A Phase 3, Randomized, Double-blind Trial of Nivolumab in Combination With Intravesical BCG Versus Standard of Care BCG Alone in Participants With High-risk Non-muscle Invasive Bladder Cancer That Is Persistent or Recurrent After Treatment With BCG
Phase: PHASE3
Conditions: Urinary Bladder Neoplasms
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 3, Randomized, Double-blind Trial of Nivolumab in Combination with Intravesical 
BCG Versus Standard of Care BCG Alone in Participants with High-risk Non-muscle Invasive 
Bladder Cancer That is Persistent or Recurrent After Treatment with BCG 
 
NCT Number: NCT04149574 
Document Date (Date in which document was last revised): 11 October 2021 

Approved v 21.0 
930143391 2.0 
 
 
Page: 1 
Protocol Number: CA2097G8 
IND Number: 123867 
EUDRACT Number: 2019-002567-96 
Date: 16-Aug-2019 
Revised Date: 11-Oct-2021 
 
CLINICAL PROTOCOL CA2097G8 
A Phase 3, Randomized, Double-blind Trial of Nivolumab in Combination with Intravesical 
BCG versus Standard of Care BCG Alone in Participants with High-risk Non-muscle Invasive 
Bladder Cancer That Is Persistent or Recurrent After Treatment with BCG 
 
(CheckMate 7G8: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 7G8) 
 
 
Short Title: A Study Comparing Nivolumab and Intravesical BCG to BCG Alone in High-risk 
Non-muscle Invasive Bladder Cancer 
Protocol Amendment No.: 01 
Incorporates Administrative Letters 01 and 02 
Clinical Trial Physician/Medical Monitor 
Clinical Scientist 
 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
Telephone (office): 
Telephone (mobile): 
Fax: 
 Fax: 
 
24-hr Emergency Telephone Number 
USA: 
International: 
 
Bristol-Myers Squibb Research and Development 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
B-1420 Braine-l’Alleud, Belgium 
 
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 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
2 
Approved v 21.0 
930143391 2.0 
 
 
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 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
3 
Approved v 21.0 
930143391 2.0 
 
 
DOCUMENT HISTORY 
 
Document 
Date of Issue 
Summary of Change 
Protocol 
Amendment 01 
11-Oct-2021 
Key updates to the protocol include: 
• 
Details of closure of the study, with provision for participants 
currently on treatment to continue. 
• 
Clarification 
that 
all 
pharmacokinetic, 
biomarker, 
patient-reported 
outcomes, 
and 
healthcare 
resource 
utilization assessments are no longer applicable per Protocol 
Amendment 01. 
• 
Clarification that study-related efficacy assessment and 
Pathology Review Committee are no longer applicable per 
Protocol Amendment 01. Sites should continue efficacy 
assessment as per local standards of care. 
Additionally, dose modification criteria and immuno-oncology 
agent management algorithms were updated per the current 
National Cancer Institute Common Terminology Criteria for 
Adverse Events version (v5). 
Administrative 
Letter 02 
18-Feb-2021 
The purpose of this letter is notification of study personnel 
change. 
Administrative 
Letter 01 
27-Nov-2019 
The purpose of this letter is to correct typographical errors and 
to update the information in the study protocol Appendix 7. In 
Spain, Italy, Peru, and France HIV laboratory testing is not a 
country-specific requirement 
Original Protocol 
16-Aug-2019 
Not applicable 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
4 
Approved v 21.0 
930143391 2.0 
 
 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 01: 
As of May 2021, the CA2097G8 study enrollment was significantly behind the projected target 
enrollment, at 5% since first patient first visit; therefore, the study will be unable to meet its 
scientific objectives. As such, the primary reason for this protocol amendment is to implement the 
decision to close participant enrollment to the study as of 02-Jun-2021. 
Key updates to the protocol include: 
• Details of closure of the study, with provision for participants currently on treatment to 
continue. 
• Clarification that all pharmacokinetic (PK), biomarker, patient-reported outcomes, and health 
care resource utilization assessments are no longer applicable per Protocol Amendment 01. 
• Clarification that study-related efficacy assessment and Pathology Review Committee are no 
longer applicable per Protocol Amendment 01. Sites should continue efficacy assessment as 
per local standards of care. 
 
