CT can be used for RECIST 1.1 measurements. 
Note, however, that the PET portion of the CT introduces additional data that may bias an 
investigator if it is not routinely or serially performed. 
Bone scans or PET scans are not adequate for the assessment RECIST 1.1 response in target 
lesions. In selected circumstances where such modalities are the sole method used to assess certain 
non-target organs, those non-target organs may be evaluated less frequently. For example, bone 
scans may need to be repeated only when CR is identified in target disease or when progression in 
bone is suspected. 
Bone scans may be collected per local standards, as clinically indicated. 
MRI of the brain (without and with contrast) should be acquired as outlined in the Schedule of 
Activities in Section 2. CT of the brain (without and with contrast) can be performed if an MRI is 
contraindicated. 
Imaging and Clinical Assessment 
Tumor assessments should continue, as described in Section 2, even if dosing is delayed or 
discontinued. Changes in tumor measurements and tumor responses will be assessed by the same 
investigator using the RECIST 1.1 criteria. Investigators will report the number and size of new 
lesions that appear while on study. The time point of tumor assessments will be reported on the 
eCRF based on the investigator’s assessment using the RECIST 1.1 criteria (see Appendix 9) for 
specifics on RECIST 1.1 criteria to be used in this study. Assessments of PR and CR must be 
confirmed by CT/MRI at least 4 weeks apart after initial documentation of response. A best overall 
response of stable disease requires a minimum of 56 days on study from the date of the first dose 
to the date of the first imaging assessment. 
9.1.2 
Outcomes Research Assessments 
9.1.2.1 
Patient-reported Outcomes 
The evaluation of PROs 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
73 
Approved v 41.0 
930144776 4.0 
 
 
Participants will be asked to complete the NCCN Functional Assessment of Cancer Therapy - 
Kidney Symptom Index (FKSI-19) in the participant’s preferred language when available. 
Participants will complete the FKSI-19 at the site during dosing visits and through the follow-up 
visits. 
The NCCN FKSI-19 is a 19-item scale that measures tumor-specific HrQoL in participants with 
kidney cancer. The symptom index questionnaire includes 3 subscales: disease-related symptoms, 
treatment side effects (TSE), and general function and well-being (FWB). The FKSI-19 uses 
5 Likert-type response categories that range from “not at all” to “very much.” Participants are 
asked to select the response category that best characterizes their response over the last 7 days on 
19 items that include symptoms such as lack of energy, fatigue, appetite, coughing, shortness of 
breath, pain, nausea, and ability to work. 
If exceptional circumstances preclude the continued administration of measures using planned 
modalities, then alternate administration methods may be required, after consultation with the 
Sponsor or the Sponsor’s representative. 
9.1.2.2 
Healthcare Resource Utilization 
Healthcare resource utilization data, associated with medical encounters, will be collected in the 
CRF by the investigator and study-site personnel for all participants throughout the study. 
Protocol-mandated procedures, tests, and encounters are excluded. 
The data collected may be used to conduct exploratory economic analyses and will include: 
• Number and duration of medical care encounters, including surgeries, and other selected 
procedures (inpatient and outpatient) 
• Duration of hospitalization (total days length of stay, including duration by wards; eg, intensive 
care unit) 
• Number and character of diagnostic and therapeutic tests and procedures 
• Outpatient medical encounters and treatments (including physician or emergency room visits, 
tests and procedures, and medications). 
 
9.2 
Adverse Events 
The definitions of an AE or serious adverse event (SAE) can be found in Appendix 3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant's legally authorized representative). 
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. 
All nonserious AEs (not only those deemed to be treatment-related) should be collected 
continuously during the treatment period and for a minimum of 100 days following discontinuation 
of study treatment. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
74 
Approved v 41.0 
930144776 4.0 
 
 
Every AE must be assessed by the investigator with regard to whether it is considered immune 
mediated. For events that are potentially immune mediated, additional information will be 
collected on the participant’s CRF. 
Contacts for SAE reporting are specified in Appendix 3. 
IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component 
for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. 
IMAEs can include events with an alternate etiology, which were exacerbated by the induction of 
autoimmunity. Information supporting the assessment will be collected on the participant’s CRF. 
9.2.1 
Time Period and Frequency for Collecting AE and SAE Information 
The collection of AE information (with the exception of non-serious AEs related to SARS-CoV-2 
infection) should begin at initiation of study treatment until the follow-up contact, at the time points 
specified in the Schedule of Activities. 
The India prescribing information for nivolumab and ipilimumab (Appendix 5) includes the 
Reference Safety Information to determine expectedness of SAEs for expedited reporting. 
Following the participant’s written consent to participate in the study, all SAEs, whether related 
or not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. 
All SAEs and all AEs (SAEs and non-serious AEs) associated with confirmed or suspected 
SARS-CoV-2 infection that occur during the screening period, during treatment, and within 
100 days after treatment discontinuation must be collected. If applicable, SAEs that are related to 
any later protocol-specified procedure (eg, a follow-up skin biopsy) must be collected. 
All SAEs must be collected from the time of signing the consent, including those thought to be 
associated with protocol-specified procedures and within 100 days of discontinuation of dosing 
For participants enrolled and never treated with study drug, SAEs should be collected for 30 days 
from the date of enrollment. 
For participants enrolled and never treated with study drug, SAEs should be collected for 30 days 
from the date of treatment assignment. 
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure (eg, a follow-up skin biopsy). 
• Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF module. 
• All SAEs will be recorded and reported to sponsor or designee within 24 hours, as indicated in 
Appendix 3. 
• The investigator will submit any updated SAE data to the sponsor or designee within 24 hours 
of updated information being available. 
 
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
75 
Approved v 41.0 
930144776 4.0 
 
 
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. 
9.2.2 
Method of Detecting AEs and SAEs 
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AE and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
AEs, when appropriate for the program or protocol. 
Every AE must be assessed by the investigator with regard to whether it is considered immune 
mediated. For events that are potentially immune-mediated, additional information will be 
collected on the participant’s CRF. 
Events with an “Outcome” of death, regardless of the type of event or relationship (ie, including 
study drug toxicity), are required to be also reported as Grade 5 events following the specifications 
below: 
• Events with an outcome of death should be reported with the grade at presentation. 
• No event that was initially reported then later known to have an outcome of death, should have 
the grade changed to Grade 5. 
• A new entry for the same event (PT) should be added as a Grade 5 AE. 
 
9.2.3 
Follow-up of AEs and SAEs 
• Nonserious 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 nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study treatment, as appropriate. 
• All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study. 
 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs 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). 
Further information on follow-up procedures is given in Appendix 3. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
76 
Approved v 41.0 
930144776 4.0 
 
 
9.2.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
product under clinical investigation are met. 
• An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the India prescribing information and will notify the IRB/IEC, if appropriate according to local 
requirements. 
 
The sponsor or designee will be reporting all SAEs to regulatory authorities and ethics committees 
according to local applicable laws. 
All SAEs that occur during the screening period and during the treatment period and within 
100 days after discontinuation of study drug or for a total of 52 weeks and 2 weeks of follow-up 
from first on-study treatment must be collected, as specified in the study design in Section 5.1. 
For participants enrolled and never treated with study drug, SAEs should be collected for 30 days 
from the date of treatment assignment. 
All SAEs after 52 weeks of study duration for participants on commercial nivolumab supply will 
be reported to India Health Authority as part of spontaneous reporting. 
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 
5 half-lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor (or designee) of this event and complete and forward a Pregnancy Surveillance 
Form to the BMS Medical Monitor (or 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 (or 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/IEC, as applicable. 
In most cases, the study treatment will be permanently discontinued in an appropriate manner 
(eg, dose tapering if necessary for participant safety). Please call the BMS Medical Monitor within 
24 hours of awareness of the pregnancy. 
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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
77 
Approved v 41.0 
930144776 4.0 
 
 
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 ICF 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 (eg, vaginal, anal, or 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 the sponsor or designee to collect any pregnancy surveillance information from the female 
partner, the female partner(s) must sign an ICF 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 nonserious AE CRF 
page or electronic SAE Report Form, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning. 
• Any laboratory test result that is clinically significant or meets the definition of an SAE 
• Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted 
• Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy 
 
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value). 
9.2.7 
Potential Drug-induced Liver Injury (DILI) 
Specific criteria for identifying potential DILI have not been identified for this protocol. Standard 
medical practice in identifying and monitoring hepatic issues should be followed. 
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 Section 9.2.7 and Appendix 3 for reporting 
details). 
Potential drug induced liver injury is defined as: 
1) Aminotransferases (ALT or AST) elevation > 3× ULN, and 
2) Tbili > 2× ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase), 
and 
3) no other immediately apparent possible causes of aminotransferase elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
78 
Approved v 41.0 
930144776 4.0 
 
 
9.2.8 
Other Safety Considerations 
Any significant worsening noted during interim or final physical examinations, electrocardiogram, 
X-ray filming, or any other potential safety assessment required or not required by the protocol 
should also be recorded as a nonserious or serious AE, as appropriate, and reported accordingly. 
9.3 
Overdose 
For this study, an overdose is defined as any treatment administered to a subject that is greater than 
125% of the protocol intended dose. 
In the event of an overdose the investigator should: 
1) Contact the Medical Monitor immediately. 
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 Medical Monitor based on the clinical evaluation of the participant. 
9.4 
Clinical Safety 
Safety will be assessed from the screening period, during the treatment phase, and, for those 
participants who discontinue treatment before 52 weeks, during the follow-up period. Safety 
assessments include physical examination, vital signs, AE/SAE assessments, recording of 
concomitant medications, and laboratory assessments. For WOCBP, a pregnancy test (serum or 
urine) is also required 24 hours prior to the first dose and at least monthly during the treatment 
phase of the study. 
Data analyses will be conducted only on the safety data collected within the maximum of the 
52-week study period and 2-week follow-up, which will include safety data collected during the 
follow-up of participants who discontinue treatment before 52 weeks. 
All SAEs after 52 weeks of study duration for patients on commercial nivolumab supply will be 
reported to India Health Authority as part of spontaneous reporting. 
Planned time points for all safety assessments are listed in the Schedule of Activities. 
9.4.1 
Physical Examinations 
Refer to the Schedule of Activities. 
9.4.2 
Vital Signs 
Refer to the Schedule of Activities. 
9.4.3 
Electrocardiograms 
Refer to the Schedule of Activities. 
9.4.4 
Clinical Safety Laboratory Assessments 
• Investigators must document their review of each laboratory safety report. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
79 
Approved v 41.0 
930144776 4.0 
 
 
• The schedule of laboratory assessment to be conducted at screening, during treatment, and 
during follow-up for those participants who discontinue treatment before 52 weeks of 
treatment is presented in the Schedule of Activities. Specific laboratory assessments to be 
performed throughout the study are listed in Table 9.4.4-1. 
 
 
Table 9.4.4-1: 
CA2097C9 - Laboratory Assessments 
 
Hematology - Complete Blood Count (CBC) with Differential 
Hemoglobin 
Hematocrit 
Total leukocyte count, including differential 
Platelet count 
Chemistry 
Aspartate aminotransferase 
Alanine aminotransferase 
Total bilirubin 
Alkaline phosphatase 
Lactate dehydrogenase 
Creatinine 
Blood urea nitrogen or serum urea 
Glucose 
Albumin - screening only 
Sodium 
Potassium 
Chloride 
Calcium (also Ca corrected at screening) 
Phosphorus 
Magnesium 
TSH, free T3 and free T4 - screening 
TSH, with reflexive fT3 and fT4 if TSH is abnormal - on treatment 
Serology 
Hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV Ab) or HCV RNA (screening only) 
Human immunodeficiency virus (HIV) if mandated locally 
Other Analyses 
Pregnancy test (WOCBP only: minimum sensitivity 25 IU/L or equivalent units of HCG) 
Follicle-stimulating hormone screening - only required to confirm menopause in women < 55years of age 
Abbreviations: HCG = human chorionic gonadotropin; IU = international unit; T3 = triiodothyronine, T4 = thyroxine; 
Tbili = total bilirubin; TSH = thyroid-stimulating hormone, WOCBP = women of childbearing potential 
 
 
9.4.5 
Imaging Safety Assessment 
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the investigator as per standard 
medical/clinical judgment. 
9.5 
Pharmacokinetics 
Samples for PK and immunogenicity assessment will be collected for participants at the time 
points indicated in Table 9.5-1. All on-treatment PK time points are intended to align with days 
on which study treatment is administered. If it is known that a dose is going to be delayed, then 
the predose sample should be collected just prior to the delayed dose. However, if a predose sample 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
80 
Approved v 41.0 
930144776 4.0 
 
 
is collected but the dose is subsequently delayed, an additional predose sample should not be 
collected. 
Serum concentration analyses for nivolumab and ipilimumab will be performed by validated 
bioanalytical methods. Further details of sample collection, processing, and shipment will be 
provided in the laboratory procedures manual. See Section 9.7.5 for information regarding 
immunogenicity information. 
Bioanalytical samples designated for assessments (eg, immunogenicity, PK, or biomarker) from 
the same collection time point may be used interchangeably for analyses, if required (eg, 
insufficient volume for complete assessment, to follow-up on suspected immunogenicity-related 
AE, etc). 
Additionally, residual bioanalytical samples will be archived and may be used for potential 
exploratory bioanalysis (including, but not limited to, analysis of drug-antidrug antibody (ADA) 
immune complexes, metabolite analyses, etc) and or for additional method purposes (including, but 
not limited to, cross-validation, ADA/PK selectivity, cut point, etc). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
81 
Approved v41.0 
930144776 4.0 
 
 
Table 9.5-1: 
Pharmacokinetic (PK) and Immunogenicity Sample Collections 
 
Study Day of Sample 
Collectiona 
1 cycle = 3 weeks for first 
4 cycles and 2 weeks starting at 
Cycle 5 Day 1 
Event Relative 
To Nivolumab 
Dosing 
(Hour) 
Time Relative 
To Nivolumab 
Dosing 
(Hour: Min) 
Nivolumab 
Pharmacokinetic 
Serum Sample 
Nivolumab 
Immunogenicity 
Serum Sample 
Ipilimumab 
Pharmacokinetic 
Serum Sample 
Ipilimumab 
Immunogenicity 
Serum Sample 
Cycle 1 Day 1 
Predoseb 
00:00 
X 
X 
X 
X 
EOIc 
See Note (c) 
X 
X 
Cycle 2 Day 1 
Predoseb 
00:00 
X 
X 
X 
X 
Cycle 3 Day 1 
Predoseb 
00:00 
X 
X 
X 
X 
Cycle 4 Day 1 
Predoseb 
00:00 
X 
X 
X 
X 
EOIc 
See Note (c) 
X 
X 
Cycle 5 Day 1 (1st nivolumab 
Maintenance Dose) 
Predoseb 
00:00 
X 
X 
X 
X 
Every 8 cycles starting at Cycle 
13 Day 1 up to 52 weeks 
Predoseb 
00:00 
X 
X 
- 
- 
Follow-up 1: approximately 
30 days after last dose 
X 
X 
Xd 
Xd 
Follow-up 2: approximately 
100 days after last dose 
X 
X 
Xd 
Xd 
a If a subject permanently discontinues study drug treatment during the sampling period, they will move to sampling at the follow-up visits. If ipilimumab is 
discontinued and nivolumab continues, ipilimumab PK and ADA should be collected only for the next 2 time points (corresponding to nivolumab sample 
collection) according to the PK table. 
b Predose: All predose samples for nivolumab and ipilimumab should be taken just before the start of nivolumab infusion (preferably within 30 minutes). If it is 
known that a dose is going to be delayed, then the predose sample should be collected just prior to the delayed dose. However, if a predose sample is collected 
but the dose is subsequently delayed, an additional predose sample should not be collected. 
c 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 sample for both nivolumab and ipilimumab when all of the ipilimumab study drug (which is administered after nivolumab) has been infused. If the site 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
82 
Approved v41.0 
930144776 4.0 
 
 
infuses drug without a flush, then collect the EOI-PK samples within approximately 5 minutes after end of infusion of ipilimumab. If a subsequent flush is 
administered to clear the IV lines of ipilimumab and to ensure delivery of the entire drug dose, then draw the EOI-PK sample within approximately 5 minutes 
after end of the flush. EOI or predose samples may not be collected from the same IV access as the drug was administered 
d Ipilimumab follow-up samples are only to be collected if a subject discontinues treatment prior to Cycle 7. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
83 
Approved v 41.0 
930144776 4.0 
 
 
9.6 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
9.7 
Pharmacogenomics 
Not applicable. 
9.7.1 
Biomarkers 
Table 9.7.1-1: 
Biomarker Samples and Schedule of Collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: 
respiratory syndrome coronavirus 2; 
b To be collected at Screening or Predose Cycle 1 Day 1 
Study Day of Sample Collection 
1 cycle = 3 weeks for first 4 cycles and 
2 weeks starting at Cycle 5 Day 1 
SARS-CoV-2 
Serologya 
Screening 
Xb 
On-Treatment Collections 
Approximately every 6 months (eg, Cycle 
11 Day 1, Cycle 23 Day 1, etc.) 
X 
Approximately 4 weeks after confirmed or 
suspected SARS-CoV-2 infection 
X 
Follow-Up Visit 1 
X 
; SARS-CoV-2 = severe acute 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
84 
Approved v 41.0 
930144776 4.0 
 
 
 
 
 
 
 
 
 
 
Serum will be collected for potential future measurements of anti-SARS-CoV-2 antibodies by 
serology (anti-SARS-CoV-2 total or IgG) to explore potential association with safety, 
effectiveness and/or immune biomarkers. 
9.7.3 
Exploratory 
Biomarkers 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
85 
Approved v 41.0 
930144776 4.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.7.5 
Immunogenicity Assessments 
Blood samples for immunogenicity analysis will be collected according to the schedule given in 
Section 9.5. Samples collected will be evaluated for development of anti-drug antibody (ADA) by 
a validated electrochemiluminescent immunoassay. Samples may also be analyzed for neutralizing 
antibodies, and PK samples may be used for ADA analysis in the event of insufficient volume, to 
complete immunogenicity assessment, or to follow up on suspected immunogenicity-related AEs. 
Further details of sample collection, processing, and shipment will be provided in the laboratory 
procedures manual. 
10 
STATISTICAL CONSIDERATIONS 
10.1 
Sample Size Determination 
The sample size of the study is mainly determined by the feasibility concern. The study plans to 
treat 100 participants. The summary of 95% exact CIs and the corresponding half widths of the 
CIs by different levels of the assumed high-grade IMAEs rate (1% to 60%) is presented in Table 
10.1-1. The maximum half width of the exact 2-sided 95% CI is 10.2% when the high-grade 
IMAEs rate is expected to be in the 1% to 60% range. The precision is deemed acceptable in 
evaluating the research hypotheses with respect to the study of this cohort in terms of high-grade 
IMAEs rates. 
Study CA209214 reports that the combination treatment arm had 45.9% high-grade (CTCAE v4.0 
Grades 3 to 4 and Grade 5) drug-related AEs in intermediate or poor risk subjects. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
86 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 10.1-1: 
95% Exact CI and Half Width by Different High-grade IMAEs 
Rates for 100 Treated Participants 
 
Incidence of High- 
grade IMAEs (%) 
Sample size (n) 
Lower bound of 
95% CI 
Upper bound of 
95% CI 
Half width of 95% 
CI 
1 
100 
0.0 
5.4 
2.7 
5 
100 
1.6 
11.3 
4.8 
10 
100 
4.9 
17.6 
6.4 
20 
100 
12.7 
29.2 
8.3 
30 
100 
21.2 
40.0 
9.4 
40 
100 
30.3 
50.3 
10.0 
50 
100 
39.8 
60.2 
10.2 
60 
100 
49.7 
69.7 
10.0 
Abbreviations: CI = confidence interval; IMAE = immune-mediated adverse event 
 
The total duration of the study from enrollment to final analysis is expected to be 36 months 
(52 weeks of patients treatment + 24 months for patient accrual), assuming a fixed accrual rate of 
approximately 5 subjects per month. 
10.2 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
 
Population 
Description 
All enrolled participants 
All participants who sign informed consent and were registered into the IRT. 
All treated participants 
All participants who received any nivolumab in combination with ipilimumab. 
This is the primary population for safety and effectiveness analysis, except 
TTR and DOR endpoints. Analyses of patient-reported outcomes will be based 
on this population. 
All response evaluable 
participants 
All treated participants who have measurable disease at baseline and at least 
one on-study assessment. TTR and DOR analyses will be based on this 
population. 
 
10.3 
Statistical Analyses 
The statistical analysis plan will be developed and finalized before database lock and will detail 
the selection of participants to be included in the analyses, and procedures to be used for analysis. 
Below is a summary of planned statistical analyses of the primary and secondary endpoints. 
The study is intended to provide information regarding the safety profile for participants in India 
and will contribute additional information to the overall safety profile of nivolumab in combination 
with ipilimumab. Due to the small sample size, this study should not be directly compared to the 
data from any other country. 
Unless specified otherwise, all analyses will be tabulated. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
87 
Approved v 41.0 
930144776 4.0 
 
 
A description of the participant population will be included in a statistical output report, including 
subgroups of age and gender. 
10.3.1 
Effectiveness Analyses 
 
Endpoint 
Statistical Analysis Methods 
Primary 
Not applicable. 
Secondary 
The ORR is defined as the number of response evaluable subjects whose confirmed best objective 
(BOR) response is a complete response (CR) or partial response (PR) divided by the number of all 
response evaluable subjects. Assessments of PR and CR must be confirmed by CT/MRI at least 4 
weeks apart after initial documentation of response. The BOR is defined as the best response, as 
determined per RECIST 1.1. For subjects without document progression or subsequent therapy, 
all available time point responses will contribute to the BOR determination. Subsequent therapy 
includes anticancer therapy, tumor directed radiotherapy, or tumor directed surgery. The BOR 
will be determined based on response designations up to the date of last evaluable tumor 
assessment prior to initiation of the subsequent therapy. The ORR will be summarized by 
binomial response rates and their corresponding 2-sided 95% exact CIs using the Clopper-Pearson 
method. This analysis will be performed for all treated participants. 
TTR is analyzed for all evaluable participants who achieved a confirmed PR or CR. Time to 
tumor response, which does not involve censoring, will be summarized using descriptive 
statistics. 
The assessed DOR will be summarized for all response-evaluable participants who achieve 
confirmed PR or CR using the Kaplan-Meier (KM) product-limit method. Median values of DOR, 
along with 2-sided 95% CI using Brookmeyer and Crowley method, will also be calculated. In 
addition, the percentage of responders still in response at different time points (3 and 6 months 
and at end of study) will be presented based on the DOR KM plot. 
Exploratory 
PFS will be summarized by KM product-limit method for all treated participants. Median values 
of PFS, along with 2-sided 95% CI using Brookmeyer and Crowley method, will be calculated. 
OS will be summarized by KM product-limit method for all treated participants and all 
response-evaluable participants, respectively. Median values of OS, along with 2-sided 95% CI 
using Brookmeyer and Crowley method, will be calculated. Survival rates at 6 and 12 months will 
also be estimated using KM estimates for all treated participants. Associated 2-sided 95% CIs will 
be calculated using the Greenwood formula. 
 
 
10.3.2 
Safety Analyses 
Data analyses will be conducted only on the safety data collected within the maximum of the 
52 week and 2-week follow-up study period, which will include safety collected during the follow- 
up of participants who discontinue treatment before 52 weeks. 
Immune-mediated Adverse Events 
Analyses of IMAEs will be conducted to further characterize AEs of special clinical interest. 
IMAEs are defined as specific events (or groups of Preferred Terms [PTs] describing specific 
events) that include diarrhea/colitis, hepatitis, pneumonitis, nephritis and renal dysfunction, rash, 
and endocrine (adrenal insufficiency, hypophysitis, hypothyroidism/thyroiditis, hyperthyroidism, 
and diabetes mellitus). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
88 
Approved v 41.0 
930144776 4.0 
 
 
IMAE analyses includes events, regardless of causality, occurring throughout study and follow-up. 
These analyses are limited to subjects who received immune-modulating medication for treatment 
of the event, with the exception of endocrine events (adrenal insufficiency, hypophysitis, 
hypothyroidism/thyroiditis, hyperthyroidism, and diabetes mellitus), which will be included in the 
analysis regardless of treatment since these events are often managed without immunosuppression. 
Specific evaluations for autoimmune endocrinopathies are not required or collected systematically. 
Therefore, specific laboratory criteria are not required to meet the case definition of endocrine 
IMAEs. 
All SAEs after 52 weeks of study duration for participants on commercial nivolumab supply will 
be reported to India Health Authority as part of spontaneous reporting. 
 
Endpoint 
Statistical Analysis Methods 
Primary 
The incidence for high grade (CTCAE v4.0 Grade 3 to 4 and Grade 5) IMAEs will be 
summarized by immune-mediated category. 
Secondary 
Additional descriptive statistics of high grade (CTCAE v4.0 Grade 3 to 4 and Grade 5) IMAEs 
will include median values using the KM product-limit method with 95% CI using Brookmeyer 
and Crowley method of time to onset and time to resolution, and will be presented for all 
treated participants by immune-mediated category. Time to onset is calculated from first dosing 
date to the event onset date. If a participant never experienced the given AE, the participant will 
be censored at the last contact date. Time to resolution is calculated from the AE onset date to 
AE end date. If an AE is ongoing at the time of analysis, the time to resolution will be censored 
at the last contact date. 
Management of high-grade (CTCAE v4.0 Grade 3 to 4 and Grade 5) IMAEs for each 
immune-mediated category will be characterized by measuring the percentage of participants 
who received immune-modulating medication (or hormonal replacement therapy), percentage 
of participants who received ≥ 40 mg prednisone equivalents, and total duration of all immune- 
modulating medications given for the event, in all treated participants who have experienced 
high-grade (CTCAE v4.0 Grade 3 to 4 and Grade 5) IMAEs. 
Exploratory 
All safety data will be summarized and listed for all treated participants. All on-study AEs, 
SAEs, treatment-related AEs, and treatment-related SAEs will be summarized using worst 
grade per NCI CTCAE v4.0 by system organ class and preferred term. On-study laboratory 
abnormalities including hematology, chemistry, liver function, thyroid function, and renal 
function will be summarized using worst grade per NCI CTCAE v4.0 criteria. 
 
10.3.3 
Pharmacokinetic Analysis 
The nivolumab and ipilimumab concentration data obtained in this study may be combined with 
data from other studies in the clinical development program to develop population PK models. 
These models may be used to evaluate the effects of intrinsic and extrinsic covariates on the PK 
of nivolumab and to determine measures of individual exposure (such as steady state peak, trough, 
and time-averaged concentration). Model-determined exposures may be used for exposure- 
response analyses of selected effectiveness and safety endpoints. If the analyses are conducted, the 
results of population PK and exposure response analyses will be reported separately. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
89 
Approved v 41.0 
930144776 4.0 
 
 
10.3.4 
Immunogenicity Analysis 
Methodology for analysis of immunogenicity will be described in the statistical analysis plan. 
10.3.5 
Biomarker Analyses 
 
 
PK and biomarker exploratory analyses will be described in the statistical analysis plan finalized 
before database lock. The population PK analysis and biomarker analyses will be presented 
separately from the main clinical study report. 
10.3.6 
Health Outcomes Assessment Analyses 
PRO measures include FKSI-19. Summary statistics for PRO measures at each assessment point 
will be provided. The mean change from baseline will also be reported at each post-baseline 
assessment point as well as completion rates. 
Clinically meaningful score changes (from baseline) reported in the literature are used to define 
improvement and deterioration. Table 10.3.6-1 provides the thresholds for clinically meaningful 
score changes to be used for the PRO scales in this study. For domains without clinically 
meaningful score changes in the literature, threshold values will be derived using the general guide 
for calculating thresholds for FACIT instruments provided by Yost and Eton (2005).30 
 
Table 10.3.6-1: 
Threshold Values for Change Scores Judged to Be Important to 
Participants 
 
Instruments and Domains 
Thresholds Reported in the Literature 
 
FKSI-19 
Total Score 
Disease Related Symptoms Score 
Disease Related Symptoms Emotional Score 
Disease Related Symptoms Physical Score 
Functional Well Being Score 
Treatment Side Effects Score 
-- 
2-331,32 
-- 
-- 
-- 
-- 
 
 
 
10.3.7 
Interim Analyses 
Not applicable. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
90 
Approved v 41.0 
930144776 4.0 
 
 
11 
REFERENCES 
 
 
1 
Manual of Urologic Malignancies AAIMS. Kumar, L. 
https://www.aiims.edu/aiims/notices/Manual%20of%20Urologic%20Malignancies%20final. 
pdf 
2 
Fisher R, Gore M, Larkin J. Current and future systemic treatments for renal cell carcinoma. 
3 
Seminars in Cancer Biology. 2013 23 1: 38-45. 
4 
Lam JS, Shvarts O, Leppert JT, et al. Renal cell carcinoma 2005: new frontiers in staging, 
prognostication and target molecular therapy.J of Urology. 2005; 173(6):1853-1862. 
5 
Escudier B, Porta C, Schmidinger M. et al. Renal cell carcinoma: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2014) 25 (suppl 3): iii49- iii56. 
6 
Bharthuar A. Metastatic renal cell carcinoma: Current scenario and future trends. South Asian 
J Cancer. 2012 Jul-Sep; 1(1): 30-35. 
7 
Motzer RJ, Tannir NM. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal Cell 
Carcinoma . N. Engl J. Med. 2018. doi: 10.1056/NEJMoa1712126. 
8 
Bray F, Ferlay J, Soerjomataram I, et al. CA: Cancer J Clin. 2018;68:394-424. 
9 
Globican Data 2018. May 2019. The Global Cancer Observatory. 
10 Rudresha AH, Chaudhuri T, Lakshmaiah KC, Babu KG, Lokanatha D, Jacob LA, et al. First- 
line tyrosine kinase inhibitors in metastatic renal cell carcinoma: A regional cancer center 
experience. Indian J Cancer 2017;54:626-30. 
11 Motzer RJ, Mazumdar M, Bacik J, et al. Survival and prognostic stratification of 670 patients 
with advanced renal cell carcinoma. J Clin Oncol 1999;17(8):2530-40. 
12 Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with 
metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: 
results from a large, multicenter study. J Clin Oncol 2009;27(34):5794-9. 
13 Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of 
the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a 
population-based study. Lancet Oncol 2013;14(2):141-8. 
14  Aldesleukin (IL-2) US Prescribing Information, April 2010. 
15 Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 subjects with metastatic 
renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin. Oncol. 
1995; 139: 688-696. 
16 Coppin C, Porzsolt F, Autenrieth M., Kumpf J., Coldman A., Wilt T., Immunotherapy for 
advanced renal cell cancer (Review). The Cochrane Library. 2008, Issue 4. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
91 
Approved v 41.0 
930144776 4.0 
 
 
 
 
17  Interferon alfa-2b, recombinant, Prescribing Information, August 2009. 
18 Mulders P. Vascular endothelial growth factor and mTOR pathways in renal cell carcinoma: 
differences and synergies of two targeted mechanisms. BJU Int 2009; 104(11):1585-1589. 
19 NCCN Clinical Practice Guidelines in Oncology; Kidney Cancer. Version 2.2014. Accessed 
at http://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf on 2-April-2014. 
20 Escudier B, Eisen T, et al. Renal cell carcinoma: ESMO Clinical Practice Guidelines for 
diagnosis, treatment and follow-up. Ann Oncol 2012; 23 Suppl 7 vii65-71. 
21 Schadendorf D, et al. Efficacy and quality of life outcomes in patients with advanced 
melanoma (MEL) who discontinued treatment with nivolumab (NIVO) plus ipilimumab (IPI) 
due to toxicity in a phase III trial (CheckMate 067). 2016 Annual Meeting of the European 
Association of Dermato-Oncology; August 31-September 3, 2016; Vienna, Austria. 
22 BMS-936558: A randomized, blinded, Phase 2 dose-ranging study of nivolumab (MDX-1106, 
BMS-936558) in subjects with progressive advanced/metastatic clear-cell renal cell carcinoma 
(RCC) who have received prior anti-angiogenic therapy; Final Clinical Study Report for Study 
CA209010. Bristol-Myers Squibb Company; 2013. Document Control No. 930074316. 
23 McDermott DF, Lee JL, Szczylik C, et al. Pembrolizumab monotherapy as first-line therapy 
in advanced clear cell renal cell carcinoma (accRCC): Results from cohort A of KEYNOTE- 
427. J Clin Oncol 2018;36 (suppl; abstr 4500). 
24 Atkins MB, McDermott DF, Powles T, et al. IMmotion150: a phase II trial in untreated 
metastatic renal cell carcinoma (mRCC) patients (pts) of atezolizumab (atezo) and 
bevacizumab (bev) vs and following atezo or sunitinib. J Clin Oncol. 2017;35 (suppl; abstr 
4505). 
25 BMS-936558: A phase 1 study of nivolumab (BMS-936558) plus sunitinib, pazopanib or 
ipilimumab in subjects with metastatic renal cell carcinoma; Final Clinical Study Report for 
Study CA209016. Bristol-Myers Squibb Company; 2016. Document Control No. 930108520. 
26 BMS-936558: A phase 3, randomized, open-label study of nivolumab combined with 
ipilimumab versus sunitinib monotherapy in subjects with previously untreated, advanced or 
metastatic renal cell carcinoma; Final Clinical Study Report for Study CA209214. Bristol- 
Myers Squibb Company; 2017. Document Control No. 930118548. 
27 A Phase 2 Open-label Study of Single Agent Ipilimumab for the Treatment of IL-2 Refractory 
or IL-2 Ineligible Patients with Stage IV Renal Cancer; NCT00057889; Final Clinical Study 
Report 930025954 v1.0 (28-January-2008). 
28 Final Clinical Study Report for Study CA209214: A phase 3, randomized, open-label study of 
nivolumab combined with ipilimumab versus sunitinib monotherapy in subjects with 
previously untreated, advanced or metastatic renal cell carcinoma. Bristol-Myers Squibb 
Company, 2016. Document Control No. 930118548. 
29 Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands 
infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. 
PNAS 2010; 107: 4275-80. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
92 
Approved v 41.0 
930144776 4.0 
 
 
 
 
30 Yost and Eton (2005). Combining distribution and anchor-based approaches to determine 
minimally important differences. The FACIT experience. Eval Health Prof 28: 172. 
31 Motzer RJ, Escudier B, Oudard S et al. Efficacy of everolimus in advanced renal cell 
carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 
2008;372(9637):449–456. 
32 Cella D, Yount S, Brucker PS et al. Development and validation of a scale to measure disease- 
related symptoms of kidney cancer. Value Health 2007; 10:285–293c. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
93 
Approved v 41.0 
930144776 4.0 
 
 
 
12 
APPENDICES 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
94 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 1 
ABBREVIATIONS AND TRADEMARKS 
 
Term 
Definition 
1L RCC 
first-line renal cell carcinoma 
2L RCC 
second-line renal cell carcinoma 
ADA 
antidrug antibody 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BICR 
blinded independent central review 
BMS 
Bristol-Myers Squibb 
BP 
blood pressure 
BUN 
blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CBC 
complete blood count 
CD 
cluster of differentiation 
CI 
confidence interval 
CL 
clearance 
CrCl 
creatinine clearance 
CLss 
steady-state clearance 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CNS 
central nervous system 
CRF 
case report form 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte antigen 4 
CV% 
percent coefficient of variation 
dMMR 
mismatch repair deficient 
DOR 
duration of response 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
95 
Approved v 41.0 
930144776 4.0 
 
 
 
Term 
Definition 
EU 
European Union 
 
 
FKSI-19 
Funtional Assesment of Cancer Therapy - Kidney Symptom Index 
HBV 
hepatitis B virus 
HBVsAg 
hepatitis B virus surface antigen 
HCC 
hepatocellular carcinoma 
HCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
HIFα 
hypoxia inducible factor alpha 
HIV 
human immunodeficiency virus 
HR 
hazard ratio 
HSCT 
hematopoietic stem cell transplantation 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G 
IMAE 
immune-mediated adverse event 
IMDC 
International Metastatic RCC Database Consortium 
IMP 
investigational medicinal product 
IP 
investigational product 
IRB 
Institutional Review Board 
IRRC 
Independent Radiology Review Committee 
IRT 
Interactive Response Technology 
IU 
international unit 
IV 
intravenous(ly) 
KM 
Kaplan-Meier 
KPS 
Karnofsky Performance Status 
LDH 
lactate dehydrogenase 
LFT 
liver function test 
mRCC 
metastatic renal cell carcinoma 
MRI 
magnetic resonance imaging 
MSI-H 
microsatellite instability-high 
MSKCC 
Memorial Sloan-Kettering Cancer Center 
mTOR 
mammalian target of rapamycin 
NCCN 
National Comprehensive Cancer Network 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
96 
Approved v 41.0 
930144776 4.0 
 
 
 
Term 
Definition 
NCI 
National Cancer Institute 
NSCLC 
non-small cell lung cancer 
ORR 
objective response rate 
OS 
overall survival 
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 
pharmacokinetic(s) 
PR 
partial response 
PRO 
patient-reported outcome 
Q2W 
every 2 weeks 
Q3W 
every 3 weeks 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RR 
respiratory rate 
RT-PCR 
reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SCCHN 
squamous cell carcinoma of the head and neck 
Tbili 
total bilirubin 
TSH 
thyroid-stimulating hormone 
TTR 
time to response 
ULN 
upper limit of normal 
US 
United States 
VEGF 
vascular endothelial growth factor 
WOCBP 
women of childbearing potential 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
97 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 2 
STUDY GOVERANCE 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 electronic case report form (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 Guidelines Good Clinical Practice (GCP), 
• as defined by the International Council f or Harmonisation (ICH) 
• in accordance with the ethical principles underlying European Union Directive 2001/20/EC 
• United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
• applicable local requirements. 
 
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study. 
All potential serious breaches must be reported to Sponsor or designee immediately. A breach of 
the conditions and principles of Good Clinical Practice (GCP) (occurring in any country) in 
connection with that trial or the protocol related to the trial which is likely to affect to a significant 
degree the safety or physical or mental integrity of 1 or more subjects of the trial or the scientific 
value of the trial. 
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks. 
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, participant recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The investigator 
or BMS should also provide the IRB/IEC with a copy of the Investigator’s Brochure or product 
labeling information to be provided to subjects and any updates. 
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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
98 
Approved v 41.0 
930144776 4.0 
 
 
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. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s), the deviation or change will be submitted, as 
soon as possible, to: 
• IRB/IEC 
• Regulatory Authority(ies), if applicable by local regulations (per national requirements) 
 
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS. 
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment. 
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s). 
FINANCIAL DISCLOSURE 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 
INFORMED CONSENT PROCESS 
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given by subjects, 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. 
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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
99 
Approved v 41.0 
930144776 4.0 
 
 
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 nontechnical 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, 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' signed ICF and, in the 
US, the subjects’ signed HIPAA Authorization. 
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The participant 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this participant become capable, he or she should personally sign and 
date the consent form as soon as possible. The explicit wish of a participant who is unable to give 
his or her written consent, but who is capable of forming an opinion and assessing information to 
refuse participation in, or to be withdrawn from, the clinical study at any time should be considered 
by the investigator. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society. 
SOURCE DOCUMENTS 
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are handwritten on paper or entered 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
100 
Approved v 41.0 
930144776 4.0 
 
 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event tracking/reporting, protocol required assessments, and/or drug accountability 
records. 
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
STUDY TREATMENT RECORDS 
Records for study treatments nivolumab or ipilimumab (whether supplied by BMS, its vendors, or 
the site) must substantiate study treatment integrity and traceability from receipt, preparation, 
administration, and through destruction or return. Records must be made available for review at 
the request of BMS/designee or a Health Authority. 
 
If 
Then 
Supplied 
vendors): 
by 
BMS 
(or 
its Records or logs must comply with applicable regulations 
and guidelines and should include: 
• amount received and placed in storage area 
• amount currently in storage area 
• label identification number or batch number 
• amount dispensed to and returned by each participant, 
including unique participant identifiers 
• amount transferred to another area/site for dispensing or 
storage 
• nonstudy disposition (eg, lost, wasted) 
• amount destroyed at study site, if applicable 
• amount returned to BMS 
• retain samples for bioavailability/bioequivalence, 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
101 
Approved v 41.0 
930144776 4.0 
 
 
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements. 
CASE REPORT FORMS 
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study. 
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s). 
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. The investigator must retain a copy of the CRFs including records of the changes and 
corrections. 
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user 
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals 
MONITORING 
Sponsor or designee representatives 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 records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. 
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
102 
Approved v 41.0 
930144776 4.0 
 
 
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee. 
RECORDS RETENTION 
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study. 
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed. 
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
RETURN OF STUDY TREATMENT 
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site. 
 
If... 
Then 
Study treatments 
supplied by BMS 
(including its vendors 
Any unused study treatments supplied by BMS can 
only be destroyed after being inspected and 
reconciled by the responsible Study Monitor unless 
study treatments containers must be immediately 
destroyed as required for safety, or to meet local 
regulations (eg, cytotoxics or biologics). 
If study treatments will be returned, the return will 
be arranged by the responsible Study Monitor. 
Study treatments sourced by site, not 
supplied by BMS (or its vendors) 
(examples include study treatments 
sourced 
from 
the 
sites 
stock 
or 
commercial supply, or a specialty 
pharmacy) 
It is the investigator’s or designee’s responsibility to 
dispose of all containers according to the 
institutional guidelines and procedures. 
 
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
103 
Approved v 41.0 
930144776 4.0 
 
 
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. 
 
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 AND PUBLICATIONS 
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria: 
• Study Steering Committee chair or their designee 
• Participant recruitment (eg, among the top quartile of enrollers) 
• Involvement in trial design 
• Other criteria (as determined by the study team) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
104 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW UP AND REPORTING 
ADVERSE EVENTS 
 
Adverse Event Definition: 
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation participant administered study treatment 
and that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, electrocardiogram, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and 
should specify "intentional overdose" as the verbatim term 
Events NOT Meeting the AE Definition 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
DEFINITION OF SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
105 
Approved v 41.0 
930144776 4.0 
 
 
SERIOUS ADVERSE EVENTS 
 
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any 
dose: 
Results in death 
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe) 
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below) 
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
• a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event) 
• elective surgery, planned prior to signing consent 
• admissions as per protocol for a planned medical/surgical procedure 
• routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy) 
• medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases 
• admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason) 
• admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols) 
Results in persistent or significant disability/incapacity 
Is a congenital anomaly/birth defect 
Is an important medical event (defined as a medical event(s) that may not be immediately life- 
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.7 for the definition of potential DILI.) 
 
Pregnancy and potential drug induced liver injury (DILI) must follow the same transmission timing 
and processes to BMS as used for SAEs (see section 9.2.5 for reporting pregnancies). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
106 
Approved v 41.0 
930144776 4.0 
 
 
EVALUATING AES AND SAES 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated. 
• The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
If only limited information is initially available, follow-up reports are required. (Note: Follow- 
up SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report. 
All SAEs must be followed to resolution or stabilization. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
107 
Approved v 41.0 
930144776 4.0 
 
 
REPORTING OF SAES TO SPONSOR OR DESIGNEE 
 
• SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event. 
• SAEs must be recorded on the SAE Report Form. 
− The required method for SAE data reporting is through the eCRF. 
− The paper SAE Report Form is only intended as a back-up option when the electronic 
data capture system is unavailable/not functioning for transmission of the eCRF to BMS 
(or designee). 
♦ In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission 
♦ When paper forms are used, the original paper forms are to remain on site 
• 
Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via email or 
confirmed facsimile (fax) transmission 
SAE Email Address: Refer to Contact Information list. 
SAE Facsimile Number: Refer to Contact Information list. 
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
108 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 4 
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION 
DEFINITIONS 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
Women in the following categories are not considered WOCBP 
• Premenarchal 
• Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
• Postmenopausal female 
− A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle-stimulating hormone level 
> 40 mIU/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 months after 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 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulationb 
− oral 
− injectable 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
109 
Approved v 41.0 
930144776 4.0 
 
 
 
Highly Effective Methods 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 
• 
Vasectomized partner 
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 necessary to use any other method of contraception when complete abstinence is 
elected. 
• WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 
• Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence 
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 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
110 
Approved v 41.0 
930144776 4.0 
 
 
 
Unacceptable Methods of Contraception* 
• Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously 
• Diaphragm with spermicide 
• Cervical cap with spermicide 
• Vaginal Sponge with spermicide 
• 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. 
 
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 3, Adverse Events and Serious 
Adverse Events: Definitions and Procedures for Evaluating, Follow-up and Reporting. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
111 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 5 
INDIA PRESCRIBING INFORMATION FOR NIVOLUMAB AND 
IPILIMUMAB 
 
APPENDIX 5-1 
NIVOLUMAB INDIA PRESCRIBING INFORMATION 
To be sold by retail on the prescription of a ‘Registered Oncologist’ only. 
 
 
 
 
Nivolumab 
OPDYTA® 
1 
GENERIC NAME 
Nivolumab 10 mg/mL concentrate for solution for infusion. 
 
 
2 
QUALITATIVE AND QUANTITATIVE COMPOSITION 
Nivolumab is a fully human anti-PD-1 monoclonal antibody (IgG4) produced in Chinese 
hamster ovary cells by recombinant DNA technology. 
Each 1 mL of concentrate contains 10 mg of nivolumab. 
For the full list of excipients, see Section 7. Description 
 
3 
DOSAGE FORM AND STRENGTH 
Nivolumab is a sterile, preservative-free, non-pyrogenic, clear to opalescent, colorless to pale- 
yellow liquid for intravenous infusion that may contain light (few) particles. The solution has 
a pH of approximately 6.0 and an osmolality of approximately 340 mOsm/kg. 
Concentrate for solution for infusion 
Injection: 40 mg/4 mL,100 mg/10 mL and 240 mg/24 mL solution in a single-dose vial. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
112 
Approved v 41.0 
930144776 4.0 
 
 
4 
CLINICAL PARTICULARS 
4.1 
THERAPEUTIC INDICATIONS 
4.1.1 
Non-Small Cell Lung Cancer (NSCLC) 
Nivolumab as a single agent is indicated for the treatment of locally advanced or metastatic non- 
small cell lung cancer (NSCLC) after prior chemotherapy. 
Nivolumab, in combination with ipilimumab, is indicated for the first-line treatment of adult 
patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) 
as determined by a validated test, with no EGFR or ALK genomic tumor aberrations. 
 
Nivolumab, in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy, is 
indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell 
lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. 
 
4.1.2 
Renal cell carcinoma (RCC) 
Nivolumab as a single agent is indicated for the treatment of patients with advanced renal cell 
carcinoma (RCC) after prior therapy in adults. 
Nivolumab is indicated for the treatment of patients with intermediate or poor risk, previously 
untreated advanced renal cell carcinoma, in combination with ipilimumab. 
4.1.3 
Squamous Cell Carcinoma of the Head and Neck (SCCHN) 
Nivolumab as monotherapy is indicated for the treatment of recurrent or metastatic squamous 
cell carcinoma of the head and neck after platinum-based therapy. 
4.1.4 
Melanoma 
Nivolumab as a single agent is indicated for the treatment of patients with BRAF V600 
wildtype unresectable or metastatic melanoma. 
Nivolumab as a single agent is indicated for the treatment of patients with BRAF V600 
mutation positive unresectable or metastatic melanoma. 
Nivolumab is indicated for the treatment of patients with melanoma with lymph node 
involvement or metastatic disease who have undergone complete resection, in the adjuvant 
settings. 
4.1.5 
Classical Hodgkin Lymphoma (cHL) 
Nivolumab is indicated for the treatment of adult patients with classical Hodgkin lymphoma 
(cHL) that has relapsed or progressed after: 
− autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, 
or 
− 3 or more lines of systemic therapy that includes autologous HSCT 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
113 
Approved v 41.0 
930144776 4.0 
 
 
4.1.6 
Urothelial Carcinoma (UC) 
Nivolumab is indicated for the treatment of patients with locally advanced or metastatic 
urothelial carcinoma who: 
− have disease progression during or following platinum-containing chemotherapy 
− have disease progression within 12 months of neoadjuvant or adjuvant treatment with 
platinum-containing chemotherapy. 
4.1.7 
Colorectal Cancer (CRC) 
Nivolumab as montherapy is indicated for the treatment adult and pediatric (12 years and 
older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient 
(dMMR) metastatic colorectal cancer that has progressed following treatment with a 
fluoropyrimidine, oxaliplatin, and irinotecan 
 
4.1.8 
Esophageal Squamous Cell Carcinoma (ESCC) 
Nivolumab is indicated for the treatment of patients with unresectable advanced, recurrent, or 
metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and 
platinum-based chemotherapy. 
4.1.9 
Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal 
Adenocarcinoma (GC, GEJC or EAC) 
Nivolumab, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is 
indicated for the treatment of patients with advanced or metastatic gastric cancer, 
gastroesophageal junction cancer, and esophageal adenocarcinoma. 
4.1.10 
Adjuvant treatment of Resected Esophageal or Gastroesophageal 
Junction Cancer (EC or GEJC) 
Nivolumab is indicated for the adjuvant treatment of completely resected esophageal or 
gastroesophageal junction cancer with residual pathologic disease in patients who have received 
neoadjuvant chemoradiotherapy (CRT). 
4.2 
POSOLOGY AND METHOD OF ADMINISTRATION 
Treatment must be initiated and supervised by physicians experienced in the treatment of 
cancer. 
4.2.1 
Recommended dosage 
The recommended doses of nivolumab as a single agent are presented in Table 1. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
114 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 1: 
Recommended doses for nivolumab as monotherapy (NSCLC, RCC, 
SCCHN, melanoma, cHL, UC, CRC, ESCC, EC and GEJC) 
 
Indication^ 
Recommended Nivolumab 
Dosage 
Duration of Therapy 
Locally advanced or metastatic 
squamous non-small cell lung 
cancer 
Treatment should be continued as long as 
clinical benefit is observed or until treatment 
is no longer tolerated. 
Advanced renal cell carcinoma 
Recurrent or metastatic squamous 
cell carcinoma of the head and 
neck 
3 mg/kg every 2 weeks 
(30-minute intravenous infusion) 
or 
240 mg every 2 weeks 
Unresectable or metastatic 
melanoma 
(30-minute intravenous infusion) 
or 
480 mg every 4 weeks 
(30-minute intravenous infusion) 
Relapsed/refractory classical 
Hodgkin lymphoma 
Unresectable or metastatic 
urothelial carcinoma 
Microsatellite instability-high 
(MSI-H) or mismatch repair 
deficient (dMMR) metastatic 
colorectal cancer 
Esophageal Squamous Cell 
Carcinoma 
Adjuvant treatment of melanoma 
3 mg/kg every 2 weeks 
Treatment should be continued as long as 
clinical benefit is observed or until treatment 
is no longer tolerated. For adjuvant treatment, 
the maximum duration of nivolumab is 1 
year. 
Adjuvant treatment of resected 
esophageal or gastro- esophageal 
junction cancer 
(30-minute intravenous infusion) 
or 
240 mg every 2 weeks 
(30-minute intravenous infusion) 
or 
480 mg every 4 weeks 
(30-minute intravenous infusion) 
^ As per monotherapy indications in Section 4.1 Therapeutic Indications. 
 
Please see section 8.4 Storage and handling instructions regarding limitation of total infusion 
volume with the 240-mg or 480-mg dosage. 
The recommended doses of nivolumab in combination with other therapeutic agents are 
presented in Table 2. Refer to the respective Product Information for each therapeutic agent 
administered in combination with nivolumab for the recommended dose information, as 
appropriate. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
115 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 2: 
Recommended Doses of Nivolumab in Combination with Other 
Therapeutic Agents 
 
Indication^ 
Recommended Nivolumab Dosage 
Duration of Therapy 
Metastatic non- small 
cell lung cancer expressing 
PD-L1 
3 mg/kg every 2 weeks 
(30-minute intravenous infusion) with 
ipilimumab 1 mg/kg every 6 weeks 
(30-minute intravenous infusion) 
In combination with ipilimumab until 
disease progression, unacceptable 
toxicity, or up to 2 years in patients 
without disease progression 
Metastatic or recurrent non- 
small cell lung cancer 
360 mg every 3 weeks 
(30-minute intravenous infusion) with 
ipilimumab 1 mg/kg every 6 weeks 
(30-minute intravenous infusion) and platinum 
chemotherapy every 3 weeks 
After completion of 2 cycles of 
chemotherapy, treatment is continued 
with 360 mg nivolumab administered 
as an intravenous infusion every 3 
weeks in combination with 1 mg/kg 
ipilimumab every 6 weeks until 
disease progression, is no longer 
tolerated, or up to 2 years in patients 
without disease progression. 
3 mg/kg every 3 weeks 
(30-minute intravenous infusion) 
In combination with ipilimumab for 4 
doses 
Advanced renal cell 
carcinoma 
Administer nivolumab in combination with 
ipilimumab 1 mg/kg 
(30-minute intravenous infusion) 
3 mg/kg every 2 weeks* 
After completing 4 doses of 
combination therapy, administer as 
single agent as long as clinical benefit 
is observed or until treatment is no 
longer tolerated by the patient. 
(30-minute intravenous infusion) or 
240 mg every 2 weeks* 
(30-minute intravenous infusion) or 
480 mg every 4 weeks* 
(30-minute intravenous infusion) 
Gastric cancer, Gastro- 
esophageal junction cancer, 
or Esophageal 
adenocarcinoma 
360 mg every 3 weeks 
(30-minute intravenous infusion) with 
fluoropyrimidine- and platinum-containing 
chemotherapy every 3 weeks 
or 
240 mg every 2 weeks 
(30-minute intravenous infusion) with 
fluoropyrimidine- and platinum-containing 
chemotherapy every 2 weeks 
Treatment should be continued until 
disease progression, is no longer 
tolerated or up to 2 years in patients 
without disease progression. 
* Following the last dose of the combination of nivolumab and ipilimumab, the first dose of nivolumab monotherapy 
should be administered after 3 weeks when using 3 mg/kg or 240 mg or 6 weeks when using 480 mg 
^ As per combination indications in Section 4.1 Therapeutic Indications. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
116 
Approved v 41.0 
930144776 4.0 
 
 
For all combination therapy 
When administered in combination with ipilimumab, with ipilimumab and chemotherapy, or with 
other therapeutic agents, nivolumab should be given first followed by ipilimumab (if applicable) 
and then chemotherapy or other therapeutic agents on the same day (see 8.4 Storage and handling 
instructions). 
Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be 
required based on individual safety and tolerability. Guidelines for permanent discontinuation or 
withholding of doses are described in Table 3. Detailed guidelines for the management of 
immune-related adverse reactions are described in 4.4.2 Product-specific warnings and 
precautions. 
 
 
Table 3: 
Recommended treatment modifications for nivolumab or 
nivolumab in combination with ipilimumab 
 
 
Immune-related 
adverse reaction 
 
Immune-related 
pneumonitis 
Severity 
Treatment modification 
 
Grade 2 pneumonitis 
Withhold dose(s) until symptoms resolve, 
radiographic abnormalities improve, and 
management with corticosteroids is 
complete. 
 
Grade 3 or 4 pneumonitis 
Permanently discontinue treatment. 
 
Grade 2 diarrhea or colitis 
Withhold dose(s) until symptoms resolve 
and management with corticosteroids, if 
needed, is complete. 
 
 
 
 
Immune-related colitis 
Grade 3 diarrhea or colitis 
 
- nivolumab monotherapy 
 
- nivolumab+ipilimumab 
Withhold dose(s) until symptoms resolve 
and management with corticosteroids is 
complete. 
 
Permanently discontinue treatment. 
 
Grade 4 diarrhea or colitis 
Permanently discontinue treatment. 
 
 
 
 
Immune-related hepatitis 
Patients with normal AST/ALT/bilirubin 
at baseline 
Grade 2 elevation in aspartate 
aminotransferase (AST), alanine 
aminotransferase (ALT), or total 
bilirubin 
 
 
Withhold dose(s) until laboratory values 
return to baseline and management with 
corticosteroids, if needed, is complete. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
117 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 3: 
Recommended treatment modifications for nivolumab or 
nivolumab in combination with ipilimumab 
 
 
Grade 3 or 4 elevation in AST, ALT, or 
total bilirubin 
Permanently discontinue treatment. 
 
 
 
Immune-related 
nephritis and renal 
dysfunction 
Grade 2 or 3 creatinine elevation 
Withhold dose(s) until creatinine returns 
to baseline and management with 
corticosteroids is complete. 
 
Grade 4 creatinine elevation 
Permanently discontinue treatment. 
 
 
 
Immune-related 
endocrinopathies 
Symptomatic Grade 2 or 3 
hypothyroidism, hyperthyroidism, 
hypophysitis 
 
Grade 2 adrenal insufficiency 
Grade 3 diabetes 
Withhold dose(s) until symptoms resolve 
and management with corticosteroids (if 
needed for symptoms of acute 
inflammation) is complete. Treatment 
should be continued in the presence of 
hormone replacement therapy as long as 
no symptoms are present. 
 
 
 
 
 
 
 
 
 
 
Immune-related skin 
adverse reactions 
Grade 4 hypothyroidism 
Grade 4 hyperthyroidism 
Grade 4 hypophysitis 
Grade 3 or 4 adrenal insufficiency 
Grade 4 diabetes 
Grade 3 rash 
 
 
 
 
Suspected Stevens-Johnson syndrome 
(SJS) or toxic epidermal necrolysis 
(TEN) 
 
 
Permanently discontinue treatment. 
 
 
Withhold dose(s) until symptoms resolve 
and management with corticosteroids is 
complete. 
 
Withhold dose(s) 
 
 
Grade 4 rash 
Confirmed SJS/TEN 
Permanently discontinue treatment. 
 
Immune-related 
myocarditis 
Grade 2 myocarditis 
Withhold dose(s) until symptoms resolve 
and management with corticosteroids is 
complete. Retreatment may be considered 
after recovery. 
 
 
 
Other immune-related 
adverse reactions 
Grade 3 or 4 myocarditis 
Permanently discontinue treatment. 
Grade 3 (first occurrence) 
Withhold dose(s) until symptoms resolve 
or improve and management with 
corticosteroids is complete. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
118 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 3: 
Recommended treatment modifications for nivolumab or 
nivolumab in combination with ipilimumab 
 
 
Grade 4 or recurrent Grade 3; persistent 
Grade 2 or 3 despite treatment 
modification; inability to reduce 
corticosteroid dose to 10 mg prednisone 
or equivalent per day 
 
 
Permanently discontinue treatment. 
 
 
Note: 
Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse 
Events Version 4.0 (NCI-CTCAE v4). 
 
 
Nivolumab or nivolumab in combination with ipilimumab should be permanently 
discontinued for: 
• Grade 4 or recurrent Grade 3 adverse reactions; 
• Persistent Grade 2 or 3 adverse reactions despite management. 
 
When nivolumab is administered in combination with ipilimumab, if either agent is withheld, 
the other agent should also be withheld. If dosing is resumed after a delay, either the 
combination treatment or nivolumab monotherapy could be resumed based on the evaluation 
of the individual patient. 
Nivolumab in combination with chemotherapy 
For GC, GEJC or EAC patients treated with nivolumab in combination with chemotherapy, 
refer to the product information for the other combination therapy agents regarding dosing. If 
any agents are withheld, the other agents may be continued. If dosing is resumed after a delay, 
either the combination treatment, or nivolumab monotherapy or chemotherapy alone, could be 
resumed based on the evaluation of the individual patient. 
4.2.2 
Renal impairment 
Based on the population pharmacokinetic (PK) results, no dose adjustment is required in 
patients with mild or moderate renal impairment (see 5.3.1 Special populations). 
4.2.3 
Hepatic impairment 
Based on the population PK results, no dose adjustment is required in patients with mild or 
moderate hepatic impairment (see 5.3.1 Special populations). 
4.2.4 
Geriatric 
No dose adjustment is required for elderly patients (≥65 years) (see 4.4.6 Geriatric use and 
5.3.1 Special populations). 
4.3 
CONTRAINDICATIONS 
None. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
119 
Approved v 41.0 
930144776 4.0 
 
 
4.4 
Special WARNINGS AND PRECAUTIONS for use 
When nivolumab is administered in combination with ipilimumab, refer to the product information 
for ipilimumab prior to initiation of treatment. Both agents are associated with immune-related 
adverse reactions. In clinical trials, immune-related adverse reactions have occurred at higher 
frequencies when nivolumab was administered in combination with ipilimumab compared with 
nivolumab as monotherapy. Most immune-related adverse reactions improved or resolved with 
appropriate management, including initiation of corticosteroids and treatment modifications. 
When an immune-related adverse reaction is suspected, alternate etiology should be ruled out and 
use of immunosuppressive therapy should be considered. Patients should be monitored 
continuously as an adverse reaction with nivolumab or nivolumab in combination with ipilimumab 
may occur at any time during or after discontinuation of nivolumab therapy. If immunosuppression 
with corticosteroids is used to treat an adverse reaction, a taper of at least 1month duration should 
be initiated upon improvement. Rapid tapering may lead to worsening or recurrence of the adverse 
reaction. Non-corticosteroid immunosuppressive therapy should be added if there is worsening or 
no improvement despite corticosteroid use. Nivolumab or nivolumab in combination with 
ipilimumab should not be resumed while the patient is receiving immunosuppressive doses of 
corticosteroids or other immunosuppressive therapy. Prophylactic antibiotics should be used to 
prevent opportunistic infections in patients receiving immunosuppressive therapy. 
4.4.1 
Drug-class–specific warnings and precautions 
Increased mortality in patients with multiple myeloma [not an approved indication] when a PD- 
1 blocking antibody is added to a thalidomide analogue and dexamethasone 
In randomized clinical trials in patients with multiple myeloma, the addition of a PD-1 blocking 
antibody, including nivolumab, to a thalidomide analogue plus dexamethasone, a use for which no 
PD-1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with 
multiple myeloma with a PD-1 blocking antibody in combination with a thalidomide analogue 
plus dexamethasone is not recommended outside of controlled clinical trials. 
4.4.2 
Product-specific warnings and precautions 
Immune-related pneumonitis 
Severe pneumonitis or interstitial lung disease, including fatal cases, has been observed with 
nivolumab monotherapy or nivolumab in combination with ipilimumab (see 4.8 Undesirable 
effects, 4.8.1 Clinical experience). Patients should be monitored for signs and symptoms of 
pneumonitis such as radiographic changes (eg, focal ground glass opacities, patchy filtrates), 
dyspnoea, and hypoxia. Infectious and disease-related etiologies should be ruled out. 
For Grade 3 or 4 pneumonitis, nivolumab or nivolumab in combination with ipilimumab must be 
permanently discontinued, and corticosteroids should be initiated at a dose of 2 to 4 mg/kg/day 
methylprednisolone equivalents. 
For Grade 2 (symptomatic) pneumonitis, nivolumab or nivolumab in combination with 
ipilimumab should be withheld and corticosteroids initiated at a dose of 1 mg/kg/day 
methylprednisolone equivalents. Upon improvement, nivolumab or nivolumab in combination 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
120 
Approved v 41.0 
930144776 4.0 
 
 
with ipilimumab may be resumed after corticosteroid taper. If worsening or no improvement 
occurs  despite  initiation  of  corticosteroids,  corticosteroid  dose  should  be  increased 
to 2 to 4 mg/kg/day methylprednisolone equivalents, and nivolumab or nivolumab in combination 
with ipilimumab must be permanently discontinued. 
Immune-related colitis 
Severe diarrhea or colitis has been observed with nivolumab monotherapy or nivolumab in 
combination with ipilimumab (see 4.8 Undesirable effects, 4.8.1 Clinical experience). Patients 
should be monitored for diarrhea and additional symptoms of colitis, such as abdominal pain and 
mucus or blood in stool. Infectious and disease-related etiologies should be ruled out. 
Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid- 
refractory immune-related colitis. Stool infections work-up (including CMV, other viral etiology, 
culture, Clostridium difficile, ova, and parasite) should be performed upon presentation of diarrhea 
or colitis to exclude infectious or other alternate etiologies. 
For Grade 4 diarrhea or colitis, nivolumab or nivolumab in combination with ipilimumab must be 
permanently discontinued, and corticosteroids should be initiated at a dose of 1 to 2 mg/kg/day 
methylprednisolone equivalents. Grade 3 diarrhea observed with nivolumab in combination with 
ipilimumab also requires permanent discontinuation of treatment and initiation of corticosteroids 
at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents. 
Nivolumab monotherapy should be withheld for Grade 3 diarrhea or colitis, and corticosteroids 
initiated at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents. Upon improvement, 
nivolumab monotherapy may be resumed after corticosteroid taper. If worsening or no 
improvement occurs despite initiation of corticosteroids, nivolumab monotherapy must be 
permanently discontinued. 
For Grade 2 diarrhea or colitis, nivolumab or nivolumab in combination with ipilimumab should 
be withheld. Persistent diarrhea or colitis should be managed with corticosteroids at a dose 
of 0.5 to 1 mg/kg/day methylprednisolone equivalents. Upon improvement, nivolumab or 
nivolumab in combination with ipilimumab may be resumed after corticosteroid taper, if needed. 
If worsening or no improvement occurs despite initiation of corticosteroids, corticosteroid dose 
should be increased to 1 to 2 mg/kg/day methylprednisolone equivalents, and nivolumab or 
nivolumab in combination with ipilimumab must be permanently discontinued. 
Addition of an alternative immunosuppressive agent to the corticosteroid therapy, or replacement 
of the corticosteroid therapy, should be considered in corticosteroid-refractory immune-related 
colitis if other causes are excluded (including CMV infection/reactivation evaluated with viral 
PCR on biopsy, and other viral, bacterial, and parasitic etiology). 
Immune-related hepatitis 
Severe hepatitis has been observed with nivolumab monotherapy or nivolumab in combination 
with ipilimumab (see 4.8 Undesirable effects, 4.8.1. Clinical experience). Patients should be 
monitored for signs and symptoms of hepatitis such as transaminase and total bilirubin elevations. 
Infectious and disease-related etiologies should be ruled out. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
121 
Approved v 41.0 
930144776 4.0 
 
 
For Grade 3 or 4 transaminase or total bilirubin elevation, nivolumab monotherapy or nivolumab 
in combination with ipilimumab must be permanently discontinued, and corticosteroids should be 
initiated at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents. 
For Grade 2 transaminase or total bilirubin elevation, nivolumab monotherapy or nivolumab in 
combination with ipilimumab should be withheld. Persistent elevations in these laboratory values 
should be managed with corticosteroids at a dose of 0.5 to 1 mg/kg/day methylprednisolone 
equivalents. Upon improvement, nivolumab monotherapy or nivolumab in combination with 
ipilimumab may be resumed after corticosteroid taper, if needed. If worsening or no improvement 
occurs  despite  initiation  of  corticosteroids,  corticosteroid  dose  should  be  increased 
to 1 to 2 mg/kg/day methylprednisolone equivalents, and nivolumab monotherapy or nivolumab 
in combination with ipilimumab must be permanently discontinued. 
Immune-related nephritis and renal dysfunction 
Severe nephritis and renal dysfunction have been observed with nivolumab monotherapy or 
nivolumab in combination with ipilimumab (see 4.8 Undesirable effects, 4.8.1 Clinical 
experience). Patients should be monitored for signs and symptoms of nephritis and renal 
dysfunction. Most patients present with asymptomatic increases in serum creatinine. 
Disease-related etiologies should be ruled out. 
For Grade 4 serum creatinine elevation, nivolumab monotherapy or nivolumab in combination 
with ipilimumab must be permanently discontinued, and corticosteroids should be initiated at a 
dose of 1 to 2 mg/kg/day methylprednisolone equivalents. 
For Grade 2 or 3 serum creatinine elevation, nivolumab monotherapy or nivolumab in 
combination with ipilimumab should be withheld, and corticosteroids should be initiated at a dose 
of 0.5 to 1 mg/kg/day methylprednisolone equivalents. Upon improvement, nivolumab 
monotherapy or nivolumab in combination with ipilimumab may be resumed after corticosteroid 
taper. If worsening or no improvement occurs despite initiation of corticosteroids, corticosteroid 
dose should be increased to 1 to 2 mg/kg/day methylprednisolone equivalents, and nivolumab 
monotherapy or nivolumab in combination with ipilimumab must be permanently discontinued. 
Immune-related endocrinopathies 
Severe endocrinopathies, including hypothyroidism, hyperthyroidism, adrenal insufficiency 
(including secondary adrenocortical insufficiency), hypophysitis (including hypopituitarism), 
diabetes mellitus, and diabetic ketoacidosis have been observed with nivolumab monotherapy or 
nivolumab in combination with ipilimumab (see 4.8 Undesirable effects, 4.8.1 Clinical 
experience). Patients should be monitored for clinical signs and symptoms of endocrinopathies 
and for changes in thyroid function. Patients may present with fatigue, headache, mental status 
changes, abdominal pain, unusual bowel habits, and hypotension, or nonspecific symptoms which 
may resemble other causes such as brain metastasis or underlying disease. Unless an alternate 
etiology has been identified, signs or symptoms of endocrinopathies should be considered 
immune-related. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
122 
Approved v 41.0 
930144776 4.0 
 
 
For symptomatic hypothyroidism, nivolumab or nivolumab in combination with ipilimumab 
should be withheld, and thyroid hormone replacement should be initiated as needed. For 
symptomatic hyperthyroidism, nivolumab or nivolumab in combination with ipilimumab should 
be withheld and antithyroid medication should be initiated as needed. Corticosteroids at a dose 
of 1 to 2 mg/kg/day methylprednisolone equivalents should also be considered if acute 
inflammation of the thyroid is suspected. Upon improvement, nivolumab or nivolumab in 
combination with ipilimumab may be resumed after corticosteroid taper, if needed. Monitoring of 
thyroid function should continue to ensure appropriate hormone replacement is utilized. 
Nivolumab or nivolumab in combination with ipilimumab must be permanently discontinued for 
life-threatening (Grade 4) hyperthyroidism or hypothyroidism. 
For symptomatic Grade 2 adrenal insufficiency, nivolumab or nivolumab in combination with 
ipilimumab should be withheld, and physiologic corticosteroid replacement should be initiated as 
needed. Nivolumab or nivolumab in combination with ipilimumab must be permanently 
discontinued for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Monitoring 
of adrenal function and hormone levels should continue to ensure appropriate corticosteroid 
replacement is utilized. 
For symptomatic Grade 2 or 3 hypophysitis, nivolumab or nivolumab in combination with 
ipilimumab should be withheld, and hormone replacement should be initiated as needed. 
Corticosteroids at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents should also be 
considered if acute inflammation of the pituitary gland is suspected. Upon improvement, 
nivolumab or nivolumab in combination with ipilimumab may be resumed after corticosteroid 
taper, if needed. Nivolumab or nivolumab in combination with ipilimumab must be permanently 
discontinued for life-threatening (Grade 4) hypophysitis. Monitoring of pituitary function and 
hormone levels should continue to ensure appropriate hormone replacement is utilized. 
For symptomatic diabetes, nivolumab or nivolumab in combination with ipilimumab should be 
withheld, and insulin replacement should be initiated as needed. Monitoring of blood sugar should 
continue to ensure appropriate insulin replacement is utilized. Nivolumab or nivolumab in 
combination with ipilimumab must be permanently discontinued for life-threatening (Grade 4) 
diabetes. 
Immune-related skin adverse reactions 
Severe rash has been observed with nivolumab. The frequency of rash is higher when nivolumab 
is administered in combination with ipilimumab (see 4.8 Undesirable effects, 4.8.1 Clinical 
experience). Nivolumab or nivolumab in combination with ipilimumab should be withheld for 
Grade 3 rash and discontinued for Grade 4 rash. Severe rash should be managed with high-dose 
corticosteroid at a dose of 1 to 2 mg/kg/day methylprednisolone equivalents. 
Rare cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some with 
fatal outcome, have been observed. If symptoms or signs of SJS or TEN appear, nivolumab or 
nivolumab in combination with ipilimumab should be withheld and the patient referred to a 
specialized unit for assessment and treatment. If the patient has confirmed SJS or TEN, permanent 
discontinuation of nivolumab or nivolumab in combination with ipilimumab is recommended. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
123 
Approved v 41.0 
930144776 4.0 
 
 
Other immune-related adverse reactions 
Other clinically significant immune-related adverse reactions have been observed. Across clinical 
trials of nivolumab or nivolumab in combination with ipilimumab investigating various doses and 
tumor types, the following immune-related adverse reactions were reported in less than 1% of 
patients: pancreatitis, uveitis, demyelination, autoimmune neuropathy (including facial and 
abducens nerve paresis), Guillain-Barré syndrome, myasthenia gravis, myasthenic syndrome, 
aseptic meningitis, gastritis, sarcoidosis, duodenitis, encephalitis, myositis, myocarditis and 
rhabdomyolysis (see 4.8.1 Undesirable effects, Clinical experience). Cases of Vogt-Koyanagi- 
Harada syndrome have been reported during post approval use of nivolumab or nivolumab in 
combination with ipilimumab (see 4.8 Undesirable effects, 4.8.2. Postmarketing experience). 
For suspected immune-related adverse reactions, adequate evaluation should be performed to 
confirm etiology or exclude other causes. Based on the severity of the adverse reaction, nivolumab 
or nivolumab in combination with ipilimumab should be withheld and corticosteroids 
administered. Upon improvement, nivolumab or nivolumab in combination with ipilimumab may 
be resumed after corticosteroid taper. Nivolumab or nivolumab in combination with ipilimumab 
must be permanently discontinued for any severe immune-related adverse reaction that recurs and 
for any life-threatening immune-related adverse reaction. 
Cases of myotoxicity (myositis, myocarditis, and rhabdomyolysis), some with fatal outcome, have 
been reported with nivolumab or nivolumab in combination with ipilimumab. Some cases of 
myocarditis can be asymptomatic, so a diagnosis of myocarditis requires a high index of suspicion. 
Therefore, patients with cardiac or cardio-pulmonary symptoms should undergo a prompt 
diagnostic workup to evaluate for myocarditis with close monitoring. Troponin is a sensitive but 
not diagnostic marker of myocarditis. If myocarditis is suspected, prompt initiation of a high dose 
of steroids (prednisone 1 to 2 mg/kg/day or methylprednisolone 1 to 2 mg/kg/day), and prompt 
cardiology consultation with diagnostic workup including electrocardiogram, troponin, and 
echocardiogram should be initiated. Additional testing may be warranted, as guided by the 
cardiologist, and may include cardiac magnetic resonance imaging. Once a diagnosis is 
established, nivolumab or nivolumab in combination with ipilimumab should be withheld. For 
grade 3 myocarditis, nivolumab or nivolumab in combination with ipilimumab therapy should be 
permanently discontinued (see section 4.2.1 Recommended dosage, Table 1). Solid organ 
transplant rejection has been reported in the post-marketing setting in patients treated with PD- 
1/PD-L1 inhibitors. Treatment with nivolumab may increase the risk of rejection in solid organ 
transplant recipients. (see 4.8 Undesirable effects, 4.8.2 Postmarketing experience). 
Rapid-onset and severe graft-versus-host disease (GVHD), some with fatal outcome, has been 
reported in the post-marketing setting in patients who had undergone prior allogeneic stem cell 
transplant and subsequently received PD-1/PD-L1 inhibitors. (see 4.8 Undesirable effects, 4.8.2 
Postmarketing experience). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
124 
Approved v 41.0 
930144776 4.0 
 
 
Complications of allogeneic hematopoietic stem cell transplant (HSCT) after treatment with 
PD-1/PD-L1 inhibitors 
PD-1/PD-L1 inhibitors including nivolumab, administered before allogeneic hematopoietic 
stem cell transplant (HSCT), may be associated with an increased risk of transplant-related 
complications, including GVHD. Fatal cases have been reported in clinical studies. Patients 
should be monitored closely for early evidence of transplant-related complications. 
Infusion reactions 
Severe infusion reactions have been reported in clinical trials of nivolumab or nivolumab in 
combination with ipilimumab (see 4.8 Undesirable effects, 4.8.1. Clinical experience). In case of 
a severe or life-threatening infusion reaction, the nivolumab or nivolumab in combination with 
ipilimumab infusion must be discontinued and appropriate medical therapy administered. Patients 
with mild or moderate infusion reaction may receive nivolumab or nivolumab in combination with 
ipilimumab with close monitoring and use of premedication according to local treatment 
guidelines for prophylaxis of infusion reactions. 
Special populations 
In all registrational studies of nivolumab or nivolumab in combination with ipilimumab, patients 
with autoimmune disease, active brain metastases (or leptomeningeal metastases), Eastern 
Cooperative Oncology Group (ECOG) performance score >2 or Karnofsky performance score 
(KPS) <70%, and patients receiving systemic immunosuppressants prior to study entry were 
excluded. Specific populations excluded from clinical studies by tumor type are listed below (See 
4.5 Drug interaction and 5.2.1 Clinical Trial Information): 
NSCLC: patients with symptomatic interstitial lung disease 
Previously untreated NSCLC: patients with sensitizing EGFR mutations or ALK translocations 
RCC: patients with any history of or concurrent brain metastases 
SCCHN: patients with carcinoma of the nasopharynx or salivary gland as the primary tumor site 
Melanoma: patients with ocular/uveal melanoma 
Adjuvant treatment of melanoma: patients with prior therapy for melanoma (except patients with 
surgery, adjuvant radiotherapy after neurosurgical resection for lesions of the central nervous 
system, and prior adjuvant interferon completed ≥6 months prior to randomization) and patients 
treated with prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti CTLA-4 
antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co- 
stimulation or checkpoint pathways) 
cHL: patients with symptomatic interstitial lung disease 
GC or GEJC: patients with diverticulitis, or symptomatic gastrointestinal ulcerative disease or 
ascites requiring treatment 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
125 
Approved v 41.0 
930144776 4.0 
 
 
ESCC: patients with apparent tumor invasion on organs located adjacent to the esophageal disease 
(eg. the aorta or respiratory tract) 
GC, GEJC, or EAC: patients with known human epidermal growth factor receptor 2 (HER2) 
positive cancer or untreated CNS metastases. 
EC or GEJC: Patients who did not receive concurrent chemoradiotherapy (CRT) prior to surgery, 
without evidence of residual pathologic disease, or with stage IV resectable disease. 
4.4.3 
Pregnancy and lactation 
Refer to section 4.6 -Use in Special Populations (Such as Pregnant Women, Lactating women.) 
4.4.4 
Labor and delivery 
Data not available 
4.4.5 
Pediatric use 
The safety and effectiveness of nivolumab have not been established in pediatric patients. 
4.4.6 
Geriatric use 
No overall differences in safety or efficacy were reported between elderly (≥65 years) and 
younger patients (<65 years). 
4.4.7 
Renal impairment 
The safety and efficacy of nivolumab have not been studied in patients with severe renal 
impairment (see 5.3.1 Special Populations, Renal impairment). 
4.4.8 
Hepatic impairment 
The safety and efficacy of nivolumab have not been studied in patients with severe hepatic 
impairment. Nivolumab must be administered with caution in patients with severe (total 
bilirubin >3 times ULN and any AST) hepatic impairment (see 5.3.1 Special Populations, Hepatic 
impairment). 
 
4.5 
DRUG INTERACTIONS 
Nivolumab is a human monoclonal antibody, as such pharmacokinetic interaction studies have not 
been conducted. As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) 
enzymes or other drug metabolising enzymes, inhibition or induction of these enzymes by 
coadministered medicinal products is not anticipated to affect the pharmacokinetics of nivolumab. 
Other forms of interaction 
Systemic immunosuppression 
The use of systemic corticosteroids and other immunosuppressants at baseline, before starting 
nivolumab, should be avoided because of their potential interference with the pharmacodynamic 
activity. However, systemic corticosteroids and other immunosuppressants can be used after 
starting nivolumab to treat immune-related adverse reactions. The preliminary results show that 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
126 
Approved v 41.0 
930144776 4.0 
 
 
systemic immunosuppression after starting nivolumab treatment does not appear to preclude the 
response on nivolumab. 
 
4.6 
USE IN SPECIAL POPULATIONS (SUCH AS PREGNANT WOMEN, 
LACTATING WOMEN) 
There are no data on the use of nivolumab in pregnant women. Studies in animals have shown 
embryofetal toxicity (see 6 Nonclinical properties). Human IgG4 is known to cross the placental 
barrier and nivolumab is an IgG4; therefore, nivolumab has the potential to be transmitted from 
the mother to the developing fetus. Nivolumab is not recommended during pregnancy and in 
women of childbearing potential not using effective contraception unless the clinical benefit 
outweighs the potential risk. Women should be advised to use effective contraception for at least 
5 months following the last dose of nivolumab. 
It is unknown whether nivolumab is secreted in human milk. Because many medicinal products, 
including antibodies, can be secreted in human milk, a risk to the newborns/infants cannot be 
excluded. A decision must be made whether to discontinue breastfeeding or to discontinue from 
nivolumab therapy, taking into account the benefit of breastfeeding for the child and the benefit of 
therapy for the woman. 
4.7 
EFFECTS ON ABILITY TO DRIVE AND TO USE MACHINES 
Based on its pharmacodynamic properties, nivolumab is unlikely to affect the ability to drive and 
use machines. Because of potential adverse reactions such as fatigue (see 4.8 Undesirable effects, 
4.8.1 Clinical experience), patients should be advised to use caution when driving or operating 
machinery until they are certain that nivolumab does not adversely affect them. 
 
4.8 
UNDESIRABLE EFFECTS 
4.8.1 
Clinical experience 
Nivolumab or nivolumab in combination with ipilimumab is associated with immune-related 
adverse reactions. Most of these, including severe reactions, resolved following initiation of 
appropriate medical therapy or withdrawal of nivolumab (see “Description of selected adverse 
reactions” below). 
Nivolumab monotherapy 
In the pooled dataset of nivolumab 3 mg/kg as monotherapy across tumor types (n=3691), the most 
frequent adverse reactions (≥10%) were fatigue (26%), rash (16%), diarrhea (13%), pruritus 
(12%), and nausea (10%). 
Adjuvant Treatment of Melanoma 
In the dataset of nivolumab 3 mg/kg as monotherapy for the adjuvant treatment of melanoma 
(n = 452), the most frequent adverse reactions (≥ 10%) were fatigue (46%), rash (29%), diarrhea 
(24%), pruritus (23%), nausea (15%), arthralgia (13%), neutropenia (12%), musculoskeletal pain 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
127 
Approved v 41.0 
930144776 4.0 
 
 
(11%), and hypothyroidism (11%). The majority of adverse reactions were mild to moderate 
(Grade 1 or 2). 
Tabulated list of adverse reactions 
Adverse reactions reported in the pooled dataset for patients treated with nivolumab monotherapy 
(n=3691are presented in Table 4. These reactions are presented by system organ class and by 
frequency. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). 
 
Table 4: 
Adverse reactions with nivolumab monotherapy 
 
Nivolumab monotherapy 
Infections and infestations 
Common 
upper respiratory tract infection 
Uncommon 
pneumonia,a bronchitis 
Neoplasms benign, malignant and unspecified (including cysts and polyps) 
Rare 
histiocytic necrotising lymphadenitis (Kikuchi lymphadenitis) 
Blood and lymphatic system disorders 
Common 
neutropeniaf 
Uncommon 
Eosinophilia 
Immune system disorders 
Common 
infusion related reaction,b hypersensitivityb 
Rare 
anaphylactic reactionb 
Endocrine disorders 
Common 
hypothyroidism, hyperthyroidism 
Uncommon 
adrenal insufficiency, hypopituitarism, hypophysitis, diabetes 
mellitus, diabetic ketoacidosis, thyroiditis 
Metabolism and nutrition disorders 
Common 
decreased appetite 
Uncommon 
dehydration, metabolic acidosis 
Nervous system disorders 
Common 
peripheral neuropathy, headache, dizziness 
Uncommon 
polyneuropathy, autoimmune neuropathy (including facial and 
abducens nerve paresis) 
Rare 
Guillain-Barré syndrome, demyelination, myasthenic syndrome, 
encephalitisa,b 
Eye disorders 
Uncommon 
uveitis, blurred vision, dry eye 
Cardiac disorders 
Uncommon 
tachycardia, atrial fibrillation 
Rare 
arrhythmia (including ventricular arrhythmia), myocarditis,a,c 
Vascular disorders 
Uncommon 
Hypertension 
Rare 
Vasculitis 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
128 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 4: 
Adverse reactions with nivolumab monotherapy 
 
Respiratory, thoracic and mediastinal disorders 
Common 
pneumonitis,a,b dyspnoea,a cough 
Uncommon 
pleural effusion 
Rare 
lung infiltration 
Gastrointestinal disorders 
Very common 
diarrhea, nausea 
Common 
colitisa, stomatitis, vomiting, abdominal pain, constipation, dry 
mouth 
Uncommon 
pancreatitis, gastritis 
Rare 
duodenal ulcer 
Hepatobiliary disorders 
Uncommon 
hepatitisb 
Skin and subcutaneous tissue disorders 
Very common 
rash d pruritus 
Common 
vitiligo, dry skin, erythema, alopecia 
Uncommon 
erythema multiforme, psoriasis, urticaria 
Rare 
Rosacea, toxic epidermal necrolysis,a,c Stevens-Johnson 
syndromea,c 
Musculoskeletal and connective tissue disorders 
Common 
musculoskeletal pain,e arthralgia 
Uncommon 
polymyalgia rheumatica, arthritis 
Rare 
myopathy, myositis (including polymyositis),a,c 
rhabdomyolysis,a,c Sjogren’s syndrome 
Common 
musculoskeletal pain,e arthralgia 
Renal and urinary disorders 
Uncommon 
tubulointerstitial nephritis, renal failure (including acute kidney 
injury)a,b 
General disorders and administration site conditions 
Very common 
Fatigue 
Common 
pyrexia, oedema (including peripheral oedema) 
Uncommon 
pain, chest pain 
Investigations 
Common 
weight decreased 
a Fatal cases have been reported in completed or ongoing clinical studies. 
b Life-threatening cases have been reported in completed or ongoing clinical studies. 
c Including those reported in studies outside the pooled dataset. The frequency is based on the program-wide 
exposure. 
d Rash is a composite term which includes maculopapular rash, rash erythematous, rash pruritic, rash follicular, rash 
macular, rash morbilliform, rash papular, rash pustular, rash papulosquamous, rash vesicular, rash generalized, 
exfoliative rash, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis bullous, 
dermatitis exfoliative, dermatitis psoriasiform, drug eruption. 
e Musculoskeletal pain is a composite term which includes back pain, bone pain, musculoskeletal chest pain, 
musculoskeletal discomfort, myalgia, neck pain, pain in extremity, spinal pain. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
129 
Approved v 41.0 
930144776 4.0 
 
 
f Frequency reflects the proportion of patients who experienced a worsening from baseline in laboratory 
measurements. 
 