Additionally, dose modification criteria and immuno-oncology (I-O) agent management 
algorithms were updated per the current National Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI CTCAE) version (v5). 
Relevant components of Administrative Letters 01 and 02 are also incorporated. Additional 
updates, including to sections of the Synopsis, have been made to align the protocol with respect 
to these changes. This protocol amendment applies to all participants and should override any 
existing protocol requirements in the event of any apparent contraindications. 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Title Page 
Updated Clinical Trial Physician and included 
Clinical Scientist. 
Provided current study contact 
information. 
Synopsis 
Modified to align with changes in body of 
protocol. 
Aligned with protocol body. 
Section 2: Schedule of 
Activities 
Added “Not applicable per Protocol Amendment 
01” to the title of Table 2-1. 
Aligned with study closure as of 
Protocol Amendment 01. 
Table 2-1: Screening 
Procedural Outline 
(CA2097G8) 
Table 2-2: On-treatment 
Procedural Outline for 
Arms A and B 
(CA2097G8) 
Updated Table 2-2 to include “per local 
standards of care” for the q52 week body 
imaging assessment. 
Updated Table 2-1, Table 2-2, and Table 2-3 to 
indicate that tumor sample submission, 
biomarker sampling, efficacy assessments, 
health outcomes, PK and immunogenicity, and 
survival and efficacy follow-ups are no longer 
applicable per Protocol Amendment 01. 
Clarify that the imaging 
assessment schedule included in 
the protocol is per local standards 
of care. 
Aligned with study closure as of 
Protocol Amendment 01. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
5 
Approved v 21.0 
930143391 2.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Table 2-3: Follow-up 
Procedural Outline 
(CA2097G8) 
Added text under “notes” for “Adverse Event 
(AE) Assessment (Including SAE)” in Tables 2- 
2 and 2-3 for the continuous collection of 
information and follow-up requirements for AEs 
associated with severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) 
infection. 
Included timing for the collection 
of AEs associated with SARS- 
CoV-2 infection and follow-up 
requirements. 
Section 3.1.1: Changes 
per Protocol Amendment 
01 
New sub-section added to describe the reason 
for study closure, procedures put into effect, and 
key changes to the protocol. 
Provided rationale for study 
closure. 
Section 3.1.2: Study 
Hypothesis 
Indicated that study hypothesis is no longer 
applicable per Protocol Amendment 01. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 4: Objectives 
and Endpoints 
Added language to clarify that only safety 
assessments will be conducted as of Protocol 
Amendment 01. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 5: Study Design 
Added language describing closure of the study 
as of 02-Jun-2021 and resulting removal of the 
initial benefit/risk assessment by the Data 
Monitoring Committee. 
Aligned with study closure as of 
Protocol Amendment 01. 
Figure 5.1-1: CA2097G8 
Study Design Schematic 
Updated the figure to indicate that efficacy 
assessments will be conducted per local standards 
of care, and participants will be for safety 
assessments through 100 days following last dose 
of study treatment. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 5.1.1: Screening 
Phase 
The following modifications were made: 
• 
Added language describing closure of the 
study as of 02-Jun-2021 and clarified that 
the screening phase is no longer applicable 
per Protocol Amendment 01. 
• 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 5.1.2: Treatment 
Phase 
Deleted text that described: 
• 
Timing of on-study cytoscopy and urine 
cytology, and bladder biopsies in 
participants with carcinoma in situ 
• 
Clinical decision-making would be based on 
investigator assessment of 
recurrence/progression. 
• 
End of treatment period 
Added the following text: 
“For all participants, follow local standards of 
care for efficacy assessments” 
Removed treatment procedures 
that were not applicable per 
Protocol Amendment 01 and 
clarified that local standards of 
care should be followed for 
efficacy assessments instead. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
6 
Approved v 21.0 
930143391 2.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Section 5.1.3: Follow-up 
Phase 
Indicated that survival and efficacy follow-ups 
after Visit 2 are no longer applicable per 
Protocol Amendment 01. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 5.1.4: Data 
Monitoring Committee 
and Other External 
Committees 
Indicated that the Data Monitoring Committee 
and Pathology Review Committee are not 
applicable per Protocol Amendment 01. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 5.2: Number of 
Participants 
Indicated what was planned prior to study 
closure and what is no longer applicable as of 
Protocol Amendment 01. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 5.3: End of 
Study Definition 
Clarified that with study closure, study 
completion will occur when all participants 
complete study procedures described in 
Section 2. 
Clarified expectations for study 
completion with study closure per 
Protocol Amendment 01. 
Section 5.4.2: Rationale 
for Event-free Survival 
as Primary Endpoint 
Indicated that rationale is not applicable per 
Protocol Amendment 01. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 6: Study 
Population 
Added sentence to clarify that enrollment into 
the study was closed and that male participants 
continuing treatment should follow the updated 
contraceptive guidance in the eligibility criteria 
and in Appendix 4. 
Clarified expectations for male 
contraceptive guidance with study 
closure per Protocol 
Amendment 01. 
Section 7.1.1: 
Nivolumab Dosing 
Updated first paragraph to include that flushing 
the intravenous line with diluent is permitted to 
ensure that the complete dose of nivolumab is 
administered over approximately 30 minutes. 
Clarified expectations for 
nivolumab administration. 
Section 7.3: Blinding 
Added language at the beginning of the section 
to clarify that blinding is not required to meet 
study objectives per Protocol Amendment 01, 
and for the requirement of following Interactive 
Response Technology instruction and alerting 
the Medical Monitor if the blind is broken. 
Provided guidance on how to 
proceed if the blind was broken 
by investigators due to it being in 
the best interest of the participant 
per Protocol Amendment 01 or in 
the case of accidental unblinding. 
Section 7.4: Dosage 
Modification 
Added Table 7.4-1 for AE criteria for delay, 
resume, and discontinuation of study treatment. 
Reorganized dose delay, resume, 
and discontinuation criteria for 
improved readability and to align 
with the current NCI CTCAE v5. 
Section 7.4.3: Dose 
Delay Criteria 
Added language for SARS-CoV-2 infection. 
Updated dose delay criteria to 
include expectations in cases of 
confirmed or suspected 
SARS-CoV-2 infection. 
Section 7.4.3.1: 
Nivolumab/ 
Nivolumab-placebo 
Dose Delay Criteria 
Modified text to align criteria for dose delay, 
resume, and discontinuation with Table 7.4-1. 
Updated dose delay, resume, and 
discontinuation criteria to align 
with the current NCI CTCAE v5. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
7 
Approved v 21.0 
930143391 2.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Section 7.4.4.1: 
Nivolumab/Nivolumab- 
placebo Criteria to 
Resume Treatment 
Section 8.1.1: 
Nivolumab/ 
Nivolumab-placebo 
Dose Discontinuation 
Section 7.4.4.1: 
Nivolumab/ 
Nivolumab-placebo 
Criteria to Resume 
Treatment 
Section 7.4.4.2: BCG 
Criteria to Resume 
Treatment 
Added language for SARS-CoV-2 infection. 
Updated criteria to resume 
treatment to include expectations 
in cases of confirmed or 
suspected SARS-CoV-2 infection. 
Section 7.7: 
Concomitant Therapy 
Added language for coronavirus disease 
2019 (COVID-19) vaccines. 
Provided expectations for 
concomitant use of COVID-19 
vaccines. 
Section 7.7.1: Prohibited 
and/or Restricted 
Treatments 
Removed language describing use of marijuana 
and its derivatives. 
Use of marijuana and its 
derivatives is permitted with BMS 
Medical Monitor (or designee) 
approval. 
Section 8.1: 
Discontinuation From 
Study Treatment 
Updated bullet for disease progression and 
recurrence to “locally diagnosed.” 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 8.1.3: Post Study 
Treatment Study 
Follow-up 
Added text to clarify that efficacy follow-up is 
no longer required as of Protocol 
Amendment 01 and that participants will be 
followed for safety only. 
Aligned with study closure as of 
Protocol Amendment 01. 
Section 9: Study 
Assessments and 
Procedures 
Updated second paragraph following bullets to 
include participant evaluation for cardiac 
toxicity. 
Clarified expectations for 
participant evaluation for cardiac 
toxicities. 
Section 9.1: Efficacy 
Assessments (and all 
related sub-sections) 
Added text to clarify that efficacy assessments 
will be conducted per local standards of care per 
Protocol Amendment 01 and that previously 
planned efficacy assessments are no longer 
applicable per Protocol Amendment 01. 
Clarified expectations for efficacy 
assessments with study closure 
per Protocol Amendment 01. 
Section 9.2.1: Time 
Period and Frequency 
Added text related to SARS-CoV-2 infection. 
Included timing for the collection 
of AEs associated SARS-CoV-2 
infection. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
8 
Approved v 21.0 
930143391 2.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
for Collecting AE and 
SAE Information 
Section 9.2.3: Follow-up 
of AEs and SAEs 
Added text related to SARS-CoV-2 infection. 
Included follow-up requirements 
for AEs associated SARS-CoV-2 
infection. 
Section 9.5: 
Pharmacokinetics 
Section 9.6: 
Pharmacodynamics 
Section 9.8: Biomarkers 
Section 9.8.2: 
Immunogenicity 
Assessments 
Section 9.8.3: Other 
Assessments (and all 
related sub-sections) 
Section 9.9: Health Care 
Resource Utilization and 
Health Economics 
Updated to clarify that previously planned PK, 
pharmacodynamics, immunogenicity, and 
biomarkers assessments as well as health care 
resource utilization and health economics 
parameters will not be evaluated, since these are 
no longer applicable as of Protocol 
Amendment 01. 
Clarified expectations for 
previously planned 
assessments/evaluations with 
study closure per Protocol 
Amendment 01. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
9 
Approved v 21.0 
930143391 2.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Section 10: Statistical 
Considerations 
Section 10.1: Sample 
Size Determination 
Section 10.2: 
Populations for Analyses 
Section 10.3.1: Efficacy 
Analyses 
Section 10.3.2: Safety 
Analyses 
Section 10.3.3: Other 
Analyses (and all related 
sub-sections) 
Section 10.3.4: Interim 
Analyses 
Added language to clarify that, per Protocol 
Amendment 01: 
• 
Descriptive analyses of 
investigator-assessed efficacy data will be 
conducted. 
• 
Sample size will be limited to the 
participants enrolled as of 02-Jun-2021. 
• 
Populations for analysis will be limited to 
enrolled, randomized, and treated 
populations. 
• 
Efficacy, outcomes research, PK, 
pharmacodynamics, immunogenicity, 
biomarker, and interim analyses are no 
longer applicable. 
• 
Only limited safety analyses will be 
conducted. 
Clarified expectations for 
statistical considerations with 
study closure per Protocol 
Amendment 01. 
Appendix 2: Study 
Governance 
Considerations 
The following modifications were made: 
• 
Updated first paragraph for Monitoring 
section to further describe that details on 
monitoring can be found in the monitoring 
plan. 
• 
Added section for Dissemination of Clinical 
Study Data. 
These changes were made to: 
• 
Clarify expectations for 
monitoring. 
• 
Provide details on how 
clinical study information 
will be made available. 
Appendix 4: Women of 
Childbearing Potential 
Definitions and Methods 
of Contraception 
“Contraception Guidance for Male Participants 
with Partner(s) of Childbearing Potential” was 
updated to the following: 
“Given that nivolumab is not a genotoxic agent, 
and that relevant systemic concentrations 
sufficient to produce a risk of fetal toxicity are 
not expected in WOCBP partners from exposure 
to a male participant’s seminal fluid, male study 
participants will not be required to use 
contraceptive measures and/or a latex or other 
synthetic condom during sexual activity with a 
WOCBP partner.” 
The use of contraception for male 
participants treated with 
nivolumab is no longer needed. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
10 
Approved v 21.0 
930143391 2.0 
 