The overall safety profile of nivolumab 3 mg/kg for the adjuvant treatment of melanoma 
(n = 452) was generally consistent with that established across tumor types for nivolumab 
monotherapy. 
The overall safety profile of nivolumab 3 mg/kg for the treatment of colorectal cancer (n=74) 
was generally consistent with that established across tumor types for nivolumab monotherapy. 
Nivolumab in combination with ipilimumab 
RCC 
In the dataset of nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC 
(n = 547), with a minimum follow-up of 17.5 months, the most frequent adverse 
reactions (≥ 10%)  were  fatigue (48%),  rash (34%),  pruritus (28%),  diarrhea (27%), 
nausea (20%),  hypothyroidism (16%),  musculoskeletal  pain (15%),  arthralgia (14%), 
decreased appetite (14%), pyrexia (14%), vomiting (11%), and hyperthyroidism (11%). The 
majority of adverse reactions were mild to moderate (Grade 1 or 2). 
Among the patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg 
in CA209214, 169/547 (31%) had the first onset of Grade 3 or 4 adverse reactions during the 
initial combination phase. Among the 382 patients in this group who continued treatment in 
the single-agent phase, 144 (38%) experienced at least one Grade 3 or 4 adverse reaction 
during the single-agent phase. With a minimum of 60 months follow-up from study CA209214 
in RCC, no new safety signals were identified. 
NSCLC 
In the dataset of nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC (n=576), 
the most frequent adverse reactions (≥10%) were rash (28%), fatigue (24%), diarrhea (17%), 
pruritus (14%), decreased appetite (13%), hypothyroidism (13%), and nausea (10%). The majority 
of adverse reactions were mild to moderate (Grade 1 or 2). Median duration of therapy was 4.19 
months (95% CI 3.71, 5.09) for nivolumab in combination with ipilimumab and 2.63 months (95% 
CI 2.56, 2.79) for chemotherapy. 
Tabulated list of adverse reactions 
Adverse reactions reported in the pooled dataset for patients treated with nivolumab in 
combination with ipilimumab (n=547 for RCC regimen and n=576 for NSCLC regimen) are 
presented in Table 5. These reactions are presented by system organ class and by frequency. 
Frequencies are defined as: 
very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 5: 
Adverse reactions with nivolumab in combination with ipilimumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
130 
Approved v 41.0 
930144776 4.0 
 
 
 
 
 
Nivolumab 3 mg/kg in combination with 
Ipilimumab 1 mg/kg in RCC** 
Nivolumab 3 mg/kg in combination 
with ipilimumab 1 mg/kg in 
NSCLC*** 
Infections and infestations 
Common 
pneumonia, upper respiratory tract 
infection 
Uncommon 
bronchitis, aseptic meningitis 
pneumonia, bronchitis, upper 
respiratory tract infection 
Blood and lymphatic system disorders 
Uncommon 
eosinophilia 
eosinophilia 
Immune system disorders 
Common 
infusion-related 
reaction, 
hypersensitivity 
infusion-related reaction 
Uncommon 
hypersensitivity 
Endocrine disorders 
Very common 
hypothyroidism, hyperthyroidism 
hypothyroidism 
Common 
adrenal insufficiencyb, hypophysitisb, 
thyroiditis, diabetes mellitusb 
adrenal insufficiency, 
hypopituitarism, 
hypophysitis, hyperthyroidism, 
diabetes mellitus 
Uncommon 
diabetic ketoacidosisb, hypopituitarism 
Thyroiditis 
Metabolism and nutrition disorders 
Very common 
decreased appetite 
decreased appetite 
Common 
Dehydration 
Dehydration 
Uncommon 
metabolic acidosis 
Hyperglycaemia 
Hepatobiliary disorders 
Common 
Hepatitisb 
Hepatitis 
Nervous system disorders 
Common 
headache, 
peripheral 
neuropathy, 
dizziness 
Headache 
Uncommon 
polyneuropathy, 
autoimmune 
neuropathy 
(including 
facial 
and 
abducens nerve paresis), myasthenia 
gravisb 
peripheral neuropathy, dizziness, 
encephalitis, neuropathy 
(including 
facial and abducens nerve 
paresis), myasthenia gravis 
Eye disorders 
Common 
blurred vision 
Uncommon 
Uveitis 
uveitis, blurred vision 
Cardiac disorders 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 5: 
Adverse reactions with nivolumab in combination with ipilimumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
131 
Approved v 41.0 
930144776 4.0 
 
 
 
 
 
Nivolumab 3 mg/kg in combination with 
Ipilimumab 1 mg/kg in RCC** 
Nivolumab 3 mg/kg in combination 
with ipilimumab 1 mg/kg in 
NSCLC*** 
Common 
Tachycardia 
Uncommon 
arrhythmia 
(including 
ventricular 
arrhythmia), myocarditisb 
atrial fibrillation, myocarditisa, 
Vascular disorders 
Common 
Hypertension 
Uncommon 
Hypertension 
Respiratory, thoracic and mediastinal disorders 
Common 
pneumonitis, 
dyspnoea, 
pleural 
effusion, cough 
Pneumonitisa, , dyspnoea, cough 
Uncommon 
pleural effusion 
Gastrointestinal disorders 
Very common 
diarrhea, vomiting, nausea 
diarrhea, nausea 
Common 
colitis, 
stomatitis, 
pancreatitis, 
abdominal pain, constipation, dry mouth 
colitis, vomiting, stomatitis, 
abdominal 
pain, constipation, dry mouth, 
pancreatitis 
Uncommon 
Gastritis 
Gastritis 
Skin and subcutaneous tissue disorder 
Very common 
rashc, pruritus 
Rashd, pruritus 
Common 
dry skin, erythema, urticaria 
dry skin, erythema 
Uncommon 
Stevens-Johnson 
syndrome, 
vitiligo, 
erythema 
multiforme, 
alopecia, 
psoriasis 
urticaria, erythema multiforme, 
vitiligo, alopecia 
Musculoskeletal and connective tissue disorders 
Very common 
musculoskeletal paine, arthralgia 
Common 
arthritis, 
muscle 
spasms, 
muscular 
weakness 
musculoskeletal paine, 
arthralgia, arthritis 
Uncommon 
polymyalgia 
rheumatica, 
myositis 
(including 
polymyositis), 
rhabdomyolysis 
Polymyalgia rheumatica, 
myositis 
(including polymyositis), 
rhabdomyolysis 
Renal and urinary disorders 
Common 
renal failure (including acute kidney 
injury)b 
renal failure (including acute 
kidney injury) 
Uncommon 
tubulointerstitial nephritis 
tubulointerstitial nephritis 
General disorders and administration site conditions 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Table 5: 
Adverse reactions with nivolumab in combination with ipilimumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
132 
Approved v 41.0 
930144776 4.0 
 
 
 
 
 
Nivolumab 3 mg/kg in combination with 
Ipilimumab 1 mg/kg in RCC** 
Nivolumab 3 mg/kg in combination 
with ipilimumab 1 mg/kg in 
NSCLC*** 
Very common 
fatigue, pyrexia 
Fatigue 
Common 
oedema (including peripheral oedema), 
pain, chest pain, chills 
pyrexia, oedema (including 
peripheral 
oedema) 
Uncommon 
chest pain 
Investigationsb 
Common 
weight decreased 
weight decreased 
 
** Nivolumab in combination with ipilimumab for the first 4 doses then followed by nivolumab monotherapy in RCC. 
*** Nivolumab every 2 weeks in combination with ipilimumab every 6 weeks in NSCLC. 
a Fatal cases have been reported in completed or ongoing clinical studies. 
b Life-threatening cases have been reported in completed or ongoing clinical studies. 
c Rash is a composite term which includes maculopapular rash, rash erythematous, rash pruritic, rash follicular, rash 
macular, rash morbilliform, rash papular, rash pustular, rash papulosquamous, rash vesicular, rash generalised, 
exfoliative rash, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis bullous, 
dermatitis exfoliative, dermatitis psoriasiform, drug eruption and pemphigoid. 
d Reported also in studies outside the pooled dataset. The frequency is based on the program-wide exposure. 
e Musculoskeletal pain is a composite term which includes back pain, bone pain, musculoskeletal chest pain, 
musculoskeletal discomfort, myalgia, neck pain, pain in extremity, and spinal pain. 
 
Nivolumab in combination with ipilimumab and chemotherapy 
NSCLC 
In the dataset of nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 2 cycles of 
chemotherapy in NSCLC (n = 358), the most frequent adverse reactions (≥10%) were fatigue 
(36%), nausea (26%), rash (25%), diarrhea (20%), pruritus (18%), decreased appetite (16%), 
hypothyroidism (15%), and vomiting (13%). The majority of adverse reactions were mild to 
moderate (Grade 1 or 2). Median duration of therapy was 6.1 months (95% CI 4.93, 7.06) for 
nivolumab in combination with ipilimumab and 2.4 months (95% CI 2.30, 2.83) for platinum- 
based chemotherapy. 
Tabulated list of adverse reactions 
Adverse reactions reported in the dataset for patients treated with nivolumab in combination with 
ipilimumab and platinum-based chemotherapy (n = 358) are presented in Table 6. These reactions 
are presented by system organ class and by frequency. Frequencies are defined as: very common 
(≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to 
<1/1,000); very rare (<1/10,000). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
133 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 6: 
Adverse reactions with nivolumab in combination with ipilimumab 
and chemotherapy 
 
Infections and infestations 
Common 
conjunctivitis, 
pneumonia, 
respiratory 
tract 
infection 
Blood and lymphatic system disorders 
Common 
febrile neutropenia 
Uncommon 
Eosinophilia 
Immune system disorders 
Common 
infusion-related reaction, hypersensitivity 
Endocrine disorders 
Very common 
Hypothyroidism 
Common 
hyperthyroidism, 
adrenal 
insufficiency, 
hypophysitis, thyroiditis 
Uncommon 
hypopituitarism, hypoparathyroidism 
Metabolism and nutrition disorders 
Very common 
decreased appetite 
Common 
dehydration, hypoalbunaemia, hypophosphatemia 
Nervous system disorders 
Common 
peripheral neuropathy, dizziness 
Uncommon 
polyneuropathy, autoimmune neuropathy (including 
facial and abducens nerve paresis), encephalitis 
Eye disorders 
Common 
dry eye 
Uncommon 
blurred vision, episcleritis 
Cardiac disorders 
Uncommon 
tachycardia, atrial fibrillation, bradycardia 
Vascular disorders 
Uncommon 
Hypertension 
Respiratory, thoracic and mediastinal disorders 
Common 
pneumonitis, dyspnoea, cough 
Uncommon 
pleural effusion 
Gastrointestinal disorders 
Very common 
nausea, diarrhea, vomiting 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
134 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 6: 
Adverse reactions with nivolumab in combination with ipilimumab 
and chemotherapy 
 
Common 
constipation, stomatitis, abdominal pain, colitis, dry 
mouth, pancreatitis 
Hepatobiliary disorders 
Common 
Hepatitis 
Skin and subcutaneous tissue disorders 
Very common 
rasha, pruritus 
Common 
alopecia, dry skin, erythema, urticaria 
Uncommon 
psoriasis, Stevens-Johnson syndrome, vitiligo 
Musculoskeletal and connective tissue disorders 
Common 
musculoskeletal painb, arthralgia, arthritis 
Uncommon 
muscular weakness, muscle spasms, polymyalgia 
rheumatica 
Renal and urinary disorders 
Common 
renal failure (including acute kidney injury) 
Uncommon 
Nephritis 
General disorders and administration site conditions 
Very common 
Fatigue 
Common 
pyrexia, oedema (including peripheral oedema) 
Uncommon 
chills, chest pain 
Investigations 
Common 
increased thyroid-stimulating hormone 
Uncommon 
increased gamma-glutamyl transferase 
* Nivolumab every 3 weeks in combination with ipilimumab every 6 weeks and platinum-based chemotherapy every 
3 weeks for 2 cycles, then followed by nivolumab every 3 weeks in combination with ipilimumab every 6 weeks 
in NSCLC. 
a Rash is a composite term which includes maculopapular rash, rash erythematous, rash pruritic, rash, macular, rash 
morbilliform, rash papular, rash generalised, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, 
dermatitis bullous, and drug eruption. 
b Musculoskeletal pain is a composite term which includes back pain, bone pain, musculoskeletal chest pain, myalgia, 
neck pain, pain in extremity, and spinal pain 
 
Nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy 
GC, GEJC, or EAC 
In the dataset of nivolumab 240 mg or 360 mg in combination with fluoropyrimidine- and 
platinum-containing chemotherapy in GC, GEJC, or EAC (n=782), with a minimum follow-up of 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
135 
Approved v 41.0 
930144776 4.0 
 
 
12.1 months, the most frequent adverse reactions (≥10%) were peripheral neuropathy (53%), 
nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), 
abdominal pain (27%), constipation (25%), musculoskeletal pain (20%), pyrexia (19%), rash 
(18%), stomatitis (17%), lipase increased (14%), palmar-plantar erythrodysaesthesia syndrome 
(13%), alkaline phosphatase increased (13%), cough (13%), edema (including peripheral edema) 
(12%), amylase increased (12%), headache (11%), and upper respiratory tract infection (10%). 
Median duration of therapy was 6.75 months (95% CI: 6.11, 7.36) for nivolumab in combination 
with chemotherapy and 4.86 months (95% CI: 4.47, 5.29) for chemotherapy. 
Tabulated list of adverse reactions 
Adverse reactions reported in the dataset for patients treated with nivolumab 240 mg or 360 mg in 
combination with fluoropyrimidine- and platinum-containing chemotherapy (n=782) are presented 
in Table 7. These reactions are presented by system organ class and by frequency. Frequencies are 
defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); 
rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
136 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 7: 
Adverse reactions with nivolumab in combination with 
fluoropyrimidine- and platinum-containing chemotherapy 
 
Infections and infestations 
Very common 
upper respiratory tract infection 
Common 
Pneumonia 
Blood and lymphatic system disorders 
Common 
febrile neutropenia, eosinophilia 
Immune system disorders 
Common 
hypersensitivity, infusion related reaction 
Endocrine disorders 
Common 
hypothyroidism, hyperthyroidism 
Uncommon 
hypopituitarism, adrenal insufficiency, hypophysitis, 
diabetes mellitus 
Metabolism and nutrition disorders 
Very common 
decreased appetite 
Nervous system disorders 
Very common 
peripheral neuropathy, headache 
Common 
paraesthesia, dizziness 
Uncommon 
Guillain-Barre syndrome 
Eye disorders 
Common 
dry eye, blurred vision 
Uncommon 
Uveitis 
Cardiac disorders 
Common 
Tachycardia 
Uncommon 
Myocarditis 
Vascular disorders 
Common 
thrombosis, hypertension 
Respiratory, thoracic and mediastinal disorders 
Very common 
cough 
Common 
pneumonitis, dyspnoea 
Gastrointestinal disorders 
Very common 
diarrhea, stomatitis, vomiting, nausea, abdominal pain, 
constipation 
Common 
colitis, dry mouth 
Uncommon 
Pancreatitis 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
137 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 7: 
Adverse reactions with nivolumab in combination with 
fluoropyrimidine- and platinum-containing chemotherapy 
 
Hepatobiliary disorders 
Uncommon 
Hepatitis 
Skin and subcutaneous tissue disorders 
Very common 
palmar-plantar erythrodysaesthesia syndrome, rasha 
Common 
pruritus, skin hyperpigmentation, alopecia, dry skin, 
erythema 
Musculoskeletal and connective tissue disorders 
Very common 
musculoskeletal painb 
Common 
arthralgia, muscular weakness 
Renal and urinary disorders 
Common 
renal failure 
Uncommon 
Nephritis 
General disorders and administration site conditions 
Very common 
Fatigue, pyrexia, edema (including peripheral edema) 
Investigations 
Very common 
increased lipase, increased alkaline phosphatase, increased 
amylase 
a Rash is a composite term that includes maculopapular rash, rash erythematous, rash pruritic, rash macular, rash 
morbilliform, rash papular, rash generalised, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, 
dermatitis bullous, drug eruption, and exfoliative rash, nodular rash, rash vesicular. 
b Musculoskeletal pain is a composite term that includes back pain, bone pain, musculoskeletal chest pain, myalgia, 
neck pain, pain in extremity, spinal pain, and musculoskeletal discomfort. 
 
Description of selected adverse reactions - nivolumab monotherapy 
Management guidelines for the following immune-related adverse reactions are described in 
Section (4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE). 
Immune-related pneumonitis 
In patients treated with nivolumab monotherapy, the incidence of pneumonitis, including 
interstitial lung disease and lung infiltration, was 3.5% (131/3691). The majority of cases were 
Grade 1 or 2 in severity reported in 1.0% (36/3691) and 1.7% (63/3691) of patients, respectively. 
Grade 3 and 4 cases were reported in 0.8% (29/3691) and <0.1% (1/2950) of patients, respectively. 
Grade 5 cases were reported in <0.1% (2/ 3691) of patients in these studies. 
Median time to onset was 3.3 months (range: 0.2-19.6). Fifty-six patients (1.5%) required 
permanent discontinuation of nivolumab. Eighty-four patients received high-dose corticosteroids 
(at least 40 mg prednisone equivalents) at a median initial dose of 1.0 mg/kg (range: 0.5- 25.3) for 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
138 
Approved v 41.0 
930144776 4.0 
 
 
a median duration of 3.4 weeks (range: 0.1-13.1). Resolution occurred in 87 patients (66.4%) with 
a median time to resolution of 6.6 weeks (range: 0.1+-96.7+); (+ denotes a censored observation). 
Immune-related colitis 
In patients treated with nivolumab monotherapy, the incidence of diarrhea, colitis or frequent 
bowel movements was 12.5% (369/2950). The majority of cases were Grade 1 or 2 in severity 
reported in 8.0% (236/2950) and 3.0% (88/2950) of patients, respectively. Grade 3 cases were 
reported in 1.5% (45/2950) of patients. No Grade 4 or 5 cases were reported. 
Median time to onset was 1.6 months (range: 1 day-26.6 months). Twenty-six patients (0.7%) 
required permanent discontinuation of nivolumab. Sixty-two patients received high-dose 
corticosteroids (at least 40 mg prednisone equivalents) at a median initial dose of 1.0 mg/kg 
(range: 0.4-4.7) for a median duration of 2.4 weeks (range: 0.1-30.7). Resolution occurred in 
417 patients (87.6 %) with a median time to resolution of 2.7 weeks (range: 0.1-124.4+). 
Immune-related hepatitis 
In patients treated with nivolumab monotherapy, the incidence of liver function test abnormalities 
was 6.9% (256/3691). The majority of cases were Grade 1 or 2 in severity reported in 3.8% 
(139/3691) and 1.4% (53/3691) of patients, respectively. Grade 3 and Grade 4 cases were reported 
in 1.5% (55/3691) and 0.2% (9/ 3691) of patients, respectively. No Grade 5 cases were reported. 
Median time to onset was 1.9 months (range: 1 day - 27.6 months). Thirty-one patients (0.8%) 
required permanent discontinuation of nivolumab. Forty-five patients received high-dose 
corticosteroids (at least 40 mg prednisone equivalents) at a median initial dose of 1.2 mg/kg 
(range: 0.4-4.7) for a median duration of 2.8 weeks (range: 0.1-22.1). Resolution occurred in 193 
patients (76.6%) with a median time to resolution of 16.1 weeks (range: 0.1- 126.4+). 
Immune-related nephritis and renal dysfunction 
In patients treated with nivolumab monotherapy, the incidence of nephritis and renal dysfunction 
was 2.2% (82/3691). The majority of cases were Grade 1 or 2 in severity reported in 1.2% 
(45/3691) and 0.6% (23/3691) of patients, respectively. Grade 3 and 4 cases were reported in 0.4% 
(13/3691) and <0.1% (1/3691) of patients, respectively. No Grade 5 nephritis or renal dysfunction 
was reported. 
Median time to onset was 2.3 months (range: 1 day - 18.2 months). Seven patients (0.3%) required 
permanent discontinuation of nivolumab. Twenty-one patients received high-dose corticosteroids 
(at least 40 mg prednisone equivalents) at a median initial dose of 0.9 mg/kg (range: 0.5-3.6) for a 
median duration of 2.9 weeks (range: 0.1-67.0). Resolution occurred in 51 patients (65.4%) with 
a median time to resolution of 9.6 weeks (range: 0.3+-79.1+). 
Immune-related endocrinopathies 
In patients treated with nivolumab monotherapy, the incidence of thyroid disorders including 
hypothyroidism or hyperthyroidism was 10.2% (376/3691). The majority of cases were Grade 1 
or 2 in severity reported in 4.9% (180/3691) and 5.2% (191/3691) of patients, respectively. Grade 
3 thyroid disorders were reported in 0.1% (5/3691) of patients. Hypophysitis (1 Grade 1, 2 Grade 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
139 
Approved v 41.0 
930144776 4.0 
 
 
2, 5 Grade 3 and 1 Grade 4), hypopituitarism (5 Grade 2 and 1 Grade 3), adrenal insufficiency 
including secondary adrenocortical insufficiency (1 Grade 1, 11 Grade 2, and 6 Grade 3), diabetes 
mellitus (10 cases, including Type 1 diabetes mellitus), and diabetic ketoacidosis (3 Grade 3 and 
1 Grade 4) were also reported. Twelve patients experienced a shift from baseline to Grade 3 or 4 
hyperglycemia. No Grade 5 endocrinopathies were reported. 
Median time to onset of these endocrinopathies was 2.7 months (range: 0.3-29.1). Three patients 
(0.3%) required permanent discontinuation of nivolumab. Twenty-five patients received high- 
dose corticosteroids (at least 40 mg prednisone equivalents) at a median initial dose of 0.9 mg/kg 
(range: 0.4-2.2) for a median duration of 2.0 weeks (range: 0.1-51.1). Resolution occurred 
in191 patients (46.7%). Time to resolution ranged from 0.4 to 150.0+ weeks. 
Immune-related skin adverse reactions 
In patients treated with nivolumab monotherapy, the incidence of rash was 25.2% (931/3691). The 
majority of cases were Grade 1 in severity reported in 18.9% (696/3691) of patients. Grade 2 and 
Grade 3 cases were reported in 5.1% (189/3691) and 1.2% (46/3691) of patients, respectively. No 
Grade 4 or 5 cases were reported. 
Median time to onset was 1.3 months (range: 1 day-27.9 months). Nineteen patients (0.5%) 
required permanent discontinuation of nivolumab. Thirty-six patients received high-dose 
corticosteroids (at least 40 mg prednisone equivalents) at a median initial dose of 0.9 mg/kg 
(range: 0.4-363.6) for a median duration of 1.9 weeks (range: 0.1- 11.9). Resolution occurred in 
581 patients (63.1%) with a median time to resolution of 17.7 weeks (range: 0.1- 163.1+). 
Infusion reactions 
In patients treated with nivolumab monotherapy, the incidence of hypersensitivity/infusion 
reactions, including anaphylactic reaction, was 3.7% (136/3691), including 6 Grade 3 (0.2%) and 
3 Grade 4 (<0.1%) cases. No Grade 5 cases were reported. 
Description of selected adverse reactions - nivolumab in combination with ipilimumab 
The management guidelines for these adverse reactions are described in section (4.4.2 PRODUCT- 
SPECIFIC WARNINGS AND PRECAUTIONS). 
Immune-related pneumonitis 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC, the 
incidence of pneumonitis including interstitial lung disease was 6.2% (34/547). Grade 2 and 
Grade 3 cases were reported in 3.1% (17/547) and 1.1% (6/547) of patients, respectively. No 
Grade 4 or 5 cases were reported in this study. Median time to onset was 2.6 months (range: 0.25- 
20.6). Resolution occurred in 31 patients (91.2%) with a median time to resolution of 6.1 weeks 
(range: 0.7-85.9+). 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of pneumonitis including interstitial lung disease was 8.0% (48/576). Grade 2, Grade 
3, and Grade 4 cases were reported in 4.0% (23/576), 3% (17/576), and 0.3% (2/576) of patients, 
respectively. Four patients died due to pneumonitis. Median time to onset was 3.6 months (range: 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
140 
Approved v 41.0 
930144776 4.0 
 
 
0.9-23.7). Resolution occurred in 41 patients (85.4%) with a median time to resolution of 6.0 weeks 
(range: 0.7-109.4+). 
Immune-related colitis 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC, the 
incidence of diarrhea or colitis was 28.2% (154/547). Grade 2 and Grade 3 cases were reported 
in 10.4% (57/547) and 4.9% (27/547) of patients, respectively. No Grade 4 or 5 cases were 
reported. Median time to onset was 1.2 months (range: 0.0-24.7). Resolution occurred in 
140 patients (91.5%) with a median time to resolution of 2.4 weeks (range: 0.1-103.1+). 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of diarrhea or colitis was 18.2% (105/576). Grade 2, Grade 3 and Grade 4 cases were 
reported in 7.5% (43/576), 2.1% (12/576) and 0.3% (2/576) of patients, respectively. Median time 
to onset was 2 months (range: 0.0-22.5). Resolution occurred in 98 patients (94.2%) with a median 
time to resolution of 2.1 weeks (range: 0.1-149.3+). 
Immune-related hepatitis 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC, the 
incidence of liver function test abnormalities was 18.5% (101/547). Grade 2, Grade 3, and Grade 4 
cases were reported in 4.8% (26/547), 6.6% (36/547), and 1.6% (9/547) of patients, respectively. 
No Grade 5 cases were reported. Median time to onset was 2.0 months (range: 0.4-26.8). 
Resolution occurred in 86 patients (85.1%) with a median time to resolution of 6.1 weeks 
(range: 0.1+-82.9+). 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of liver function test abnormalities was 15.8% (91/576). Grade 2, Grade 3, and Grade 
4 cases were reported in 2.8% (16/576), 7.5% (43/576), and 0.7% (4/576) of patients, respectively. 
Median time to onset was 2.4 months (range: 0.2-20.3). Resolution occurred in 82 patients (90.1%) 
with a median time to resolution of 5.3 weeks (range: 0.4-155.1+). 
Immune-related nephritis and renal dysfunction 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC, the 
incidence of nephritis or renal dysfunction was 8.8% (48/547). Grade 2, Grade 3, and Grade 4 
cases were reported in 4.4% (24/547), 0.7% (4/547), and 0.5% (3/547) of patients, respectively. 
No Grade 5 cases were reported. Median time to onset was 2.1 months (range: 0.0-16.1). 
Resolution occurred in 37 patients (77.1%) with a median time to resolution of 13.2 weeks 
(range: 0.1+-106.0+). 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of nephritis or renal dysfunction was 4.3% (25/576). Grade 2, Grade 3, and Grade 4 
cases were reported in 1.4% (8/576), 0.5% (3/576), and 0.2% (1/576) of patients, respectively. 
Median time to onset was 4.9 months (range: 0.5-21.2). Resolution occurred in 23 patients (92.0%) 
with a median time to resolution of 2.4 weeks (range: 0.3-152.4+). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
141 
Approved v 41.0 
930144776 4.0 
 
 
Immune-related endocrinopathies 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC, the 
incidence of thyroid disorders was 27.2% (149/547). Grade 2 and Grade 3 thyroid disorders were 
reported in 15.7% (86/547) and 1.3% (7/547) of patients, respectively. Hypophysitis occurred in 
4.0% (22/547) of patients. Grade 2, Grade 3, and Grade 4 cases were reported in 0.5% (3/547), 
2.4% (13/547), and 0.4% (2/547) of patients, respectively. Grade 2 hypopituitarism occurred in 
0.4% (2/547) of patients. Grade 2, Grade 3, and Grade 4 adrenal insufficiency (including 
secondary adrenocortical insufficiency) occurred in 2.9% (16/547), 2.2% (12/547) and 0.4% 
(2/547) of patients, respectively. Diabetes mellitus including Type 1 diabetes mellitus (3 Grade 2, 
2 Grade 3, and 3 Grade 4), and diabetic ketoacidosis (1 Grade 4) were reported. No Grade 5 
endocrinopathy was reported. Median time to onset of these endocrinopathies was 1.9 months 
(range: 0.0-22.3). Resolution occurred in 76 patients (42.7%). Time to resolution ranged 
from 0.4 to 130.3+ weeks. 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of thyroid disorders was 20.0% (115/576). Grade 2, Grade 3 and Grade 4 thyroid 
disorders were reported in 10.6% (61/576), 0.3% (2/576) and 0.2% (1/576) of patients, 
respectively. Hypophysitis occurred in 2.1% (12/576) of patients. Grade 2, Grade 3, and Grade 4 
cases were reported in 0.7% (4/576), 0.9% (5/576), and 0.2% (1/576) of patients, respectively. 
Grade 2 and Grade 3 hypopituitarism occurred in 0.2% (1/576) and 0.5% (3/576) of patients, 
respectively. Grade 2 and Grade 3 adrenal insufficiency occurred in 1% (6/576) and 1.7% (10/576) 
of patients, respectively. Diabetes mellitus including, Type 1 diabetes mellitus, occurred in 0.9% 
(5/576) of patients (1 Grade 2, 3 Grade 3, and 1 Grade 4). Median time to onset of these 
endocrinopathies was 2.3 months (range: 0.5-16.1). Resolution occurred in 57 patients (41.9%). 
Time to resolution ranged from 0.7 to 176.6+ weeks. 
Immune-related skin adverse reactions 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in RCC, the 
incidence of rash was 48.8% (267/547). Grade 2 and Grade 3 cases were reported in 13.7% 
(75/547) and 3.7% (20/547) of patients, respectively. No Grade 4 or 5 cases were reported. Median 
time to onset was 0.9 months (range: 0.0-17.9). Resolution occurred in 192 patients (72.2%) with 
a median time to resolution of 11.6 weeks (range: 0.1-126.7+). 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of rash was 34.0% (196/576). Grade 2 and Grade 3 cases were reported in 10.6% 
(61/576) and 4.2% (24/576) of patients, respectively. Median time to onset was 1.0 month (range: 
0.0-18). Resolution occurred in 148 patients (75.5%) with a median time to resolution of 9.9 weeks 
(range: 0.1-165.0+). 
 
Infusion reactions 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg//kg in RCC, the 
incidence of hypersensitivity/infusion reactions was 4.0% (22/547); all were Grade 1 or 2 in 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
142 
Approved v 41.0 
930144776 4.0 
 
 
severity. Grade 2 cases were reported in 2.4% (13/547) of patients. No Grade 3-5 cases were 
reported. 
In patients treated with nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in NSCLC, 
the incidence of hypersensitivity/infusion reactions was 4.0% (23/576); all were Grade 1 or 2 in 
severity. Grade 2 cases were reported in 2.4% (14/576) of patients. 
Description of selected adverse reactions - nivolumab in combination with ipilimumab 
and chemotherapy 
The management guidelines for these adverse reactions are described in section 4.4.2. 
Immune-related pneumonitis 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of pneumonitis including interstitial lung disease was 
5.3% (19/358). Grade 2, Grade 3, and Grade 4 cases were reported in 2.2% (8/358), 1.1% (4/358), 
and 0.6% (2/358) of patients, respectively. No Grade 5 cases were reported. Median time to onset 
was 18.1 weeks (range: 0.6-52.4). Resolution occurred in 14 patients (74%) with a median time to 
resolution of 4.3 weeks (range: 0.7-27.9+). 
Immune-related colitis 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of diarrhea or colitis was 22.3% (80/358). Grade 2, Grade 
3, Grade 4, and Grade 5 cases were reported in 7% (25/358), 5% (18/358), 0.3% (1/358), and 0.3% 
(1/358) of patients, respectively. Median time to onset was 5.1 weeks (range: 0.1- 53.6). Resolution 
occurred in 70 patients (87.5%) with a median time to resolution of 1.4 weeks (range: 0.1-76.9+). 
Immune-related hepatitis 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of liver function test abnormalities was 13.4% (48/358). 
Grade 2, Grade 3, and Grade 4 cases were reported in 3.1% (11/358), 3.4% (12/358), and 1.1% 
(4/358) of patients, respectively. No Grade 5 cases were reported. Median time to onset was 10.6 
weeks (range: 1.1-68.3). Resolution occurred in 37 patients (80.4%) with a median time to 
resolution of 5 weeks (range: 0.3+-45.0+). 
Immune-related nephritis and renal dysfunction 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of nephritis or renal dysfunction was 7% (25/358). Grade 
2, Grade 3, and Grade 4 cases were reported in 2.2% (8/358), 1.7% (6/358), and 0.6% (2/358) of 
patients, respectively. No Grade 5 cases were reported. Median time to onset was 10.6 weeks 
(range: 0.1-51.3). Resolution occurred in 14 patients (56%) with a median time to resolution of 6.3 
weeks (range: 0.1+-82.9+). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
143 
Approved v 41.0 
930144776 4.0 
 
 
Immune-related endocrinopathies 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of thyroid disorders was 24% (86/358). Grade 2 and Grade 
3 thyroid disorders were reported in 12.3% (44/358) and 0.3% (1/358) of patients, respectively. 
Hypophysitis occurred in 1.4% (5/358) of patients. Grade 2 and Grade 3 cases were reported in 
0.6% (2/358) and 0.8% (3/358) of patients, respectively. Grade 2 hypopituitarism occurred in 0.3% 
(1/358) of patients. Grade 2 and Grade 3 adrenal insufficiency occurred in 1.7% (6/358) and 1.4% 
(5/358) of patients, respectively. Diabetes mellitus including Type 1 diabetes mellitus was not 
reported. No Grade 5 endocrinopathy was reported. Median time to onset of these endocrinopathies 
was 12.1 weeks (range: 1.9-58.3). Resolution occurred in 30 patients (35.3%). Time to resolution 
ranged from 1.4 to 72.4+ weeks. 
Immune-related skin adverse reactions 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of rash was 37.7% (135/358). Grade 2, Grade 3, and Grade 
4 cases were reported in 11.5% (41/358), 4.2% (14/358), and 0.3% (1/358) of patients, 
respectively. No Grade 5 cases were reported. Median time to onset was 3.3 weeks (range: 0.1- 
83.1). Resolution occurred in 96 patients (71.6%) with a median time to resolution of 9.4 weeks 
(range: 0.1+-84.1+). 
Infusion reactions 
In patients treated with nivolumab 360 mg in combination with ipilimumab 1 mg/kg and 
chemotherapy in NSCLC, the incidence of hypersensitivity/infusion reactions was 4.7% (17/358). 
Grade 2, Grade 3, and Grade 4 cases were reported in 2.2% (8/358), 0.3% (1/358), and 0.3% 
(1/358) of patients, respectively. No Grade 5 cases were reported. 
 
Description of selected adverse reactions - nivolumab in combination with 
fluoropyrimidine- and platinum-based chemotherapy 
Immune-related pneumonitis 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
GEJC, or EAC, the incidence of pneumonitis including interstitial lung disease was 5.1% (40/782). 
Grade 2, Grade 3, and Grade 4 cases were reported in 2.3% (18/782), 1.4% (11/782), and 0.4% 
(3/782) of patients, respectively. No Grade 5 cases were reported in this study. Median time to 
onset was 23.9 weeks (range: 1.6-96.9). Resolution occurred in 28 patients (70%) with a median 
time to resolution of 10.1 weeks (range: 0.3+-121.3+). 
Immune-related colitis 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
GEJC or EAC, the incidence of diarrhea or colitis was 33.5% (262/782). Grade 2, Grade 3, and 
Grade 4 cases were reported in 10.2% (80/782), 4.9% (38/782), and 0.6% (5/782) of patients, 
respectively. No Grade 5 cases were reported in this study. Median time to onset was 4.3 weeks 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
144 
Approved v 41.0 
930144776 4.0 
 
 
(range: 0.1-93.6). Resolution occurred in 228 patients (87.4%) with a median time to resolution of 
1.6 weeks (range: 0.1-117.6+). 
 
 
Immune-related hepatitis 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
GEJC or EAC, the incidence of liver function test abnormalities was 26% (203/782). Grade 2 and 
Grade 3 cases were reported in 9.0% (70/782) and 3.7% (29/782) of patients, respectively. No 
Grade 4 or Grade 5 cases were reported in this study. Median time to onset was 7.9 weeks (range: 
0.1-61.3). Resolution occurred in 156 patients (78%) with a median time to resolution of 10.1 
weeks (range: 0.4-150.6+). 
Immune-related nephritis and renal dysfunction 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
GEJC or EAC, the incidence of nephritis or renal dysfunction was 3.3% (26/782). Grade 2, Grade 
3, and Grade 4 cases were reported in 1% (8/782), 0.6% (5/782), and 0.1% (1/782) of patients, 
respectively. No Grade 5 cases were reported in this study. Median time to onset was 12.4 weeks 
(range: 1.7-59.4). Resolution occurred in 19 patients (73.1%) with a median time to resolution of 
3.1 weeks (range: 0.1-42.4+). 
Immune-related endocrinopathies 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
GEJC or EAC, the incidence of thyroid disorders was 12.3% (96/782). Grade 2 thyroid disorder 
was reported in 6% (47/782) of patients. There were no cases of Grade 3 thyroid disorder. Grade 
3 hypophysitis occurred in 0.1% (1/782) of patients. Grade 2 and Grade 3 hypopituitarism occurred 
in 0.3% (2/782) and 0.3% (2/782) of patients, respectively. Grade 2 and Grade 3 adrenal 
insufficiency occurred in 0.4% (3/782) and 0.1% (1/782) of patients, respectively. Grade 2 and 
Grade 3 Diabetes mellitus including Type 1 diabetes mellitus were reported in 0.3% (2/782) of 
patients. Median time to onset of these endocrinopathies was 15.0 weeks (range: 2.0-124.3). 
Resolution occurred in 46 patients (43%). Time to resolution ranged from 0.4 to 139.1+ weeks. 
Immune-related skin adverse reactions 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
GEJC, or EAC, the incidence of rash was 27.4% (214/782). Grade 2 and Grade 3 cases were 
reported in 7% (55/782) and 3.3% (26/782) of patients, respectively. No Grade 4 or 5 cases were 
reported in this study. Median time to onset was 9.6 weeks (range: 0.1-97.4). Resolution occurred 
in 124 patients (57.9%) with a median time to resolution of 23.4 weeks (range: 0.1-153.6+). 
Infusion reactions 
In patients treated with nivolumab 240 mg or 360 mg in combination with chemotherapy in GC, 
the incidence of hypersensitivity/infusion reactions was 14.2% (111/782). Grade 2, Grade 3 and 
Grade 4 cases were reported in 8.8% (69/782), 1.9% (15/782) and 0.3% (2/782) of patients, 
respectively. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
145 
Approved v 41.0 
930144776 4.0 
 
 
4.8.2 
Postmarketing experience 
The following event has been identified during post approval use of nivolumab or nivolumab in 
combination with ipilimumab. Because reports are voluntary from a population of unknown size, 
an estimate of frequency cannot be made. 
Eye disorders: Vogt-Koyanagi-Harada syndrome 
Immune system disorders: solid organ transplant rejection, graft-versus-host-disease 
Blood and lymphatic system disorders: hemophagocytic lymphohistiocytosis (HLH) autoimmune 
hemolytic anemia 
 
Cardiac disorder: pericarditis 
4.8.3 
Laboratory findings 
A summary of laboratory abnormalities that worsened from baseline is presented in Table 8 
and 9, 10 11 and 12. 
Table 8: 
Laboratory abnormalities: nivolumab monotherapy 
 
Number (%) of Patients with Worsening Laboratory Test from Baseline 
Nivolumab monotherapy 
Test 
Na 
Grades 
1-4 
Grades 
3-4 
Anemiab 
3614 
1320 (36.5) 
207 (5.7) 
Thrombocytopenia 
3611 
493 (13.7) 
33 (0.9) 
Leukopenia 
3620 
581 (16.0) 
31 (0.9) 
Lymphopenia 
3600 
1507 (41.9) 
407 (11.3) 
Neutropenia 
3602 
469 (13.0) 
37 (1.0) 
Increased alkaline 
3584 
1004 (28.0) 
109 (3.0) 
phosphatase 
Increased AST 
3593 
1075 (29.9) 
130 (3.6) 
Increased ALT 
3600 
818 (22.7) 
96 (2.7) 
Increased total 
3598 
359 (10.0) 
65 (1.8) 
bilirubin 
Increased creatinine 
3608 
1059 (29.4) 
29 (0.8) 
Increased total 
amylase 
1560 
270 (17.3) 
56 (3.6) 
Increased total 
lipase 
1722 
334 (19.4) 
113 (6.6) 
Hypercalcemia 
2990 
326 (10.9) 
41 (1.4) 
Hypocalcemia 
2990 
536 (17.9) 
19 (0.6) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
146 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 8: 
Laboratory abnormalities: nivolumab monotherapy 
 
Hyperkalemia 
3551 
696 (19.6) 
58 (1.6) 
Hypokalemia 
3551 
404 (11.4) 
59 (1.7) 
Hypermagnesemiad 
Hypomagnesemiad 
Hypernatremia 
3555 
185 (5.2) 
4 (0.1) 
Hyponatremia 
3555 
1059 (29.8) 
225 (6.3) 
Hyperglycemiac,d 
485 
195(40.2) 
13(2.7) 
Hypoglycemiae 
1016 
118(11.6) 
13 (1.3) 
Toxicity scale: CTC Version 4.0. 
Includes laboratory results reported after the first dose and within 30 days of the last dose of study therapy, except for 
ONO-4538-12. For ONO-4538-12 includes events reported between the first dose and the earlier date between 28 
days after the end of the treatment period or the start date of the post-treatment observation period. The frequencies 
are regardless of causality. 
a The total number of patients who had both baseline and on-study laboratory measurements available. 
b Per anemia criteria in CTC version 4.0, there is no Grade 4 for hemoglobin. 
c Life-threatening hyperglycemia has been reported in completed or ongoing clinical studies. 
d Does not include ONO-4538-12. 
e Does not include CA209066, CA209037, CA209017, CA209057, CA209025, and CA209039 
 
 
Table 9: 
Laboratory abnormalities: nivolumab 3 mg/kg in combination 
with ipilimumab 1 mg/kg (RCC) 
 
Number (%) of Patients with Worsening Laboratory Test from Baseline 
 
Nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in 
RCC 
 
Test 
Na 
Grades 
1-4 
Grades 
3-4 
Anemiab 
541 
231 (42.7) 
18 (3.3) 
Thrombocytopenia 
541 
96 (17.7) 
7 (1.3) 
Leukopenia 
541 
85 (15.7) 
8 (1.5) 
Lymphopenia 
540 
204 (37.8) 
36 (6.7) 
Neutropenia 
540 
76 (14.1) 
11 (2) 
Increased alkaline phosphatase 
542 
167 (30.8) 
14 (2.6) 
Increased AST 
541 
225 (41.6) 
33 (6.1) 
Increased ALT 
542 
235 (43.4) 
44 (8.1) 
Increased total bilirubin 
541 
74 (13.7) 
8 (1.5) 
2256 
111 (4.9) 
15 (0.7) 
2256 
365 (16.2) 
10 (0.4) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
147 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 9: 
Laboratory abnormalities: nivolumab 3 mg/kg in combination 
with ipilimumab 1 mg/kg (RCC) 
 
Number (%) of Patients with Worsening Laboratory Test from Baseline 
 
Nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg in 
RCC 
 
Test 
Na 
Grades 
1-4 
Grades 
3-4 
Increased creatinine 
541 
215 (39.7) 
14 (2.6) 
Increased total amylase 
491 
188 (38.3) 
61 (12.4) 
Increased total lipase 
518 
236 (45.6) 
97 (18.7) 
Hypercalcemia 
529 
71 (13.4) 
9 (1.7) 
Hypocalcemia 
529 
115 (21.7) 
6 (1.1) 
Hyperkalemia 
534 
147 (27.5) 
15 (2.8) 
Hypokalemia 
534 
61 (11.4) 
13 (2.4) 
Hypermagnesemia 
528 
34 (6.4) 
6 (1.1) 
Hypomagnesemia 
528 
86 (16.3) 
2 (0.4) 
Hypernatremia 
534 
40 (7.5) 
0 
Hyponatremia 
534 
206 (38.6) 
56 (10.5) 
Toxicity scale: CTC Version 4.0. 
Includes laboratory results reported after the first dose and within 30 days of the last dose of study therapy. The 
frequencies are regardless of causality. 
a The total number of patients who had both baseline and on-study laboratory measurements available. 
b Per anemia criteria in CTC version 4.0, there is no Grade 4 for hemoglobin. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
148 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 10: 
Laboratory abnormalities: nivolumab 3 mg/kg in combination with 
ipilimumab 1 mg/kg (NSCLC) 
 
Number (%) of Patients with Worsening Laboratory Test from Baseline 
 
Nivolumab 3mg/kg in combination with ipilimumab 1 mg/kg in NSCLC 
 
Test 
Na 
Grades 
1-4 
Grades 
3-4 
Anemia 
556 
255 (45.9) 
20 (3.6) 
Thrombocytopenia 
555 
58 (10.5) 
5 (0.9) 
Leukopenia 
559 
35 (6.3) 
3 (0.5) 
Lymphopenia 
553 
254 (45.9) 
29 (5.2) 
Neutropenia 
555 
53 (9.5) 
5 (0.9) 
Increased alkaline 
552 
185 (33.5) 
21 (3.8) 
phosphatase 
Increased AST 
551 
217 (39.4) 
30 (5.4) 
Increased ALT 
555 
202 (36.4) 
39 (7.0) 
Increased total Bilirubin 
554 
63 (11.4) 
6 (1.1) 
Increased Creatinine 
554 
119 (21.5) 
5 (0.9) 
Increased total amylase 
494 
139 (28.1) 
46 (9.3) 
Increased total lipase 
524 
181 (34.5) 
73 (13.9) 
Hypernatremia 
552 
42 (7.6) 
2 (0.4) 
Hyponatremia 
552 
227 (41.1) 
64 (11.6) 
Hyperkalemia 
551 
151 (27.4) 
19 (3.4) 
Hypokalemia 
551 
83 (15.1) 
22 (4.0) 
Hypercalcemia 
545 
75 (13.8) 
10 (1.8) 
Hypocalcemia 
545 
155 (28.4) 
9 (1.7) 
Hypermagnesemia 
542 
62 (11.4) 
19 (3.5) 
Hypomagnesemia 
542 
115 (21.2) 
3 (0.6) 
 
Toxicity scale: CTC Version 4.0. 
Includes laboratory results reported after the first dose and within 30 days of the last dose of study therapy. The 
frequencies are regardless of causality. 
a The total number of patients who had both baseline and on-study laboratory measurements available. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
149 
Approved v 41.0 
930144776 4.0 
 
 
1-
 
Table 11: 
Laboratory abnormalities: nivolumab 360 mg in combination 
with ipilimumab 1 mg/kg and chemotherapy (NSCLC) 
 
Number (%) of Patients with Worsening Laboratory Test from 
Baseline 
 
Nivolumab 360 mg in combination with ipilimumab 1 mg/kg 
and chemotherapy in NSCLC 
Test 
Na 
Grades 
Grades 
3-4 
 
Anemiab 
347 
243 (70.0) 
32 (9.2) 
Thrombocytopenia 
347 
80 (23.1) 
15 (4.3) 
Leukopenia 
347 
126 (36.3) 
34 (9.8) 
Lymphopenia 
257 
105 (40.9) 
15 (5.8) 
Neutropenia 
346 
140 (40.5) 
51 (14.7) 
Increased alkaline phosphatase 
342 
106 (31.0) 
4 (1.2) 
Increased AST 
345 
102 (29.6) 
12 (3.5) 
Increased ALT 
345 
118 (34.2) 
15 (4.3) 
Increased total bilirubin 
344 
26 (7.6) 
0 
Increased creatinine 
346 
91 (26.3) 
4 (1.2) 
Increased total amylase 
312 
95 (30.4) 
21 (6.7) 
Increased total lipase 
337 
105 (31.2) 
40 (11.9) 
Hypercalcemia 
345 
39 (11.3) 
4 (1.2) 
Hypocalcemia 
345 
95 (27.5) 
5 (1.4) 
Hyperkalemia 
345 
77 (22.3) 
6 (1.7) 
Hypokalemia 
345 
53 (15.4) 
12 (3.5) 
Hypermagnesemia 
334 
35 (10.5) 
1 (0.3) 
Hypomagnesemia 
334 
107 (32.0) 
4 (1.2) 
Hypernatremia 
345 
15 (4.3) 
0 
Hyponatremia 
345 
128 (37.1) 
37 (10.7) 
Hyperglycemia 
197 
89 (45.2) 
14 (7.1) 
Hypoglycemia 
273 
35 (12.8) 
0 
Toxicity scale: CTC Version 4.0. 
Includes laboratory results reported after the first dose and within 30 days of the last dose of study therapy. The 
frequencies are regardless of causality. 
a The total number of patients who had both baseline and on-study laboratory measurements available. 
b Per anemia criteria in CTC version 4.0, there is no Grade 4 for hemoglobin. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
150 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 12: 
Laboratory abnormalities: nivolumab 240 mg or 360 mg in 
combination with fluoropyrimidine- and platinum-containing 
chemotherapy (GC, GEJC or EAC) 
 
Number (%) of Patients with Worsening Laboratory Test from 
Baseline 
 
Nivolumab 240 mg or 360 mg in combination with 
chemotherapy in GC, GEJC or EAC 
 
Test 
Na 
Grades 
1-4 
Grades 
3-4 
Hemoglobin 
765 
450 (58.8) 
106 (13.9) 
Platelet count 
762 
515 (67.6) 
52 (6.8) 
Leukocytes 
764 
524 (68.6) 
90 (11.8) 
Lymphocytes (absolute) 
763 
446 (58.5) 
93 (12.2) 
Absolute neutrophil count 
764 
556 (72.8) 
224 (29.3) 
Aspartate aminotransferase 
764 
395 (51.7) 
35 (4.6) 
Alanine aminotransferase 
764 
283 (37.0) 
26 (3.4) 
Bilirubin, total 
761 
182 (23.9) 
23 (3.0) 
Creatinine 
765 
115 (15.0) 
8 (1.0) 
Hypernatremia 
767 
84 (11.0) 
4 (0.5) 
Hyponatremia 
767 
258 (33.6) 
48 (6.3) 
Hyperkalemia 
766 
110 (14.4) 
11 (1.4) 
Hypokalemia 
766 
203 (26.5) 
50 (6.5) 
Hypercalcemia 
748 
46 (6.1) 
2 (0.3) 
Hypocalcemia 
748 
326 (43.6) 
12 (1.6) 
Hyperglycemia 
408 
166 (40.7) 
17 (4.2) 
Hypoglycemia 
407 
48 (11.8) 
3 (0.7) 
Toxicity scale: CTC Version 4.0. 
Includes laboratory results reported after the first dose and within 30 days of the last dose of study therapy. The 
frequencies are regardless of causality. 
a The total number of patients who had both baseline and on-study laboratory measurements available. 
 
4.8.4 
Immunogenicity 
As with all therapeutic proteins, there is a potential for an immune response to nivolumab. Of 
2232 patients who were treated with nivolumab monotherapy 3 mg/kg every 2 weeks and 
evaluable for the presence of anti-product-antibodies, 287 patients (12.9%) tested positive for 
treatment-emergent anti-product-antibodies by an electrochemiluminescent (ECL) assay. Sixteen 
patients (0.7%) had neutralizing antibodies. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
151 
Approved v 41.0 
930144776 4.0 
 
 
Of the patients who were treated with nivolumab in combination with ipilimumab and evaluable 
for the presence of anti-nivolumab antibodies, the incidence of anti-nivolumab antibodies was 26% 
with nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks 36.7% with nivolumab 3 mg/kg 
every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. The incidence of neutralizing antibodies 
against nivolumab was 0.5% with nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks 
1.4% with nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Of patients 
evaluable for the presence of anti-ipilimumab antibodies, the incidence of anti-ipilimumab 
antibodies ranged from 6.3 to 13.7% and neutralizing antibodies against ipilimumab ranged from 
0 to 0.4%. 
Of the patients who were treated with nivolumab in combination with ipilimumab and platinum- 
based chemotherapy and evaluable for the presence of anti-nivolumab antibodies, the incidence of 
anti-nivolumab antibodies was 33.8% and the incidence of neutralizing antibodies was 2.6%. Of 
the patients who were treated with nivolumab in combination with ipilimumab and chemotherapy 
and evaluable for the presence of anti-ipilimumab antibodies or neutralizing antibodies against 
ipilimumab, the incidence of anti-ipilimumab antibodies was 7.5%, and neutralizing antibodies 
was 1.6%. 
Although the clearance of nivolumab was increased by approximately 20% when anti-nivolumab 
antibodies were present, there was no evidence of loss of efficacy or altered toxicity profile in 
presence of nivolumab antibodies. 
4.9 
OVERDOSE 
No cases of overdose have been reported in clinical trials. 
In case of overdose, patients should be closely monitored for signs or symptoms of adverse 
reactions, and appropriate symptomatic treatment instituted. 
5 
PHARMACOLOGICAL PROPERTIES 
5.1 
Mechanism of action 
Nivolumab is a fully human IgG4 monoclonal antibody (HuMAb), which binds to the programmed 
death-1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2. The PD-1 receptor is a 
negative regulator of T-cell activity that has been shown to be involved in the control of T-cell 
immune responses. Engagement of PD-1 with the ligands PD-L1 and PD-L2, which are expressed 
in antigen presenting cells and may be expressed by tumors or other cells in the tumor 
microenvironment, results in inhibition of T-cell proliferation and cytokine secretion. Nivolumab 
potentiates T-cell responses, including anti-tumor responses, through blockade of PD-1 binding to 
PD-L1 and PD-L2 ligands. In syngeneic mouse models, blocking PD-1 activity resulted in 
decreased tumor growth. 
Combined nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) mediated inhibition results in 
enhanced T-cell function that is greater than the effects of either antibody alone, and results in 
improved anti-tumor responses in metastatic melanoma. In murine syngeneic tumor models, dual 
blockade of PD-1 and CTLA-4 resulted in synergistic anti-tumor activity. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
152 
Approved v 41.0 
930144776 4.0 
 
 
5.2 
Pharmacodynamics 
5.2.1 
Clinical Trial Information 
Non-small cell lung cancer (NSCLC) 
Randomized phase 3 study vs. docetaxel (CA209017) 
The safety and efficacy of nivolumab 3 mg/kg or the treatment of advanced or metastatic 
squamous NSCLC were evaluated in a phase 3, randomized, open-label study (CA209017). The 
study included patients (18 years or older) who have experienced disease progression during or 
after one prior platinum doublet-based chemotherapy regimen and an ECOG performance status 
score of 0 or 1. Patients were enrolled regardless of their PD-L1 status. Patients with active 
autoimmune disease, symptomatic interstitial lung disease, or untreated brain metastasis were 
excluded from the study. Patients with treated brain metastases were eligible if neurologically 
returned to baseline at least 2 weeks prior to enrollment, and either off corticosteroids, or on a 
stable or decreasing dose of <10 mg daily prednisone equivalents. 
Patients were randomized on a 1:1 basis to receive either nivolumab 3 mg/kg administered 
intravenously over 60 minutes every 2 weeks or docetaxel 75 mg/m2 every 3 weeks. Treatment 
was continued as long as clinical benefit was observed or until treatment was no longer tolerated. 
Tumor assessments, according to RECIST, version 1.1, were conducted 9 weeks after 
randomization and continued every 6 weeks thereafter. The primary efficacy outcome measure 
was OS. Key secondary efficacy outcome measures were investigator-assessed ORR and PFS. In 
addition, symptom improvement and overall health status were assessed using the Lung Cancer 
Symptom Score (LCSS) average symptom burden index and the EQ-5D Visual Analogue Scale 
(EQ-VAS), respectively. 
A total of 272 patients were randomized to either nivolumab (n=135) or docetaxel (n=137). 
Baseline characteristics were generally balanced between the two groups. The median age 
was 63 years (range: 39-85) with 44% ≥65 years of age and 11% ≥75 years of age. The majority 
of patients were white (93%) and male (76%). Thirty-one percent had progressive disease reported 
as the best response to their most recent prior regimen and 45% received nivolumab within 
3 months of completing their most recent prior regimen. Baseline ECOG performance status was 
0 (24%) or 1 (76%). 
Nivolumab demonstrated a statistically significant improvement in OS compared with docetaxel. 
At the pre-defined PD-L1 tumor membrane expression cut-off levels of 1%, 5%, and 10%, similar 
survival was observed regardless of PD-L1 expression status. OS results are shown in Figure 1. 
The observed OS benefit was consistently demonstrated across subgroups of patients. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
153 
Approved v 41.0 
930144776 4.0 
 
 
Figure 1: 
Kaplan-Meier curves of OS (CA209017) 
 
 
The investigator-assessed ORR using RECIST version 1.1 criteria was significantly higher in the 
nivolumab group than in the docetaxel group. Nivolumab treatment also demonstrated statistically 
significant improvement in PFS compared with docetaxel (Figure 2). Efficacy results based on the 
primary and updated analyses are shown in Table 13. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
154 
Approved v 41.0 
930144776 4.0 
 
 
Figure 2: 
Kaplan-Meier curves of PFS (CA209017) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
155 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 13: 
Efficacy results (CA209017) 
 
nivolumab 
docetaxel 
(n = 135) 
(n = 137) 
Primary analysis 
Minimum follow-up: 10.6 months 
Overall survival 
Events 
86 (63.7%) 
113 (82.5%) 
Hazard ratio 
0.59 
96.85% CI 
(0.43, 0.81) 
p-value 
0.0002 
Median (95% CI) 
9.2 months (7.3, 13.3) 
6.0 months (5.1, 7.3) 
Rate (95% CI) at 
42.1% (33.7, 50.3) 
23.7% (16.9, 31.1) 
12 months 
 
Confirmed objective response n 
27 
(20.0%) 
12 
(8.8%) 
(%) 
(95% CI) 
(13.6, 27.7) 
(4.6, 14.8) 
Odds ratio (95% CI) 
2.64 (1.27, 5.49) 
p-value 
Complete response (CR) 
1 
(0.7%) 
0.0083 
0 
Partial response (PR) 
26 
(19.3%) 
12 
(8.8%) 
Stable disease (SD) 
39 
(28.9%) 
47 
(34.3%) 
Median duration of 
response 
(range) 
Not 
(2.9-20.5+) 
8.4 months 
(1.4+-15.2+) 
reached 
Median time to response 
(range) 
2.2 months 
(1.6-11.8) 
2.1 months 
(1.8-9.5) 
 
Progression-free survival 
Events 
105 (77.8%) 
122 (89.1%) 
Hazard ratio 
0.62 
95% CI 
(0.47, 0.81) 
p-value 
< 0.0004 
Median (95% CI) 
Rate (95% CI) at 
12 months 
3.5 months (2.1, 4.9) 
20.8% (14.0, 28.4) 
2.8 months (2.1, 3.5) 
6.4% (2.9, 11.8) 
Updated analysis 
Minimum follow-up: 24.2 months 
 
Overall survivala 
Events 
110 (81.4%) 
128 (93.4%) 
Hazard ratio 
0.62 
95% CI 
(0.47, 0.80) 
Rate (95% CI) at 
22.9% (16.2, 30.3) 
8.0% (4.3, 13.3) 
24 months 
Confirmed objective 
20.0% 
8.8% 
response 
(95% CI) 
(13.6, 27.7) 
(4.6, 14.8) 
Median duration of 
response 
(range) 
25.2 months (2.9-30.4) 
8.4 months (1.4+-18.0+) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
156 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 13: 
Efficacy results (CA209017) 
nivolumab 
(n = 135) 
 
 
docetaxel 
(n = 137) 
 
 
Progression-free survival 
Rate (95% CI) at 
24 months 
 
15.6% (9.7, 22.7) 
 
All patients had either 
progressed, were censored, or 
lost to follow-up 
 
a Six patients (4%) randomised to docetaxel crossed over at any time to receive nivolumab treatment. 
“+” denotes a censored observation. 
 
The rate of disease-related symptom improvement, as measured by LCSS, was similar between 
the nivolumab group (18.5%) and the docetaxel group (21.2%). The average LCSS symptom score 
in the nivolumab group generally decreased (improved) over time and the change from baseline 
exceeded the clinically meaningful threshold at about 10 months; in the docetaxel group, the 
average symptom index was stable over the period for which there were enough patients to 
interpret the data (about 6 months). The average EQ-VAS increased over time for both treatment 
groups, indicating better overall health status for patients remaining on treatment. 
Single-arm phase 2 study (CA209063) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of squamous 
NSCLC were evaluated in a phase 2, single-arm, multinational, multicenter study (CA209063). 
All patients had progressed after receiving a platinum doublet-based therapy and at least one 
additional systemic treatment regimen. Patients were enrolled regardless of their PD-L1 status. 
Patients with active autoimmune disease, symptomatic interstitial lung disease, or untreated brain 
metastasis were excluded from the study. Patients with treated brain metastases were eligible if 
neurologically returned to baseline at least 2 weeks prior to enrollment, and either off 
corticosteroids, or on a stable or decreasing dose of <10 mg daily prednisone equivalents. 
Patients  received 3 mg/kg  of nivolumab  administered  intravenously  over 60 minutes 
every 2 weeks as long as clinical benefit was observed or until treatment was no longer tolerated. 
Tumor assessments took place at week 8 and every 6 weeks thereafter. The primary efficacy 
outcome measure was confirmed ORR as assessed by an independent review committee (IRC) 
according to RECIST version 1.1. Duration and timing of responses were also assessed. Additional 
outcome measures included IRC-assessed PFS and OS, as exploratory endpoints. 
A total of 117 patients received treatment with nivolumab. The median age of patients 
was 65 years (range: 37-87) with 50% ≥65 years of age and 14% ≥75 years of age. The majority 
of patients were male (73%) and white (85%). All patients received two or more prior systemic 
treatments: 35% received two, 44% received three, and 21% received four or more. Sixty-one 
percent had progressive disease reported as the best response to their most recent prior regimen. 
The majority of patients (76%) received nivolumab within 3 months of completing their most 
recent prior regimen. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
157 
Approved v 41.0 
930144776 4.0 
 
 
The most common tumor sites at baseline were lung (86%), lymph node (46%), liver (25%), 
mediastinum (20%), bone (18%), and kidney (10%). Fifty percent of patients had 3 or more 
baseline disease sites. Baseline ECOG performance status was 0 (22%) or 1 (78%). 
Efficacy results based on a minimum follow up of approximately 11 months are shown in Table 14 
and Figure 3. 
 
 
Table 14: 
Efficacy Results (CA209063) 
 
nivolumab 
(n = 117) 
 
Confirmed objective response n (%) 
17 (14.5%) 
(95% CI) 
 (8.7, 22.2) 
Complete response (CR) 
0 
Partial response (PR) 
17 (14.5%) 
Stable disease (SD) a 
30 (25.6%) 
Median duration of response 
Months (range) 
Not reached (1.9+- 11.5+) 
Median time to response 
(range) 
3.25 months (1.7 - 8.8) 
Median PFS 
(95% CI) 
1.87 months (1.77, 3.15) 
PFS rate at 12 months (95% CI) 
20 % (12.7, 28.5) 
Median OS 95% CI) 
8.21 months (6.05, 10.91) 
OS rate at 12 months (95% CI) 
40.8% (31.6, 49.7) 
 
a Median duration of SD was 6 months (95% CI: 4.7, 10.9). 
“+” denotes a censored observation 
 
At the pre-defined PD-L1 tumor membrane expression cut-off levels of 1%, 5%, and 10%, similar 
response rates were observed regardless of PD-L1 expression status. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
158 
Approved v 41.0 
930144776 4.0 
 
 
Figure 3: 
Waterfall plot of best reduction in target lesion, per IRC 
according to survival status 
 
Subjects 
 
Note: Symbol (“●”) represents confirmed responders. 
 
 
Randomized phase 3 study vs. docetaxel (CA209057) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of advanced or 
metastatic non-squamous NSCLC were evaluated in a phase 3, randomized, open-label study 
(CA209057). The study included patients (18 years or older) who have experienced disease 
progression during or after one prior platinum doublet-based chemotherapy regimen which may 
have included maintenance therapy and who had an ECOG performance status score of 0 or 1. An 
additional line of TKI therapy was allowed for patients with known EGFR mutation or ALK 
translocation. Patients were enrolled regardless of their PD-L1 status. Patients with active 
autoimmune disease, symptomatic interstitial lung disease, or untreated brain metastasis were 
excluded from the study. Patients with treated brain metastases were eligible if neurologically 
returned to baseline at least 2 weeks prior to enrollment, and either off corticosteroids, or on a 
stable or decreasing dose of <10 mg daily prednisone equivalents. 
Patients were randomized to receive either nivolumab 3 mg/kg administered intravenously 
over 60 minutes every 2 weeks or docetaxel 75 mg/m2 every 3 weeks . Treatment was continued 
 
Alive 
Best Reduction from Baseline in Target Lesion (%) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
159 
Approved v 41.0 
930144776 4.0 
 
 
as long as clinical benefit was observed or until treatment was no longer tolerated. Tumor 
assessments, according to RECIST, version 1.1, were conducted 9 weeks after randomization and 
continued every 6 weeks thereafter. The primary efficacy outcome measure was overall survival 
(OS). Key secondary efficacy outcome measures were investigator-assessed ORR and PFS. The 
study evaluated whether PD-L1 expression was a predictive biomarker for efficacy. In addition, 
symptom improvement and overall health status were assessed using the LCSS average symptom 
burden index and the EQ-5D VAS, respectively. 
A total of 582 patients were randomized to receive nivolumab (n = 292) or docetaxel (n = 290). 
Baseline characteristics were generally balanced between the two groups. The median age was 
62 years (range: 21 to 85) with 34% ≥65 years of age and 7% ≥75 years of age. The majority of 
patients were white (92%) and male (55%). Thirty-nine percent had progressive disease reported 
as the best response to their most recent prior regimen and 62.5% received nivolumab within 
3 months of completing their most recent prior regimen. Baseline ECOG performance status was 
0 (31%) or 1 (69%). Seventy-nine percent of patients were former/current smokers. 
The Kaplan-Meier curves for OS are shown in Figure 4. 
Figure 4: 
Kaplan-Meier curves of OS (CA209057) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
160 
Approved v 41.0 
930144776 4.0 
 
 
The trial demonstrated a statistically significant improvement in OS for patients randomized to 
nivolumab as compared with docetaxel at the prespecified interim analysis when 413 events were 
observed (93% of the planned number of events for final analysis). Efficacy results are shown in 
Table 15. 
 
Table 15: 
Efficacy Results (CA209057) 
nivolumab 
(n = 292) 
Primary analysis 
Minimum follow-up: 13.2 months 
 
 
docetaxel 
(n = 290) 
Overall survival n (%) 
Events 
190 (65.1%) 
223 (76.9%) 
Hazard ratioa 
0.73 
(95.92% CI) 
(0.59, 0.89) 
p-valueb 
0.0015 
Median (95% CI) 
12.2 months (9.7, 15.0) 
9.4 months (8.1, 10.7) 
Rate (95% CI) at 12 months 
50.5% (44.6, 56.1) 
39.0% (33.3, 44.6) 
Confirmed objective response n 
56 (19.2%) 
36 (12.4%) 
(%) 
(95% CI) 
Odds ratio (95% CI) 
(14.8, 24.2) 
1.68 (1.07, 2.64) 
(8.8, 16.8) 
p-value 
0.0246 
Complete response (CR) 
4 (1.4%) 
1 (0.3%) 
Partial response (PR) 
52 (17.8%) 
35 (12.1%) 
Stable disease (SD) 
74 (25.3%) 
122 (42.1%) 
Median duration of response 
(range) 
17.15 months (1.8-22.6+) 
5.55 months (1.2+-15.2+) 
Median time to response 
(range) 
2.1 months (1.2-8.6) 
2.6 months (1.4-6.3) 
Progression-free survival 
Events n (%) 
234 (80.1%) 
245 (84.5%) 
Hazard ratio 
0.92 
95% CI 
(0.77, 1.11) 
p-value 
0.3932 
Median (95% CI) 
2.33 months (2.17, 3.32) 
4.21 months (3.45, 4.86) 
Rate (95% CI) at 12 months 
18.5% (14.1, 23.4) 
8.1% (5.1, 12.0) 
Updated analysis 
Minimum follow-up: 24.2 months 
Overall survivalc 
Events n (%) 
228 (78.1%) 
247 (85.2%) 
Hazard ratioa 
0.75 
(95% CI) 
(0.63, 0.91) 
Rate (95% CI) at 24 months 
28.7% (23.6, 34.0) 
15.8% (11.9, 20.3) 
 
Confirmed objective response 
19.2% 
12.4% 
(95% CI) 
(14.8, 24.2) 
(8.8, 16.8) 
Median duration of response 
(range) 
17.2 months (1.8-33.7+) 
5.6 months (1.2+-16.8) 
 
Progression-free survival 
Rate (95% CI) at 24 months 
11.9% (8.3, 16.2) 
1.0% (0.2, 3.3) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
161 
Approved v 41.0 
930144776 4.0 
 
 
a Derived from a stratified proportional hazards model. 
b P-value is derived from a log-rank test stratified by prior maintenance therapy and line of therapy; the corresponding 
O’Brien-Fleming efficacy boundary significance level is 0.0408. 
c Sixteen patients (6%) randomised to docetaxel crossed over at any time to receive nivolumab treatment. 
“+” 
denotes a censored observation. 
 
Pre-study tumor tissue specimens were systematically collected prior to randomization in order to 
conduct pre-planned analyses of efficacy according to tumor PD-L1 expression. Quantifiable PD- 
L1 expression was measured in 79% of patients in the nivolumab group and 77% of patients in the 
docetaxel group. Tumor PD-L1 expression levels were balanced between the two treatment groups 
(nivolumab vs docetaxel) at each of the predefined PD-L1 expression levels of ≥1% (53% vs 55%), 
≥5% (41% vs 38%), or ≥10% (37% vs 35%). Tumor PD-L1 expression was determined using the 
PD-L1 IHC 28-8 pharmDx assay. 
Patients with tumor PD-L1 expression by all predefined expression levels in the nivolumab group 
demonstrated greater likelihood of enhanced survival compared to docetaxel, whereas survival 
was similar to docetaxel in patients with low or no tumor PD-L1 expression. Results are shown 
below in Figures 5, 6, and 7. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
162 
Approved v 41.0 
930144776 4.0 
 
 
Figure 5: 
Overall Survival: Patients with ≥1% PD-L1 Expression 
(CA209057) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
163 
Approved v 41.0 
930144776 4.0 
 
 
Figure 6: 
Overall Survival: Patients with <1% PD-L1 Expression 
(CA209057) 
 
 
 
Figure 7: 
Forest Plot for OS based on PD-L1 Expression (CA209057) 
 
Number of Events 
(Number of Subjects) 
Nivolumab Docetaxel 
 
Unstratified Hazard Ratio 
(95% CI) 
 
Median (95% CI) 
Nivolumab 
Docetaxel 
 
17.15 (12.09, 20.63) 
9.00 (7.10, 10.55) 
10.41 (7.29, 14.26) 
10.09 (7.36, 11.93) 
18.17 (15.21, NA) 
8.11 (6.47, 10.05) 
9.66 6.87, 12.62) 
10.09 (8.05, 11.93) 
19.38 (15.21, NA) 
7.95 (6.28, 9.99) 
9.86 (6.87, 12.81) 
10.28 (8.54, 11.96) 
9.20 (5.91, 12.75) 
10.48 (7.20, 13.90) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
164 
Approved v 41.0 
930144776 4.0 
 
 
The rate of disease-related symptom improvement, as measured by LCSS, was similar between 
the nivolumab group (17.8%) and the docetaxel group (19.7%). The average EQ-VAS increased 
over time for both treatment groups, indicating better overall health status for patients remaining 
on treatment. 
As compared to the overall study population, no meaningful differences in safety were observed 
based on PD-L1 expression levels of 1% or 5%. 
Open-label phase 1 dose-escalation study (MDX1106-03) 
The safety and tolerability of nivolumab were investigated in a phase 1, open-label, 
dose-escalation study in various tumour types, including NSCLC. Of the 306 patients enrolled in 
the study, 129 had NSCLC and received nivolumab at a dose of 1 mg/kg (n=33), 3 mg/kg (n=37), 
or 10 mg/kg (n=59) every 2 weeks for a maximum of 2 years. Objective response was reported 
in 22/129 patients (17% [95% CI: 11.0, 24.7]) in the entire NSCLC cohort (across histologies and 
dose levels) and 4/18 patients (22% [95% CI: 6.4, 47.6]) with squamous NSCLC treated at the 
3 mg/kg dose level. 
In the entire NSCLC cohort, the median duration of response was 17 months. The median PFS 
was 2.3 months (95% CI: 1.8, 3.7). The estimated milestone PFS rates were 22% (95% CI: 15, 30) 
at 1 year and 9% (95% CI: 4, 15) at 2 years. The median OS was 9.9 months (95% CI: 7.8, 12.4), 
and  the  estimated  milestone  OS  rates  were 42%  (95% CI: 34, 51)  at  1 year  and 24% 
(95% CI: 16, 32) at 2 years. 
Randomized, open-label, Phase 3 study of nivolumab alone or in combination with 
ipilimumab or platinum-doublet chemotherapy vs platinum-doublet chemotherapy 
(CA209227, Part 1) 
The safety and efficacy of nivolumab 3 mg/kg every 2 weeks in combination with ipilimumab 1 
mg/kg every 6 weeks for the treatment of NSCLC were evaluated in a Phase 3, randomized, open- 
label study (CA209227, Part 1). The study included patients (18 years of age or older) with 
histologically confirmed Stage IV or recurrent NSCLC (per the 7th International Association for 
the Study of Lung Cancer classification ((ASLC)), ECOG performance status 0 or 1, and no prior 
anticancer therapy (including EGFR and ALK inhibitors). Patients were enrolled regardless of 
their tumor PD-L1 status. Patients with known EGFR mutations or ALK translocations sensitive 
to available targeted inhibitor therapy, untreated brain metastases, carcinomatous meningitis, 
active autoimmune disease, or medical conditions requiring systemic immunosuppression were 
excluded from the study. Patients with treated brain metastases were eligible if neurologically 
returned to baseline at least 2 weeks prior to enrollment, and either off corticosteroids, or on a 
stable or decreasing dose of <10 mg daily prednisone equivalents. 
Patients were enrolled into Part 1a or Part 1b according to PD-L1 status. In Part 1a, patients with 
PD-L1 tumor expression ≥1% were randomized 1:1:1 to either nivolumab 3 mg/kg administered 
intravenously over 30 minutes every 2 weeks in combination with ipilimumab 1 mg/kg 
administered intravenously over 30 minutes every 6 weeks; platinum-doublet chemotherapy 
administered every 3 weeks for up to 4 cycles; or nivolumab 240 mg administered intravenously 
over 30 minutes every 2 weeks. In Part 1b, patients with PD-L1 tumor expression <1% were 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
165 
Approved v 41.0 
930144776 4.0 
 
 
randomized 1:1:1 to either nivolumab 3 mg/kg administered intravenously over 30 minutes every 
2 weeks in combination with ipilimumab 1 mg/kg administered intravenously over 30 minutes 
every 6 weeks; platinum-doublet chemotherapy administered every 3 weeks for up to 4 cycles; or 
nivolumab 360 mg administered intravenously over 30 minutes in combination with platinum- 
doublet chemotherapy every 3 weeks for 4 cycles, followed by nivolumab 360 mg administered 
intravenously over 30 minutes every 3 weeks. Stratification factors were identical between Part 1a 
and Part 1b (tumor histology [non-squamous versus squamous]). Platinum-doublet chemotherapy 
consisted of: 
• pemetrexed (500 mg/m2) and cisplatin (75 mg/m2), or pemetrexed (500 mg/m2) and 
carboplatin (AUC 5 or 6) for non-squamous NSCLC; 
• or gemcitabine (1000 or 1250 mg/m2) and cisplatin (75 mg/m2), or gemcitabine (1000 mg/m2) 
and carboplatin (AUC 5) (gemcitabine was administered on Days 1 and 8 of each cycle) for 
squamous NSCLC. 
• Study treatment continued until disease progression, unacceptable toxicity, or for up to 24 
months. Treatment continued beyond disease progression if a patient was clinically stable and 
was considered to be deriving clinical benefit by the investigator. Patients who discontinued 
combination therapy because of an adverse event attributed to ipilimumab were permitted to 
continue nivolumab monotherapy. Tumor assessments were performed every 6 weeks from 
the first dose of study treatment for the first 12 months, then every 12 weeks until disease 
progression or study treatment was discontinued. The primary efficacy outcome measure was 
OS. Additional efficacy outcome measures included PFS, ORR, and duration of response as 
assessed by BICR. 
• In Part 1a, a total of 793 patients were randomized to receive either nivolumab in combination 
with ipilimumab (n=396) or platinum-doublet chemotherapy (n=397). The median age was 64 
years (range: 26 to 87) with 49% of patients ≥65 years and 10% of patients ≥75 years, 76% 
White, 65% male. Baseline ECOG performance status was 0 (34%) or 1 (65%), 50% with PD- 
L1 ≥50%, 29% with squamous and 71% with non-squamous histology, 10% had brain 
metastases, and 85% were former/current smokers. 
 
The study demonstrated a statistically significant benefit in OS, and a clinically meaningful benefit 
in PFS, ORR, and duration of response for patients randomized to nivolumab in combination with 
ipilimumab compared to platinum-doublet chemotherapy alone. Efficacy results for patients 
whose tumors expressed PD-L1 ≥1% are presented in Table 16 and Figure 8 below. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
166 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 16: 
Efficacy results (PD-L1 ≥1%) - CA209227 Part 1a 
 
nivolumab + ipilimumab 
(n=396) 
Chemotherapy 
(n=397) 
Overall Survival 
Events (%) 
258 (65.2) 
298 (75.1) 
Median (months) 
17.1 
14.9 
(95% CI) 
(15, 20.1) 
(12.7, 16.7) 
Hazard ratio 
(97.72% CI)a 
0.79 
(0.65, 0.96) 
Stratified log-rank p-value 
0.0066 
Rate (95% CI) at 12 months 
62.6 
(57.7, 67.2) 
56.2 
(51.1, 61.0) 
Rate (95% CI) at 24 months 
40.0 
(35.1, 44.9) 
32.8 
(28.2, 37.5) 
Progression-Free Survival 
Events (%) 
288 (72.7) 
286 (72.0) 
Hazard ratio 
(95% CI)a 
0.82 
(0.69, 0.97) 
Median (months)b 
5.1 
5.6 
(95% CI) 
(4.07, 6.31) 
(4.63, 5.82) 
Objective Response Rate (%)c 
142 (35.9) 
119 (30.0) 
(95% CI) 
(31.1, 40.8) 
(25.5, 34.7) 
Complete response (%) 
23 (5.8) 
7 (1.8) 
Partial response (%) 
119 (30.1) 
112 (28.2) 
Duration of Response 
Median (months) 
(95% CI)b 
23.2 
(15.2, 32.2) 
6.2 
(5.6, 7.4) 
% with duration ≥12 monthsd 
64 
28 
% with duration ≥24 monthsd 
49 
11 
a Based on a stratified Cox proportional hazard model. 
b Kaplan-Meier estimate. 
c Proportion with complete or partial response; confidence interval based on the Clopper and Pearson Method. 
d Based on Kaplan-Meier estimates of duration of response. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
167 
Approved v 41.0 
930144776 4.0 
 
 
Figure 8: 
Kaplan-Meier plot of OS (PD-L1 ≥1%) - CA209227 Part 1a 
 
 
Randomized, open-label, Phase 3 study of nivolumab in combination with ipilimumab and 
platinum-based chemotherapy vs platinum-based chemotherapy (CA2099LA) 
The safety and efficacy of nivolumab 360 mg every 3 weeks in combination with ipilimumab 
1mg/kg every 6 weeks and 2 cycles of platinum-based chemotherapy were evaluated for the 
treatment of NSCLC in a Phase 3, randomized, open-label study (CA2099LA). The study included 
patients (18 years of age or older) with histologically confirmed Stage IV or recurrent NSCLC (per 
the 7th International Association for the Study of Lung Cancer classification ((IASLC)), ECOG 
performance status 0 or 1, and no prior anticancer therapy (including EGFR and ALK inhibitors). 
Patients were enrolled regardless of their tumor PD-L1 status. Patients with known EGFR 
mutations or ALK translocations sensitive to available targeted inhibitor therapy, untreated brain 
metastases, carcinomatous meningitis, active autoimmune disease, or medical conditions requiring 
systemic immunosuppression were excluded from the study. Patients with treated brain metastases 
were eligible if neurologically returned to baseline at least 2 weeks prior to enrollment, and either 
off corticosteroids, or on a stable or decreasing dose of < 10 mg daily prednisone equivalents. 
Patients were randomized 1:1 to receive either nivolumab 360 mg administered intravenously over 
30 minutes every 3 weeks in combination with ipilimumab 1 mg/kg administered intravenously 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
168 
Approved v 41.0 
930144776 4.0 
 
 
over 30 minutes every 6 weeks and platinum-based chemotherapy administered every 3 weeks for 
2 cycles; or platinum-based chemotherapy administered every 3 weeks for 4 cycles; patients with 
non-squamous NSCLC could receive optional pemetrexed maintenance therapy. Stratification 
factors for randomization were tumor PD-L1 expression level (≥1% versus <1%), histology 
(squamous versus non-squamous), and gender (male versus female). Platinum-based 
chemotherapy consisted of: 
• carboplatin (AUC 5 or 6) and pemetrexed 500 mg/mg2; or cisplatin 75 mg/m2 and pemetrexed 
500 mg/m2 for non-squamous NSCLC; 
• or carboplatin (AUC 6) and paclitaxel 200 mg/m2 for squamous NSCLC. 
 
Study treatment continued until disease progression, unacceptable toxicity, or for up to 24 months 
in patients without disease progression. Treatment continued beyond disease progression if a 
patient was clinically stable and was considered to be deriving clinical benefit by the investigator. 
Patients who discontinued combination therapy because of an adverse event attributed to 
ipilimumab were permitted to continue nivolumab monotherapy. Tumor assessments were 
performed every 6 weeks from the first dose of study treatment for the first 12 months, then every 
12 weeks until disease progression or study treatment was discontinued. 
The primary efficacy outcome measure was OS. Additional efficacy outcome measures included 
PFS, ORR, and duration of response as assessed by BICR. 
A total of 719 patients were randomized to receive either nivolumab in combination with 
ipilimumab and platinum-based chemotherapy (n=361) or platinum-based chemotherapy (n=358). 
The median age was 65 years (range: 26 to 86) with 51% of patients ≥65 years and 10% of patients 
≥75 years, 89% White, 70% male. Baseline ECOG performance status was 0 (31%) or 1 (68%), 
57% with PD-L1 ≥1% and 37% with PD-L1 <1%, 31% with squamous and 69% with non- 
squamous histology, 17% had brain metastases, and 86% were former/current smokers. 
The study demonstrated a statistically significant benefit in OS, PFS, and ORR, and a clinically 
meaningful benefit in duration of response for patients randomized to nivolumab in combination 
with ipilimumab and platinum-based chemotherapy compared to platinum-based chemotherapy 
alone. Minimum follow-up for OS was 8.1 months. Efficacy results are presented in Table 17and 
Figure 9. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
169 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 17: 
Efficacy results - CA2099LA 
 
Nivolumab + ipilimumab + 
chemotherapy 
(n=361) 
Chemotherapy 
(n=358) 
OS 
Events (%) 
156 (43.2) 
195 (54.5) 
Median (months) (95% 
14.1 
10.7 
CI) 
(13.24, 16.16) 
(9.46, 12.45) 
Hazard ratio (96.71% CI)a 
0.69 (0.55, 0.87) 
Stratified log-rank p-valueb 
0.0006 
Rate (95% CI) at 6 months 
80.9 (76.4, 84.6) 
72.3 (67.4, 76.7) 
PFS 
Events (%) 
232 (64.3) 
249 (69.6) 
Hazard ratio (97.48% CI)a 
0.70 (0.57, 0.86) 
Stratified log-rank p-valuec 
0.0001 
Median (months)d 
(95% CI) 
6.83 
(5.55, 7.66) 
4.96 
(4.27, 5.55) 
Rate (95% CI) at 6 months 
51.7 (46.2, 56.8) 
35.9 (30.5, 41.3) 
ORR (%)e 
136 (37.7) 
90 (25.1) 
(95% CI) 
(32.7, 42.9) 
(20.7, 30.0) 
Stratified CMH test p-valuef 
0.0003 
Complete response (%) 
7 (1.9) 
3 (0.8) 
Partial response (%) 
129 (35.7) 
87 (24.3) 
Duration of Response 
Median (months) 
10.02 
5.09 
(95% CI)d 
(8.21, 13.01) 
(4.34, 7.00) 
% with duration ≥6 
monthsg 
74 
41 
a Based on a stratified Cox proportional hazard model. 
b p-value is compared with the allocated alpha of 0.0329 for this interim analysis. 
c p-value is compared with the allocated alpha of 0.0252 for this interim analysis. 
d Kaplan-Meier estimate. 
e Proportion with complete or partial response; confidence interval based on the Clopper and Pearson Method. 
f p-value is compared with the allocated alpha of 0.025 for this interim analysis. 
g Based on Kaplan-Meier estimates of duration of response. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
170 
Approved v 41.0 
930144776 4.0 
 
 
Figure 9: 
Kaplan-Meier plot of OS - CA2099LA 
 
Subsequent systemic therapy was received by 28.8% and 41.1% of patients in the combination and 
chemotherapy arms, respectively. Subsequent immunotherapy (including anti-PD-1, anti-PD-L1, 
and anti- CTLA4) was received by 3.9% and 27.9% of patients in the combination and 
chemotherapy arms, respectively. 
In study CA2099LA, subgroup descriptive analysis relative to chemotherapy, OS benefit was 
shown in patients treated with nivolumab in combination with ipilimumab and chemotherapy with 
squamous histology (HR (95% CI) 0.65 (0.46, 0.93), n = 227) and in patients with non-squamous 
histology (HR (95% CI) 0.72 (0.55, 0.93), n = 492). 
Table 18 summarizes efficacy results of OS by tumour PD-L1 expression in pre-specified 
subgroup analyses. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
171 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 18: 
Efficacy results by tumor PD-L1 expression (CA2099LA) 
 
PD-L1 <1% 
(n=264) 
PD-L1 ≥1% 
(n=406) 
PD- 
L1 ≥1% to 49% 
(n=233) 
PD-L1 ≥50% 
(n=173) 
OS hazard ratio 
0.65 
0.67 
0.69 
0.64 
(95% CI)a 
(0.46, 0.92) 
(0.51, 0.89) 
(0.48, 0.98) 
(0.41, 1.02) 
a Hazard ratio based on unstratified Cox proportional hazards model. 
 
Renal cell carcinoma (RCC) 
Randomized, open-label, phase 3 study vs. everolimus (CA209025) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of advanced RCC 
was evaluated in a Phase 3, randomized, open-label study (CA209025). The study included 
patients (18 years or older) who have experienced disease progression during or after 1 or 2 prior 
anti-angiogenic therapy regimens and no more than 3 total prior systemic treatment regimens. 
Patients had to have a Karnofsky Performance Score (KPS) ≥70%. This study included patients 
regardless of their PD-L1 status. Patients with any history of or concurrent brain metastases, prior 
treatment with a mammalian target of rapamycin (mTOR) inhibitor, active autoimmune disease, 
or medical conditions requiring systemic immunosuppression were excluded from the study. 
Patients were randomized to receive either nivolumab 3 mg/kg administered intravenously over 
60 minutes every 2 weeks or everolimus 10 mg daily, administered orally. Treatment was 
continued as long as clinical benefit was observed or until treatment was no longer tolerated. The 
first tumor assessments were conducted 8 weeks after randomization and continued every 8 weeks 
thereafter for the first year and then every 12 weeks until progression or treatment discontinuation, 
whichever occurred later. Tumor assessments were continued after treatment discontinuation in 
patients who discontinued treatment for reasons other than progression. Treatment beyond initial 
investigator-assessed RECIST 1.1-defined progression was permitted if the patient had a clinical 
benefit and was tolerating study drug as determined by the investigator. The primary efficacy 
outcome measure was OS. Secondary efficacy assessments included investigator-assessed ORR 
and PFS. 
A total of 821 patients were randomized to receive either nivolumab (n=410) or everolimus 
(n=411). Baseline characteristics were generally balanced between the two groups. The median 
age was 62 years (range: 18-88) with 40% ≥65 years of age and 9% ≥75 years of age. The majority 
of patients were male (75%) and white (88%), all Memorial Sloan Kettering Cancer Center 
(MSKCC) risk groups were represented, and 34% and 66% of patients had a baseline KPS of 
70% to 80% and 90% to 100%, respectively. The majority of patients (72%) were treated with one 
prior anti-angiogenic therapy. The median duration of time from initial diagnosis to randomization 
was 2.6 years in both the nivolumab and everolimus groups. The median duration of treatment was 
5.5 months (range: 0- 29.6+ months) for nivolumab and 3.7 months (range: 6 days-25.7+ months) 
for everolimus. 
Nivolumab was continued beyond progression in 44% of patients. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
172 
Approved v 41.0 
930144776 4.0 
 
 
The Kaplan-Meier curves for OS are shown in Figure 10. 
 