 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Appendix 5: 
Management Algorithms 
Replaced I-O agent management algorithms 
with those aligned with NCI CTCAE v5. 
Updated management algorithms 
for immune-mediated AEs to 
align with current NCI CTCAE 
v5 and nivolumab Investigator’s 
Brochure. 
Appendix 7: Country 
Specific Requirements 
Updated list of countries to which exclusion 
criteria related to human immunodeficiency 
virus (HIV) apply. 
Clarified country-specific 
differences for HIV-positive 
participants. 
All 
Minor formatting and typographical corrections. 
These changes are minor and 
therefore have not been 
summarized. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
11 
Approved v 21.0 
930143391 2.0 
 
 
TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
1 
DOCUMENT HISTORY.............................................................................................. 
3 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 01: ............................ 
4 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01................ 
4 
TABLE OF CONTENTS.............................................................................................. 
11 
1 SYNOPSIS................................................................................................................. 
15 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
24 
3 INTRODUCTION ..................................................................................................... 
33 
3.1 Study Rationale ................................................................................................. 
33 
3.1.1 Changes per Protocol Amendment 01 ..................................................... 
33 
3.1.2 Study Hypothesis ...................................................................................... 
34 
3.2 Background ....................................................................................................... 
34 
3.2.1 Indication Background............................................................................. 
34 
3.2.2 Nivolumab Mechanism of Action ............................................................. 
36 
3.2.3 BCG Mechanism of Action....................................................................... 
37 
3.3 Benefit/Risk Assessment .................................................................................. 
37 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
39 
5 STUDY DESIGN....................................................................................................... 
40 
5.1 Overall Design .................................................................................................. 
40 
5.1.1 Screening Phase....................................................................................... 
42 
5.1.2 Treatment Phase ...................................................................................... 
43 
5.1.3 Follow-up Phase ...................................................................................... 
43 
5.1.4 Data Monitoring Committee and Other External Committees ................ 
44 
5.2 Number of Participants ..................................................................................... 
45 
5.3 End of Study Definition .................................................................................... 
46 
5.4 Scientific Rationale for Study Design............................................................... 
46 
5.4.1 Rationale for the Combination of Nivolumab with BCG in NMIBC ....... 
46 
5.4.2 Rationale for Event-free Survival as Primary Endpoint.......................... 
47 
5.4.3 Rationale for Stratification Factors......................................................... 
47 
5.4.4 Rationale for 2-year Duration of Treatment............................................ 
48 
5.4.5 Rationale for Duration of BCG Treatment .............................................. 
48 
5.4.6 Rationale for Double-blind Study Design................................................ 
49 
5.5 Justification for Dose ........................................................................................ 
49 
5.5.1 Justification for Nivolumab Dose ............................................................ 
49 
5.5.2 Justification for BCG Dose ...................................................................... 
50 
6 STUDY POPULATION ............................................................................................ 
50 
6.1 Inclusion Criteria .............................................................................................. 
50 
6.2 Exclusion Criteria ............................................................................................. 
52 
6.2.1 BCG Unresponsive Definition and Patient Eligibility............................. 
54 
6.3 Lifestyle Restrictions ........................................................................................ 
54 
6.4 Screen Failures.................................................................................................. 
55 
6.4.1 Retesting During Screening or Lead-In Period ....................................... 
55 
7 TREATMENT ........................................................................................................... 
55 
7.1 Treatments Administered.................................................................................. 
57 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
12 
Approved v 21.0 
930143391 2.0 
 
 
7.1.1 Nivolumab Dosing ................................................................................... 
57 
7.1.2 BCG Dosing ............................................................................................. 
58 
7.2 Method of Treatment Assignment .................................................................... 
59 
7.3 Blinding............................................................................................................. 
60 
7.4 Dosage Modification......................................................................................... 
61 
7.4.1 Nivolumab/Nivolumab-placebo Dose Modifications ............................... 
68 
7.4.2 BCG Dose Modifications ......................................................................... 
68 
7.4.3 Dose Delay Criteria ................................................................................. 
68 
7.4.3.1 Nivolumab/Nivolumab-placebo Dose Delay Criteria..................... 
68 
7.4.3.2 BCG Dose Delay Criteria ............................................................... 
68 
7.4.4 Criteria to Resume Treatment.................................................................. 
68 
7.4.4.1 Nivolumab/Nivolumab-placebo Criteria to Resume Treatment ..... 
68 
7.4.4.2 BCG Criteria to Resume Treatment................................................ 
69 
7.4.5 Management Algorithms for Immuno-oncology Agents .......................... 
69 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
70 
7.5.1 Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
70 
7.6 Treatment Compliance...................................................................................... 
70 
7.7 Concomitant Therapy........................................................................................ 
70 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
71 
7.7.2 Other Restrictions and Precautions......................................................... 
71 
7.7.2.1 Imaging Restriction and Precautions ............................................. 
71 
7.7.3 Permitted Therapy ................................................................................... 
72 
7.7.4 Treatment of Infusion-related Reactions ................................................. 
72 
7.8 Treatment After the End of the Study............................................................... 
73 
8 DISCONTINUATION CRITERIA ........................................................................... 
73 
8.1 Discontinuation From Study Treatment............................................................ 
73 
8.1.1 Nivolumab/Nivolumab-placebo Dose Discontinuation ........................... 
74 
8.1.2 Discontinuation of BCG........................................................................... 
75 
8.1.3 Post Study Treatment Study Follow-up.................................................... 
75 
8.1.4 CIS and/or TaHG at Week 13: Continued Treatment.............................. 
75 
8.2 Discontinuation from the Study ........................................................................ 
76 
8.3 Lost to Follow-up.............................................................................................. 
76 
9 STUDY ASSESSMENTS AND PROCEDURES..................................................... 
77 
9.1 Efficacy Assessments........................................................................................ 
78 
9.1.1 Event-free Survival Evaluation ................................................................ 
78 
9.1.2 Complete Response Assessment in CIS Participants ............................... 
78 
9.1.2.1 Complete Response at First On-study Assessment (Week 13) ........ 
78 
9.1.2.2 Persistent CIS at First On-study Assessment (Week 13) ................ 
79 
9.1.2.3 Complete Response After First On-study Assessment in Participants 
with Persistent CIS at First Assessment................................................ 
79 
9.1.2.4 Disease Recurrence/Progression.................................................... 
79 
9.1.3 Cystoscopy ............................................................................................... 
82 
9.1.4 Urine Cytology......................................................................................... 
82 
9.1.4.1 Positive Cytology with Normal Cystoscopy .................................... 
83 
9.1.4.2 Suspicious Cytology with Normal Cystoscopy................................ 
84 
9.1.4.3 Suspicious Cytology, Abnormal Cystoscopy................................... 
84 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
13 
Approved v 21.0 
930143391 2.0 
 
 
9.1.5 Bladder Biopsy......................................................................................... 
9.1.6 Patient-reported Outcomes ...................................................................... 
9.1.6.1 EORTC QLQ-C30 ........................................................................... 
9.1.6.2 EORTC QLQ-NMIBC24 ................................................................. 
9.1.6.3 EQ-5D-5L ....................................................................................... 
9.1.7 Imaging Assessment for the Study............................................................ 
9.1.8 Clinical and Pathology Review Committee Review of Efficacy 
Assessments................................................................................................. 
9.2 Adverse Events ................................................................................................. 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
9.2.2 Method of Detecting AEs and SAEs......................................................... 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
9.2.4 Regulatory Reporting Requirements for SAEs......................................... 
9.2.5 Pregnancy ................................................................................................ 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
9.2.7 Potential Drug-induced Liver Injury ....................................................... 
9.2.8 Other Safety Considerations .................................................................... 
9.3 Overdose ........................................................................................................... 
9.4 Safety ................................................................................................................ 
9.4.1 Physical Examinations............................................................................. 
9.4.2 Vital Signs ................................................................................................ 
9.4.3 Electrocardiograms ................................................................................. 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
9.4.5 Imaging Safety Assessment ...................................................................... 
9.5 Pharmacokinetics .............................................................................................. 
9.6 Pharmacodynamics ........................................................................................... 
9.7 Pharmacogenomics ........................................................................................... 
9.8 Biomarkers ........................................................................................................ 
 
9.8.2 Immunogenicity Assessments ................................................................... 
9.8.3 Other Assessments ................................................................................... 
9.8.3.1 Tumor Tissue Specimens................................................................. 
9.8.3.2 Peripheral Blood Markers .............................................................. 
9.8.3.3 Urine Markers................................................................................. 
9.8.3.4 Microbiome Analysis ...................................................................... 
9.9 Health Care Resource Utilization and Health Economics ................................ 
10 STATISTICAL CONSIDERATIONS .................................................................... 
10.1 Sample Size Determination............................................................................. 
10.2 Populations for Analyses ................................................................................ 
10.3 Statistical Analyses ......................................................................................... 
10.3.1 Efficacy Analyses ................................................................................... 
10.3.2 Safety Analyses....................................................................................... 
10.3.3 Other Analyses ....................................................................................... 
10.3.3.1 Pharmacokinetic Analyses ............................................................ 
10.3.3.2 Immunogenicity Analyses.............................................................. 
10.3.3.3 Outcomes Research Analyses ....................................................... 
85 
86 
86 
87 
87 
87 
88 
89 
89 
90 
90 
91 
91 
92 
92 
92 
92 
93 
93 
93 
93 
93 
94 
94 
95 
95 
95 
97 
98 
98 
98 
99 
101 
102 
102 
102 
102 
105 
106 
106 
108 
108 
109 
109 
109 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
14 
Approved v 21.0 
930143391 2.0 
 
 
10.3.4 Interim Analyses .................................................................................... 
11 REFERENCES ........................................................................................................ 
12 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW UP AND REPORTING......................................................................... 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION..................................................................... 
APPENDIX 5 MANAGEMENT ALGORITHMS....................................................... 
APPENDIX 6 ECOG PERFORMANCE STATUS SCALE ....................................... 
APPENDIX 7 COUNTRY SPECIFIC REQUIREMENTS ......................................... 
109 
110 
115 
116 
121 
 
 
129 
133 
136 
145 
146 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
15 
Approved v 21.0 
930143391 2.0 
 
 
 
1 
SYNOPSIS 
Protocol Title: A Phase 3, Randomized, Double-blind Trial of Nivolumab in Combination 
with Intravesical BCG versus Standard of Care BCG Alone in Participants with High-risk 
Non-muscle Invasive Bladder Cancer That Is Persistent or Recurrent After Treatment with 
BCG 
Short Title: A Study Comparing Nivolumab and Intravesical BCG to BCG Alone in High- 
risk Non-muscle Invasive Bladder Cancer 
Study Phase: 3 
Rationale: 
High-risk non-muscle invasive bladder cancer (NMIBC) is treated with transurethral resection of 
bladder tumor (TURBT) followed intravesical bacillus Calumette-Guerin (BCG). Patients may 
have persistent or recurrent disease after this treatment. In patients that have persistent or recurrent 
disease that is not classified as BCG unresponsive,1 standard of care is repeat TURBT and 
intravesical induction and maintenance BCG. Available evidence suggests the rate of recurrence 
for these patients is approximately 40% at 24 months, which is significantly worse than the rate of 
recurrence in BCG-naïve patients treated with BCG.2 
Intravesical BCG results in tumor inflammation and nivolumab enhances T-cell activity within the 
tumor; combining BCG with nivolumab therefore offers the potential for improved response of 
the tumor to immunotherapy. This study aims to demonstrate that treatment with nivolumab in 
combination with intravesical BCG will improve event-free survival (EFS) vs intravesical BCG 
alone. Additional clinical endpoints include worsening-free survival (WFS), complete response 
rate (CRR) in patients with carcinoma in situ (CIS), and overall survival (OS). Additional 
objectives of the study include characterization of safety and tolerability, pharmacokinetics, 
potential predictive biomarkers, and changes in patient-reported outcomes for quality of life 
assessment. 
Changes per Protocol Amendment 01 
As of May 2021, the CA2097G8 study was behind its enrollment target. Bristol-Myers Squibb 
undertook several mitigation actions to improve participant recruitment. Unfortunately, despite all 
efforts, the study was less than 5% of target enrollment since first patient first visit. Based on 
current timelines, the study would be unable to meet its scientific objectives within a projected 
timeline. As a result, a decision was made to close the study. It is important to note that there is no 
change to the understanding of the safety profile of nivolumab in combination with BCG for the 
participants with bladder cancer. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
16 
Approved v 21.0 
930143391 2.0 
 
 
As of 02-Jun-2021 (Dear Investigator Letter; Approved v1.0 930170267), the following measures 
were put into effect: 
• Enrollment for new participants was closed effective immediately. 
• Participants who signed study consent prior to this notification and were undergoing screening 
were permitted to be randomized to study treatment. 
• Participants currently on treatment were allowed to continue study treatment. 
• For participants currently on efficacy follow-up, it is at the discretion of the investigator and 
participant whether to continue the efficacy follow-up, until Protocol Amendment 01 is 
approved by the relevant Health Authorities and Ethics Committees/Institutional Review 
Boards at the site. 
 