Figure 10: 
Kaplan-Meier curves of OS (CA209025) 
 
 
The trial demonstrated a statistically significant improvement in OS for patients randomized to 
nivolumab as compared with everolimus at the prespecified interim analysis when 398 events were 
observed (70% of the planned number of events for final analysis) (Table 19 and Figure 12). OS 
benefit was observed regardless of PD-L1 expression level. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
173 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 19: 
Efficacy results (CA209025) 
nivolumab 
(n = 410) 
 
 
everolimus 
(n = 411) 
Overall survival 
Events n (%) 
183 (45%) 
215 (52%) 
Hazard ratio 
0.73 
98.52% CI 
(0.57, 0.93) 
p-value 
0.0018 
Median (95% CI) 
25.0 months (21.7, NE) 
19.6 months (17.6, 23.1) 
Rate (95% CI) 
At 6 months 
89.2% (85.7, 91.8) 
81.2% (77.0, 84.7) 
At 12 months 
76.0% (71.5, 79.9) 
66.7 % (61.8, 71.0) 
Objective response n (%) 
103 
(25.1%) 
22
(5.4%) 
(95% CI) 
Odds ratio (95% CI) 
(21.0, 29.6) 
(
5.98 (3.68, 9.72) 
.4, 8.0) 
p-value 
< 0.0001 
Complete response (CR) 
4 
(1.0%) 
2
(0.5%) 
Partial response (PR) 
99 
(24.1%) 
20
(4.9%) 
Stable disease (SD) 
141 
(34.4%) 
227
(55.2%) 
 
Median duration of response 
(range) 
12.0 
months 
 
(0.0-27.6+) 
12.0 
months 
 
(0.0+-22.2+) 
 
Median time to response 
(range) 
3.5 months 
(1.4-24.8) 
3.7 
months 
(1.5-11.2) 
Progression-free survival 
Events n (%) 
318 (77.6%) 
322 (78.3%) 
Hazard ratio 
0.88 
95% CI 
(0.75, 1.03) 
p-value 
0.1135 
Median (95% CI) 
4.6 months (3.7, 5.4) 
4.4 months (3.7, 5.5) 
NE=not estimable 
“+” denotes a censored observation. 
The Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease Related 
Symptoms (FKSI-DRS) subscale of the FKSI-15 was used to assess disease-related symptom 
progression rate in each treatment arm. With a completion rate of 80% in the first year, nivolumab 
demonstrated a favourable impact on disease-related symptom progression rate. The scores for the 
nivolumab group increased over time and differed significantly from median changes in the 
everolimus group at each assessment point through week 104. 
Randomized Phase 3 study of nivolumab in combination with ipilimumab vs. sunitinib 
(CA209214) 
The safety and efficacy of nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg for the 
treatment of advanced/metastatic RCC was evaluated in a Phase 3, randomized, open-label study 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
174 
Approved v 41.0 
930144776 4.0 
 
 
(CA209214). The study included patients (18 years or older) with previously untreated, advanced 
or metastatic renal cell carcinoma with a clear-cell component. The primary efficacy population 
included those intermediate/poor risk patients with at least 1 or more of 6 prognostic risk factors 
as per the International Metastatic RCC Database Consortium (IMDC) criteria (less than one year 
from time of initial renal cell carcinoma diagnosis to randomization, Karnofsky performance status 
<80%, haemoglobin less than the lower limit of normal, corrected calcium of greater than 10 
mg/dL, platelet count greater than the upper limit of normal, and absolute neutrophil count greater 
than the upper limit of normal). This study included patients regardless of their tumor PD-L1 
status. Patients with Karnofsky performance status <70% and patients with any history of or 
concurrent brain metastases, active autoimmune disease, or medical conditions requiring systemic 
immunosuppression were excluded from the study. Patients were stratified by IMDC prognostic 
score and region. 
A total of 1096 patients were randomized in the trial, of which 847 patients had intermediate/poor- 
risk RCC and received either nivolumab 3 mg/kg (n=425) administered intravenously over 60 
minutes in combination with ipilimumab 1 mg/kg administered intravenously over 30 minutes 
every 3 weeks for 4 doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks or sunitinib 
(n=422) 50 mg daily, administered orally for 4 weeks followed by 2 weeks off, every cycle. 
Treatment was continued as long as clinical benefit was observed or until treatment was no longer 
tolerated. The first tumor assessments were conducted 12 weeks after randomization and continued 
every 6 weeks thereafter for the first year and then every 12 weeks until progression or treatment 
discontinuation, whichever occurred later. Treatment beyond initial investigator-assessed 
RECIST, version 1.1-defined progression was permitted if the patient had a clinical benefit and 
was tolerating study drug as determined by the investigator. The primary efficacy outcome 
measures were OS, ORR and PFS as determined by a Blinded Independent Central Review (BICR) 
in intermediate/poor-risk patients. 
Baseline characteristics were generally balanced between the two groups. The median age was 61 
years (range: 21-85) with 38% ≥65 years of age and 8% ≥75 years of age. The majority of patients 
were male (73%) and white (87%), and 31% and 69% of patients had a baseline KPS of 70 to 80% 
and 90 to 100%, respectively. The median duration of time from initial diagnosis to randomization 
was 0.4 years in both the nivolumab 3 mg/kg in combination with ipilimumab 1 mg/kg and 
sunitinib groups. The median duration of treatment was 7.9 months (range: 1 day- 21.4+ months) 
in nivolumab with ipilimumab-treated patients and was 7.8 months (range: 1 days- 20.2+ months) 
in sunitinib-treated patients. Nivolumab with ipilimumab was continued beyond progression in 
29% of patients. 
The Kaplan-Meier curves for OS (with a minimum follow-up of 60 months) in intermediate/poor- 
risk patients are shown in Figure 11. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
175 
Approved v 41.0 
930144776 4.0 
 
 
Figure 11: 
Kaplan-Meier curves of OS in intermediate/poor-risk patients 
(CA209214) 
 
 
The trial demonstrated statistically significant improvement in OS, clinically relevant 
improvement in ORR, and a numerical improvement (not statistically significant) in PFS for 
intermediate/poor-risk patients randomized to nivolumab in combination with ipilimumab as 
compared with sunitinib (Table 10). With a longer follow-up (a minimum follow-up of 60 months), 
as shown in Figure 11, the trial continued to demonstrate significant improvement in OS for 
patients randomized to nivolumab and ipilimumab as compared with sunitinib. 
In intermediate/poor-risk patients, OS benefit was observed in the nivolumab in combination with 
ipilimumab arm vs. sunitinib regardless of tumor PD-L1 expression. Median OS for tumor PD-L1 
expression ≥1% was not reached for nivolumab in combination with ipilimumab, and was 19.61 
months in the sunitinib arm (HR=0.45; 95% CI: 0.29, 0.71). For tumor PD-L1 expression <1%, 
the median OS was not reached for the nivolumab in combination with ipilimumab and the 
sunitinib arms (HR=0.73; 95% CI: 0.56, 0.96). 
CA209214 also randomized 249 favorable-risk patients as per IMDC criteria to nivolumab plus 
ipilimumab (n=125) or to sunitinib (n=124). These patients were not evaluated as part of the 
primary efficacy population. With 60 month minimum follow-ups. OS in favorable-risk patients 
receiving nivolumab plus ipilimumab compared to sunitinib had a hazard ratio of 0.94 (95% 
CI:0.65, 1.37). 
There are no data on the use of nivolumab in combination with ipilimumab in patients with only a 
non-clear-cell histology in first-line RCC. 
Efficacy results for the intermediate/poor risk patients are shown in Table 20. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
176 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 20: 
Efficacy results in intermediate/poor-risk patients (CA209214) 
nivolumab + 
ipilimumab 
(n = 425) 
sunitinib 
(n = 422) 
Overall survivala 
Events 
Hazard ratiob 
140 (33%) 
0.63 
188 (45%) 
99.8% CI 
p-valuec,d 
(0.44, 0.89) 
<0.0001 
Median (95% CI) 
NE (32.5, NE) 
27.0 (22.1, 34.8) 
Rate (95% CI) 
At 6 months 
89.5 (86.1, 92.1) 
86.2 (82.4, 89.1) 
At 12 months 
80.1 (75.9, 83.6) 
72.1 (67.4, 76.2) 
Progression-free survival 
Events 
228 (53.6%) 
228 (54.0%) 
Hazard ratiob 
0.82 
99.1% CI 
(0.64, 1.05) 
p-valuec,i 
0.0331 
Median (95% CI) 
11.6 (8.71, 15.51) 
8.4 (7.03, 10.81) 
Confirmed objective response (BICR) 
177 
(41.6%)
112 
(26.5%) 
(95% CI) 
(36.9, 46.5) 
(22.4, 31.0) 
Difference in ORR (95% CI)e 
16.0 (9.8, 22.2) 
p-valuef,g 
<0.0001 
 
Complete response (CR) 
40 
(9.4%) 
5 
(1.2%) 
Partial response (PR) 
137 
(32.2%) 
107 
(25.4%) 
Stable disease (SD) 
133 
(31.3%) 
188 
(44.5%) 
Median duration of responseh 
Months (range) 
NE 
(1.4+, 25.5+) 
18.2 
(1.3+, 23.6+) 
Median time to response 
Months (range) 
2.8 
(0.9-11.3) 
3.0 
(0.6-15.0) 
a Results are based on the final analysis with 24 months of minimum follow-up. 
b Based on a stratified proportional hazards model. 
c Based on a stratified log-rank test. 
d p-value is compared to alpha 0.002 in order to achieve statistical significance. 
e Strata adjusted difference. 
f Based on the stratified DerSimonian-Laird text. 
g p-value is compared to alpha 0.001 in order to achieve statistical significance. 
h Computed using Kaplan-Meier method. 
i p-value is compared to alpha 0.009 in order to achieve statistical significance. 
“+” denotes a censored observation. 
NE = non-estimable. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
177 
Approved v 41.0 
930144776 4.0 
 
 
An updated OS analysis was performed when all patients had a minimum follow-up of 24 months. 
At the time of this analysis, the hazard ratio was 0.66; (99.8% CI: 0.48-0.91) with 166/425 events 
in the combination arm and 209/422 events in the sunitinib arm. At 18 months, the OS rate was 
74.3% (95% CI: 69.8-78.2) for nivolumab in combination with ipilimumab and 59.9 (95% CI: 
54.9-64.5) for sunitinib. At 24 months, the OS rate was 66.5% (95% CI: 61.8-70.9) for nivolumab 
in combination with ipilimumab and 52.9 (95% CI: 47.9- 57.7) for sunitinib. An updated OS 
analysis was performed when all patients had a minimum follow-up of 60 months. At the time of 
analysis the median OS was 47.0 months in the nivolumab and ipilimumab arm and 26.6 months 
in the sunitinib arm (HR: 0.68; 95% CI: 0.58, 0.81). 
The median time to onset of objective response was 2.8 months (range: 0.9-11.3 months) after the 
start of nivolumab with ipilimumab treatment. Among the 177 responders, 128 (72.3%) had an 
ongoing response with a duration ranging from 1.4+-25.5+ months. 
Patients ≥75 years of age represented 8% of all intermediate/poor-risk patients in CA209214, and 
the combination of nivolumab and ipilimumab showed numerically less effect on OS (HR 0.97, 
95% CI: 0.48, 1.95) in this subgroup versus the overall population. Because of the small size of 
this subgroup, no definitive conclusions can be drawn from these data. 
Overall survival was accompanied by fewer patients experiencing patient-reported deterioration 
on disease-related symptoms, cancer symptoms and non-disease specific Quality of Life (QoL) as 
assessed using valid and reliable scales in the FKSI-19, FACT-G, and EQ-5D. In those patients 
who deteriorated, the time to deterioration was significantly longer for all three scales for those in 
the nivolumab in combination with ipilimumab arm relative to those in the sunitinib arm 
(p<0.0001). While both arms of the study received active therapy, the QoL data should be 
interpreted in the context of the open-label study design and therefore cautiously taken. 
Squamous Cell Carcinoma of the Head and Neck (SCCHN) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of metastatic or 
recurrent SCCHN were evaluated in a Phase 3, randomized, open-label study (CA209141). The 
study included patients (18 years or older) who had disease progression during or after a prior 
platinum-based therapy regimen and had an ECOG performance status score of 0 or 1. Prior 
platinum-based therapy was administered in either the adjuvant, neo-adjuvant, primary, recurrent, 
or metastatic setting. Patients were enrolled regardless of their tumor PD-L1 or human papilloma 
virus (HPV) status. Patients with active autoimmune disease, medical conditions requiring 
immunosuppression, recurrent or metastatic carcinoma of the nasopharynx, squamous cell 
carcinoma of unknown primary, salivary gland or non-squamous histologies (e.g., mucosal 
melanoma), or untreated brain metastasis were excluded from the study. Patients with treated brain 
metastases were eligible if neurologically returned to baseline at least 2 weeks prior to enrollment, 
and either off corticosteroids, or on a stable or decreasing dose of < 10 mg daily prednisone 
equivalents. 
A total of 361 patients were randomized to receive either nivolumab 3 mg/kg (n = 240) 
administered intravenously over 60 minutes every 2 weeks or investigator’s choice of either 
cetuximab (n = 15), 400 mg/m2 loading dose followed by 250 mg/m2 weekly or methotrexate 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
178 
Approved v 41.0 
930144776 4.0 
 
 
(n = 52) 40 to 60 mg/m2 weekly, or docetaxel (n = 54) 30 to 40 mg/m2 weekly. Randomization 
was stratified by prior cetuximab treatment. Treatment was continued as long as clinical benefit 
was observed or until treatment was no longer tolerated. Tumor assessments, according to RECIST 
version 1.1, were conducted 9 weeks after randomization and continued every 6 weeks thereafter. 
Treatment beyond initial investigator-assessed RECIST, version 1.1-defined progression was 
permitted in patients receiving nivolumab if the patient had a clinical benefit and was tolerating 
study drug, as determined by the investigator. The primary efficacy outcome measure was OS. 
Key secondary efficacy outcome measures were investigator-assessed PFS and ORR. Additional 
prespecified subgroup analyses were conducted to evaluate the efficacy by tumor PD-L1 
expression at predefined levels of 1%, 5%, and 10%. 
Baseline characteristics were generally balanced between the two groups. The median age 
was 60 years (range: 28-83) with 31% ≥ 65 years of age and 5% ≥ 75 years of age, 83% were men, 
and 83% were white. Baseline ECOG performance status score was 0 (20%) or 1 (78%), 77% were 
former/current smokers, 90% had Stage IV disease, 66% had two or more lesions, 45%, 34% and 
20% received 1, 2, or 3 or more prior lines of systemic therapy, respectively, and 25% were HPV- 
16 status positive. 
With a minimum follow-up of 11.4 months, the trial demonstrated a statistically significant 
improvement in OS for patients randomized to nivolumab compared with investigator’s choice. 
The Kaplan-Meier curves for OS are shown in Figure 12. Efficacy results are shown in Table 21. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
179 
Approved v 41.0 
930144776 4.0 
 
 
Figure 12: 
Kaplan-Meier curves of OS (CA209141) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
180 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 21: 
Efficacy results (CA209141) 
 
nivolumab 
investigator’s choice 
(n = 240) 
(n = 121) 
Overall survival 
Events 
184 (76.7%) 
105 (86.8%) 
Hazard ratioa 
0.71 
(95% CI) 
(0.55, 0.90) 
p-valueb 
0.0048 
 
Median (95% CI) 
7.7 months (5.7, 8.8) 
5.1 months (4.0, 6.2) 
Rate (95% CI) at 6 months 
56.5% (49.9, 62.5) 
43.0% (34.0, 51.7) 
Rate (95% CI) at 12 months 
34.0% (28.0, 40.1) 
19.7% (13.0, 27.3) 
Rate (95% CI) at 18 months 
21.5% (16.2, 27.4) 
8.3% (3.6, 15.7) 
Progression-free survival 
Events 
204 (85%) 
104 (86%) 
Hazard ratio 
0.87 
95% CI 
(0.69, 1.11) 
p-value 
0.2597 
Median (95% CI) 
2.0 months (1.9, 2.1) 
2.3 months (2.0, 3.1) 
Rate (95% CI) at 6 months 
21.0% (15.9, 26.6) 
11.1% (5.9, 18.3) 
Rate (95% CI) at 12 months 
9.5% (6.0, 13.9) 
2.5% (0.5, 7.8) 
Confirmed objective responsec n 
32 (13.3%) 
7 (5.8%) 
(%) 
(95% CI) 
(9.3, 18.3) 
(2.4, 11.6) 
Odds ratio (95% CI) 
2.49 (1.07, 5.82) 
Complete response (CR) 
6 (2.5%) 
1 (0.8%) 
Partial response (PR) 
26 (10.8%) 
6 (5.0%) 
Stable disease (SD) 
55 (22.9%) 
43 (35.5%) 
Median time to response 
(range) 
2.1 months (1.8- 7.4) 
2.0 months (1.9 - 4.6) 
Median duration of response 
(range) 
9.7 months (2.8- 20.3+) 
4.0 months (1.5+- 8.5+) 
a Derived from a stratified proportional hazards model. 
b P-value is derived from a log-rank test stratified by prior cetuximab; the corresponding O’Brien-Fleming efficacy 
boundary significance level is 0.0227. 
c In the nivolumab group there were two patients with CRs and seven patients with PRs who had tumor PD-L1 
expression < 1%. 
“+” denotes a censored observation. 
 
Pre-study tumor tissue specimens were systematically collected prior to randomisation in order to 
conduct pre-planned analyses of efficacy according to tumor PD-L1 expression. Tumor PD-L1 
expression was determined using the PD-L1 IHC 28-8 pharmDx assay. Quantifiable tumor PD-L1 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
181 
Approved v 41.0 
930144776 4.0 
 
 
expression was measured in 67% of patients in the nivolumab group and 82% of patients in the 
investigator’s choice group. Tumor PD-L1 expression levels were balanced between the two 
treatment groups (nivolumab vs. investigator’s choice) at each of the predefined tumor PD-L1 
expression levels of ≥ 1% (55% vs. 62%), ≥ 5% (34% vs. 43%), or ≥ 10% (27% vs. 34%). 
Patients with tumor PD-L1 expression by all predefined expression levels in the nivolumab group 
demonstrated greater likelihood of improved survival compared with those in the investigator’s 
choice group. The magnitude of OS benefit was consistent for ≥ 1%, ≥ 5% or ≥ 10% tumor PD- 
L1 expression levels (Table 22). 
Table 22: 
OS by tumor PD-L1 expression (CA209141) 
 
PD-L1 Expression 
nivolumab 
investigator’s 
choice 
 
OS by tumor PD-L1 expression 
Number of events (number of patients) 
Unstratified Hazard 
Ratio (95% CI) 
 
< 1% 
56 (73) 
32 (38) 
0.83 (0.54, 1.29) 
≥ 1% 
66 (88) 
55 (61) 
0.53 (0.37, 0.77) 
≥ 5% 
39 (54) 
40 (43) 
0.51 (0.32, 0.80) 
≥ 10% 
30 (43) 
31 (34) 
0.57 (0.34, 0.95) 
 
Patients with investigator-assessed primary site of oropharyngeal cancer were tested for HPV. OS 
benefit was observed regardless of HPV status (HPV-positive oropharyngeal: HR = 0.63; 95% CI: 
0.38, 1.04 and HPV-negative oropharyngeal and non-oropharyngeal SCCHN: HR = 0.74; 95% CI: 
0.56, 0.98). 
Patient-reported outcomes (PROs) were assessed using three measures: the EORTC QLQ-C30, 
EORTC QLQ-H&N35, and 3-level version of the EQ-5D. Over 15 weeks of follow-up, patients 
treated with nivolumab exhibited generally stable PROs, while those assigned to investigator’s 
choice therapy exhibited statistically significant and clinically meaningful declines in functioning 
(e.g., physical, role, social) and health status as well as increases in symptomatology (e.g., fatigue, 
dyspnea, appetite loss, pain, sensory problems, social contact problems). 
Unresectable or metastatic melanoma 
Randomized phase 3 study vs. dacarbazine (CA209066) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of advanced 
(unresectable or metastatic) melanoma were evaluated in a phase 3, randomized, double-blind 
study (CA209066). The study included patients (18 years or older) with confirmed, 
treatment-naive, Stage III or IV BRAF wild-type melanoma and an Eastern Cooperative Oncology 
Group (ECOG) performance status score of 0 or 1. Patients who had received previous adjuvant 
therapy were not excluded. Patients with active autoimmune disease, ocular melanoma, or active 
brain or leptomeningeal metastases were excluded from the study. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
182 
Approved v 41.0 
930144776 4.0 
 
 
Patients were randomized on a 1:1 basis to receive either nivolumab administered intravenously 
over 60 minutes at 3 mg/kg every 2 weeks or dacarbazine at 1000 mg/m2 every 3 weeks. 
Randomization was stratified by PD-L1 status and M stage (M0/M1a/M1b versus M1c). Treatment 
was continued as long as clinical benefit was observed or until treatment was no longer tolerated. 
Treatment after disease progression was permitted for patients who had a clinical benefit and did 
not have substantial adverse effects with the study drug, as determined by the investigator. Tumor 
assessments, according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 
1.1, were conducted 9 weeks after randomization and continued every 6 weeks for the first year 
and then every 12 weeks thereafter. The primary efficacy outcome measure was overall survival 
(OS). Key secondary efficacy outcome measures were investigator-assessed progression-free 
survival (PFS) and objective response rate (ORR). 
A total of 418 patients were randomized to either nivolumab (n=210) or dacarbazine (n=208). 
Baseline characteristics were balanced between the two groups. The median age was 65 years 
(range: 18-87), 59% were men, and 99% were white. Most patients had ECOG performance score 
of 0 (64%) or 1 (34%). Sixty-one percent of patients had M1c stage disease at study entry. 
Seventy-four percent of patients had cutaneous melanoma, and 11% had mucosal melanoma; 35% 
of patients had PD-L1 positive melanoma (>5% tumor cell membrane expression). Four percent 
of patients had a history of brain metastasis, and 37% of patients had a baseline LDH level greater 
than ULN at study entry. 
Nivolumab demonstrated a statistically significant improvement in OS over dacarbazine in 
treatment-naive patients with BRAF wild-type advanced (unresectable or metastatic) melanoma 
(HR = 0.42; 99.79% CI: 0.25, 0.73; p-value <0.0001). Median OS was not reached for nivolumab 
and was 10.8 months (95% CI: 9.33, 12.09) for dacarbazine. The estimated OS rates at 12 months 
were 73% (95% CI: 65.5, 78.9) and 42% (95% CI: 33.0, 50.9), respectively. 
The observed OS benefit was consistently demonstrated across subgroups of patients including 
baseline ECOG performance status, M stage, history of brain metastases, and baseline LDH level. 
Survival benefit was observed regardless of whether PD-L1 expression was above or below a 
PD-L1 tumor membrane expression cut-off of 5% or 10%. The Kaplan-Meier curves for OS are 
shown in Figure 13. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
183 
Approved v 41.0 
930144776 4.0 
 
 
Figure 13: 
Kaplan-Meier curves of OS (CA209066) 
 
 
Nivolumab also demonstrated statistically significant improvement in PFS compared with 
dacarbazine (HR = 0.43 [95% CI: 0.34, 0.56]; p <0.0001). The median PFS was 5.1 months (95% 
CI: 3.48, 10.81) for nivolumab and 2.2 months (95% CI: 2.10, 2.40) for dacarbazine. The estimated 
PFS rates at 6 months were 48% (95% CI: 40.8, 54.9) and 18% (95% CI: 13.1, 24.6), respectively. 
The estimated PFS rate at 12 months was 42% (95% CI: 34.0, 49.3) for nivolumab. The Kaplan- 
Meier curves for PFS are shown in Figure 14. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
184 
Approved v 41.0 
930144776 4.0 
 
 
Figure 14: 
Kaplan-Meier curves of progression-free survival (CA209066) 
 
 
The investigator-assessed ORR using RECIST v1.1 criteria was significantly higher in the 
nivolumab group than in the dacarbazine group (Odds Ratio: 4.06 [95% CI: 2.52, 6.54], 
p <0.0001). Response rates, time to response, and duration of response are shown in Table 23. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
185 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 23: 
Best overall response, time, and duration of response 
(CA209066) 
 
nivolumab 
dacarbazine 
(n=210) 
(n=208) 
Objective response n (%) 
84 (40.0%) 
29 (13.9%) 
(95% CI) 
(33.3, 47.0) 
(9.5, 19.4) 
Odds ratio (95% CI) 
4.06 (2.52, 6.54) 
p-value 
< 0.0001 
Complete response (CR) 
16 (7.6%) 
2 (1.0%) 
Partial response (PR) 
68 (32.4%) 
27 (13.0%) 
Stable disease (SD) 
35 (16.7%) 
46 (22.1%) 
Median duration of 
response 
(range) 
Not reached (0+ - 12.5+) 
6.0 months (1.1 - 10.0+) 
Median time to response 
(range) 
2.1 months (1.2 - 7.6) 
2.1 months (1.8 - 3.6) 
“+” denotes a censored observation. 
 
At the time of analysis, 82% (69/84) of nivolumab-treated patients and 31% (9/29) of 
dacarbazine-treated patients had ongoing responses, which included 46 and 4 patients, 
respectively, with ongoing response of 6 months or longer. 
In 54 nivolumab-treated patients, treatment was continued beyond an initial investigator 
assessment of RECIST disease progression if the investigator determined the patient had sufficient 
ongoing clinical benefit and was tolerating therapy. Of these patients, 12 (22.2%) had target lesion 
reductions (>30% compared to baseline). 
Randomized phase 3 study vs. chemotherapy (CA209037) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of advanced 
(unresectable or metastatic) melanoma were evaluated in a phase 3, randomized, open-label study 
(CA209037). The study included adult patients who had progressed on or after ipilimumab and, if 
BRAF V600 mutation positive, had also progressed on or after BRAF kinase inhibitor therapy. 
Patients with active autoimmune disease, ocular melanoma or a known history of prior 
ipilimumab-related high-grade (Grade 4 per CTCAE v4.0) adverse reactions, except for resolved 
nausea, fatigue, infusion reactions, or endocrinopathies, were excluded from the study. 
Patients were randomized on a 2:1 basis to receive either nivolumab administered intravenously 
over 60 minutes at 3 mg/kg every 2 weeks or chemotherapy. Chemotherapy consisted of the 
investigator’s choice of either dacarbazine (1000 mg/m2 every 3 weeks) or carboplatin 
(AUC 6 every 3 weeks) and paclitaxel (175 mg/m2 every 3 weeks). Randomization was stratified 
by BRAF and PD-L1 status and best response to prior ipilimumab. Tumor assessments were 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
186 
Approved v 41.0 
930144776 4.0 
 
 
conducted 9 weeks after randomization and continued every 6 weeks for the first year and then 
every 12 weeks thereafter. 
The co-primary efficacy outcome measures were confirmed ORR, as measured by independent 
radiology review committee (IRRC) using RECIST 1.1, and comparison of OS of nivolumab to 
chemotherapy. Additional outcome measures included duration and timing of response. 
A total of 405 patients were randomized to receive either nivolumab (n=272) or chemotherapy 
(n = 133). The median age was 60 years (range: 23-88). Sixty-four percent of patients were men 
and 98% were white. ECOG performance scores were 0 for 61% of patients and 1 for 39% of 
patients. The majority (75%) of patients had M1c stage disease at study entry. Seventy-three 
percent of patients had cutaneous melanoma and 10% had mucosal melanoma. The number of 
prior systemic regimen received was 1 for 27% of patients, 2 for 51% of patients, and >2 for 21% 
of patients. Twenty-two percent of patients were BRAF mutation positive and 50% of patients 
were PD-L1 positive. Sixty-four percent of patients had no prior clinical benefit (CR/PR or SD) 
on ipilimumab. Baseline characteristics were balanced between groups except for the proportions 
of patients who had a history of brain metastasis (19% and 13% in the nivolumab group and 
chemotherapy group, respectively) and patients with LDH greater than ULN at baseline (51% and 
35%, respectively). 
At the time of this final ORR analysis, results from 120 nivolumab-treated patients and 
47 chemotherapy-treated patients who had a minimum of 6 months of follow-up were analyzed. 
Efficacy results are presented in Table 24 and Figure 15. 
Table 24: 
Best overall response, time, and duration of response 
(CA209037) 
 
nivolumab 
chemotherapy 
(n=120) 
(n=47) 
Confirmed Objective 
Response (IRRC) n (%) 
38 (31.7%) 
5 (10.6%) 
(95% CI) 
(23.5, 40.8) 
(3.5, 23.1) 
Complete Response (CR) 
4 (3.3%) 
0 
Partial Response (PR) 
34 (28.3%) 
5 (10.6%) 
Stable Disease (SD) 
28 (23.3%) 
16 (34.0%) 
Median Duration of Response 
(range) 
Not Reached 
3.6 months (Not available) 
Median Time to Response 
(range) 
2.1 months (1.6-7.4) 
3.5 months (2.1-6.1) 
 
 
Of the 38 nivolumab-treated patients with a confirmed response, 33 were still in response at the 
time of analysis. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
187 
Approved v 41.0 
930144776 4.0 
 
 
Objective responses to nivolumab were observed in patients with or without BRAF 
mutation-positive melanoma. Of the patients who received nivolumab, the ORR in the BRAF 
mutation-positive subgroup was 23% (95% CI: 9.0, 43.6), and 34% (95% CI: 24.6, 44.5) in 
patients whose tumors were BRAF wild-type. Objective responses to nivolumab were observed 
regardless of whether PD-L1 expression was above or below a PD-L1 tumor membrane expression 
cut-off of 5% or 10%. 
Figure 15: 
Waterfall plot of best reduction in target lesion, per IRRC 
(CA209037) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Symbol (“*”) represents confirmed responders. 
 
 
In 37 (31%) nivolumab-treated patients, treatment was continued beyond an initial investigator 
assessment of RECIST disease progression if the investigator determined that the patient had 
sufficient ongoing clinical benefit and was tolerating therapy. Of these patients, 10 (27%) had 
target lesion reductions (>30% compared to baseline). 
Updated analysis (24-month follow-up) 
Among all randomized patients, the ORR was 27.2% (95% CI: 22.0, 32.9) in the nivolumab group 
and 9.8% (95% CI: 5.3, 16.1) in the chemotherapy group. Median duration of response was 
31.9 months (range: 1.4+-31.9) and 12.8 months (range: 1.3+-13.6+), respectively. 
Subjects 
Best Reduction from Baseline in Target Lesion (%) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
188 
Approved v 41.0 
930144776 4.0 
 
 
There was no statistically significant difference between nivolumab and chemotherapy in the 
primary OS analysis. The OS analysis was not adjusted to account for subsequent therapies, with 
54 (41%) patients in the chemotherapy arm subsequently receiving an anti-PD1 treatment. OS may 
be confounded by dropout, imbalance of subsequent therapies and differences in baseline factors. 
More patients in the nivolumab arm had poor prognostic factors (elevated LDH and brain 
metastases) than in the chemotherapy arm. 
Open-label phase 1 dose-escalation study (MDX1106-03) 
The safety and tolerability of nivolumab were investigated in a phase 1, open-label dose-escalation 
study in various tumor types, including malignant melanoma. 
Of the 306 previously treated patients enrolled in the study, 107 had melanoma and received 
nivolumab at a dose of 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, or 10 mg/kg for a maximum of 2 
years. In this patient population, objective response was reported in 33 patients (31%) with a 
median duration of response of 22.9 months (95% CI: 17.0, NR). The median PFS was 3.7 months 
(95% CI: 1.9, 9.3). The median OS was 17.3 months (95% CI: 12.5, 36.7), and the estimated OS 
rates were 63% (95% CI: 53, 71) at 1 year, 48% (95% CI: 38, 57) at 2 years, and 41% 
(95% CI: 31, 51) at 3 years. 
Randomized phase 3 study of nivolumab in combination with ipilimumab or nivolumab as 
monotherapy vs ipilimumab (CA209067) 
The safety and efficacy of nivolumab in combination with ipilimumab and nivolumab 
monotherapy for the treatment of advanced (unresectable or metastatic) melanoma were evaluated 
in a phase 3, randomized, double-blind study (CA209067). The study included adult patients 
(18 years or older) with confirmed unresectable Stage III or Stage IV melanoma, regardless of PD- 
L1 expression. Patients were to have ECOG performance status score of 0 or 1. Patients who had 
not received prior systemic anticancer therapy for unresectable or metastatic melanoma were 
enrolled. Prior adjuvant or neoadjuvant therapy was allowed if it was completed at least 6 weeks 
prior to randomization. Patients with active autoimmune disease, ocular/uveal melanoma, or active 
brain or leptomeningeal metastases were excluded from the study. 
A total of 945 patients were randomized to receive nivolumab in combination with ipilimumab 
(n = 314), nivolumab as monotherapy (n = 316), or ipilimumab as monotherapy (n = 315). Patients 
in the combination arm received nivolumab 1 mg/kg over 60 minutes and ipilimumab 3 mg/kg 
administered intravenously every 3 weeks for the first 4 doses, followed by nivolumab 3 mg/kg as 
monotherapy every 2 weeks. Patients in the nivolumab monotherapy arm received nivolumab 
3 mg/kg every 2 weeks. Patients in the comparator arm received ipilimumab 3 mg/kg and 
nivolumab-matched placebo intravenously every 3 weeks for 4 doses followed by placebo every 
2 weeks. Randomization was stratified by PD-L1 expression (≥5% vs. <5% tumor cell membrane 
expression), BRAF status, and M stage per the American Joint Committee on Cancer (AJCC) 
staging system. Treatment was continued as long as clinical benefit was observed or until treatment 
was no longer tolerated. Tumor assessments were conducted 12 weeks after randomization then 
every 6 weeks for the first year, and every 12 weeks thereafter. The co-primary outcome measures 
were progression-free survival and OS. ORR and the duration of response were also assessed. This 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
189 
Approved v 41.0 
930144776 4.0 
 
 
study evaluated whether PD-L1 expression was a predictive biomarker for the co-primary 
endpoints. The efficacy of nivolumab in combination with ipilimumab and nivolumab 
monotherapy was each compared with that of ipilimumab. In addition, the differences between the 
two nivolumab-containing groups were evaluated descriptively, but not included in formal 
hypothesis testing. Health Related Quality of Life (HRQoL) was assessed by the European 
Organization for Research and Treatment of Care (EORTC) QLQ-C30. 
Baseline characteristics were balanced across the three treatment groups. The median age 
was 61 years (range: 18-90 years), 65% of patients were men, and 97% were white. ECOG 
performance status score was 0 (73%) or 1 (27%). The majority of the patients had AJCC Stage 
IV disease (93%); 58% had M1c disease at study entry. Twenty-two percent of patients had 
received prior adjuvant therapy. Thirty-two percent of patients had BRAF mutation-positive 
melanoma; 26.5% of patients had PD-L1 ≥5% tumor cell membrane expression. Four percent of 
patients had a history of brain metastasis, and 36% of patients had a baseline LDH level greater 
than ULN at study entry. 
Note: The results for nivolumab monotherapy compared with ipilimumab monotherapy are 
included here. 
Nivolumab arm demonstrated a significant PFS and OS benefit and greater ORR compared with 
ipilimumab monotherapy. Efficacy results for the randomized patients are shown in Table 25, 
Figure 16, and Figure 17. 
The observed PFS, OS, and ORR results for nivolumab monotherapy were consistently 
demonstrated across subgroups of patients including baseline ECOG performance status, BRAF 
status, M stage, age, history of brain metastases, and baseline LDH level. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
190 
Approved v 41.0 
930144776 4.0 
 
 
(0+ - 32.3+) 
 
Table 25: 
Efficacy results (CA209067) 
 
 
nivolumab 
(n=316) 
ipilimumab 
(n=315) 
Progression-free survivala 
Events n (%) 
174 (55%) 
234 (74%) 
Hazard ratio (vs. ipilimumab) 
0.57 
(99.5% CI) 
(0.43, 0.76) 
p-value 
p<0.0001 
Median 
6.9 months 
2.9 months 
(95% CI) 
(4.3, 9.5) 
(2.8, 3.4) 
Rate (95% CI) 
At 6 months 
52% (46, 57) 
29% (24, 34) 
At 9 months 
45% (40, 51) 
21% (17, 26) 
Overall survivalb 
Events n (%) 
142 (45%) 
197 (63%) 
Hazard ratio (vs. ipilimumab) 
0.63 
(98% CI) 
(0.48, 0.81) 
p-value 
p<0.0001 
Median 
Not reached 
20.0 months 
(95% CI) 
(29.1, NE) 
(17.1, 24.6) 
Rate (95% CI) 
At 12 months 
74% (69, 79) 
67% (61, 72) 
At 24 months 
59% (53, 64) 
45% (39, 50) 
Objective responseb n (%) 
141 (45%) 
60 (19%) 
(95% CI) 
(39.1, 50.3) 
(14.9, 23.8) 
Odds ratio (vs ipilimumab) 
3.54 
(95% CI) 
(2.10, 5.95) 
Complete response (CR) 
47 (15%) 
14 (4%) 
Partial response (PR) 
94 (30%) 
46 (15%) 
Stable disease (SD) 
31 (10%) 
67 (21%) 
 
Duration of response 
Median (range) 
31.1 months 
 
18.2 months 
(0+ - 31.5+) 
Proportion >12 months in duration 
70% 
53% 
Proportion >24 months in duration 
49% 
32% 
 
a Minimum follow up of 9 months. 
b Minimum follow up of 28 months. 
NE=not estimable. 
“+” denotes a censored observation. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
191 
Approved v 41.0 
930144776 4.0 
 
 
Figure 16: 
Progression-free survival (CA209067) 
 
1.0 
0.9 
0.8 
0.7 
0.6 
0.5 
0.4 
0.3 
0.2 
0.1 
0.0 
 
 
0 
3 
6 
9 
12 
15 
18 
21 
Progression Free Survival per Investigator (Months) 
 
Number of Subjects at Risk 
 
OPDIVO 
316 
177 
147 
124 
50 
9 
1 
0 
Ipilimumab 
315 
137 
77 
54 
24 
4 
0 
0 
 
 
Probability of Progression Free Survival 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
192 
Approved v 41.0 
930144776 4.0 
 
 
Figure 17: 
Overall survival (CA209067) 
 
1.0 
0.9 
0.8 
0.7 
0.6 
0.5 
0.4 
0.3 
0.2 
0.1 
0.0 
 
 
0 
3 
6 
9 
12 
15 
18 
21 
24 
27 
30 
33 
36 
39 
Overall Survival (Months) 
 
Number of Subjects at Risk 
 
OPDIVO 
316 
292 
265 
244 
230 
213 
201 
191 
181 
175 
157 
55 
3 
0 
Ipilimumab 
315 
285 
254 
228 
205 
182 
164 
149 
136 
129 
104 
34 
4 
0 
 
 
 
Quality of life measured by the EORTC QLQ-C30 Global Health Status remained stable in both 
treatment groups, with no mean change in score from baseline reaching the minimal important 
difference for the patient (i.e., mean change ≥10 points) at any time point for any of the three 
treatment arms. 
Efficacy by BRAF status: Efficacy results by BRAF status are shown in Table 26 for PFS, Table 
27 for OS, and Table 28 for ORR. 
 
Table 26: 
PFS by BRAF [V600]-mutation status (CA209067) 
 
BRAF [V600] mutation-positive 
BRAF wild-type 
 
 
 
 
nivolumab 
 
 
 
Minimum follow up of 9 months. 
NE=not estimable. 
OPDIVO 
Ipilimumab 
Probability of Overall Survival 
Median PFS 
HR vs 
ipilimumab 
Median PFS 
HR vs 
ipilimumab 
Treatment 
(95% CI) 
(95% CI) 
(95% CI) 
(95% CI) 
5.6 months 
0.77 
7.9 months 
0.50 
(2.8, 9.5) 
(0.54, 1.09) 
(4.9, 12.7) 
(0.39, 0.63) 
ipilimumab 
4.0 months 
(2.8, 5.5) 
-- 
2.8 months 
(2.8, 3.1) 
-- 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
193 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 27: 
OS by BRAF[V600]-mutation status (CA209067) 
 
BRAF [V600] mutation-positive 
BRAF wild-type 
 
 
 
Nivolumab 
Ipilimumab 
Minimum follow up of 28 months. 
NE=not estimable. 
 
 
Table 28: 
Objective response by BRAF[V600]-mutation statusa (CA209067) 
 
BRAF [V600] mutation-positive 
BRAF wild-type 
 
 
Nivolumab 
Ipilimumab 
Minimum follow up of 28 months. 
 
Efficacy by PD-L1 tumor Expression: Baseline tumor tissue specimens were systematically 
collected prior to randomization in order to conduct planned analyses of efficacy according to PD- 
L1 expression. Quantifiable tumor PD-L1 expression was measured in 91% (288/316) of patients 
randomized to nivolumab monotherapy, and 88% (277/315) of patients randomized to ipilimumab 
monotherapy. Among patients with quantifiable tumor PD-L1 expression, the distribution of 
patients was balanced across the three treatment groups at each of the predefined tumor PD-L1 
expression levels of ≥1% (59% in the nivolumab monotherapy arm, and 59% in the ipilimumab 
arm) and ≥5% (24%, 28%, and 27%, respectively). Tumor PD-L1 expression was determined 
using the PD-L1 IHC 28-8 pharmDx assay. 
In patients with low or no tumor PD-L1 expression (based on the predefined expression level of 
<5% and <1%), nivolumab monotherapy demonstrated significant improvements in PFS and OS 
compared with ipilimumab monotherapy. In patients with ≥5% and ≥1% tumor PD-L1 expression, 
a significant improvement in PFS and OS relative to ipilimumab was also observed for nivolumab 
arm. Results by PD-L1 expression level are shown in Figure 18 for PFS and in Figure 19 for OS. 
Median OS 
HR vs 
ipilimumab 
Median OS 
HR vs 
ipilimumab 
Treatment 
(95% CI) 
(95% CI) 
(95% CI) 
(95% CI) 
Not reached 
0.60 
Not reached 
0.64 
(26.4, NE) 
(0.40, 0.89) 
(25.8, NE) 
(0.49, 0.83) 
24.6 months 
-- 
18.5 months 
-- 
(17.9, 31.0) 
(14.8, 23.0) 
Treatment 
Number of 
responses/patients 
ORR 
(95% CI) 
Number of 
responses/patients 
ORR 
(95% CI) 
36/98 
37% 
105/218 
48% 
(27, 47) 
(41, 55) 
23/100 
23% 
37/215 
17% 
(15, 33) 
(12, 23) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
194 
Approved v 41.0 
930144776 4.0 
 
 
Figure 18: 
Progression-free survival by tumor PD-L1 expression level 
(CA209067) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
195 
Approved v 41.0 
930144776 4.0 
 
 
Figure 19: 
Overall survival by tumor PD-L1 expression level (CA209067) 
 
 
 
 
Table 29 shows the objective response rates in CA209067 based on PD-L1 expression level. 
Nivolumab arm demonstrated greater objective response rates than ipilimumab regardless of tumor 
PD-L1 expression levels. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
196 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 29: 
Objective response by PD-L1 Expression Level (CA209067) 
 
ORR % (95% CI) 
nivolumab 
(n=316) 
ipilimumab 
(n=315) 
<5% 
42% (35.5, 49.3) 
n=208 
18% (12.8, 23.8) 
n=202 
≥5% 
59% (47.2, 69.6) 
n=80 
21% (12.7, 32.3) 
n=75 
<1% 
35% (26.5, 44.4) 
n=117 
19% (11.9, 27.0) 
n=113 
≥1% 
55% (47.2, 62.6) 
n=171 
19% (13.2, 25.7) 
n=164 
No clear cutoff for PD-L1 expression can reliably be established when considering the relevant 
endpoints of tumor response, PFS, and OS. 
As compared to the overall study population, no meaningful differences in safety were observed 
based on BRAF status or tumor PD-L1 expression levels of 1% or 5%. 
Randomized Phase 3 study of nivolumab vs ipilimumab 10 mg/kg (CA209238) 
The safety and efficacy of nivolumab 3 mg/kg as a single agent for the treatment of patients with 
completely resected melanoma were evaluated in a Phase 3, randomized, double-blind study 
(CA209238). The study included adult patients who had an ECOG performance status score of 0 
or 1, with Stage IIIB/C or Stage IV American Joint Committee on Cancer (AJCC), 7th edition, 
histologically confirmed melanoma that was completely surgically resected. Per the AJCC 8th 
edition, this corresponds to patients with lymph node involvement or metastases. Patients were 
enrolled regardless of their tumor PD-L1 status. Patients with prior autoimmune disease, and any 
condition requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisone or 
equivalent) or other immunosuppressive medications, as well as patients with prior therapy for 
melanoma (except patients with surgery, adjuvant radiotherapy after neurosurgical resection for 
lesions of the central nervous system, and prior adjuvant interferon completed ≥6 months prior to 
randomization) prior therapy with, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti 
CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T- 
cell co-stimulation or checkpoint pathways), were excluded from the study. 
A total of 906 patients were randomized to receive either nivolumab 3 mg/kg (n = 453) 
administered every 2 weeks or ipilimumab 10 mg/kg (n = 453) administered every 3 weeks for 
4 doses then every 12 weeks beginning at week 24 for up to 1 year. Randomization was stratified 
by tumor PD-L1 expression (≥5% vs. < 5%/indeterminate), and stage of disease per the AJCC 
staging system. Tumor assessments were conducted every 12 weeks for the first 2 years then every 
6 months thereafter. The primary endpoint was recurrence-free survival (RFS). RFS, assessed by 
investigator, was defined as the time between the date of randomization and the date of first 
recurrence (local, regional, or distant metastasis), new primary melanoma, or death due to any 
cause, whichever occurred first. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
197 
Approved v 41.0 
930144776 4.0 
 
 
Baseline characteristics were generally balanced between the two groups. The median age was 
55 years (range: 18-86), 58% were men, and 95% were white. Baseline ECOG performance status 
score was 0 (90%) or 1 (10%). The majority of patients had AJCC Stage III disease (81%), and 
19% had Stage IV disease. Forty-eight percent of patients had macroscopic lymph nodes and 32% 
had tumor ulceration. Forty-two percent of patients were BRAF V600 mutation positive while 
45% were BRAF wild type and 13% BRAF status was unknown. For tumor PD-L1 expression, 
34% of patients had PD-L1 expression ≥ 5% and 62% had < 5% as determined by clinical trial 
assay. Among patients with quantifiable tumor PD-L1 expression, the distribution of patients was 
balanced across the treatment groups. Tumor PD-L1 expression was determined using the PD- 
L1 IHC 28-8 pharmDx assay. 
Minimum follow-up was approximately 24 months. OS was not mature at the time of this analysis. 
RFS results are shown in Table 30 and Figure 20 (all randomized population). 
 