Protocol Amendment 01 describes the modification to study procedures. All participants must be 
re-consented upon approval and implementation of Protocol Amendment 01. These changes affect 
all participants and should be implemented when this Protocol Amendment 01 is implemented at 
the site. 
Key changes in Protocol Amendment 01 include: 
• Details of closure of the study, with provision for participants currently on treatment to 
continue. 
• Clarification that all pharmacokinetic, biomarker, patient-reported outcomes, and health care 
resource utilization assessments are no longer applicable per Protocol Amendment 01. 
• Clarification that study-related efficacy assessment and Pathology Review Committee are no 
longer applicable per Protocol Amendment 01. Sites should continue efficacy assessment as 
per local standards of care. 
 
The changes instituted in Protocol Amendment 01 should override any existing protocol 
requirements in the event of any apparent contraindications. 
Study Hypothesis: 
Not applicable per Protocol Amendment 01: 
Treatment of high-risk persistent or recurrent NMIBC that is not classified as BCG unresponsive 
with systemically administered nivolumab in combination with intravesical BCG will result in 
improvement in EFS when compared with intravesical BCG alone. 
Study Population: 
This study will enroll eligible adult participants (male and female, ages 18 years or age of majority, 
and older) with high-risk NMIBC that is persistent or recurrent after treatment with BCG and does 
not qualify as BCG unresponsive. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
17 
Approved v 21.0 
930143391 2.0 
 
 
Key Inclusion Criteria: 
• Histologically confirmed persistent or recurrent high-risk non-muscle-invasive urothelial 
carcinoma (UC) (high-grade [HG] Ta [TaHG] and/or T1 and/or CIS) 
• Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma 
• Persistent or recurrent disease ≤ 24 months of last BCG dose, but not classified as BCG 
unresponsive 
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 
• Participants with multiple prior diagnoses of NMIBC which may have been treated with BCG 
or other intravesical therapy, that preceded the qualifying episode and associated recurrence 
are permitted 
• Must have undergone each of the following procedures within 90 days of randomization. If 
these procedures are performed as part of the participant’s routine care, they do not need to be 
repeated provided that they were performed within the required time period: 
o Complete excision of all papillary disease (T1/TaHG) 
o Resection or fulguration of all detectable CIS, if feasible 
o The presence of any suspicious lesions must be recorded and these lesions will be 
biopsied. 
o Urine cytology must be obtained from a voided specimen (except from the first 
morning urination) or by bladder wash. 
o Computed Tomography (CT) scan of the chest and CT or MRI of the abdomen, 
pelvis, and all other areas of suspected disease < 90 days prior to randomization 
o Pelvic examination, preferably under anesthesia to exclude locally advanced disease 
 
Patients who have received less than adequate BCG as defined here (ie, only 1 course of induction 
BCG ± 1 additional BCG dose) cannot be considered BCG unresponsive (except patients with 
disease within 6 months of induction BCG therapy). T1 patients are eligible for the study if they 
have recurrence 6-24 months after the last BCG dose. 
Key Exclusion Criteria: 
• UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 
24 months of enrollment 
• UC and/or CIS in the prostatic urethra within 12 months of enrollment 
• Previous or concurrent muscle invasive, locally advanced, or disseminated/metastatic UC 
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cytotoxic T-lymphocyte- 
associated protein 4 antibody, or any other antibody or drug specifically targeting T-cell 
costimulation or checkpoint pathways 
• Recurrent high-risk NMIBC that is classified as BCG unresponsive: 
o Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary 
disease/tumor invades the subepithelial connective tissue) disease within 12 months of 
completion of adequate BCG therapy** 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
18 
Approved v 21.0 
930143391 2.0 
 
 
o Recurrent TaHG/any T1 disease within 6 months of completion of adequate BCG 
therapy** 
o T1HG disease < 6 months following an induction BCG course (at least 5 of 6 induction 
doses) 
o ** Adequate BCG treatment is defined as at least 2 courses of BCG. This can 
include 2 induction courses (at least 5 of 6 doses of an initial induction course plus 
at least 2 of 6 doses of a second induction course) or 1 induction course (at least 5 
of 6 induction doses) and at least 2 of 3 doses of a maintenance cycle (“5+2”). 
• Prior systemic chemotherapy or immunotherapy for UC. Intravesical chemotherapy and/or 
interferon administered prior to the current recurrence or as a single dose at the time of TURBT 
is permitted. 
• Prior radiation therapy for bladder cancer 
• Prior surgery for bladder cancer other than TURBT and/or bladder biopsies 
 
Objectives and Endpoints: 
Objectives and endpoints are no longer applicable per Protocol Amendment 01. 
As of Protocol Amendment 01, only descriptive safety and investigator-assessed efficacy analyses 
will be conducted. No other analyses of efficacy, quality of life/patient-reported outcomes, 
pharmacokinetics, or health care resource utilization are planned. Previously collected biomarker 
samples may be analyzed, but no further collections are planned with Protocol Amendment 01. 
 
Objectives 
Endpoints 
Primary 
• 
To compare the EFS per PRC of nivolumab plus 
BCG vs BCG alone in all randomized 
participants 
• 
EFS, defined as the time from randomization until any 
of the following events: recurrence (TaHG, T1 or CIS) 
or progression of disease, or death from any cause. For 
participants with CIS (+/- papillary disease) at study 
entry, a lack of complete response of the CIS 
component at the 13-week assessment will be 
considered an event. 
Secondary 
• 
To compare the WFS of nivolumab plus BCG vs 
BCG alone in all randomized participants 
• 
WFS, defined as the time from randomization to 
progression to muscle invasive disease, cystectomy, 
systemic chemotherapy, radiotherapy, or death from 
any cause. 
• 
To compare the OS of nivolumab plus BCG vs 
BCG alone in all randomized participants 
• 
OS, defined as the time from randomization to death 
from any cause. 
• 
To evaluate the CRR at first disease assessment 
(week 13) in all randomized participants with CIS 
(+/- papillary disease) at study entry by treatment 
arm (nivolumab plus BCG and BCG alone) 
• 
CRR, defined as the proportion of participants with 
CIS (+/- papillary disease) at study entry who are 
disease free at the first disease assessment. 
• 
To evaluate the duration of response (DoR) in all 
randomized participants with CIS (+/- papillary 
disease) at study entry who achieved CRR at first 
disease assessment by treatment arm (nivolumab 
plus BCG and BCG alone) 
• 
DoR is restricted to participants with CIS (+/- 
papillary disease) at study entry who are disease free 
at the first disease assessment and is defined as the 
time between the date of the first CR to the date of 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
19 
Approved v 21.0 
930143391 2.0 
 