Table 30: 
Efficacy results (CA209238) 
nivolumab 
ipilimumab 10 mg/kg 
(n = 453) 
(n = 453) 
Recurrence-free Survival 
Events 
171 (37.7%) 
221 (48.8%) 
Hazard ratioa 
0.66 
95% CI 
(0.54, 0.81) 
p-value 
p<0.0001 
Median (95% CI) months 
30.75 (30.75, NR)b 
24.08 (16.56, NR)b 
Rate (95% CI) at 
70.4 (65.9, 74.4) 
60.0 (55.2, 64.5) 
12 months 
Rate (95% CI) at 
65.8 (61.2, 70.0) 
53.0 (48.1, 57.6) 
18 months 
Rate (95% CI) at 
62.6 (57.9, 67.0) 
50.2 (45.3, 54.8) 
24 months 
a Derived from a stratified Cox proportional hazards model. 
b Based on Kaplan-Meier estimates. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
198 
Approved v 41.0 
930144776 4.0 
 
 
Figure 20: 
Recurrence-free Survival (CA209238) 
 
 
 
The trial demonstrated a statistically significant improvement in RFS for patients randomized to 
the nivolumab arm compared with the ipilimumab 10 mg/kg arm. RFS benefit was consistently 
demonstrated across subgroups, including tumor PD-L1 expression, BRAF status, and stage of 
disease. 
Quality of life (QoL) with nivolumab remained stable and close to baseline values during 
treatment, as assessed by valid and reliable scales like the European Organization for Research 
and Treatment of Cancer (EORTC) QLQ-C30 and the EQ-5D utility index and visual analog scale 
(VAS). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
199 
Approved v 41.0 
930144776 4.0 
 
 
Classical Hodgkin lymphoma (cHL) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of relapsed or 
refractory cHL following ASCT and treatment with brentuximab vedotin were evaluated in two 
global, multicenter, open-label, single-arm studies (CA209205 and CA209039). 
CA209205 is an ongoing Phase 2, open-label, multi-cohort, single-arm study of nivolumab in cHL. 
Cohort A included 63 patients who had received ASCT and were brentuximab vedotin naïve; 
Cohort B included 80 patients who had received brentuximab vedotin after ASCT failure; Cohort 
C included 100 patients who had received brentuximab vedotin before and/or after ASCT out of 
which 33 patients received brentuximab vedotin only prior to ASCT. The first tumor assessments 
were conducted 9 weeks after the start of treatment and continued thereafter until disease 
progression or treatment discontinuation. The primary efficacy outcome measure was ORR as 
determined by IRRC. Additional efficacy measures included duration of response and PFS. 
CA209039 was a Phase 1b open-label, multicenter, dose-escalation, and multidose study of 
nivolumab in relapsed or refractory hematologic malignancies, including 23 patients with cHL; 
amongst which, 15 patients received prior brentuximab vedotin treatment as a salvage therapy 
following ASCT, similar to Cohort B of study CA209205. The first tumor assessments were 
conducted 4 weeks after the start of treatment and continued thereafter until disease progression 
or treatment discontinuation. Efficacy assessments included investigator-assessed ORR, 
retrospectively evaluated by an IRRC, and duration of response. 
Both studies included patients regardless of their PD-L1 status, and excluded patients with 
autoimmune disease, symptomatic interstitial lung disease, known central nervous system (CNS) 
lymphoma or patients with nodular lymphocyte-predominant HL. Patients received 3 mg/kg of 
nivolumab administered intravenously over 60 minutes every 2 weeks. 
Data from the 80 patients from CA209205 Cohort B and the 15 patients from CA209039 who 
received prior brentuximab vedotin treatment following ASCT were integrated. Baseline 
characteristics were similar across the two studies (Table 31). Efficacy from both studies was 
evaluated by the same IRRC. Results are shown in Table 32. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
NE=not estimable. 
“+” denotes a censored observation. 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
200 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 31: 
Baseline patient characteristics (CA209205 Cohort B and CA209039) 
 
CA209205 Cohort B 
and CA209039 
(n = 95) 
CA209205 Cohort B a 
(n = 80) 
CA209039 
(n = 15) 
Median age (range) 
37.0 years (18–72) 
37.0 years (18–72) 
40.0 years (24–54) 
Gender 
61 (64%)M / 34 (36%)F 
51 (64%)M / 29 (36%)F 
10 (67%)M / 5 (33%)F 
ECOG status 
0 
49 (52%) 
42 (52.5%) 
7 (47%) 
1 
46 (48%) 
38 (47.5%) 
8 (53%) 
≥5 prior lines of systemic therapy 
49 (52%) 
39 (49%) 
10 (67%) 
Prior ASCT 
1 
87 (92%) 
74 (92.5%) 
13 (87%) 
≥2 
8 (8%) 
6 (7.5%) 
2 (13%) 
Years from most recent transplant 
3.5 years (0.2-19.0) 
3.4 years (0.2-19.0) 
5.6 years (0.5-15.0) 
to first dose of study therapy, 
median (range) 
a 18/80 (22.5%) of the patients in CA209205 Cohort B presented B-Symptoms at baseline. 
 
 
Table 32: 
Efficacy results (CA209205 Cohort B and CA209039) 
 
CA209205 
Cohort Ba and 
CA209039 
(n = 95) 
CA209205 
Cohort Ba 
(n = 80) 
CA209039 
(n = 15) 
Objective Response Rate; (95% CI) 
63 (66%); (56, 76) 
54 (68%); (56, 78) 
9 (60%); (32, 
84) 
Complete Remission Rate; (95% CI) 
6 (6%); (2, 13) 
6 (8%); (3, 16) 
0 (0%); (0, 22) 
Partial Remission Rate; (95% CI) 
57 (60%); (49, 70) 
48 (60%); (48, 71) 
9 (60%); (32, 
84) 
Stable disease, n (%) 
22 (23%) 
17 (21%) 
5 (33%) 
Median Duration of Responseb 
13.1 months 
13.1 months 
12.0 months 
(95% CI) 
(9.5, NE) 
(8.7, NE) 
(1.8, NE) 
Range 
0.0+ - 23.1+ 
0.0+ - 14.2+ 
1.8 - 23.1+ 
Median Time to Response 
2.0 months 
2.1 months 
0.8 months 
Range 
0.7 - 11.1 
1.6 - 11.1 
0.7 - 4.1 
Median Duration of Follow-up 
15.8 months 
15.4 months 
21.9 months 
Range 
1.9 - 27.6 
1.9 - 18.5 
11.2 - 27.6 
PFS rate at 12 months 
57% 
55% 
69% 
(95% CI) 
(45, 68) 
(41, 66) 
(37, 88) 
a Follow-up was ongoing at the time of data submission 
b Data unstable due to the limited duration of response for Cohort B resulting from censoring. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
NE=not estimable. 
“+” denotes a censored observation. 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
201 
Approved v 41.0 
930144776 4.0 
 
 
Nine patients received allogeneic stem cell transplant (5 in CA209205 and 4 in CA209039) as 
subsequent therapy. 
Objective response per IRRC with nivolumab was observed regardless of baseline tumor PD-L1 
expression status. 
In a post-hoc analysis of the 80 patients in CA209205 Cohort B, 37 had no response to prior 
brentuximab vedotin treatment. Among these 37 patients, treatment with nivolumab resulted in an 
ORR of 59.5% (22/37). The median duration of response is 13.1 months (13.1, NE) for the 
22 responders to nivolumab who had failed to achieve response with prior brentuximab vedotin 
treatment. 
B-symptoms were present in 22.5% (18/80) of the patients in CA209205 Cohort B at baseline. 
Nivolumab treatment resulted in rapid resolution of B-symptoms in 88.9% (16/18) of the patients, 
with a median time to resolution of 1.9 months. 
Efficacy was also evaluated in 258 patients who had relapsed or progressive cHL after autologous 
HSCT (243 patients in Cohorts A+B+C from CA209205 and 15 patients from CA209039). The 
median age was 34 years (range: 18-72). The majority were male (59%) and white (86%). Patients 
had a median of 4 prior systemic regimens (range: 2-15), with 85% having 3 or more prior systemic 
regimens and 76% having prior brentuximab vedotin. Of the 195 patients having prior 
brentuximab vedotin, 17% received it only before autologous HSCT, 78% received it only after 
HSCT, and 5% received it both before and after HSCT. Efficacy results for this population are 
shown in Table 33. 
Table 33: 
Efficacy in cHL after autologous HSCT (CA209205 Cohort 
A+B+C and CA209039) 
 
 
Objective Response Rate, n (%) 
(95% CI) 
Complete Remission Rate 
(95% CI) 
Partial Remission Rate 
(95% CI) 
Duration of Response (months) 
Mediana,b 
(95% CI) 
Range 
Time to Response 
Median 
Range 
Nivolumab 
(n=258) 
179 (69%) 
(63, 75) 
37 (14%) 
(10, 19) 
142 (55%) 
(49, 61) 
 
Not reached 
(12.0, NE) 
0+ - 23.1+ 
 
2.0 months 
0.7 - 11.1 
 
a Kaplan-Meier estimate. Among responders, the median follow-up for DOR, measured from the date of first 
response, was 6.7 months. 
b The estimated median duration of PR was 13.1 months (95% CI, 9.5, NE). The median duration of CR was not 
reached. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
202 
Approved v 41.0 
930144776 4.0 
 
 
Health related Quality of Life (QoL) was assessed among overall patients (Cohort A+B+C) in 
CA209205 using the patient reported EQ 5D VAS and EORTC-QLQ-C30 (global health status). 
Over 81 weeks of follow up, mean EQ-5D VAS scores increased over time, indicating superior 
overall health status for patients remaining on treatment with clinically relevant improvements. 
EORTC QLQ-C30 scores remained generally stable over time with mean changes from baseline 
trending toward an improvement on treatment in global health status. 
Urothelial Carcinoma (UC) 
Open-label Phase 2 study (CA209275) 
The safety and efficacy of nivolumab 3 mg/kg as monotherapy for the treatment of locally 
advanced or metastatic UC were evaluated in a Phase 2, multicenter, open-label, single-arm study 
(CA209275). 
The study included patients (18 years or older) who had disease progression during or after 
platinum-containing chemotherapy for advanced or metastatic disease or had disease progression 
within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. 
Patients had an ECOG performance status score of 0 or 1 and were enrolled regardless of their 
tumor PD-L1 status. Patients with active brain metastases or leptomeningeal metastases, active 
autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded 
from the study. 
Patients received nivolumab 3 mg/kg administered intravenously over 60 minutes every 2 weeks. 
Treatment was continued as long as clinical benefit was observed or until treatment was no longer 
tolerated. Treatment beyond initial investigator-assessed RECIST, version 1.1-defined 
progression was permitted if the patient had a clinical benefit, did not have rapid disease 
progression, and was tolerating study drug. The first tumor assessments were conducted 8 weeks 
after the start of treatment and continued every 8 weeks up to 48 weeks, then every 12 weeks 
thereafter until disease progression or treatment discontinuation, whichever occurred later. Tumor 
assessments were continued after treatment discontinuation in patients who discontinued treatment 
for reasons other than progression. The primary efficacy outcome measure was ORR as determined 
by IRRC. Additional efficacy measures included duration of response, PFS, and OS. 
A total of 270 patients with a minimum follow-up of 8.3 months were evaluable for efficacy. The 
median age was 66 years (range: 38-90) with 55% ≥65 years of age and 14% ≥75 years of age. 
The majority of patients were white (86%) and male (78%). Baseline ECOG performance status 
was 0 (54%) or 1 (46%). 
Efficacy results are shown in Table 34. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
203 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 34: 
Efficacy results (CA209275)a 
 
 
nivolumab 
(n = 270) 
Confirmed objective response n (%) 
54 (20.0%) 
(95% CI) 
(15.4, 25.3) 
Complete response (CR) 
8 (3.0%) 
Partial response (PR) 
46 (17.0%) 
Stable disease (SD) 
60 (22.2%) 
Median duration of responseb (range) 
10.4 months (1.9+-12.0+) 
Median time to response (range) 
1.9 months (1.6-7.2) 
Progression-Free Survival 
Events (%) 
216 (80%) 
Median (95% CI) 
2.0 months (1.9, 2.6) 
Rate (95% CI) at 6 months 
26.1% (20.9, 31.5) 
Overall survival 
Events 
n (%) 
154 (57%) 
Median (95% CI) 
8.6 months (6.1, 11.3) 
Rate (95% CI) at 12 months 
41.0% (34.8, 47.1) 
 
Tumor PD-L1 expression level 
< 1% 
≥ 1% 
Confirmed objective response 
(95% CI) 
16% (10.3, 22.7) 
n=146 
25% (17.7, 33.6) 
n=124 
Median duration of response 
(range) 
Progression-free survival 
10.4 months (3.7-12.0+) 
Not Reached (1.9+-12.0+) 
Median (95% CI) 
1.9 months (1.8, 2.0) 
3.6 months (1.9, 3.7) 
Rate (95% CI) at 6 months 
22.0% (15.6, 29.2) 
30.8% (22.7, 39.3) 
Overall survival 
Median (95% CI) 
5.9 months (4.4, 8.1) 
11.6 months (9.1, NE) 
Rate (95% CI) at 12 months 
34.0% (26.1, 42.1) 
49.2% (39.6, 58.1) 
 
a Median follow-up 11.5 months. 
b Data unstable due to the limited duration of response. 
NE=not estimable. 
“+” denotes a censored observation. 
 
Objective response per IRRC with nivolumab was observed regardless of baseline tumor PD-L1 
expression status. 
Disease related and non-disease specific quality of life (QoL) was assessed using the validated 
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and the 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
204 
Approved v 41.0 
930144776 4.0 
 
 
EuroQoL EQ-5D. Overall QoL scores remained stable while Global Health Status (GHS) based 
on the EORTC-QLQ-C30, continued to improve through Week 49. EQ-5D VAS scores showed 
clinically relevant improvement in QoL by Week 9, with continued improvement through 
Week 49. Both scales showed no detriment. 
Open-label Phase 1/2 study (CA209032) 
CA209032 was a Phase 1/2 open-label multi-cohort study which included a cohort of 78 patients 
with UC. Inclusion criteria were similar to those in study CA209275. Patients were treated with 
nivolumab 3 mg/kg as monotherapy. At a minimum follow-up of 9 months, investigator-assessed 
confirmed ORR was 24.4% (95% CI: 15.3, 35.4). The median duration of response was not reached 
(range: 4.4-16.6+ months). The median OS was 9.7 months (95% CI: 7.3, 16.2) and the estimated 
OS rates were 69.2% (CI: 57.7, 78.2) at 6 months and 45.6% (CI: 34.2, 56.3) at 12 months. 
Colorectal Cancer (CRC) 
The safety and efficacy of nivolumab as a single agent or in combination with ipilimumab were 
evaluated for the treatment of dMMR or MSI-H metastatic CRC in a Phase 2, multicenter, 
open-label, single-arm study (CA209142). 
The study included patients (18 years or older) with locally determined dMMR or MSI-H status, 
who had disease progression during, after, or were intolerant to, prior therapy with 
fluoropyrimidine and oxaliplatin or irinotecan, and had an ECOG performance status score of 0 or 
1. This study included patients regardless of their tumor PD-L1 status. Patients with active brain 
metastases, 
active 
autoimmune 
disease, 
or 
medical 
conditions 
requiring 
systemic 
immunosuppression were excluded from the study. 
Nivolumab monotherapy 
A total of 74 patients received treatment with nivolumab 3 mg/kg administered intravenously over 
60 minutes every 2 weeks. Treatment was continued as long as clinical benefit was observed or 
until treatment was no longer tolerated. Tumor assessments according to RECIST version 1.1 were 
conducted every 6 weeks for the first 24 weeks and every 12 weeks thereafter. The primary and 
secondary outcome measures were investigator-assessed ORR and blinded independent central 
review (BICR) ORR, respectively. Exploratory outcome measures included duration of and time 
to response, PFS, OS, and QoL. 
The median age was 53 years 
 with 23% ≥ 65 years of age and 5% ≥ 75 years of 
age, 59% were male and 88% were white. Baseline ECOG performance status was 0 (43%) or 
1 (55%), 16% of patients were BRAF mutation positive, 35% were KRAS mutation positive, and 
11% were unknown. 15%, 30%, 30%, and 24% received 1, 2, 3, or 4 or more prior lines of therapy, 
respectively, and 42% of patients had received EGFR inhibitor therapy. 
Efficacy results based on a minimum follow-up of approximately 15.7 months for all 74 patients 
and a subgroup of 53 patients who had prior fluoropyrimidine, oxaliplatin and irinotecan therapy 
are shown in Table 35. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
205 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 35: 
Nivolumab monotherapy efficacy results (CA209142) 
nivolumab 
All patients 
nivolumab 
Prior treatment with 
fluoropyrimidine, oxaliplatin 
and irinotecan 
(n = 74) 
(n = 53) 
Confirmed objective responsea, n 
(%) 
24 (32.4) 
15 (28.3) 
(95% CI) 
(22.0, 44.3) 
(16.8, 42.3) 
Complete response (CR), n 
2 (2.7) 
1 (1.9) 
(%) 
Partial response (PR), n (%) 
22 (29.7) 
14 (26.4) 
Stable disease (SD), n (%) 
25 (33.8) 
16 (30.2) 
Median duration of responsea 
Months (range) 
NE (1.4+, 26.5+) 
NE (2.8+, 22.1+) 
Median time to responsea 
Months (range) 
2.79 (1.2, 22.6) 
2.89 (1.2, 22.6) 
Disease control ratea,b, n (%) 
47 (63.5) 
30 (56.6) 
(95% CI) 
(51.5, 74.4) 
(42.3, 70.2) 
Progression-free survivala 
Events 
40 
30 
Median (months) (95% CI) 
6.6 (3.0, NE) 
4.2 (1.4, NE) 
Overall survival 
Events 
25 
19 
Median (months) (95% CI) 
Not reached (19.6, NE) 
Not reached (18.0, NE) 
6-month rate (%) (95% CI) 
83.3 (72.4, 90.1) 
80.3 (66.5, 88.9) 
12-month rate (%) (95% CI) 
72.0 (60.0, 80.9) 
68.3 (53.5, 79.2) 
“+” denotes a censored observation. 
a BICR assessment. 
b CR + PR + SD (for at least 12 weeks). 
NE = non-estimable. 
 
 
Confirmed responses were observed regardless of BRAF and KRAS mutation status, and tumor 
PD-L1 expression levels. 
 
Esophageal Squamous Cell Carcinoma (ESCC) 
Randomized, open-label, multicenter Phase 3 study (CA209473/ONO-24/ ATTRACTION-3) 
The safety and efficacy of nivolumab monotherapy for the treatment of ESCC were evaluated in a 
Phase 3, multicenter, randomized (1:1), active-controlled, open-label study in patients with 
unresectable advanced, recurrent, or metastatic ESCC, refractory or intolerant to at least one 
fluoropyrimidine- and platinum-based regimen (CA209473/ONO-24). The study included patients 
regardless of PD-L1 status. The study excluded patients with a baseline performance score ≥ 2, 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
206 
Approved v 41.0 
930144776 4.0 
 
 
brain metastases that were symptomatic or required treatment, apparent tumor invasion on organs 
located adjacent to the esophagus (e.g., the aorta or respiratory tract), active autoimmune disease, 
or use of systemic corticosteroids or immunosuppressants. Patients received nivolumab 240 mg 
by intravenous infusion over 30 minutes every 2 weeks (n=210) or investigator’s choice taxane 
chemotherapy of either: 
• docetaxel (n=65) 75 mg/m2 intravenously every 3 weeks, or 
• paclitaxel (n=144) 100 mg/m2 intravenously once a week for 6 weeks followed by 1 week off. 
 
Patients were treated until disease progression, assessed by the investigator per RECIST v1.1, or 
unacceptable toxicity. Treatment beyond initial investigator-assessed progression was permitted 
in patients receiving nivolumab or chemotherapy if there was no worsening of symptoms due to 
progression, treatment could be safely administered and there was an expectation continued 
treatment would lead to clinical benefit, as determined by the investigator. 
The tumor assessments were conducted every 6 weeks for 1 year and every 12 weeks thereafter. 
The major efficacy outcome measure was OS. Additional efficacy outcome measures included 
ORR and PFS, as assessed by the investigator using RECIST v1.1, and DOR. The trial population 
characteristics were: median age 65 years (range: 33 to 87), 53% were ≥ 65 years of age, 87% were 
male, 96% were Asian, and 4% were White. Baseline ECOG performance status was 0 (50%) or 
1 (50%). 
The study demonstrated a statistically significant improvement in OS for patients randomized to 
nivolumab as compared with investigator’s choice taxane chemotherapy. OS benefit was observed 
regardless of PD-L1 expression level. The minimum follow-up was 17.6 months. 
Efficacy results are shown in Table 36 and Figure 21. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
207 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 36: 
Efficacy Results - CA209473/ONO-24/ ATTRACTION-3 
 
Nivolumab 
(n=210) 
Chemotherapy 
(n=209) 
Overall Survivala 
Deaths (%) 
160 (76%) 
173 (83%) 
Median (months) 
10.9 
8.4 
(95% CI) 
(9.2, 13.3) 
(7.2, 9.9) 
Hazard ratio (95% CI)b 
0.77 (0.62, 0.96) 
p-valuec 
0.0189 
Progression-free Survivala 
Disease progression or death (%) 
187 (89) 
176 (84) 
Median (months) 
1.7 
3.4 
(95% CI) 
(1.5, 2.7) 
(3.0, 4.2) 
Hazard ratio (95% CI)b 
1.1 (0.9, 1.3) 
Objective Response Rated, e 
33 (19.3) 
34 (21.5) 
(95% CI) 
(13.7, 26.0) 
(15.4, 28.8) 
Complete response (%) 
1 (0.6) 
2 (1.3) 
Partial response (%) 
32 (18.7) 
32 (20.3) 
Median duration of response 
6.9 
3.9 
(months) 
(5.4, 11.1) 
(2.8, 4.2) 
(95% CI) 
a Based on ITT analysis. 
b Based on a stratified proportional hazards model. 
c Based on a stratified log-rank test. 
d Based on Response Evaluable Set (RES) analysis, n=171 in nivolumab group and n=158 in investigator’s choice 
group. 
e Not significant, p-value 0.6323. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
208 
Approved v 41.0 
930144776 4.0 
 
 
Figure 21: 
Overall Survival - CA209473/ONO-24/ ATTRACTION-3 
 
 
Tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a 
central laboratory and the results were used to define subgroups for prespecified analyses. Of the 
419 patients, 48% were defined as having PD-L1 expression of ≥1% (defined as ≥1% of tumor 
cells expressing PD-L1). The remaining 52% of patients were classified as having PD-L1 
expression of <1% (defined as <1% of tumor cells expressing PD-L1). 
The hazard ratio (HR) for survival was 0.69 (95% CI: 0.51, 0.94) with median survivals of 10.9 
and 8.1 months for the nivolumab and chemotherapy arms, respectively, in the tumor PD-L1 ≥1% 
subgroup. The HR for survival was 0.84 (95% CI: 0.62, 1.14) with median survivals of 10.9 and 
9.3 months for the nivolumab and chemotherapy arms, respectively, in the tumor PD-L1 <1% 
subgroup. 
 
Gastric, Gastroesophageal Junction or Esophageal Adenocarcinoma (GC, GEJC or EAC) 
The safety and efficacy of nivolumab 240 mg every 2 weeks or 360 mg every 3 weeks in 
combination with chemotherapy was evaluated in a phase 3, randomised, open-label study 
(CA209649). The study included adult patients (18 years or older) with previously untreated 
advanced or metastatic gastric, gastro-esophageal junction (GEJ) or esophageal adenocarcinoma, 
no prior systemic treatment (including HER2 inhibitors), and ECOG performance status score 0 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
209 
Approved v 41.0 
930144776 4.0 
 
 
or 1. Patients were enrolled regardless of their tumour PD-L1 status, and tumour PD-L1 expression 
was determinated using the PD-L1 IHC 28-8 pharmDx assay. Patients with known HER2-positive 
tumours, baseline performance score ≥2 or who had untreated central nervous system metastases 
were excluded from the study. Randomization was stratified by tumor PD-L1 status (≥1% vs. <1% 
or indeterminate), region (Asia vs. US vs. rest of world), ECOG performance status (0 vs. 1), and 
chemotherapy regimen. Chemotherapy consisted of FOLFOX (fluorouracil, leucovorin, and 
oxaliplatin) or CapeOX (capecitabine and oxaliplatin). 
A total of 1581 patients were randomised to receive either nivolumab in combination with 
chemotherapy (n=789) or chemotherapy (n=792). Patients in the nivolumab plus chemotherapy 
arm received either nivolumab 240 mg by intravenous infusion over 30 minutes in combination 
with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 
intravenously on Day 1 and fluorouracil 1200 mg/m2 intravenously daily on Days 1 and 2) every 
2 weeks, or nivolumab 360 mg by intravenous infusion over 30 minutes in combination with 
CapeOX (oxaliplatin 130 mg/m2 intravenously on Day 1 and capecitabine 1000 mg/m2 orally 
twice daily on Days 1-14) every 3 weeks. Treatment continued until disease progression, 
unacceptable toxicity, or for up to 24 months for nivolumab only. In patients who received 
nivolumab plus chemotherapy and in whom chemotherapy was discontinued, nivolumab 
monotherapy was allowed to be given at 240 mg every 2 weeks, 360 mg every 3 weeks or 480 mg 
every 4 weeks up to 24 months after treatment initiation. Tumor assessments were performed every 
6 weeks up to and including week 48, then every 12 weeks thereafter. 
Baseline characteristics were generally balanced across treatment groups. The median age was 61 
years (range: 18 to 90), 39% were ≥65 years of age, 70% were male, 24% were Asian and 69% 
were white. Baseline ECOG performance status was 0 (42%) or 1 (58%). Tumor locations were 
distributed as gastric (70%), gastro-esophageal junction (16%), and esophagus (13%). 
Primary efficacy outcome measures were PFS (by BICR) and OS assessed in patients with PD-L1 
combined positive score (CPS) ≥5 based on the PD-L1 IHC 28-8 pharmDX. Secondary endpoints 
per the pre-specified hierarchical testing were OS in patients with PD-L1 CPS ≥1 and in all 
randomized patients; further endpoints included ORR (BICR) in PD-L1 CPS ≥5 and all 
randomized patients. 
With a minimum follow-up of 12.1 months, the study demonstrated a statistically significant 
improvement in OS and PFS in patients with PD-L1 CPS ≥5. Statistically significant improvement 
in OS was also demonstrated for all randomized patients. Efficacy results are shown in Figures 22, 
23, and 24 and Table 37 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
210 
Approved v 41.0 
930144776 4.0 
 
 
Figure 22: 
Kaplan-Meier curves of OS in patients with PD-L1 CPS ≥5 
(CA209649) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
211 
Approved v 41.0 
930144776 4.0 
 
 
Figure 23: 
Kaplan-Meier curves of PFS in patients with PD-L1 CPS ≥5 
(CA209649) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
212 
Approved v 41.0 
930144776 4.0 
 
 
Figure 24: 
Kaplan-Meier curves of OS in all randomized patients (CA209649) 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
213 
Approved v 41.0 
930144776 4.0 
 
 
Table 37: 
Efficacy results (CA209649) 
nivolumab + 
chemotherapy 
(n=473) 
 
chemotherapy 
(n=482) 
nivolumab + 
chemotherapy 
(n=789) 
 
chemotherapy 
(n=792) 
 
 
PD-L1 CPS ≥5 
All patients 
Overall survival 
Events (%) 
309 (65) 
362 (75) 
544 (69) 
591 (75) 
Hazard ratio (CI)a 
0.71 (98.4% CI: 0.59, 0.86) 
0.80 (99.3% CI: 0.68, 0.94) 
p-valueb 
<0.0001 
0.0002 
Median (95% CI) (months)c 
14.4 (13.1, 
11.1 (10.0, 
13.8 (12.6, 
11.6 (10.9, 
 
 
 
 
 
Hazard ratio (CI)a 
0.68 (98% CI: 0.56, 0.81) 
0.77 (95% CI: 0.68, 0.87) 
p-valueb 
<0.0001 
-e 
 
Median (95% CI) (months)c 
7.69 (7.03, 
6.05 (5.55, 
7.66 (7.10, 
6.93 (6.60, 
9.17) 
6.90) 
8.54) 
7.13) 
Rate (95% CI) at 12 months 
36.3 (31.7, 
21.9 (17.8, 
33.4 (29.9, 
23.2 (19.9, 
41.0) 
26.1) 
37.0) 
26.7) 
Overall response rate, n 
226/378 
177/391 
350/603 
280/608 
(%)d,f 
(60) 
(45) 
(58) 
(46) 
(95% CI) 
(55, 65) 
(40, 50) 
(54, 62) 
(42, 50) 
Complete response 
44 (12) 
27 (7) 
59 (10) 
39 (6) 
Partial response 
182 (48) 
150 (38) 
291 (48) 
241 (40) 
Duration of responsed,f 
Median (95% CI) (months)c 
9.49 (7.98, 
6.97 (5.65, 
8.51 (7.23, 
6.93 (5.82, 
Range
11.37) 
7.85) 
9.92) 
7.16) 
1.1+, 29.6+ 
1.2+, 30.8+ 
1.0+, 29.6+ 
1.2+, 30.8+ 
a Based on stratified log Cox proportional hazard model. 
b Based on stratified log-rank test. 
c Kaplan-Meier estimate. 
d Confirmed by BICR. 
e Not evaluated for statistical significance. 
f Based on patients with measurable disease at baseline. 
 
Statistically significant improvement in OS was also demonstrated for patients with PD-L1 CPS 
≥1 (HR = 0.77; 99.3% CI: 0.64, 0.92; p-value <0.0001). The median OS was 13.96 months (95% 
CI: 12.55, 14.98) for nivolumab plus chemotherapy and 11.33 months (95% CI: 10.64, 12.25) for 
chemotherapy. 
16.2) 
12.1) 
14.6) 
12.5) 
Rate (95% CI) at 12 months 
57.3 (52.6, 
46.4 (41.8, 
55.0 (51.4, 
47.9 (44.4, 
61.6) 
50.8) 
58.4) 
51.4) 
Progression-free survivald 
Events(%) 
328 (69.3) 
350 (72.6) 
559 (70.8) 
557 (70.3) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
214 
Approved v 41.0 
930144776 4.0 
 
 
Further exploratory analyses were performed in patients who had PD-L1 CPS <1 [nivolumab plus 
chemotherapy n=140 (17.9%) vs. chemotherapy n=125 (16.0%)] and PD-L1 CPS <5 [nivolumab 
plus chemotherapy n=308 (39.4%) vs. chemotherapy n=298 (38.2%)] (see Table 38). 
 
 
Table 38: 
OS by PD-L1 CPS <1 and <5 (CA209649) 
PD-L1 
Expression 
nivolumab 
+chemotherapy 
chemotherapy 
 
OS by PD-L1 CPS expression 
Unstratified hazard 
Number (%) of patients with event 
ratio (95% CI) 
CPS <1 
103 (74%) 
91 (73%) 
0.92 (0.70, 1.23) 
CPS <5 
228 (74%) 
221 (74%) 
0.94 (0.78, 1.13) 
 
Microsatellite instability (MSI) status was also assessed in CA209649 and determined 
retrospectively on pre-treatment tissues using the Idylla™ MSI Test. Of the 1581 randomised 
patients, 44 (2.8%) patients were MSI-high (MSI-H), and 1377 (87.1%) patients were 
microsatellite stable (MSS). The HR of OS in MSI-H was 0.37 (95% CI: 0.16, 0.87) and in MSS 
was 0.80 (95% CI: 0.71, 0.91). 
Adjuvant treatment of Resected Esophageal or Gastroesophageal Junction Cancer (EC or 
GEJC) 
The safety and efficacy of nivolumab monotherapy for the adjuvant treatment of esophageal or 
gastro-esophageal junction cancer was evaluated in a phase 3 multicentre, randomized, 
placebocontrolled, double-blinded study (CA209577). The study included adult patients who had 
received CRT, followed by complete resection of carcinoma prior to randomisation, and who had 
residual pathologic disease, with at least ypN1 or ypT1. Patients who did not receive concurrent 
CRT prior to surgery or had stage IV resectable disease, autoimmune disease, any condition 
requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) 
or other immunosuppressive medications were excluded from the study. Patients were enrolled 
regardless of tumor PD-L1 expression level. 
A total of 794 patients were randomized 2:1 to receive either nivolumab (n=532) or placebo 
(n=262). Patients were administered nivolumab 240 mg intravenously over 30 minutes every 2 
weeks for 16 weeks followed respectively by 480 mg infused over 30 minutes every 4 weeks 
beginning at week 17. Patients were administered placebo over 30 minutes with the same dosing 
schedule as nivolumab. Randomization was stratified by tumour PD-L1 status (≥1% vs. <1% or 
indeterminate or non-evaluable), pathologic lymph node status (positive ≥ypN1 vs. negative 
ypN0), and histology (squamous vs. adenocarcinoma). Treatment continued until disease 
recurrence, unacceptable toxicity, or for up to 1 year in total duration. The primary efficacy 
outcome measure was disease-free survival (DFS), as assessed by the investigator, defined as the 
time between the date of randomization and the date of first recurrence (local, regional, or distant 
from the primary resected site) or death from any cause, whichever occurred first. Patients on 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
215 
Approved v 41.0 
930144776 4.0 
 
 
treatment underwent imaging for tumour every 12 weeks for 2 years, and a minimum of one scan 
every 6 to 12 months for years 3 to 5. 
Baseline characteristics were generally balanced between the two groups. The median age was 62 
years (range: 26-86) with 36% ≥65 years of age and 5% ≥75 years of years. The majority of patients 
were white (82%) and male (85%). Baseline ECOG performance status was 0 (58%) or 1 (42%). 
With a minimum of 6.2 months and a median of 24.4 months follow-up (range 6.2 to 44.9 months), 
the study demonstrated a statistically significant improvement for patients randomised to 
nivolumab compared with placebo, with DFS observed in 241 (45%) patients and a hazard ratio 
of 0.69 (95% CI: 0.56, 0.86). Efficacy results are shown in Table 39 and Figure 25. 
 
Table 39: 
Efficacy results (CA209577) 
nivolumab 
(n=532) 
 
 
placebo 
(n=262) 
 
 
Disease-free Survivala 
Events (%) 
241 (45%) 
155 (59%) 
Hazard ratio (96.4% CI)b 
0.69 (0.56, 0.86) 
p-valuec 
0.0003 
Median (95% CI) (months) 
22.4 (16.6, 34.0) 
11.0 (8.3, 14.3) 
a Based on all randomized patients 
b Based on a stratified cox proportional hazards model. 
c Based on a stratified log-rank test. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
216 
Approved v 41.0 
930144776 4.0 
 
 
Figure 25: 
Kaplan-Meier curves of DFS (CA 209577) 
 
DFS benefit was observed regardless of histology and tumor cell PD-L1 expression. 
In the adenocarcinoma subgroup (n=376), the hazard ratio (HR) for DFS was 0.75 (95% CI: 0.59, 
0.96) with median DFS of 19.35 and 11.10 months for the nivolumab and placebo arms, 
respectively. In the squamous cell carcinoma subgroup (n=155), the HR for DFS was 0.61 (95 CI: 
0.42, 0.88) with median DFS of 29.73 and 11.04 months for the nivolumab and placebo arms, 
respectively. 
Of the 794 patients, 16.2% had tumor cell PD-L1 expression ≥1%, 71.8% had tumor cell PD-L1 
expression <1%, and 12.0% had tumor cell PD-L1 expression indeterminate or non-evaluable. In 
the tumor cell PD-L1 ≥1% subgroup, the HR for DFS was 0.75 (95% CI: 0.45, 1.24) with median 
DFS of 19.65 and 14.13 months for the nivolumab and placebo arms, respectively. In the tumor 
cell PD-L1 <1% subgroup, the HR for DFS was 0.73 (95 % CI: 0.57, 0.92) with median DFS of 
21.26 and 11.10 months for the nivolumab and placebo arms, respectively. In the tumor cell PD- 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
217 
Approved v 41.0 
930144776 4.0 
 
 
L1 indeterminate or non-evaluable subgroup, the HR for DFS was 0.54 (95% CI: 0.27, 1.05) with 
median DFS not reached and of 9.49 months for the nivolumab and placebo arms, respectively. 
Patient-reported outcomes were assessed using the EQ-5D-3L and FACT-E. At baseline, mean 
FACT-E or mean FACT-E total scores in all randomized subjects were similar between treatment 
arms. From baseline through week 53 of follow-up, patients in both treatment arms had 
improvements in mean change from baseline score in both measures. 
5.3 
Pharmacokinetics 
The PK of nivolumab is linear in the dose range of 0.1 to 10 mg/kg. Nivolumab clearance (CL) 
decreases over time, with a mean maximal reduction (% coefficient of variation [CV%]) from 
baseline values of 26 (32.6%) resulting in a geometric mean steady-state clearance (CLss) (CV%) 
of 7.91 mL/h (46%) in patients with metastatic tumors; the decrease in CLss is not considered 
clinically relevant. Nivolumab clearance does not decrease over time in patients with completely 
resected melanoma, as the geometric mean population clearance is 24% lower in this patient 
population compared with patients with metastatic melanoma at steady state. The geometric mean 
volume of distribution at steady state (Vss) (CV%) is 6.6 L (24.4%) and geometric mean 
elimination half-life (t1/2) is 25 days (55.4%). Steady-state concentrations of nivolumab were 
reached by 12 weeks when administered at 3 mg/kg every 2 weeks and systemic accumulation was 
approximately 4-fold. 
The predicted exposure of nivolumab after a 30-minute infusion is comparable to that observed 
with a 60-minute infusion. 
Nivolumab CL increased with increasing body weight. Body weight normalized dosing produced 
approximately uniform steady-state trough concentration over a wide range of body weights 
(34-162 kg). 
The metabolic pathway of nivolumab has not been characterized. As a fully human IgG4 
monoclonal antibody, nivolumab is expected to be degraded into small peptides and amino acids 
via catabolic pathways in the same manner as endogenous IgG. 
Nivolumab in combination with ipilimumab: 
When administered in combination with ipilimumab, the CL of nivolumab increased by 20% in 
the presence of anti-nivolumab antibodies and the CL of ipilimumab increased by 5.7% in the 
presence of anti-ipilimumab antibodies. These changes were not considered clinically relevant. 
Nivolumab in combination with ipilimumab and 2-cycles of chemotherapy: When nivolumab 360 
mg every 3 weeks was administered in combination with ipilimumab 1 mg/kg every 6 weeks and 
chemotherapy, the CL of nivolumab decreased approximately 10% and the CL of ipilimumab 
increased approximately 22%, which were not considered clinically relevant. 
When administered in combination with ipilimumab and chemotherapy, the CL of nivolumab 
increased by approximately 29% in the presence of anti-nivolumab antibodies. There was no 
apparent impact on efficacy or safety with nivolumab ADA-positive subjects. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
218 
Approved v 41.0 
930144776 4.0 
 
 
5.3.1 
Special populations 
A population PK analysis suggested no difference in CL of nivolumab based on age, gender, race, 
solid tumor type, tumor size, and hepatic impairment. Although ECOG status, baseline glomerular 
filtration rate (GFR), albumin and body weight had an effect on nivolumab CL, the effect was not 
clinically meaningful. 
Renal impairment 
The effect of renal impairment on the CL of nivolumab was evaluated in patients with mild* 
(n=1399), moderate* (n=651), or severe* (n=6) renal impairment compared to patients with 
normal* renal function (n=1354) in the population PK analysis. No clinically important differences 
in the CL of nivolumab were found between patients with mild or moderate renal impairment and 
patients with normal renal function. Data from patients with severe renal impairment are too 
limited to draw conclusions on this population (see 4.2 Posology and method of administration, 
renal impairment). 
* Definitions 
• 
Normal: GFR ≥90 mL/min/1.73 m2 
• 
Mild: GFR <90 and ≥60 mL/min/1.73 m2 
• 
Moderate: GFR <60 and ≥30 mL/min/1.73 m2 
• 
Severe: GFR <30 and ≥15 mL/min/1.73 m2 
Hepatic impairment 
The effect of hepatic impairment on the CL of nivolumab was evaluated in patients with different 
tumor types (NSCLC, SCLC, melanoma, RCC, SCCHN, UC, gastric cancer, and cHL) with mild* 
hepatic impairment (n=351) and in patients with moderate* hepatic impairment (n=10) compared 
to patients with normal* hepatic function (n=3096) in the population PK analyses. No clinically 
important differences in the CL of nivolumab were found between patients with mild or moderate 
hepatic impairment and normal hepatic function. Nivolumab has not been studied in patients with 
severe* hepatic impairment (see 4.2 Posology and method of administration, Hepatic impairment). 
 
*Per National Cancer Institute criteria of hepatic dysfunction: 
• 
Normal: total bilirubin and AST ≤ ULN 
• 
Mild: total bilirubin >1.0 to 1.5 times ULN or AST > ULN 
• 
Moderate: total bilirubin >1.5 to 3 times ULN and any AST 
• 
Severe: total bilirubin >3 times ULN and any AST 
 
 
6 
NONCLINICAL PROPERTIES 
6.1 
Animal Toxicology or Pharmacology 
Nivolumab was well tolerated by cynomolgus monkeys when administered intravenously, twice 
weekly, up to three months and at doses up to approximately 35 times the human exposure at the 
clinical dose of 3 mg/kg based on AUC. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
219 
Approved v 41.0 
930144776 4.0 
 
 
A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal 
immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of 
pregnancy to disrupt tolerance to the fetus and to increase fetal loss. The effects of nivolumab on 
prenatal and postnatal development were evaluated in monkeys that received nivolumab twice 
weekly from the onset of organogenesis in the first trimester through delivery, at exposure levels 
either 8 or 35 times higher than those observed at the clinical dose of 3 mg/kg of nivolumab (based 
on AUC). No treatment-related adverse effects on reproduction were detected during the first two 
trimesters of pregnancy. Beginning in the third trimester, dose-dependent increases in fetal losses 
and increased neonatal mortality was observed. 
The remaining offspring of nivolumab-treated females survived to scheduled termination, with no 
treatment-related clinical signs, alterations to normal development, organ-weight effects, or gross 
and microscopic pathology changes. Results for growth indices, as well as teratogenic, 
neurobehavioral, immunological, and clinical pathology parameters throughout the 6-month 
postnatal period were comparable to the control group. However, based on its mechanism of 
action, fetal exposure to nivolumab may increase the risk of developing immune-related disorders 
or altering the normal immune response, and immune-related disorders have been reported in PD-1 
knockout mice. 
Carcinogenesis, mutagenesis, impairment of fertility 
No studies have been performed to assess the potential of nivolumab for carcinogenicity or 
genotoxicity. Fertility studies have not been performed with nivolumab. In 1-month and 3-month 
repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female 
reproductive organs; however, most animals in these studies were not sexually mature. 
7 
DESCRIPTION 
Nivolumab is a fully human anti-PD-1 monoclonal antibody (IgG4) produced in Chinese hamster 
ovary cells by recombinant DNA technology. 
Nivolumab is a sterile, preservative-free, non-pyrogenic, clear to opalescent, colorless to pale- 
yellow liquid for intravenous infusion that may contain light (few) particles. The solution has a pH 
of approximately 6.0 and an osmolality of approximately 340 mOsm/kg. 
List of excipients: Sodium citrate dihydrate, Sodium chloride, Mannitol , Pentetic acid 
(diethylenetriaminepentaacetic acid), Polysorbate 80, Sodium hydroxide (for pH adjustment), 
Hydrochloric acid (for pH adjustment), Water for injections. 
8 
PHARMACEUTICAL PARTICULARS 
8.1 
Incompatibilities 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products. Nivolumab should not be infused concomitantly in the same intravenous line 
with other medicinal products. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
220 
Approved v 41.0 
930144776 4.0 
 
 
8.2 
Shelf life 
Unopened vial 
Refer to the outer carton, for the expiry date. 
The unopened vial can be stored at controlled room temperature up to 25°C with room light for up 
to 48 hours. 
After opening 
• From a microbiological point of view, once opened, the medicinal product should be prepared 
for infusion immediately. 
 
After preparation of infusion 
• The prepared infusion solution may be stored under refrigeration conditions: 2°C to 8°C and 
protected from light for up to 7 days (a maximum of 8 hours of the total 7 days can be at room 
temperature 20°C to 25°C and room light – the maximum 8-hour period under room 
temperature and room light conditions should be inclusive of the product administration 
period). The administration of the nivolumab infusion must be completed within 7 days of 
preparation. 
 