 
 
Objectives 
Endpoints 
first documented recurrence, progression, or death 
due to any cause. 
• 
To describe the safety and tolerability of 
nivolumab plus BCG and BCG alone in all 
treated participants 
• 
Overall safety and tolerability will be measured by the 
incidence 
of 
AEs, 
SAEs, 
AEs 
leading 
to 
discontinuation, IMAEs, deaths, and laboratory 
abnormalities and changes from baseline. 
Overall Design: 
• This is a Phase 3, randomized, double-blind, international, multicenter study of nivolumab in 
combination with BCG vs nivolumab-placebo with BCG in adult patients with high-risk 
NMIBC that is persistent or recurrent after treatment with BCG and does not qualify as BCG 
unresponsive. 
• Participants are assigned 1 of 2 treatment groups (Arm A and Arm B). Treatment assignment 
is based on 3 stratification factors used in randomization: 
1. Disease status per PRC: 
i) CIS (+/- papillary disease)* 
ii) T1 (+/- TaHG)* 
iii) TaHG only 
2. Time from last dose of BCG until NMIBC high risk recurrence per investigator: 
i) early recurrence* (for participants enrolled with CIS, early recurrence is defined as any 
recurrence within 12 months after last BCG dose; for participants enrolled without CIS, 
early recurrence is defined as any recurrence within 6 months after last BCG dose) 
ii) late recurrence (for participants enrolled with CIS, late recurrence is defined as any 
recurrence occurring more than 12 months after last BCG dose; for participants 
enrolled without CIS, late recurrence is defined as any recurrence occurring more than 
6 months after last BCG dose) 
3. Intended BCG strain: 
i) TICE 
ii) Other 
 
* Participants enrolled with T1 recurrence within 6 months of last BCG dose will be excluded from the randomization, 
per eligibility criteria, as they are considered as BCG unresponsive. 
 
Number of Participants: 
Prior to Protocol Amendment 01, it was expected that approximately 700 participants would be 
randomized in a 1:1 ratio to 1 of 2 treatment arms. 
As of 02-Jun-2021, enrollment into this study was closed. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
20 
Approved v 21.0 
930143391 2.0 
 
 
Not applicable per Protocol Amendment 01: 
Assuming a 20% screen failure rate, it is estimated that approximately 875 participants with 
persistent or recurrent high-risk NMIBC after prior BCG treatment will be enrolled. It will take 
approximately 20.5 months to randomize 700 participants in the study. 
The sample size is based on a comparison of the EFS distribution between participants randomized 
to receive nivolumab plus BCG and participants randomized to receive nivolumab-placebo plus 
BCG. 
Treatment Arms and Duration: 
 
Study Treatments for CA2097G8 
Medication 
Potency 
IP/Non-IP 
BMS-936558 (Nivolumab) Solution for Injection 
10 mg/mL 
IP 
BCGa 
Various per BCG 
strain 
IP 
0.9% Sodium Chloride for Injection 
n/a 
IP 
5% Dextrose for Injection 
n/a 
IP 
n/a=not applicable 
a This product may be obtained by the investigational sites as local commercial product in certain countries as allowed 
by local regulations. These products should be prepared/stored/administered in accordance with the package insert 
or the Summary of Product Characteristics. 
 
The study schematic is presented in Figure 1. 

 
Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Figure 1: 
CA2097G8 Study Design Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
21 
Approved v21.0 
930143391 2.0 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
22 
Approved v 21.0 
930143391 2.0 
 
 
During the treatment phase: 
• Participants will receive: 
o Arm A: Nivolumab 480 mg intravenous (IV) every 4 weeks (Q4W) for up to 24 
months (104 weeks) and intravesical BCG (induction) weekly for 6 weeks followed 
by maintenance intravesical BCG weekly for 3 weeks at 3, 6, 12, 18, 24, 30, and 
36 months 
o Arm B: Nivolumab-placebo IV Q4W for up to 24 months (104 weeks) and 
intravesical BCG (induction) weekly for 6 weeks followed by maintenance 
intravesical BCG weekly for 3 weeks at 3, 6, 12, 18, 24, 30, and 36 months 
 
• The dose of BCG used for each weekly intravesical treatment will be based on current 
prescribing information for the particular BCG strain and preparation administered. This 
may vary as BCG strain and/or preparation administered may vary based on geographic 
region. BCG will be given at full dose. 
• For each arm, 1 treatment cycle equals 4 weeks. 
Per Protocol Amendment 01, participants are permitted to continue on study treatment. The 
treatment period will end when the participant is discontinued from the last dose of study treatment 
(nivolumab/nivolumab-placebo or BCG) or completes 3 years of study treatment. 
Nivolumab/nivolumab-placebo may be delayed (withhold dose) or permanently discontinued. 
Participants who require delay should be re-evaluated weekly or more frequently if clinically 
indicated and resume dosing when re-treatment criteria are met. There will be no dose escalations 
or reductions of nivolumab/nivolumab-placebo allowed. Administration of nivolumab/nivolumab- 
placebo should not be delayed if BCG treatment is delayed. 
BCG can be delayed, modified, or discontinued for BCG-related toxicity. Administration of BCG 
should not be delayed if nivolumab/nivolumab-placebo treatment is delayed. 
The follow-up phase will begin when the decision to discontinue a participant from the last study 
treatment is made or when 3 years of study treatment has been completed. There will be a standard 
safety follow-up for a minimum of 100 days after last dose of last study treatment. 
Not applicable per Protocol Amendment 01: 
Survival follow-up begins after safety follow-up, with visits every 3 months until the end of the 
study. Efficacy assessments will occur until disease recurrence (other than low-grade Ta) or 
progression per PRC (based on a positive urinary cytology, bladder biopsy, or imaging) or 
treatment discontinuation, whichever is later. 
Data Monitoring Committee: Yes; however, no longer applicable per Protocol Amendment 01 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
23 
Approved v 21.0 
930143391 2.0 
 
 
References: 
1 US Department of Health and Human Services, Food and Drug Administration, Center for Drug 
Evaluation and Research, Center for Biologics Evaluation and Research. BCG-unresponsive 
non-muscle invasive bladder cancer: Developing drugs and biologics for treatment guidance for 
industry. February 2018 (Accessed June 18, 2019). 
2 Steinberg RL, Thomas LJ1, Mott SL, O’Donnell MA. Bacillus Calmette-Guérin (BCG) 
treatment failures with non-muscle invasive bladder cancer: A data-driven definition for BCG 
unresponsive disease. Bladder Cancer 2016;2(2):215-24. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
24 
Approved v21.0 
930143391 2.0 
 
 
2 
SCHEDULE OF ACTIVITIES 
Table 2-1: 
Screening Procedural Outline (CA2097G8)⎯Not Applicable per Protocol Amendment 01 
 
Procedure 
Screening 
Visit 
Notesa 
(All windows are based on calendar days) 
Eligibility Assessments 
Informed Consent 
X 
Register in Interactive Response Technology (IRT) system to obtain participant number. 
Informed consent must be obtained prior to any study procedure, except for those done as 
part of routine clinical practice including, but not limited to, cystoscopy, urine cytology, 
transurethral resection of the bladder tumor (TURBT), or cross-sectional imaging. 
Study allows for re-enrollment of a participant who has discontinued participation as a 
pretreatment failure. If re-enrolled, the participant must be re-consented and assigned a new 
participant number from IRT. 
Inclusion/Exclusion Criteria 
X 
Must be confirmed prior to randomization. 
Medical History 
X 
All medical history relevant to the disease under study, which includes concomitant 
medications, prior cancer therapy, and American Joint Committee on Cancer stage. Also 
include smoking history (including electronic cigarettes) and alcohol history. 
Tumor Sample Submission (Bladder Biopsy)b 
X 
Participants with CIS should have bladder mapping at baseline (see Section 9.1.5) by random 
biopsy or by fluorescence cystoscopy with biopsy of all areas of abnormality. If bladder 
mapping is not performed at baseline, this must be performed at Week 26 (± 5 week). 
For participants with clinical stage T1 disease, a repeat TURBT is required within 
approximately 8 weeks after the initial TURBT to confirm complete resection of disease and 
to ensure that no tumor has invaded the muscularis propria of the bladder prior to 
randomization. 
Cystoscopy 
X 
See Section 9.1.3. 
Urine Cytologyb 
X 
Sample will be reviewed by PRC prior to randomization. See Section 9.1.4. 
Body Imaging 
X 
Contrast enhanced computed tomography (CT) of the chest, contrast-enhanced CT/magnetic 
resonance imaging (MRI) of the abdomen and pelvis (including excretory imaging) and all 
other known/suspected sites of disease should be performed during screening within 90 days 
prior to randomization. Options for participants with contraindications to intravenous (IV) 
contrast are delineated in the protocol. See Section 9.1.7. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
25 
Approved v21.0 
930143391 2.0 
 
 
Table 2-1: 
Screening Procedural Outline (CA2097G8)⎯Not Applicable per Protocol Amendment 01 
 
Procedure 
Screening 
Visit 
Notesa 
(All windows are based on calendar days) 
Other Imaging 
X 
As clinically indicated (see Section 9.1.7). 
Biomarker Sampling 
Not applicable per Protocol Amendment 01. 
Safety Assessments 
Targeted Physical Examination, Measurements, 
Vital Signs and Performance Status 
X 
Height, weight, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 
(Appendix 6), blood pressure, heart rate, and temperature must be collected within 14 days 
prior to randomization. 
Electrocardiogram (ECG) 
X 
ECGs should be recorded after the participant has been supine for at least 5 minutes. 
Assessment of Signs and Symptoms 
X 
Must be performed within 14 days prior to randomization. 
Concomitant Medication Use 
X 
Must be collected within 14 days prior to randomization. 
Record vaccine use within 30 days prior to randomization. 
Serious Adverse Event (SAE) Assessment 
X 
SAE collection from time of consent. 
All AEs (SAEs or non-serious AEs) associated with severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infection collected from time of consent. 
Laboratory Tests 
Complete Blood Count (CBC) with Differential, 
Chemistry, Endocrine, Viral, Urinalysis 
X 
All testing, except viral, must be performed within 14 days prior to randomization. 
Viral testing must be within 28 days prior to randomization. For human immunodeficiency 
virus (HIV): testing at sites where locally mandated; see Appendix 7. 
Refer to Section 9.4.4 for list of laboratory tests to conduct. 
Pregnancy Test (WOCBP Only) 
X 
Serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human 
chorionic gonadotropin [HCG]) to be done at screening visit and within 24 hours of first dose 
of study treatment. 
a Some of the assessments referred to in this section may not be captured as data in the case report form (CRF). They are intended to be used as safety monitoring 
by the treating physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 
b Complete instructions on collecting, processing, handling, and shipment of samples will be provided in a separate lab manual. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 2-2: 
On-treatment Procedural Outline for Arms A and B (CA2097G8) 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
26 
Approved v21.0 
930143391 2.0 
 
 
 
 
Arm A: Nivolumab 480 mg IV Q4W Plus Intravesical BCG 
Arm B: Nivolumab-placebo IV Q4W Plus Intravesical BCG 
Nivolumab/Nivolumab- 
BCG 
Notesd 
Procedurea 
placebo Visitsb 
Visitsb,c 
Cycle 1 – Cycle 26 
(± 3 days) 
(Day 1 ± 3 days) 
(1 Cycle = 4 Weeks) 
Study Treatment 
Randomize 
X 
X 
Participant will be randomized via IRT to Arm A or Arm B. 
Dispense Study Drug 
X 
X 
First dose should be administered within 3 calendar days following 
randomization, but no earlier than ≥ 14 days following last 
TURBT/bladder biopsy. 
Nivolumab/nivolumab-placebo will be administered at Day 1 of each 
cycle. 
Bacillus Calumette-Guerin (BCG) will be administered as described in 
footnote “c.” 
Safety Assessments 
Targeted Physical Examination, 
Measurements, Vital Signs, 
Performance Status 
X 
For each cycle, weight, ECOG PS, blood pressure, heart rate, and 
temperature within 3 calendar days prior to dosing. 
For Cycle 1 Day 1 and beyond, targeted physical examination to be 
performed only as clinically indicated. 
Adverse Event (AE) Assessment 
(Including SAE) 
Continuously 
Record at each visit. Collect continuously throughout the treatment 
period and for a minimum of 100 days following the last dose of study 
treatment. 
All AEs (SAEs or non-serious AEs), including those associated with 
SARS-CoV-2 infection, must be collected continuously during the 
treatment period. 
Participants will be followed for all SAEs and non-serious AEs of special 
interest (as defined in Section 9.2). All AEs (SAEs and non-serious AEs) 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 2-2: 
On-treatment Procedural Outline for Arms A and B (CA2097G8) 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
27 
Approved v21.0 
930143391 2.0 
 
 
 
 
Arm A: Nivolumab 480 mg IV Q4W Plus Intravesical BCG 
Arm B: Nivolumab-placebo IV Q4W Plus Intravesical BCG 
Nivolumab/Nivolumab- 
BCG 
Notesd 
Procedurea 
placebo Visitsb 
Visitsb,c 
Cycle 1 – Cycle 26 
(± 3 days) 
(Day 1 ± 3 days) 
(1 Cycle = 4 Weeks) 
associated with confirmed or suspected SARS-CoV-2 infection will be 
followed until: 
• 
Resolution 
• 
Condition stabilizes 
• 
Event is otherwise explained 
• 
Event is deemed irreversible 
• 
Participant is lost to follow-up (as defined in Section 8.3) 
• 
For suspected cases, until SARS-CoV-2 infection is ruled out 
See Section 9.2 for additional information on collection of AEs and 
SAEs. 
Concomitant Medication Use 
Continuously 
Record at each visit. 
Laboratory Tests 
CBC with Differential, Chemistry 
Panel 
Thyroid Testing 
X 
Must be performed within 72 hours prior to nivolumab dosing. 
Refer to Section 9.4.4 for list of laboratory tests. 
Thyroid testing to be performed every 8 weeks (2 cycles). 
Urinalysis 
X 
Performed prior to dosing at visits BCG is administered. 
Microscopic analysis required for abnormal dipstick urinalysis or clinical 
symptoms suggestive of urinary tract infection. A urine culture should be 
sent if there is suspicion of a urinary tract infection. 
Pregnancy Test (WOCBP Only) 
X 
Serum or urine within 24 hours prior to first dose and then every 4 weeks 
(± 1 week) regardless of dosing schedule. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 2-2: 
On-treatment Procedural Outline for Arms A and B (CA2097G8) 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
28 
Approved v21.0 
930143391 2.0 
 