8.3 
Packaging information 
Each 10 mL vial contains 40 mg of nivolumab in 4 mL. 
Each 10 mL vial contains 100 mg of nivolumab in 10 mL. 
Each 25 mL vial contains 240 mg of nivolumab in 24 mL. 
Pack of 1 Vial. 
8.4 
Storage and handling instructions 
Store in a refrigerator (2°C-8°C). 
Do not freeze. 
Store in the original package in order to protect from light. 
For storage conditions after preparation of the infusion, see 8.2 Shelf life. 
Preparation and administration 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
221 
Approved v 41.0 
930144776 4.0 
 
 
Calculating the dose 
More than one vial of nivolumab concentrate may be needed to give the total dose for the patient. 
 
Flat dose 
(240 mg, 360 mg or 480 
mg) 
Weight-based dose 
• The prescribed dose for 
the patient is 240 mg,360 
mg or 480 mg given 
regardless of body 
weight. 
The prescribed dose for the patient is given in mg/kg. 
Based on this prescribed dose, calculate the total dose 
to be given. 
• The total nivolumab dose in mg = the patient’s 
weight in kg × the prescribed dose in mg/kg. 
• The volume of nivolumab concentrate to prepare 
the dose (mL) = the total dose in mg, divided by 10 
(the 
nivolumab concentrate 
strength 
is 10 mg/mL). 
Preparing the infusion 
Preparation should be performed by trained personnel in accordance with good practices rules, 
especially with respect to asepsis. 
Nivolumab can be used for intravenous administration either: 
• without dilution, after transfer to an infusion container using an appropriate sterile syringe; or 
• after diluting, 
 
Flat dose (240 mg, 360 mg or 480 mg)* 
Weight-based dose 
The concentrate may be diluted so as not to 
exceed a total infusion volume of 160 mL. 
The final infusion concentration should 
range between 1 and 10 mg/mL. 
* For adult and pediatric patients with body weight less than 40 kg, the total volume of infusion must 
not exceed 4 mL/kg of body weight 
 
• Nivolumab concentrate may be diluted with either: 
− sodium chloride 9 mg/mL (0.9%) solution for injection; or 
− 50 mg/mL (5%) glucose solution for injection. 
STEP 1 
• Inspect the nivolumab concentrate for particulate matter or discoloration. Do not shake the 
vial. Nivolumab concentrate is a clear to opalescent, colorless to pale-yellow liquid. Discard 
the vial if the solution is cloudy, is discolored, or contains particulate matter other than a few 
translucent-to-white particles. 
• Withdraw the required volume of nivolumab concentrate using an appropriate sterile syringe. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
222 
Approved v 41.0 
930144776 4.0 
 
 
STEP 2 
• Transfer the concentrate into a sterile, evacuated glass bottle or intravenous container (PVC or 
polyolefin). 
• If applicable, dilute with the required volume of sodium chloride 9 mg/mL (0.9%) solution for 
injection or 50 mg/mL (5%) glucose solution for injection. For ease of preparation, the 
concentrate can also be transferred directly into a pre-filled bag containing the appropriate 
volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose 
solution for injection. 
• Gently mix the infusion by manual rotation. Do not shake. 
 
Administration 
Nivolumab infusion must not be administered as an intravenous push or bolus injection. 
Administer the nivolumab infusion intravenously over a period of 30 minutes. 
Nivolumab infusion should not be infused at the same time in the same intravenous line with other 
agents. Use a separate infusion line for the infusion. 
Use an infusion set and an in-line, sterile, non-pyrogenic, low protein binding filter (pore size 
of 0.2 μm to 1.2 μm). 
Nivolumab infusion is compatible with: 
• PVC containers 
• Polyolefin containers 
• Glass bottles 
• PVC infusion sets 
• In-line filters with polyethersulfone membranes with pore sizes of 0.2 µm to 1.2 µm. 
 
After administration of the nivolumab dose, flush the line with sodium chloride 9 mg/mL (0.9%) 
solution for injection or 50 mg/mL (5%) glucose solution for injection. 
When administered in combination with ipilimumab, or other therapeutic agents, nivolumab 
should be given first followed by ipilimumab and/or other therapeutic agents (if applicable) on the 
same day. Use separate infusion bags and filters for each infusion. 
Disposal 
Do not store any unused portion of the infusion solution for reuse. Any unused medicinal product 
or waste material should be disposed of in accordance with local requirements. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
223 
Approved v 41.0 
930144776 4.0 
 
 
9 
PATIENT COUNSELLING INFORMATION 
Please refer to section: SPECIAL WARNINGS AND PRECAUTIONS FOR USE (4.4) and 4.6 - 
Use in Special Populations (Such as Pregnant Women, Lactating Women) and see Use in Specific 
Populations (5.3.1) for Patient Counselling Information. 
10 
DETAILS OF MANUFACTURER 
Bristol-Myers Squibb Holdings Pharma, Ltd. Liability Company, Road 686 Km 2.3, Bo. 
Tierras Nuevas, Manatí, Puerto Rico 00674, USA 
And 
Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics, 
Cruiserath Road, Mulhuddart, Dublin 15, D15, H6EF, Ireland 
Importer and marketed by: 
Bristol-Myers Squibb India Private Limited, 
Bldg.B-4, Gala No. 3B & 4B, Citylink Warehousing Complex, Mumbai Nashik Highway, 
Vadape Village, Taluka: Bhiwandi – 16, District: Thane Z5, Pin- 421302 
Registered office address- 
Bristol-Myers Squibb India Private Limited, 6th floor, Tower 1, One International Center, S.B. 
Marg, Elphinstone (W), Mumbai - 400013, Tel: + 91 22 6628 8600 
11 
DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE 
Form 45 Permission No.IMP-88/2016 dated 09-June 2016 
12 
DATE OF REVISION 
Date of Revision – 02 May 2023 
Document Version Number – 14.2 
Source – Nivolumab CCDS dated –16 Nov 2021 
 
 
Opdyta® is a registered trademark of Bristol-Myers Squibb. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
224 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 5-2   IPILIMUMAB INDIA PRESCRIBING INFORMATION 
 
To be sold by retail on the prescription of a Registered Oncologist only 
 
 
Ipilimumab 
YERVOI® 
1 
GENERIC NAME 
Ipilimumab 5 mg/mL concentrate for solution for infusion. 
 
 
2 
QUALITATIVE AND QUANTITATIVE COMPOSITION 
YERVOI® (Ipilimumab) is a recombinant, fully human monoclonal antibody that binds to the 
cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Ipilimumab is an IgG1 kappa 
immunoglobulin with an approximate molecular weight of 148 kDa. Ipilimumab is produced in 
mammalian (Chinese hamster ovary) cell culture by recombinant DNA technology. 
Each ml of concentrate contains 5 mg Ipilimumab. 
Each 10 ml vial contains 50 mg of Ipilimumab. 
For the full list of excipients, see section 7 Description. 
 
 
3 
DOSAGE FORM AND STRENGTH 
Injection: 50 mg/10 mL (5 mg/mL) as a clear to slightly opalescent, colorless to pale-yellow 
solution in a single-dose vial. 
 
 
4 
CLINICAL PARTICULARS 
4.1 
Therapeutic Indications 
Renal Cell Carcinoma (RCC) 
Ipilimumab is indicated for treatment of patients with intermediate or poor risk, previously 
untreated advanced renal cell carcinoma, in combination with nivolumab. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
225 
Approved v 41.0 
930144776 4.0 
 
 
Non-Small Cell Lung Cancer (NSCLC) 
Ipilimumab, in combination with nivolumab, is indicated for the first-line treatment of adult 
patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) 
as determined by a validated test, with no EGFR or ALK genomic tumor aberrations. 
Ipilimumab, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy, is 
indicated for the first-line treatment of adult patients with metastatic or recurrent NSCLC, with no 
EGFR or ALK genomic tumor aberrations. 
 
 
4.2 
Posology and method of administration 
Ipilimumab should be administered under the supervision of physicians experienced in the 
treatment of cancer. 
4.2.1 
Recommended dosage 
RCC 
Combination phase: The recommended dose during the combination phase is Ipilimumab 1 mg/kg 
administered intravenously over a period of 30 minutes every 3 weeks for the first 4 doses in 
combination with Nivolumab 3 mg/kg administered intravenously over a period of 30 minutes, 
followed by the single-agent phase. 
Single-agent phase: The recommended dose of Nivolumab during the single-agent phase is 3 
mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks administered 
intravenously over a period of 30 minutes. 
The first dose of nivolumab monotherapy should be administered 3 weeks following the last dose 
of the combination of ipilimumab and nivolumab. 
When administered in combination with nivolumab, nivolumab should be given first followed by 
ipilimumab on the same day. 
Review the Prescribing Information for nivolumab for dosage information. 
 
 
NSCLC 
The recommended dose of ipilimumab in combination with nivolumab is nivolumab 3 mg/kg 
administered as an intravenous infusion over 30 minutes every 2 weeks and ipilimumab 1 mg/kg 
administered as an intravenous infusion over 30 minutes every 6 weeks until disease progression, 
unacceptable toxicity, or for up to 2 years in patients without disease progression. 
 
The recommended dose of ipilimumab in combination with nivolumab and platinum-doublet 
chemotherapy is nivolumab 360 mg administered as an intravenous infusion over 30 minutes every 
3 weeks and ipilimumab 1 mg/kg administered as an intravenous infusion over 30 minutes every 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
226 
Approved v 41.0 
930144776 4.0 
 
 
6 weeks and histology-based platinum-doublet chemotherapy every 3 weeks for 2 cycles until 
disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression. 
Review the Prescribing Information for nivolumab and platinum-based chemotherapy for 
recommended dosing information. 
Recommended Dosage Modifications for Adverse Reactions 
No dose reduction for ipilimumab is recommended. In general, withhold ipilimumab for severe 
(Grade 3) immune-mediated adverse reactions. Permanently discontinue ipilimumab for life- 
threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune- 
mediated reactions that require systemic immunosuppressive treatment, persistent moderate 
(Grade 2) or severe (Grade 3) reactions lasting 12 weeks or longer after last ipilimumab dose 
(excluding endocrinopathy), or an inability to reduce corticosteroid dose to 10 mg or less of 
prednisone or equivalent per day within 12 weeks of initiating steroids. Dosage modifications for 
ipilimumab or ipilimumab in combination with nivolumab for adverse reactions that require 
management different from these general guidelines are summarized in Table 1. 
When ipilimumab is administered in combination with nivolumab, withhold or permanently 
discontinue both ipilimumab and nivolumab for toxicity. 
Table 1: 
Recommended Dosage Modifications for Adverse Reactions 
 
Adverse Reaction 
Severity* 
Dosage Modifications 
Immune-Mediated Adverse Reactions [See Warnings and Precautions (5.1)] 
Colitis/diarrhea 
Grade 2 
Withholda 
Grade 3 or 4 
Permanently discontinue 
AST or ALT increases to more 
than 3 times and up to 5 times the 
ULN 
Hepatitis with no tumor involvement of 
the liver 
Or 
or 
Total bilirubin increases to more 
than 1.5 times and up to 3 times 
the ULN 
Withholda 
Hepatitis with tumor involvement of the 
liver/non-HCC 
AST or ALT more than 5 times 
the ULN 
or 
Permanently discontinue 
Total bilirubin more than 3 times 
the ULN 
Hepatitis with tumor involvement of the 
liverb 
Baseline AST/ALT is more than 1 
and up to 3 times ULN and 
increases to more than 5 and up to 
10 times ULN 
Withholda 
or 
Baseline AST/ALT is more than 3 
and up to 5 times ULN and 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
227 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 1: 
Recommended Dosage Modifications for Adverse Reactions 
 
Adverse Reaction 
Severity* 
Dosage Modifications 
increases to more than 8 and up to 
10 times ULN. 
AST/ALT increases to more than 
10 times ULN 
or 
Total bilirubin increases to more 
than 3 times ULN. 
Permanently discontinue 
Exfoliative Dermatologic Conditions 
Suspected SJS, TEN, or DRESS 
Withhold 
Confirmed SJS, TEN, or DRESS 
Permanently discontinue 
Endocrinopathiesc 
Grades 3 or 4 
Withhold until clinically stable 
or permanently discontinue 
depending on severity 
Pneumonitis 
Grade 2 
Withholda 
Grade 3 or 4 
Permanently discontinue 
Nephritis with Renal Dysfunction 
Grade 2 or 3 increased blood 
creatinine 
Withholda 
Grade 4 increased blood 
creatinine 
Permanently discontinue 
Myocarditis 
Grade 2, 3 or 4 
Permanently discontinue 
Ophthalmologic 
Grade 2, 3, or 4 that does not 
improve to Grade 1 within 2 
weeks while receiving topical 
therapy or that requires systemic 
treatment 
Permanently discontinue 
Other Adverse Reactions 
Infusion-Related Reactions [see 4.4 
Special warnings and precautions for 
use] 
Grade 1 or 2 
Interrupt or slow the rate of 
infusion 
Grade 3 or 4 
Permanently discontinue 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; DRESS = Drug Rash with Eosinophilia and 
Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit of 
normal 
* Based on Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 
a Resume in patients with complete or partial resolution (Grade 0 or 1) after corticosteroid taper. Permanently 
discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 
mg per day (or equivalent) or less within 12 weeks of initiating steroids. 
b If AST/ALT are less than or equal to ULN at baseline, withhold or permanently discontinue ipilimumab based on 
recommendations for hepatitis with no liver involvement. 
c Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with 
hormone replacement. Resume once acute symptoms have resolved. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
228 
Approved v 41.0 
930144776 4.0 
 
 
 
 
4.3 
Contraindications 
None. 
4.4 
Special warnings and precautions for use 
Severe and Fatal Immune-Mediated Adverse Reactions 
Ipilimumab is a fully human monoclonal antibody that blocks T-cell inhibitory signals induced by 
the CTLA-4 pathway, thereby removing inhibition of the immune response with the potential for 
induction of immune-mediated adverse reactions. Immune-mediated adverse reactions listed 
herein may not be inclusive of all possible severe and fatal immune-mediated reactions. 
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system 
or tissue. Immune-mediated adverse reactions can occur at any time after starting ipilimumab. 
While immune-mediated adverse reactions usually manifest during treatment, immune-mediated 
adverse reactions can also manifest after discontinuation of ipilimumab. 
Early identification and management are essential to ensure safe use of ipilimumab. Monitor for 
signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse 
reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic 
hormone (ACTH) level, and thyroid function at baseline and before each dose. Institute medical 
management promptly, including specialty consultation as appropriate. 
Withhold or permanently discontinue ipilimumab depending on severity [see4.2 Posology and 
method of administration]. In general, if ipilimumab requires interruption or discontinuation, 
administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until 
improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper 
and continue to taper over at least 1 month. Consider administration of other systemic 
immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with 
corticosteroid therapy. 
Immune-Mediated Colitis 
Ipilimumab can cause immune-mediated colitis, which may be fatal. Cytomegalovirus (CMV) 
infection/reactivation has been reported in patients with corticosteroid-refractory immune- 
mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup 
to exclude alternative etiologies. 
Immune-mediated colitis occurred in 10% (52/547) of patients who received Ipilimumab 1 mg/kg 
with nivolumab for the treatment of RCC. Median time to onset was 1.7 months (range: 2 days to 
19.2 months). Immune-mediated colitis led to permanent discontinuation or withholding of 
nivolumab with Ipilimumab in 3.5% and 4.2% of patients, respectively. Approximately 83% of 
patients with colitis received high-dose corticosteroids (at least 40 mg prednisone equivalents per 
day) for a median duration of 21 days (range: 1 day to 27 months). Approximately 23% of patients 
required addition of infliximab to high-dose corticosteroids. Complete resolution occurred in 89% 
of patients. Two patients had recurrence of colitis after re-initiation of nivolumab with Ipilimumab. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
229 
Approved v 41.0 
930144776 4.0 
 
 
Immune-Mediated Hepatitis 
Immune-mediated hepatitis occurred in 7% (38/547) of patients who received Ipilimumab 1 mg/kg 
with nivolumab for the treatment of RCC. Median time to onset was 2 months (range: 14 days to 
26.8 months). Immune-mediated hepatitis led to permanent discontinuation or withholding of 
nivolumab with Ipilimumab in 3.7% and 3.1% of patients, respectively. Approximately 92% of 
patients with hepatitis received high-dose corticosteroids (at least 40 mg prednisone equivalents 
per day) for a median duration of 1.0 month (range: 1 day to 4.0 months). Complete resolution 
occurred in 87% of patients without recurrence of hepatitis after re-initiation of nivolumab with 
Ipilimumab. 
Immune-Mediated Dermatologic Adverse Reactions 
Ipilimumab can cause immune-mediated rash or dermatitis, including bullous and exfoliative 
dermatitis, Stevens Johnson Syndrome, toxic epidermal necrolysis (TEN) and DRESS (Drug Rash 
with Eosinophilia and Systemic Symptoms). Topical emollients and/or topical corticosteroids may 
be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently 
discontinue ipilimumab depending on severity [see 4.2 Posology and method of administration]. 
Immune-mediated rash occurred in 16.6% (91/547) of patients. Median time to onset was 1.5 
months (range: 1 day to 20.9 months). Immune-mediated rash led to permanent discontinuation or 
withholding of nivolumab with Ipilimumab in 0.5% and 2.9% of patients, respectively. 
Approximately 19% of patients with rash received high-dose corticosteroids (at least 40 mg 
prednisone equivalents per day) for a median duration of 25 days (range: 1 day to 23.1 months). 
Complete resolution occurred in 64% of patients. Approximately 3.6% of patients who resumed 
nivolumab and Ipilimumab after resolution had recurrence of rash. 
Immune-Mediated Endocrinopathies 
Hypophysitis: 
Ipilimumab can cause immune-mediated hypophysitis. Hypophysitis can present with acute 
symptoms associated with mass effect such as headache, photophobia, or visual field cuts. 
Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. 
Withhold or permanently discontinue ipilimumab depending on severity [see 4.2 Posology and 
method of administration]. 
Hypophysitis occurred in 4.6% (25/547) of patients who received Ipilimumab 1 mg/kg with 
nivolumab for the treatment of RCC. Median time to onset was 2.8 months (range: 1.3 months to 
7.3 months). Hypophysitis led to permanent discontinuation or withholding of nivolumab with 
Ipilimumab in 1.3% and 2.6% of patients, respectively. Approximately 72% of patients with 
hypophysitis received hormone replacement therapy and 60% received high-dose corticosteroids 
(at least 40 mg prednisone equivalents per day) for a median duration of 10 days (range: 1 day to 
1.6 months). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
230 
Approved v 41.0 
930144776 4.0 
 
 
Adrenal Insufficiency: 
Adrenal insufficiency occurred in 7% (41/547) of patients who received Ipilimumab 1 mg/kg with 
nivolumab for the treatment of RCC. Median time to onset was 3.4 months (range: 2.0 months to 
22.3 months). Adrenal insufficiency led to permanent discontinuation or withholding of nivolumab 
with Ipilimumab in 1.3% and 2.0% of patients, respectively. Approximately 93% of patients with 
adrenal insufficiency received hormone replacement therapy and 18% received high-dose 
corticosteroids (at least 40 mg prednisone equivalents per day) for a median duration of 12 days 
(range: 1 day to 5.6 months). 
Hypothyroidism and Hyperthyroidism: 
Hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (119/547) of patients 
who received Ipilimumab 1 mg/kg with nivolumab for the treatment of RCC. Median time to onset 
was 2.2 months (range: 1 day to 21.4 months). Approximately 76% of patients with 
hypothyroidism or thyroiditis received levothyroxine. Resolution occurred in 31% of patients. 
 
Hyperthyroidism occurred in 12% (66/547) of patients with RCC. Median time to onset was 1.4 
months (range: 6 days to 14.2 months) in RCC. Approximately 14% of patients with 
hyperthyroidism received methimazole and 3% received carbimazole. Resolution occurred in 85% 
of patients. 
Type 1 Diabetes Mellitus: 
 
Diabetes occurred in 2.7% (15/547) of patients who received Ipilimumab 1 mg/kg with nivolumab 
for the treatment of RCC. Median time to onset was 3.2 months (range: 19 days to 16.8 months). 
Nivolumab with Ipilimumab was withheld in 33% of patients and permanently discontinued in 
20% of patients who developed diabetes. 
 
Immune-Mediated Pneumonitis 
Immune-mediated pneumonitis occurred in 4.4% (24/547) of patients who received Ipilimumab 1 
mg/kg with nivolumab for the treatment of RCC. Median time to onset was 2.6 months (range: 8 
days to 9.2 months). Immune-mediated pneumonitis led to permanent discontinuation or 
withholding of nivolumab with Ipilimumab in 2.0% and 1.6% of patients, respectively. 
Approximately 92% of patients with pneumonitis received high-dose corticosteroids (at least 
40 mg prednisone equivalents per day) for a median duration of 19 days (range: 4 days to 3.2 
months). Approximately 8% of patients required addition of infliximab to high-dose 
corticosteroids. Complete resolution occurred in 79% of patients without recurrence of 
pneumonitis after re-initiation of nivolumab with Ipilimumab. 
In NSCLC, immune-mediated pneumonitis occurred in 9% (50/576) of patients receiving 
Ipilimumab 1 mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks, including Grade 4 
(0.5%), Grade 3 (3.5%), and Grade 2 (4.0%) immune-mediated pneumonitis. Four patients (0.7%) 
died due to pneumonitis. The median duration was 1.5 months (range: 5 days to 25+ months). 
Immune-mediated pneumonitis led to permanent discontinuation of Ipilimumab with nivolumab 
in 5% of patients and withholding of Ipilimumab with nivolumab in 3.6% of patients. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
231 
Approved v 41.0 
930144776 4.0 
 
 
Systemic corticosteroids were required in 100% of patients with pneumonitis followed by a 
corticosteroid taper. Pneumonitis resolved in 72% of the patients. Approximately 13% (2/16) of 
patients had recurrence of pneumonitis after re-initiation of Ipilimumab with nivolumab. 
 
Immune-Mediated Nephritis with Renal Dysfunction 
Immune-mediated nephritis and renal dysfunction occurred in 4.6% (25/547) of patients who 
received Ipilimumab 1 mg/kg with nivolumab for the treatment of RCC. Median time to onset was 
2.5 months (range: 1 day to 13.2 months). Immune-mediated nephritis and renal dysfunction led 
to permanent discontinuation or withholding of nivolumab with Ipilimumab in 1.1% and 2.7% of 
patients, respectively. Approximately 76% of patients received high-dose corticosteroids (at least 
40 mg prednisone equivalents per day) for a median duration of 15 days (range: 1 day to 5.9 
months). Complete resolution occurred in 64% of patients. One patient had recurrence of nephritis 
or renal dysfunction after re-initiation of nivolumab with Ipilimumab. 
Other Immune-Mediated Adverse Reactions 
Across clinical trials of ipilimumab administered as a single agent or in combination with 
nivolumab, the following clinically significant immune-mediated adverse reactions, some with 
fatal outcome, occurred in <1% of patients unless otherwise specified, as shown below: 
Nervous System: Autoimmune neuropathy (2%), meningitis, encephalitis, myelitis and 
demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, 
motor dysfunction 
Cardiovascular: Angiopathy, myocarditis, pericarditis, temporal arteritis, vasculitis 
Ocular: Blepharitis, episcleritis, iritis, orbital myositis, scleritis, uveitis. Some cases can be 
associated with retinal detachment. If uveitis occurs in combination with other immune-mediated 
adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, which has been observed in 
patients receiving ipilimumab and may require treatment with systemic corticosteroids to reduce 
the risk of permanent vision loss. 
Gastrointestinal: Duodenitis, gastritis, pancreatitis (1.3%) 
Musculoskeletal and Connective Tissue: Arthritis, myositis, polymyalgia rheumatica, 
polymyositis, rhabdomyolysis 
Other (hematologic/immune): Aplastic anemia, conjunctivitis, cytopenias (2.5%), eosinophilia 
(2.1%), erythema multiforme, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), 
hypersensitivity vasculitis, meningitis, neurosensory hypoacusis, psoriasis, sarcoidosis, systemic 
inflammatory response syndrome and solid organ transplant rejection. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
232 
Approved v 41.0 
930144776 4.0 
 
 
Infusion-Related Reactions 
Severe infusion-related reactions can occur with ipilimumab. Discontinue ipilimumab in patients 
with severe or life-threatening infusion reactions. Interrupt or slow the rate of infusion in patients 
with mild or moderate infusion reactions [see 4.2 Posology and method of administration]. 
Infusion-related reactions occurred in 5.1% (28/547) of patients. 
 
Complications of Allogeneic Hematopoietic Stem Cell Transplant after Ipilimumab 
Fatal or serious graft-versus-host disease (GVHD) can occur in patients who receive ipilimumab 
either before or after allogeneic hematopoietic stem cell transplantation (HSCT). These 
complications may occur despite intervening therapy between CTLA-4 receptor blocking antibody 
and allogeneic HSCT. 
Follow patients closely for evidence of GVHD and intervene promptly [see 4.8 Undesirable 
effects]. Consider the benefit versus risks of treatment with ipilimumab after allogeneic HSCT. 
 
Embryo-Fetal Toxicity 
Based on its mechanism of action and findings from animal studies, ipilimumab can cause fetal 
harm when administered to a pregnant woman. In animal reproduction studies, administration of 
ipilimumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in 
higher incidences of abortion, stillbirth, premature delivery (with corresponding lower birth 
weight) and higher incidences of infant mortality in a dose-related manner. The effects of 
ipilimumab are likely to be greater during the second and third trimesters of pregnancy. Advise 
pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use 
effective contraception during treatment with ipilimumab and for 3 months after the last dose [see 
4.6 Use in Specific Populations (such as pregnant women, lactating women, pediatric patients, 
geriatric patients, etc.)]. 
Risks Associated When Administered in Combination with Nivolumab 
Ipilimumab is indicated for use in combination with nivolumab for patients with advanced RCC 
and NSCLC. Refer to the nivolumab Full Prescribing Information for additional risk information 
that applies to the combination use treatment. 
 
4.5 
DRUG INTERACTIONS 
Ipilimumab is a human monoclonal antibody that is not metabolized by cytochrome P450 enzymes 
(CYPs) or other drug metabolizing enzymes. In a drug-interaction study, ipilimumab did not have 
a significant effect on the pharmacokinetics of substrates of CYP1A2, CYP2E1, CYP2C8, and 
CYP3A4 when coadministered with substrates of these CYP isozymes (dacarbazine or 
paclitaxel/carboplatin). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
233 
Approved v 41.0 
930144776 4.0 
 
 
Other forms of interaction 
Corticosteroids 
The use of systemic corticosteroids at baseline, before starting ipilimumab, should be avoided 
because of their potential interference with the pharmacodynamic activity and efficacy of 
ipilimumab. However, systemic corticosteroids or other immunosuppressants can be used after 
starting ipilimumab to treat immune-related adverse reactions. The use of systemic corticosteroids 
after starting ipilimumab treatment does not appear to impair the efficacy of ipilimumab. 
Anticoagulants 
The use of anticoagulants is known to increase the risk of gastrointestinal hemorrhage. Since 
gastrointestinal hemorrhage is an adverse reaction with ipilimumab (see 4.8 Undesirable effects), 
patients who require concomitant anticoagulant therapy should be monitored closely. 
4.6 
USE IN SPECIAL POPULATIONS (SUCH AS PREGNANT WOMEN, 
LACTATING WOMEN, PEDIATRIC PATIENTS, GERIATRIC PATIENTS 
ETC.) 
Pregnancy 
Risk Summary 
Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology 
(12.1)], ipilimumab can cause fetal harm when administered to a pregnant woman. There is 
insufficient human data for ipilimumab exposure in pregnant women. In animal reproduction 
studies, administration of ipilimumab to cynomolgus monkeys from the onset of organogenesis 
through delivery resulted in higher incidences of abortion, stillbirth, premature delivery (with 
corresponding lower birth weight), and higher incidences of infant mortality in a dose-related 
manner (see Data). The effects of Ipilimumab are likely to be greater during the second and third 
trimesters of pregnancy. Human IgG1 is known to cross the placental barrier and ipilimumab is an 
IgG1; therefore, ipilimumab has the potential to be transmitted from the mother to the developing 
fetus. Advise pregnant women of the potential risk to a fetus. 
Data 
Animal Data 
In a combined study of embryo-fetal and peri-postnatal development, pregnant cynomolgus 
monkeys received ipilimumab every 3 weeks from the onset of organogenesis in the first trimester 
through parturition. No treatment-related adverse effects on reproduction were detected during the 
first two trimesters of pregnancy. Beginning in the third trimester, administration of ipilimumab 
at doses resulting in exposures approximately 2.6 to 7.2 times the human exposure at a dose of 3 
mg/kg resulted in dose-related increases in abortion, stillbirth, premature delivery (with 
corresponding lower birth weight), and an increased incidence of infant mortality. In addition, 
developmental abnormalities were identified in the urogenital system of 2 infant monkeys exposed 
in utero to 30 mg/kg of ipilimumab (7.2 times the humans exposure based on area under the curve 
at a dose of 3 mg/kg). One female infant monkey had unilateral renal agenesis of the left kidney 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
234 
Approved v 41.0 
930144776 4.0 
 
 
and ureter, and 1 male infant monkey had an imperforate urethra with associated urinary 
obstruction and subcutaneous scrotal edema. 
Genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/−), the target for ipilimumab, 
appeared healthy and gave birth to healthy CTLA-4+/− heterozygous offspring. Mated CTLA- 
4+/− heterozygous mice also produced offspring deficient in CTLA-4 (homozygous negative, 
CTLA-4−/−). The CTLA-4−/− homozygous negative offspring appeared healthy at birth, 
exhibited signs of multiorgan lymphoproliferative disease by 2 weeks of age, and all died by 3 to 
4 weeks of age with massive lymphoproliferation and multiorgan tissue destruction. 
Lactation 
Risk Summary 
There are no data on the presence of ipilimumab in human milk or its effects on the breastfed child 
or milk production. In monkeys, ipilimumab was present in milk (see Data). Because of the 
potential for serious adverse reactions in breastfed children, advise women not to breastfeed during 
treatment with ipilimumab and for 3 months following the last dose. 
Data 
In monkeys treated at dose levels resulting in exposures 2.6 and 7.2 times higher than those in 
humans at a 3 mg/kg dose, ipilimumab was present in milk at concentrations of 0.1 mcg/mL and 
0.4 mcg/mL, representing a ratio of up to 0.3% of the steady-state serum concentration of the drug. 
Females and Males of Reproductive Potential 
 
Pregnancy Testing 
Verify pregnancy status in females of reproductive potential prior to initiating Ipilimumab [see 4.6 
Use in Special Populations-Pregnancy]. 
 
Contraception 
Ipilimumab can cause fetal harm when administered to a pregnant woman [see 4.6 Use in Special 
Populations (8.1)]. Advise females of reproductive potential to use effective contraception during 
treatment with Ipilimumab and for 3 months following the last dose. 
 
Pediatric use 
The safety and effectiveness for pediatric patients 12 years and older have not been established or 
for the treatment of renal cell carcinoma. In addition, the safety and effectiveness have not been 
established with ipilimumab for any indication in pediatric patients less than 12 years of age. 
Ipilimumab was evaluated in a total of 45 pediatric patients across two clinical trials. In a dose 
finding trial (NCT01445379), 33 pediatric patients with relapsed or refractory solid tumors were 
evaluated. The median age was 13 years (range 2 to 21 years) and 20 patients were ≥12 years old. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
235 
Approved v 41.0 
930144776 4.0 
 
 
Geriatric use 
Of the 550 patients randomized to ipilimumab 1 mg/kg with nivolumab in CA209227, Part 1 
[CHECKMATE-214] (renal cell carcinoma), 38% were 65 years or older and 8% were 75 years 
or older. No overall difference in safety was observed between these patients and younger patients. 
In geriatric patients with intermediate or poor risk, no overall difference in effectiveness was 
observed. 
Of the 576 patients randomized to Ipilimumab 1 mg/kg every 6 weeks with nivolumab 3 mg/kg 
every 2 weeks in CHECKMATE-227 (NSCLC), 48% were 65 years or older and 10% were 75 
years or older. No overall difference in safety was reported between older patients and younger 
patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 
75 years or older (29%) relative to all patients who received Ipilimumab with nivolumab (18%). 
Of the 396 patients in the primary efficacy population (PD-L1 ≥1%) randomized to Ipilimumab 1 
mg/kg every 6 weeks with nivolumab 3 mg/kg every 2 weeks with in CHECKMATE-227, the 
hazard ratio for overall survival was 0.70 (95% CI: 0.55, 0.89) in the 199 patients younger than 65 
years compared to 0.91 (95% CI: 0.72, 1.15) in the 197 patients 65 years or older [see 5.2.1 Clinical 
Trials]. 
Of the 361 patients randomized to Ipilimumab 1 mg/kg every 6 weeks in combination with 
nivolumab 360 mg every 3 weeks and platinum-doublet chemotherapy every 3 weeks (for 2 cycles) 
in CA2099LA [CHECKMATE-9LA] (NSCLC), 51% were 65 years or older and 10% were 75 
years or older. No overall difference in safety was reported between older patients and younger 
patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 
75 years or older (43%) relative to all patients who received Ipilimumab with nivolumab and 
chemotherapy (24%). For patients aged 75 years or older who received chemotherapy only, the 
discontinuation rate due to adverse reactions was 16% relative to all patients who had a 
discontinuation rate of 13%. Based on an updated analysis for overall survival, of the 361 patients 
randomized to Ipilimumab in combination with nivolumab and platinum-doublet chemotherapy in 
CHECKMATE-9LA, the hazard ratio for overall survival was 0.61 (95% CI: 0.47, 0.80) in the 176 
patients younger than 65 years compared to 0.73 (95% CI: 0.56, 0.95) in the 185 patients 65 years 
or older. 
 
4.7 
Effects on ability to drive and to use machines 
Because of potential adverse reactions such as fatigue (see 4.8 Undesirable effects), patients 
should be advised to use caution when driving or operating machinery until they are certain that 
ipilimumab does not adversely affect them. 
 
4.8 
Undesirable effects 
The following clinically significant adverse reactions are described elsewhere in the labeling: 
• Severe and fatal immune-mediated adverse reactions [see 4.4 Special warnings and precautions 
for use]. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
236 
Approved v 41.0 
930144776 4.0 
 
 
• Infusion-related reactions [see 4.4 Special warnings and precautions for use]. 
 
4.8.1 
Clinical experience 
Because clinical trials are conducted under widely varying conditions, adverse reaction rates 
observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials 
of another drug and may not reflect the rates observed in clinical practice. 
 
RCC 
The safety of ipilimumab in combination with nivolumab was evaluated in 1082 patients with 
previously untreated advanced RCC in CHECKMATE-214 [see 5.2.1 Clinical Trial Studies]. 
Patients received ipilimumab 1 mg/kg with nivolumab 3 mg/kg intravenously every 3 weeks for 4 
doses followed by nivolumab as a single agent at a dose of 3 mg/kg every 2 weeks (n=547) or 
sunitinib 50 mg orally daily for first 4 weeks of each 6-week cycle (n=535). The median duration 
of treatment was 7.9 months (range: 1 day to 21.4+ months) in ipilimumab and nivolumab arm. In 
this trial, 57% of patients in the ipilimumab and nivolumab arm were exposed to treatment for 
greater than 6 months and 38% of patients were exposed to treatment for greater than 1 year. 
Serious adverse reactions occurred in 59% of patients receiving ipilimumab with nivolumab. The 
most frequent serious adverse reactions reported in >2% of patients treated with Ipilimumab and 
nivolumab were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, 
dyspnea, adrenal insufficiency, and colitis. 
In patients who received ipilimumab with nivolumab, study therapy was discontinued for adverse 
reactions in 31% and delayed for adverse reactions in 54%. 
The most common adverse reactions (>20%) in the ipilimumab and nivolumab arm were fatigue, 
rash, diarrhea, musculoskeletal pain, pruritus, nausea, cough, pyrexia, arthralgia, vomiting, 
dyspnea, and decreased appetite. Table 2 summarizes adverse reactions in CHECKMATE-214. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
237 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 2: 
Adverse Reactions (>15%) in Patients Receiving Ipilimumab with 
Nivolumab in CHECKMATE-214 
 
Adverse Reaction 
Ipilimumab 1 mg/kg with 
Nivolumab 
n=547 
Sunitinib 
n=535 
Grades 1-4 
(%) 
Grades 3-4 
(%) 
Grades 1-4 
(%) 
Grades 3-4 
(%) 
General and Administration Site Conditions 
Fatiguea 
58 
8 
69 
13 
Pyrexia 
25 
0.7 
17 
0.6 
Edemab 
16 
0.5 
17 
0.6 
Skin and Subcutaneous Tissue 
Rashc 
39 
3.7 
25 
1.1 
Pruritus/generalized pruritus 
33 
0.5 
11 
0 
Gastrointestinal 
Diarrhea 
38 
4.6 
58 
6 
Nausea 
30 
2.0 
43 
1.5 
Vomiting 
20 
0.9 
28 
2.1 
Abdominal pain 
19 
1.6 
24 
1.9 
Constipation 
17 
0.4 
18 
0 
Musculoskeletal and Connective Tissue 
Musculoskeletal paind 
37 
4.0 
40 
2.6 
Arthralgia 
23 
1.3 
16 
0 
Respiratory, Thoracic, and Mediastinal 
Cough/productive cough 
28 
0.2 
25 
0.4 
Dyspnea/exertional dyspnea 
20 
2.4 
21 
2.1 
Metabolism and Nutrition 
Decreased appetite 
21 
1.8 
29 
0.9 
Nervous System 
Headache 
19 
0.9 
23 
0.9 
Endocrine 
Hypothyroidism 
18 
0.4 
27 
0.2 
Toxicity was graded per NCI CTCAE v4. 
a Includes asthenia. 
b Includes peripheral edema, peripheral swelling. 
c Includes dermatitis described as acneiform, bullous, and exfoliative, drug eruption, rash described as exfoliative, 
erythematous, follicular, generalized, macular, maculopapular, papular, pruritic, and pustular, fixed-drug eruption. 
d Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in 
extremity, spinal pain. 
 
Table 3 summarizes the laboratory abnormalities in CHECKMATE-214. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
238 
Approved v 41.0 
930144776 4.0 
 
 
Table 3: Laboratory Abnormalities (>15%) Worsening from Baseline in Patients 
Receiving Ipilimumab with Nivolumab in CHECKMATE-214 
Laboratory Abnormality 
Ipilimumab 1 mg/kg with 
Nivolumaba 
Sunitiniba 
Grades 1-4 
(%) 
Grades 3-4 
(%) 
Grades 1-4 
(%) 
Grades 3-4 (%) 
Chemistry 
Increased lipase 
48 
20 
51 
20 
Increased creatinine 
42 
2.1 
46 
1.7 
Increased ALT 
41 
7 
44 
2.7 
Increased AST 
40 
4.8 
60 
2.1 
Increased amylase 
39 
12 
33 
7 
Hyponatremia 
39 
10 
36 
7 
Increased alkaline phosphatase 
29 
2.0 
32 
1.0 
Hyperkalemia 
29 
2.4 
28 
2.9 
Hypocalcemia 
21 
0.4 
35 
0.6 
Hypomagnesemia 
16 
0.4 
26 
1.6 
Hematology 
Anemia 
43 
3.0 
64 
9 
Lymphopenia 
36 
5 
63 
14 
a Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory 
measurement available: nivolumab and Ipilimumab group (range: 490 to 538 patients) and sunitinib group (range: 
485 to 523 patients). 
In addition, among patients with TSH ≤ ULN at baseline, a lower proportion of patients 
experienced a treatment-emergent elevation of TSH > ULN in the ipilimumab with nivolumab 
group compared to the sunitinib group (31% and 61%, respectively). 
First-line Treatment of Metastatic NSCLC: In Combination with Nivolumab 
The safety of Ipilimumab in combination with nivolumab was evaluated in CHECKMATE-227, a 
randomized, multicenter, multi-cohort, open-label trial in patients with previously untreated 
metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations [see 5.2.1 
Clinical Trials]. The trial excluded patients with untreated brain metastases, carcinomatous 
meningitis, 
active 
autoimmune 
disease, 
or 
medical 
conditions 
requiring 
systemic 
immunosuppression. Patients received Ipilimumab 1 mg/kg by intravenous infusion over 30 
minutes every 6 weeks and nivolumab 3 mg/kg by intravenous infusion over 30 minutes every 2 
weeks or platinum-doublet chemotherapy every 3 weeks for 4 cycles. The median duration of 
therapy in Ipilimumab and nivolumab-treated patients was 4.2 months (range: 1 day to 25.5 
months): 39% of patients received Ipilimumab and nivolumab for >6 months and 23% of patients 
received Ipilimumab and nivolumab for >1 year. The population characteristics were: median age 
64 years (range: 26 to 87); 48% were ≥65 years of age, 76% White, and 67% male. Baseline ECOG 
performance status was 0 (35%) or 1 (65%), 85% were former/current smokers, 11% had brain 
metastases, 28% had squamous histology and 72% had non-squamous histology. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
239 
Approved v 41.0 
930144776 4.0 
 
 
Serious adverse reactions occurred in 58% of patients. Ipilimumab and nivolumab were 
discontinued for adverse reactions in 24% of patients and 53% had at least one dose withheld for 
an adverse reaction. 
The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, 
hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions 
occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute 
kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. The most 
common (≥20%) adverse reactions were fatigue, rash, decreased appetite, musculoskeletal pain, 
diarrhea/colitis, dyspnea, cough, hepatitis, nausea, and pruritus. 
Tables 4 and 5 summarize selected adverse reactions and laboratory abnormalities, respectively, 
in CHECKMATE-227. 
Table 4: 
Adverse Reactions in ≥10% of Patients Receiving Ipilimumab and 
Nivolumab - CHECKMATE-227 
 
Ipilimumab and Nivolumab 
(n=576) 
Platinum-doublet Chemotherapy 
(n=570) 
All Grades (%) 
Grades 3-4 (%) 
All Grades (%) 
Grades 3-4 (%) 
General 
Fatiguea 
44 
6 
42 
4.4 
Pyrexia 
18 
0.5 
11 
0.4 
Edemab 
14 
0.2 
12 
0.5 
Skin and Subcutaneous Tissue 
Rashc 
34 
4.7 
10 
0.4 
Pruritusd 
21 
0.5 
3.3 
0 
Metabolism and Nutrition 
Decreased appetite 
31 
2.3 
26 
1.4 
Musculoskeletal and Connective Tissue 
Musculoskeletal paine 
27 
1.9 
16 
0.7 
Arthralgia 
13 
0.9 
2.5 
0.2 
Gastrointestinal 
Diarrhea/colitisf 
26 
3.6 
16 
0.9 
Nausea 
21 
1.0 
42 
2.5 
Constipation 
18 
0.3 
27 
0.5 
Vomiting 
13 
1.0 
18 
2.3 
Abdominal paing 
10 
0.2 
9 
0.7 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
240 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 4: 
Adverse Reactions in ≥10% of Patients Receiving Ipilimumab and 
Nivolumab - CHECKMATE-227 
 
Ipilimumab and Nivolumab 
(n=576) 
Platinum-doublet Chemotherapy 
(n=570) 
All Grades (%) 
Grades 3-4 (%) 
All Grades (%) 
Grades 3-4 (%) 
Respiratory, Thoracic, and Mediastinal 
Dyspneah 
26 
4.3 
16 
2.1 
Coughi 
23 
0.2 
13 
0 
Hepatobiliary 
Hepatitisj 
21 
9 
10 
1.2 
Endocrine 
Hypothyroidismk 
16 
0.5 
1.2 
0 
Hyperthyroidisml 
10 
0 
0.5 
0 
Infections and Infestations 
Pneumoniam 
13 
7 
8 
4.0 
Nervous System 
Headache 
11 
0.5 
6 
0 
a Includes fatigue and asthenia. 
b Includes eyelid edema, face edema, generalized edema, localized edema, edema, edema peripheral, and periorbital 
edema. 
c Includes autoimmune dermatitis, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis atopic, dermatitis 
bullous, dermatitis contact, dermatitis exfoliative, dermatitis psoriasiform, granulomatous dermatitis, rash 
generalized, drug eruption, dyshidrotic eczema, eczema, exfoliative rash, nodular rash, rash, rash erythematous, 
rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, toxic skin eruption. 
d Includes pruritus and pruritus generalized. 
e Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, 
myalgia, and pain in extremity. 
f Includes colitis, colitis microscopic, colitis ulcerative, diarrhea, enteritis infectious, enterocolitis, enterocolitis 
infectious, and enterocolitis viral. 
g Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal 
tenderness. 
h Includes dyspnea and dyspnea exertional. 
i Includes cough and productive cough. 
j Includes alanine aminotransferase increased, aspartate aminotransferase increased, autoimmune hepatitis, blood 
bilirubin increased, hepatic enzyme increased, hepatic failure, hepatic function abnormal, hepatitis, hepatitis E, 
hepatocellular injury, hepatotoxicity, hyperbilirubinemia, immune-mediated hepatitis, liver function test abnormal, 
liver function test increased, transaminases increased. 
k Includes autoimmune thyroiditis, blood thyroid stimulating hormone increased, hypothyroidism, primary 
hypothyroidism, thyroiditis, and tri-iodothyronine free decreased. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
241 
Approved v 41.0 
930144776 4.0 
 
 
l Contains blood thyroid stimulating hormone decreased, hyperthyroidism, and tri-iodothyronine free increased. 
m Includes lower respiratory tract infection, lower respiratory tract infection bacterial, lung infection, pneumonia, 
pneumonia adenoviral, pneumonia aspiration, pneumonia bacterial, pneumonia klebsiella, pneumonia influenzal, 
pneumonia viral, atypical pneumonia, organizing pneumonia. 
 
Other clinically important adverse reactions in CHECKMATE-227 were: 
Skin and Subcutaneous Tissue: urticaria, alopecia, erythema multiforme, vitiligo 
Gastrointestinal: stomatitis, pancreatitis, gastritis 
Musculoskeletal and Connective Tissue: arthritis, polymyalgia rheumatica, rhabdomyolysis 
Nervous System: peripheral neuropathy, autoimmune encephalitis 
Blood and Lymphatic System: eosinophilia 
Eye Disorders: blurred vision, uveitis 
Cardiac: atrial fibrillation, myocarditis 
 
Table 5: 
Laboratory Values Worsening from Baselinea Occurring in ≥20% of 
Patients on Ipilimumab and Nivolumab - CHECKMATE-227 
 
Laboratory 
Abnormality 
Ipilimumab and Nivolumab 
Platinum-doublet Chemotherapy 
Grades 1-4 
(%) 
Grades 3-4 
(%) 
Grades 1-4 
(%) 
Grades 3-4 
(%) 
Hematology 
Anemia 
46 
3.6 
78 
14 
Lymphopenia 
46 
5 
60 
15 
Chemistry 
Hyponatremia 
41 
12 
26 
4.9 
Increased AST 
39 
5 
26 
0.4 
Increased ALT 
36 
7 
27 
0.7 
Increased lipase 
35 
14 
14 
3.4 
Increased alkaline 
phosphatase 
34 
3.8 
20 
0.2 
Increased amylase 
28 
9 
18 
1.9 
Hypocalcemia 
28 
1.7 
17 
1.3 
Hyperkalemia 
27 
3.4 
22 
0.4 
Increased creatinine 
22 
0.9 
17 
0.2 
a Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory 
measurement available: Ipilimumab and nivolumab group (range: 494 to 556 patients) and chemotherapy group 
(range: 469 to 542 patients). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
242 
Approved v 41.0 
930144776 4.0 
 
 
First-line Treatment of Metastatic or Recurrent NSCLC: In Combination with Nivolumab and 
Platinum-Doublet Chemotherapy 
The safety of Ipilimumab in combination with nivolumab and platinum-doublet chemotherapy was 
evaluated in CHECKMATE-9LA [see 5.2.1 Clinical Trials]. Patients received either Ipilimumab 
1 mg/kg administered every 6 weeks in combination with nivolumab 360 mg administered every 
3 weeks and platinum-doublet chemotherapy administered every 3 weeks for 2 cycles; or platinum- 
doublet chemotherapy administered every 3 weeks for 4 cycles. The median duration of therapy 
in Ipilimumab in combination with nivolumab and platinum-doublet chemotherapy was 6 months 
(range: 1 day to 19 months): 50% of patients received Ipilimumab and nivolumab for >6 months 
and 13% of patients received Ipilimumab and nivolumab for >1 year. 
Serious adverse reactions occurred in 57% of patients who were treated with Ipilimumab in 
combination with nivolumab and platinum-doublet chemotherapy. The most frequent (>2%) 
serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney 
injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions 
occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, 
diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. 
Study therapy with Ipilimumab in combination with nivolumab and platinum-doublet 
chemotherapy was permanently discontinued for adverse reactions in 24% of patients and 56% 
had at least one treatment withheld for an adverse reaction. The most common (>20%) adverse 
reactions were fatigue, musculoskeletal pain, nausea, diarrhea, rash, decreased appetite, 
constipation, and pruritus. 
Tables 6 and 7 summarize selected adverse reactions and laboratory abnormalities, respectively, 
in CHECKMATE-9LA. 
 
 
Table 6: 
Adverse Reactions in >10% of Patients Receiving Ipilimumab and 
Nivolumab and Platinum-Doublet Chemotherapy - CHECKMATE- 
9LA 
 
Adverse Reaction 
Ipilimumab and Nivolumab and 
Platinum-Doublet Chemotherapy 
(n=358) 
Platinum-Doublet 
Chemotherapy 
(n=349) 
All Grades (%) 
Grades 3-4 (%) 
All Grades (%) 
Grades 3-4 (%) 
General 
Fatiguea 
49 
5 
40 
4.9 
Pyrexia 
14 
0.6 
10 
0.6 
Musculoskeletal and Connective Tissue 
Musculoskeletal painb 
39 
4.5 
27 
2.0 
Gastrointestinal 
Nausea 
32 
1.7 
41 
0.9 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
243 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 6: 
Adverse Reactions in >10% of Patients Receiving Ipilimumab and 
Nivolumab and Platinum-Doublet Chemotherapy - CHECKMATE- 
9LA 
 
Adverse Reaction 
Ipilimumab and Nivolumab and 
Platinum-Doublet Chemotherapy 
(n=358) 
Platinum-Doublet 
Chemotherapy 
(n=349) 
All Grades (%) 
Grades 3-4 (%) 
All Grades (%) 
Grades 3-4 (%) 
Diarrheac 
31 
6 
18 
1.7 
Constipation 
21 
0.6 
23 
0.6 
Vomiting 
18 
2.0 
17 
1.4 
Abdominal paind 
12 
0.6 
11 
0.9 
Skin and Subcutaneous Tissue 
Rashe 
30 
4.7 
10 
0.3 
Pruritusf 
21 
0.8 
2.9 
0 
Alopecia 
11 
0.8 
10 
0.6 
Metabolism and Nutrition 
Decreased appetite 
28 
2.0 
22 
1.7 
Respiratory, Thoracic and Mediastinal 
Coughg 
19 
0.6 
15 
0.9 
Dyspneah 
18 
4.7 
14 
3.2 
Endocrine 
Hypothyroidismi 
19 
0.3 
3.4 
0 
Nervous System 
Headache 
11 
0.6 
7 
0 
Dizzinessj 
11 
0.6 
6 
0 
Toxicity was graded per NCI CTCAE v4. 
a Includes fatigue and asthenia 
b Includes myalgia, back pain, pain in extremity, musculoskeletal pain, bone pain, flank pain, muscle spasms, 
musculoskeletal chest pain, musculoskeletal disorder, osteitis, musculoskeletal stiffness, non-cardiac chest pain, 
arthralgia, arthritis, arthropathy, joint effusion, psoriatic arthropathy, synovitis 
c Includes colitis, ulcerative colitis, diarrhea, and enterocolitis 
d Includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain, and gastrointestinal 
pain 
e Includes acne, dermatitis, acneiform dermatitis, allergic dermatitis, atopic dermatitis, bullous dermatitis, 
generalized exfoliative dermatitis, eczema, keratoderma blenorrhagica, palmar-plantar erythrodysaesthesia 
syndrome, rash, erythematous rash, generalized rash, macular rash, maculo-papular rash, morbilliform rash, papular 
rash, pruritic rash, skin exfoliation, skin reaction, skin toxicity, Stevens-Johnson syndrome, urticaria 
f Includes pruritus and generalized pruritus 
g Includes cough, productive cough, and upper-airway cough syndrome 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
244 
Approved v 41.0 
930144776 4.0 
 
 
h Includes dyspnea, dyspnea at rest, and exertional dyspnea 
i Includes autoimmune thyroiditis, increased blood thyroid stimulating hormone, hypothyroidism, thyroiditis, and 
decreased free tri-iodothyronine 
j Includes dizziness, vertigo and positional vertigo 
 
 
Table 7: 
Laboratory Values Worsening from Baselinea Occurring in >20% of 
Patients on Ipilimumab and Nivolumab and Platinum-Doublet 
Chemotherapy - CHECKMATE-9LA 
Laboratory Abnormality 
Ipilimumab and Nivolumab 
and Platinum-Doublet 
Platinum-Doublet Chemotherapy 
Grades 1-4 (%) 
Grades 3-4 (%) 
Grades 1-4 (%) 
Grades 3-4 (%) 
Hematology 
Anemia 
70 
9 
74 
16 
Lymphopenia 
41 
6 
40 
11 
Neutropenia 
40 
15 
42 
15 
Leukopenia 
36 
10 
40 
9 
Thrombocytopenia 
23 
4.3 
24 
5 
Chemistry 
Hyperglycemia 
45 
7 
42 
2.6 
Hyponatremia 
37 
10 
27 
7 
Increased ALT 
34 
4.3 
24 
1.2 
Increased lipase 
31 
12 
10 
2.2 
Increased alkaline phosphatase 
31 
1.2 
26 
0.3 
Increased amylase 
30 
7 
19 
1.3 
Increased AST 
30 
3.5 
22 
0.3 
Hypomagnesemia 
29 
1.2 
33 
0.6 
Hypocalcemia 
26 
1.4 
22 
1.8 
Increased creatinine 
26 
1.2 
23 
0.6 
Hyperkalemia 
22 
1.7 
21 
2.1 
a Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory 
measurement available: Ipilimumab and nivolumab and platinum-doublet chemotherapy group (range: 197 to 347 
patients) and platinum-doublet chemotherapy group (range: 191 to 335 patients). 
 
4.8.2 
Post-marketing experience 
The following adverse reactions have been identified during post approval use of ipilimumab. 
Because these reactions are reported voluntarily from a population of uncertain size, it is not 
always possible to reliably estimate their frequency or establish a causal relationship to drug 
exposure. 
Blood and lymphatic system disorders: hemophagocytic lymphohistiocytosis (HLH) 
Immune System: graft-versus-host disease, solid organ transplant rejection 
Skin and Subcutaneous Tissue: Drug reaction with eosinophilia and systemic symptoms (DRESS 
syndrome) 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
245 
Approved v 41.0 
930144776 4.0 
 
 
4.8.3 
Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody 
formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the 
observed incidence of antibody (including neutralizing antibody) positivity in an assay may be 
influenced by several factors including assay methodology, sample handling, timing of sample 
collection, concomitant medications, and underlying disease. For these reasons, comparison of the 
incidence of antibodies in the studies described below with the incidences of antibodies to other 
studies or to other products may be misleading. 
Of 483 patients evaluable for anti-ipilimumab antibodies in CHECKMATE-227 Part 1, 8.5% were 
positive for treatment-emergent anti-ipilimumab antibodies. No patients had neutralizing 
antibodies against ipilimumab. In Part 1 of the same study, of 491 patients evaluable for anti- 
nivolumab antibodies, 36.7% were positive for anti-nivolumab antibodies and 1.4% had 
neutralizing antibodies against nivolumab. 
Of 305 patients evaluable for anti-ipilimumab antibodies in CHECKMATE-9LA, 8% were 
positive for anti-ipilimumab antibodies and 1.6% were positive for anti-ipilimumab neutralizing 
antibodies. There was no evidence of increased incidence of infusion reactions to Ipilimumab in 
patients with anti-ipilimumab antibodies. Of 308 patients evaluable for anti-nivolumab antibodies 
in CHECKMATE-9LA, 34% were positive for anti-nivolumab antibodies and 2.6% had 
neutralizing antibodies against nivolumab. 
4.9 
Overdose 
The maximum tolerated dose of ipilimumab has not been determined. In clinical trials, patients 
received up to 20 mg/kg without apparent toxic effects. 
In case of overdosage, patients should be closely monitored for signs or symptoms of adverse 
reactions, and appropriate symptomatic treatment instituted. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
246 
Approved v 41.0 
930144776 4.0 
 
 
5 
PHARMACOLOGICAL PROPERTIES 
5.1 
Mechanism of action 
CTLA-4 is a negative regulator of T-cell activity. Ipilimumab is a monoclonal antibody that binds 
to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of 
CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation 
and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also 
reduce T-regulatory cell function, which may contribute to a general increase in T cell 
responsiveness, including the anti-tumor immune response. 
 
5.2 
Pharmacodynamics Properties 
5.2.1 
Clinical Trials 
Renal cell carcinoma (RCC) 
The efficacy of ipilimumab with nivolumab was evaluated in CHECKMATE-214 
(NCT02231749), a randomized (1:1), open-label study in patients with previously untreated 
advanced RCC. Patients were included regardless of their PD-L1 status. CHECKMATE-214 
excluded patients with any history of or concurrent brain metastases, active autoimmune disease, 
or medical conditions requiring systemic immunosuppression. Patients were randomized to 
nivolumab 3 mg/kg and ipilimumab 1 mg/kg administered intravenously every 3 weeks for 4 doses 
followed by nivolumab 3 mg/kg every two weeks or to sunitinib administered orally 50 mg daily 
for the first 4 weeks of each 6-week cycle. Treatment continued until disease progression or 
unacceptable toxicity. Patients were stratified by International Metastatic RCC Database 
Consortium (IMDC) prognostic score and region. The major efficacy outcome measures were OS, 
PFS (IRRC-assessed), and confirmed ORR (IRRC-assessed) in intermediate/poor risk patients. 
Intermediate/poor risk patients had at least 1 or more of 6 prognostic risk factors as per the IMDC 
criteria: less than one year from time of initial RCC diagnosis to randomization, Karnofsky 
performance status (KPS) <80%, hemoglobin less than the lower limit of normal, corrected 
calcium >10 mg/dL, platelet count > ULN, and absolute neutrophil count > ULN. 
A total of 847 patients were randomized, 425 to ipilimumab with nivolumab and 422 to sunitinib. 
The median age was 61 years (range: 21 to 85) with 38% ≥65 years of age and 8% ≥75 years of 
age. The majority of patients were male (73%) and White (87%) and 26% and 74% of patients had 
a baseline KPS of 70% to 80% and 90% to 100%, respectively. 
Efficacy results from CHECKMATE-214 are presented in Table 8 and Figure 1. In 
intermediate/poor risk patients, the trial demonstrated statistically significant improvement in OS 
and ORR for patients randomized to ipilimumab and nivolumab arm as compared with sunitinib 
arm. OS benefit was observed regardless of PD-L1 expression level. The trial did not demonstrate 
a statistically significant improvement in PFS. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
247 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 8: 
Efficacy Results for CHECKMATE-214 
 
Efficacy Parameter 
Intermediate/Poor-Risk 
Ipilimumab 1 mg/kg with 
Nivolumab 
n=425 
Sunitinib 
n=422 
Overall Survival 
Number of deaths 
140 (32.9%) 
188 (44.5%) 
Median in months 
NE 
25.9 
Hazard ratio (99.8% CI)a 
0.63 (0.44, 0.89) 
p-valueb,c 
<0.0001 
Confirmed Objective Response Rate (95% CI) 
41.6% (36.9%, 46.5%) 
26.5% (22.4%, 31.0%) 
Complete Response 
40 (9.4%) 
5 (1.2%) 
Partial Response 
137 (32.2%) 
107 (25.4%) 
Median duration of response in months (95% CI) 
NE (21.8, NE) 
18.2 (14.8, NE) 
p-valued,e 
<0.0001 
Progression-free Survival 
Number of events (progression or death) 
228 (53.6%) 
228 (54.0%) 
Median in months 
11.6 
8.4 
Hazard ratio (99.1% CI)a 
0.82 (0.64, 1.05) 
p-valueb 
NSf 
a Based on a stratified proportional hazards model. 
b Based on a stratified log-rank test. 
c p-value is compared to alpha 0.002 in order to achieve statistical significance. 
d Based on the stratified DerSimonian-Laird test. 
e p-value is compared to alpha 0.001 in order to achieve statistical significance. 
f Not Significant at alpha level of 0.009 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
248 
Approved v 41.0 
930144776 4.0 
 
 
Figure 1: 
Kaplan-Meier Curves for Overall Survival (Intermediate/Poor Risk 
Population) in CHECKMATE-214 
 
 
 
CHECKMATE-214 also randomized 249 favorable risk patients as per IMDC criteria to 
nivolumab and ipilimumab (n=125) or to sunitinib (n=124). These patients were not evaluated as 
part of the efficacy analysis population. OS in favorable risk patients receiving nivolumab and 
ipilimumab compared to sunitinib has a hazard ratio of 1.45 (95% CI: 0.75, 2.81). The efficacy of 
nivolumab and ipilimumab in previously untreated renal cell carcinoma with favorable risk disease 
has not been established. 
 
Metastatic Non-Small Cell Lung Cancer 
First-line Treatment of Metastatic Non-Small Cell Lung Cancer (NSCLC) Expressing PD-L1 
(≥1%): In Combination with Nivolumab 
CHECKMATE-227 (NCT02477826) was a randomized, open-label, multi-part trial in patients 
with metastatic or recurrent NSCLC. The study included patients (18 years of age or older) with 
histologically confirmed Stage IV or recurrent NSCLC (per the 7th International Association for 
the Study of Lung Cancer [ASLC] classification), ECOG performance status 0 or 1, and no prior 
anticancer therapy. Patients were enrolled regardless of their tumor PD-L1 status. Patients with 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
249 
Approved v 41.0 
930144776 4.0 
 
 
known EGFR mutations or ALK translocations sensitive to available targeted inhibitor therapy, 
untreated brain metastases, carcinomatous meningitis, active autoimmune disease, or medical 
conditions requiring systemic immunosuppression were excluded from the study. Patients with 
treated brain metastases were eligible if neurologically returned to baseline at least 2 weeks prior 
to enrolment, and either off corticosteroids, or on a stable or decreasing dose of <10 mg daily 
prednisone equivalents. 
Primary efficacy results were based on Part 1a of the study, which was limited to patients with 
PD-L1 tumor expression ≥1%. Tumor specimens were evaluated prospectively using the PD-L1 
IHC 28-8 pharmDx assay at a central laboratory. Randomization was stratified by tumor histology 
(non-squamous versus squamous). The evaluation of efficacy relied on the comparison between: 
• Ipilimumab 1 mg/kg administered intravenously over 30 minutes every 6 weeks in 
combination with nivolumab 3 mg/kg administered intravenously over 30 minutes every 2 
weeks; or 
• Platinum-doublet chemotherapy 
 
Chemotherapy regimens consisted of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) or 
pemetrexed (500 mg/m2) and carboplatin (AUC 5 or 6) for non-squamous NSCLC or gemcitabine 
(1000 or 1250 mg/m2) and cisplatin (75 mg/m2) or gemcitabine (1000 mg/m2) and carboplatin 
(AUC 5) (gemcitabine was administered on Days 1 and 8 of each cycle) for squamous NSCLC. 
Study treatment continued until disease progression, unacceptable toxicity, or for up to 24 months. 
Treatment continued beyond disease progression if a patient was clinically stable and was 
considered to be deriving clinical benefit by the investigator. Patients who discontinued 
combination therapy because of an adverse event attributed to Ipilimumab were permitted to 
continue nivolumab as a single agent. Tumor assessments were performed every 6 weeks from the 
first dose of study treatment for the first 12 months, then every 12 weeks until disease progression 
or study treatment was discontinued. The primary efficacy outcome measure was OS. Additional 
efficacy outcome measures included PFS, ORR, and duration of response as assessed by BICR. 
In Part 1a, a total of 793 patients were randomized to receive either Ipilimumab in combination 
with nivolumab (n=396) or platinum-doublet chemotherapy (n=397). The median age was 64 years 
(range: 26 to 87) with 49% of patients ≥65 years and 10% of patients ≥75 years, 76% White, and 
65% male. Baseline ECOG performance status was 0 (34%) or 1 (65%), 50% with PD-L1 ≥50%, 
29% with squamous and 71% with non-squamous histology, 10% had brain metastases, and 85% 
were former/current smokers. 
The study demonstrated a statistically significant improvement in OS for PD-L1 ≥1% patients 
randomized to the Ipilimumab and nivolumab arm compared to platinum-doublet chemotherapy 
arm. The OS results are presented in Table 9 and Figure 2. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
250 
Approved v 41.0 
930144776 4.0 
 
 
Table 9: 
Efficacy Results (PD-L1 ≥1%) - CHECKMATE-227 Part 1a 
 
Ipilimumab and 
Nivolumab (n=396) 
Platinum-Doublet Chemotherapy 
(n=397) 
Overall Survival 
Events (%) 
258 (65%) 
298 (75%) 
Median (months)a 
(95% CI) 
17.1 
(15, 20.1) 
14.9 
(12.7, 16.7) 
Hazard ratio (95% CI)b 
0.79 (0.67, 0.94) 
Stratified log-rank p-value 
0.0066 
a Kaplan-Meier estimate. 
b Based on a stratified Cox proportional hazard model. 
 
Figure 2: 
Overall Survival (PD-L1 ≥1%) - CHECKMATE-227 
 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
251 
Approved v 41.0 
930144776 4.0 
 
 
BICR-assessed PFS showed a HR of 0.82 (95% CI: 0.69, 0.97), with a median PFS of 5.1 months 
(95% CI: 4.1, 6.3) in the Ipilimumab and nivolumab arm and 5.6 months (95% CI: 4.6, 5.8) in the 
platinum-doublet chemotherapy arm. The BICR-assessed confirmed ORR was 36% (95% CI: 31, 
41) in the Ipilimumab and nivolumab arm and 30% (95% CI: 26, 35) in the platinum-doublet 
chemotherapy arm. Median duration of response observed in the Ipilimumab and nivolumab arm 
was 23.2 months and 6.2 months in the platinum-doublet chemotherapy arm. 
First-line Treatment of Metastatic or Recurrent NSCLC: In Combination with Nivolumab 
and Platinum-Doublet Chemotherapy 
CHECKMATE-9LA (NCT03215706) was a randomized, open-label trial in patients with 
metastatic or recurrent NSCLC. The trial included patients (18 years of age or older) with 
histologically confirmed Stage IV or recurrent NSCLC (per the 7th International Association for 
the Study of Lung Cancer classification [IASLC]), ECOG performance status 0 or 1, and no prior 
anticancer therapy (including EGFR and ALK inhibitors) for metastatic disease. Patients were 
enrolled regardless of their tumor PD-L1 status. Patients with known EGFR mutations or ALK 
translocations sensitive to available targeted inhibitor therapy, untreated brain metastases, 
carcinomatous meningitis, active autoimmune disease, or medical conditions requiring systemic 
immunosuppression were excluded from the study. Patients with stable brain metastases were 
eligible for enrollment. 
Patients were randomized 1:1 to receive either: 
• Ipilimumab 1 mg/kg administered intravenously over 30 minutes every 6 weeks, nivolumab 
360 mg administered intravenously over 30 minutes every 3 weeks, and platinum-doublet 
chemotherapy administered intravenously every 3 weeks for 2 cycles, or 
• platinum-doublet chemotherapy administered every 3 weeks for 4 cycles. 
 
Platinum-doublet chemotherapy consisted of either carboplatin (AUC 5 or 6) and pemetrexed 500 
mg/mg2, or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 for non-squamous NSCLC; or 
carboplatin (AUC 6) and paclitaxel 200 mg/m2 for squamous NSCLC. Patients with non-squamous 
NSCLC in the control arm could receive optional pemetrexed maintenance therapy. Stratification 
factors for randomization were tumor PD-L1 expression level (≥1% versus <1% or non- 
quantifiable), histology (squamous versus non-squamous), and sex (male versus female). Study 
treatment continued until disease progression, unacceptable toxicity, or for up to 2 years. 
Treatment could continue beyond disease progression if a patient was clinically stable and was 
considered to be deriving clinical benefit by the investigator. Patients who discontinued 
combination therapy because of an adverse reaction attributed to Ipilimumab were permitted to 
continue nivolumab as a single agent as part of the study. Tumor assessments were performed 
every 6 weeks from the first dose of study treatment for the first 12 months, then every 12 weeks 
until disease progression or study treatment was discontinued. The primary efficacy outcome 
measure was OS. Additional efficacy outcome measures included PFS, ORR, and duration of 
response as assessed by BICR. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
252 
Approved v 41.0 
930144776 4.0 
 
 
A total of 719 patients were randomized to receive either Ipilimumab in combination with 
nivolumab and platinum-doublet chemotherapy (n=361) or platinum-doublet chemotherapy 
(n=358). The median age was 65 years (range: 26 to 86) with 51% of patients ≥65 years and 10% 
of patients ≥75 years. The majority of patients were White (89%) and male (70%). Baseline ECOG 
performance status was 0 (31%) or 1 (68%), 57% had tumors with PD-L1 expression ≥1% and 
37% had tumors with PD-L1 expression that was <1%, 32% had tumors with squamous histology 
and 68% had tumors with non-squamous histology, 17% had CNS metastases, and 86% were 
former or current smokers. 
The study demonstrated a statistically significant benefit in OS, PFS, and ORR. Efficacy results 
from the prespecified interim analysis when 351 events were observed (87% of the planned 
number of events for final analysis) are presented in Table 10. 
Table 10: 
Efficacy Results - CHECKMATE-9LA 
 
Ipilimumab and Nivolumab 
and Platinum-Doublet 
Chemotherapy 
(n=361) 
Platinum- 
Doublet 
Chemotherapy 
(n=358) 
Overall Survival 
Events (%) 
156 (43.2) 
195 (54.5) 
Median (months) 
14.1 
10.7 
(95% CI) 
(13.2, 16.2) 
(9.5, 12.5) 
Hazard ratio (96.71% CI)a 
0.69 (0.55, 0.87) 
Stratified log-rank p-valueb 
0.0006 
Progression-free Survival per BICR 
Events (%) 
232 (64.3) 
249 (69.6) 
Hazard ratio (97.48% CI)a 
0.70 (0.57, 0.86) 
Stratified log-rank p-valuec 
0.0001 
Median (months)d 
6.8 
5.0 
(95% CI) 
(5.6, 7.7) 
(4.3, 5.6) 
Overall Response Rate per BICR (%) 
38 
25 
(95% CI)e 
(33, 43) 
(21, 30) 
Stratified CMH test p-valuef 
0.0003 
Duration of Response per BICR 
Median (months) 
10.0 
5.1 
(95% CI)d 
(8.2, 13.0) 
(4.3, 7.0) 
a Based on a stratified Cox proportional hazard model. 
b p-value is compared with the allocated alpha of 0.033 for this interim analysis. 
c p-value is compared with the allocated alpha of 0.0252 for this interim analysis. 
d Kaplan-Meier estimate. 
e Confidence interval based on the Clopper and Pearson Method. 
f p-value is compared with the allocated alpha of 0.025 for this interim analysis. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
253 
Approved v 41.0 
930144776 4.0 
 
 
With an additional 4.6 months of follow-up the hazard ratio for overall survival was 0.66 (95% CI: 
0.55, 0.80) and median survival was 15.6 months (95% CI: 13.9, 20.0) and 10.9 months (95% CI: 9.5, 
12.5) for patients receiving ipilimumab and nivolumab and platinum-doublet chemotherapy or 
platinum-doublet chemotherapy, respectively (Figure 3). 
Figure 3: 
Overall Survival - CHECKMATE-9LA 
 
 
 
 
5.3 
Pharmacokinetic Properties 
The pharmacokinetics (PK) of ipilimumab was studied in 785 patients with unresectable or 
metastatic melanoma who received doses of 0.3, 3, or 10 mg/kg once every 3 weeks for 4 doses. 
The PK of ipilimumab is linear in the dose range of 0.3 mg/kg to 10 mg/kg. Following 
administration of Ipilimumab every 3 weeks, the systemic accumulation was 1.5-fold or less. 
Steady-state concentrations of ipilimumab were reached by the third dose; the mean minimum 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
254 
Approved v 41.0 
930144776 4.0 
 
 
concentration (Cmin) at steady state was 19.4 mcg/mL at 3 mg/kg and 58.1 mcg/mL at 10 mg/kg 
every 3 weeks. 
Elimination 
The mean (percent coefficient of variation) terminal half-life (t1/2) was 15.4 days (34%) and then 
mean (percent coefficient of variation) clearance (CL) was 16.8 mL/h (38%). 
The CL of ipilimumab was unchanged in presence of anti-ipilimumab antibodies. 
Specific Populations 
The CL of ipilimumab increased with increasing body weight supporting the recommended body 
weight (mg/kg) based dosing. The following factors had no clinically important effect on the CL 
of ipilimumab: age (range: 23 to 88 years), sex, performance status, renal impairment (glomerular 
filtration rate ≥15 mL/min/1.73 m2), mild hepatic impairment (total bilirubin [TB] >1 to 1.5 times 
the upper limit of normal [ULN] or AST > ULN), previous cancer therapy, and baseline lactate 
dehydrogenase (LDH) levels. The effect of race was not examined due to limited data available in 
non-White racial groups. ipilimumab has not been studied in patients with moderate (TB > 1.5 to 
3 times ULN and any AST) or severe (TB >3 times ULN and any AST) hepatic impairment. 
Pediatric Patients: Based on a population PK analysis using available pooled data from 565 
patients from four adult studies (n=521) and two pediatric studies (n=44), body weight normalized 
clearance of ipilimumab is comparable between adult and pediatric patients. In pediatric patients 
with a dosing regimen of 3 mg/kg every 3 weeks, the model simulated geometric mean (CV%) 
steady-state serum peak and trough concentrations of ipilimumab were 65.8 (17.6%) and 20.7 
(33.1%) mcg/mL (for 2 to 6 years old), 70.1 (19.6%) and 19.6 (42.9%) mcg/mL (for 6 to <12 years 
old), and 73.3 (20.6%) and 17.8 (50.8%) mcg/mL (for 12 years and older), which are comparable 
to those in adult patients. 
Drug Interaction Studies 
Ipilimumab with Nivolumab 
When ipilimumab 1 mg/kg was administered with nivolumab 3 mg/kg every 3 weeks, the CL of 
ipilimumab was unchanged compared to when ipilimumab was administered alone. 
When Ipilimumab 1 mg/kg every 6 weeks was administered in combination with nivolumab 3 
mg/kg every 2 weeks, the CL of ipilimumab increased by 30% compared to Ipilimumab 
administered alone and the CL of nivolumab was unchanged compared to nivolumab administered 
alone. 
When Ipilimumab 1 mg/kg every 6 weeks was administered in combination with nivolumab 360 
mg every 3 weeks and chemotherapy, the CL of ipilimumab increased by 22% compared to 
Ipilimumab administered alone and the CL of nivolumab was unchanged compared to nivolumab 
administered alone. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
255 
Approved v 41.0 
930144776 4.0 
 
 
6 
NON CLINICALPROPERTIES 
6.1 
Animal Toxicology 
Please refer section 4.6 Use in special populations (such as pregnant women, lactating women, 
pediatric patients, geriatric patients etc.), sub-section Animal data. 
Carcinogenesis, mutagenesis, impairment of fertility 
The carcinogenic potential of ipilimumab has not been evaluated in long-term animal studies, and 
the genotoxic potential of ipilimumab has not been evaluated. 
Fertility studies have not been performed with ipilimumab. 
 
 
7 
DESCRIPTION 
Ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody. 
Ipilimumab is a recombinant IgG1 kappa immunoglobulin with an approximate molecular weight 
of 148 kDa. ipilimumab is produced in mammalian (Chinese hamster ovary) cell culture. 
• Ipilimumab injection, for intravenous use is a sterile, preservative-free, clear to slightly 
opalescent, 
colorless to pale-yellow solution, which may contain a small amount of visible translucent-to- 
white, amorphous ipilimumab particulates. It is supplied in single-dose vials of 50 mg/10 mL. 
Each milliliter contains 5 mg of ipilimumab and the following excipients: Tris hydrochloride 
(2-amino-2-hydroxymethyl-1,3-propanediol hydrochloride), Sodium chloride, Mannitol, 
Pentetic acid (diethylenetriaminepentaacetic acid), Polysorbate 80, Sodium hydroxide (for pH 
adjustment), Hydrochloric acid (for pH adjustment) and Water for injection. 
 
8 
PHARMACEUTICAL PARTICULARS 
8.1 
Incompatibilities 
In the absence of compatibility studies, this medicinal product must not be mixed with other 
medicinal products. 
8.2 
Shelf life 
Unopened vial: Refer to the outer carton, for the expiry date. 
Solution for infusion: Once opened, the product should be infused or diluted and infused 
immediately. The chemical and physical in-use stability of the undiluted or diluted concentrate 
(between 1 mg/mL and 4 mg/mL) has been demonstrated for 24 hours at 25°C (77°F) and 2°C to 
8°C (36°F to 46°F). If not used immediately, the infusion solution (undiluted or diluted) may be 
stored for up to 24 hours either under refrigeration (2°C to 8°C, 36°F to 46°F) or at room 
temperature (20°C to 25°C, 68°F to 77°F). 
Ipilimumab must be stored in a refrigerator (2°C - 8°C). Do not freeze.Store in the original package 
in order to protect from light. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
256 
Approved v 41.0 
930144776 4.0 
 
 
8.3 
Packaging Information 
Each 10 ml vial contains 50 mg of ipilimumab. 
Pack of 1 Vial. 
8.4 
Storage and handling instructions 
Preparation for administration 
• Do not shake product. 
• Visually inspect for particulate matter and discoloration prior to administration. Discard vial if 
solution is cloudy, there is pronounced discoloration (solution may have pale-yellow color), or 
there is foreign particulate matter other than translucent-to-white, amorphous particles. 
 
Preparation of Solution 
• Allow the vial(s) to stand at room temperature for approximately 5 minutes prior to preparation 
of infusion. 
• Withdraw the required volume of ipilimumab and transfer into an intravenous bag. 
• Dilute with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final 
concentration ranging from 1 mg/mL to 2 mg/mL. Mix diluted solution by gentle inversion. 
• After preparation, store the diluted solution either refrigerated at 2°C to 8°C (36°F to 46°F) or 
at room temperature of 20°C to 25°C (68°F to 77°F) for no more than 24 hours from the time 
of preparation to the time of infusion. 
• Discard partially used or empty vials of ipilimumab. 
 
Administration 
• Do not co-administer other drugs through the same intravenous line. 
• Flush the intravenous line with 0.9% Sodium Chloride Injection, USP or 5% Dextrose 
• Injection, USP after each dose. 
• Administer diluted solution through an intravenous line containing a sterile, non-pyrogenic, 
• low-protein-binding in-line filter. 
• When administered in combination with nivolumab, infuse nivolumab first followed by 
ipilimumab on the same day. When administered with nivolumab and platinum-doublet 
chemotherapy, infuse nivolumab first followed by ipilimumab and then platinum-doublet 
chemotherapy on the same day. Use separate infusion bags and filters for each infusion. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
257 
Approved v 41.0 
930144776 4.0 
 
 
9 
PATIENT COUSELLING INFORMATION 
Immune-Mediated Adverse Reactions 
Advise patients that ipilimumab can cause immune-mediated adverse reactions including the 
following [see 4.4 Special warnings and precautions for use]: 
• Immune-Mediated Diarrhea or Colitis: Advise patients to contact their healthcare provider 
immediately for signs or symptoms of diarrhea or colitis. 
• Immune-Mediated Hepatitis: Advise patients to contact their healthcare provider immediately 
for signs or symptoms of hepatitis. 
• Immune-Mediated Dermatologic Adverse Reactions: Advise patients to contact their 
healthcare provider immediately if they develop a new rash. 
• Immune-Mediated Endocrinopathies: Advise patients to contact their healthcare provider 
immediately for signs or symptoms of hypophysitis, adrenal insufficiency, hypothyroidism, 
hyperthyroidism, and diabetes mellitus 
• Immune-Mediated Pneumonitis: Advise patients to contact their healthcare provider 
immediately for any new or worsening symptoms of pneumonitis. 
• Immune-Mediated Nephritis with Renal Dysfunction: Advise patients to contact their 
healthcare provider immediately for signs or symptoms of nephritis. 
 
Infusion-Related Reactions 
• Advise patients who are receiving ipilimumab of the potential risk of an infusion-related 
reaction [see 4.4 Special warnings and precautions for use]. 
 
Embryo-Fetal Toxicity 
• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive 
potential to inform their healthcare provider of a known or suspected pregnancy [see 4.4 
Special warnings and precautions for use and 4.6 Use in special populations (such as pregnant 
women, lactating women, pediatric patients, geriatric patients etc.)]. 
• Advise females of reproductive potential to use effective contraception during treatment with 
ipilimumab and for 3 months after the last dose [see 4.4 Special warnings and precautions for 
use]. 
 
Lactation 
• Advise women not to breastfeed during treatment with Ipilimumab and for 3 months after the 
last dose [see 4.6 Use in special populations (such as pregnant women, lactating women, 
pediatric patients, geriatric patients etc.)]. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
258 
Approved v 41.0 
930144776 4.0 
 
 
10 
DETAILS OF MANUFACTURER 
Bristol-Myers Squibb Holdings Pharma, Ltd. Liability Company, Road 686 Km 2.3, Bo. Tierras 
Nuevas, Manatí, Puerto Rico 00674, USA 
And 
Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics, 
Cruiserath Road, Mulhuddart, Dublin 15, D15, H6EF, Ireland 
Importer: 
Bristol-Myers Squibb India Private Limited, 
Bldg.B-4, Gala No. 3B & 4B, Citylink Warehousing Complex, Mumbai Nashik Highway, Vadape 
Village, Taluka: Bhiwandi – 16, District: Thane Z5, Pin- 421302 
 
Registered office address- 
Bristol-Myers Squibb India Private Limited, 6th floor, Tower 1, One International Center, S.B. 
Marg, Elphinstone (W), Mumbai - 400 013, Tel: + 91 22 6628 8600 
 
11 
DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE 
CT-20 Permission No. IMP/BIO/20/000008 dated 21-FEB 2020 
 
 
12 
DATE OF REVISION 
Date of Revision – 03 May 2023 
Document Version Number – 4.1 
Source – US PI dated Nov 2020 and Ipilimumab CCDS dated 11 Feb 2020 
Yervoi® is a registered trademark of Bristol-Myers Squibb. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
259 
Approved v 41.0 
930144776 4.0 
 
 
 
APPENDIX 6 
INTERNATIONAL METASTATIC RCC DATABASE 
CONSORTIUM (IMDC) PROGNOSTIC CRITERIA 
 
Adverse Prognostic Factors 
Clinical 
KPS < 80% 
Time from initial diagnosis (including original localized disease if applicable) to treatment < 1 year 
Laboratory 
Hemoglobin < LLN 
Corrected calcium > 10 mg/dL 
Absolute neutrophil count > ULN 
Platelet count > ULN 
Abbreviations: KPS = Karnofsky Performance Status; LLN = lower limit of normal; ULN = upper limit of normal 
Note: The corrected calcium criterion was adapted from to Heng et al, 2009 to account for local laboratories that may 
not provide an ULN for corrected calcium. 
 
 
Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 
4.0 represents the average albumin level in g/dL. 
Corrected calcium (mmol/L) = measured total Ca (mmol/L) + 0.02 (40 - serum albumin [g/L]), 
where 40 represents the average albumin level in g/L 
 
Risk Group Based on Number of Adverse Prognostic Factors 
Number of Adverse Prognostic Factors Present 
Risk Group 
0 
Favorable 
1-2 
Intermediate 
3-6 
Poor 
Reference: Heng D, Xie W, Regan M, et al. Prognostic factors for overall survival in patients with metastatic renal 
cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. 
J Clin Oncol 2009; 27(34):5794-5799. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
260 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 7 
PERFORMANCE STATUS SCALES 
 
STATUS 
SCALES 
STATUS 
KARNOFSKY 
ZUBROD-ECOG- 
WHO 
Normal, no complaints 
100 
0 
Normal activity 
Able to carry on normal activities Minor 
signs or symptoms of disease 
90 
0 
Symptoms, but fully 
ambulatory 
Normal activity with effort 
80 
1 
Cares for self. Unable to carry on normal 
activity or to do active work 
70 
1 
Symptomatic, but in 
bed < 50% of the day. 
Requires occasional assistance, but able to 
care for most of his needs 
60 
2 
Requires considerable assistance and 
frequent medical care 
50 
2 
Needs to be in bed 
> 50% of the day, but 
not bedridden 
Disabled. Requires special care and 
assistance 
40 
3 
Severely disabled. Hospitalization 
indicated though death non imminent 
30 
3 
Unable to get out of 
bed 
Very sick. Hospitalization necessary. 
Active supportive treatment necessary 
20 
4 
Moribund 
10 
4 
Dead 
0 
5 
Dead 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
261 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 8 
COUNTRY SPECIFIC REQUIREMENTS 
Any Countries Where Exclusion of HIV Positive Participants Is Locally Mandated 
 
Country-specific language 
Section 2 Flow Chart/Time and 
Events Schedule, Table 2-1: Screening 
Assessments- Laboratory Tests 
Add “HIV” to the list of laboratory tests 
Section 6.2 Exclusion 
Criteria, Exclusion criterion 1.a 
“Known history of testing positive for human immunodeficiency virus 
(HIV) or known acquired immunodeficiency syndrome (AIDS)”to be 
replaced with “Positive test for HIV”. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
262 
Approved v 41.0 
930144776 4.0 
 
 
APPENDIX 9 
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS 
1 
EVALUATION OF LESIONS 
Solid tumors will be evaluated using Response Evaluation Criteria In Solid Tumors version 1.1 
(RECIST 1.1) guideline with BMS modifications.1 
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows: 
1.1 
Measurable 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ≥2x slice thickness if 
greater than 5mm. 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be ≥ 15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm). 
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥ 10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed. 
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions. 
1.2 
Non-Measurable 
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 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. 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
263 
Approved v 41.0 
930144776 4.0 
 
 
1.3 
Special considerations regarding lesion measurability 
1.3.1 
Bone lesions 
• Bone scan, PET scan and plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 
• Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above. 
• Blastic bone lesions are non-measurable. 
 
1.4 
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions 
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline (this means in 
instances where patients have only one or two organ sites involved a maximum of two and four 
lesions respectively will be recorded). 
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum of 
two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’). 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
264 
Approved v 41.0 
930144776 4.0 
 
 
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, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions. 
2.1.1.2 
Target lesions that become ‘too small to measure’ 
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned 
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
265 
Approved v 41.0 
930144776 4.0 
 
 
default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm. 
2.1.1.3 
Lesions that split or coalesce on treatment 
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’. 
2.2 
Evaluation of Non-Target Lesions 
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need 
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol. 
• Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10 mm short axis). 
• Non-CR/Non-PD: Persistence of one or more non-target lesion(s) 
• Progressive Disease (PD): Unequivocal progression of existing non-target lesions. 
 
2.2.1 
Special Notes on Assessment of Progression of Non-Target Disease 
The concept of progression of non-target disease requires additional explanation as follows: 
2.2.1.1 
When the patient also has measurable disease 
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy A modest ‘increase’ in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. Pleural effusions, pericardial 
effusions and ascites will not be followed as target or non-target lesions and will not contribute to 
response or progression. The designation of overall progression solely on the basis of change in 
non-target disease in the face of SD or PR of target disease will therefore be extremely rare. 
2.2.1.2 
When the patient has only non-measurable disease 
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
266 
Approved v 41.0 
930144776 4.0 
 
 
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 this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD). 
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. While FDG-PET 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according 
to the following algorithm: 
1. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion. 
2. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
267 
Approved v 41.0 
930144776 4.0 
 
 
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 
confirmation and 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 2.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) disease 
only, Table 2.3.2-2 is to be used. 
 
Table 2.3.2-1: 
Time Point Response: Patients With Target (± Non-Target) Disease 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable 
 
 
Table 2.3.2-2: 
Time Point Response: Patients with Non-target Disease Only 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
268 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 2.3.2-2: 
Time Point Response: Patients with Non-target Disease Only 
Non-Target Lesions 
New Lesions 
Overall Response 
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 can be 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 CR and PR Required) 
Overall Response 
First Time Point 
Overall Response 
Subsequent Time Point 
Best Overall 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 

Clinical Protocol 
BMS-936558 
CA2097C9 
nivolumab 
Protocol Amendment No.: 02 
Date: 10-Nov-2023 
269 
Approved v 41.0 
930144776 4.0 
 
 
 
Table 2.3.3-1: 
Best Overall Response (Confirmation of CR and PR Required) 
Overall Response 
First Time Point 
Overall Response 
Subsequent Time Point 
Best Overall 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 duration met, 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 subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a 
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation. 
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease. 
REFERENCES 
 
 
 
1 Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47.