 
 
 
Arm A: Nivolumab 480 mg IV Q4W Plus Intravesical BCG 
Arm B: Nivolumab-placebo IV Q4W Plus Intravesical BCG 
Nivolumab/Nivolumab- 
BCG 
Notesd 
Procedurea 
placebo Visitsb 
Visitsb,c 
Cycle 1 – Cycle 26 
(± 3 days) 
(Day 1 ± 3 days) 
(1 Cycle = 4 Weeks) 
Efficacy Assessments 
Not applicable per Protocol Amendment 01. Sites should continue efficacy assessments as per local standards of care. 
Imaging Assessments 
Body Imaging 
See Notes 
Contrast-enhanced CT of the chest, contrast-enhanced CT/MRI of the 
abdomen and pelvis (including excretory imaging) and all other 
known/suspected sites of disease. 
Imaging will be performed, per local standards of care,every 52 weeks 
(± 4 weeks) from randomization, as described in Section 9.1.7, or at the 
discretion of the investigator due to symptoms, to exclude disease 
progression, or to exclude UC in the upper urinary tracts. 
Other Imaging 
As clinically indicated (see Section 9.1.7). 
Health Outcomes 
Not applicable per Protocol Amendment 01. 
Biomarker Sampling 
Not applicable per Protocol Amendment 01. 
Pharmacokinetic (PK) and Immunogenicity 
Not applicable per Protocol Amendment 01. 
a If a dose is delayed, the procedures scheduled for that same time point (except efficacy assessments) should also be delayed to coincide with when that time 
point’s dosing actually occurs. 
b Where possible, BCG can be administered on the same visits as nivolumab/nivolumab-placebo and assessments for both study treatments can be combined. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
29 
Approved v21.0 
930143391 2.0 
 
 
c Participants in the study will receive one induction course of BCG (6 doses - 1 dose weekly for 6 weeks) followed by maintenance BCG for a total of 3 years 
treatment. Maintenance dosing includes 3 doses of BCG at weekly intervals at months 3, 6, 12, 18, 24, 30, and 36 (see Table 7.1.2-1 for dosing detail by week). 
BCG dose will be administered ± 3 days of nivolumab/nivolumab-placebo dosing (with a minimum of 5 days between BCG doses). BCG treatment should not 
be given within 14 days after TURBT/bladder biopsy. Fourteen days is the minimum requirement; BCG can be delayed greater than 14 days after TURBT/bladder 
biopsy based on routine clinical practice. BCG administration is independent of nivolumab/nivolumab-placebo cycles and study visits, however, where possible, 
BCG can be administered on the same visits as nivolumab/nivolumab-placebo, in which case assessments for both study treatments can be combined. 
d Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 2-3: 
Follow-up Procedural Outline (CA2097G8) 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
30 
Approved v21.0 
930143391 2.0 
 
 
 
 
Procedure 
Follow-upa 
(FU) Visits 
1 and 2 
Not applicable per 
Protocol Amendment 01 
Survival 
Follow-upb 
Not applicable per 
Protocol Amendment 01 
Efficacy 
Follow-up 
Notesc 
Safety Assessments 
Targeted Physical Examination, 
Measurements, Vital Signs, and 
Performance Status 
See note 
Weight, ECOG PS, blood 
pressure, heart rate, and 
temperature, to be performed 
only as clinically indicated. 
Record at each visit. 
All SAEs and non-serious AEs 
should be collected 
continuously during the 
treatment period and for a 
minimum of 100 days 
following discontinuation of 
study treatment. 
Adverse Events Assessment 
(Including Serious Adverse Events) 
X 
See Notes 
See Notes 
Participants will be followed 
for all SAEs, non-serious AEs 
of special interest (as defined 
in Section9.2), and all AEs 
(SAEs and non-serious AEs) 
associated with confirmed or 
suspected SARS-CoV-2 
infection until: 
• 
Resolution 
• 
Condition stabilizes 
• 
Event is otherwise 
explained 
• 
Event is deemed 
irreversible 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 2-3: 
Follow-up Procedural Outline (CA2097G8) 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
31 
Approved v21.0 
930143391 2.0 
 
 
 
 
Procedure 
Follow-upa 
(FU) Visits 
1 and 2 
Not applicable per 
Protocol Amendment 01 
Survival 
Follow-upb 
Not applicable per 
Protocol Amendment 01 
Efficacy 
Follow-up 
Notesc 
• 
Participant is lost to 
follow-up (as defined in 
Section 8.3) 
• 
For suspected cases, until 
SARS-CoV-2 infection is 
ruled-out 
See Section 9.2 for additional 
information on collection of 
AEs and SAEs. 
Concomitant Medication Assessment 
X 
Record at each visit. 
Subsequent Bladder Cancer 
Treatment and Disease Assessment 
X 
X 
To include cystectomy, 
radiotherapy, systemic 
chemotherapy, and 
progression. 
Survival Status 
X 
X 
Every 3 months after FU visit 
2; may be accomplished by 
site visit or phone contact. 
Laboratory Tests 
CBC with Differential, Chemistry 
Panel, Thyroid Testing 
FU visit 1 - yes 
FU visit 2 - only if 
toxicities are present 
Refer to Section 9.4.4 for full 
list of laboratory tests. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 2-3: 
Follow-up Procedural Outline (CA2097G8) 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
32 
Approved v21.0 
930143391 2.0 
 
 
 
 
Procedure 
Follow-upa 
(FU) Visits 
1 and 2 
Not applicable per 
Protocol Amendment 01 
Survival 
Follow-upb 
Not applicable per 
Protocol Amendment 01 
Efficacy 
Follow-up 
Notesc 
Pregnancy (WOCBP Only) 
X 
See Notes 
See Notes 
Serum or urine pregnancy 
testing is only required at FU 
visit 1 and 2, unless increased 
frequency and duration is 
required per local regulations. 
Imaging Assessments 
Not applicable per Protocol Amendment 01. Sites should continue imaging assessments as per local standards of care. 
Efficacy Assessments 
Not applicable per Protocol Amendment 01. Sites should continue efficacy assessments as per local standards of care. 
Health Outcomes 
Not applicable per Protocol Amendment 01. 
PK and Immunogenicity Assessments 
Not applicable per Protocol Amendment 01. 
a FU visit 1 should occur 30 days from the last dose (± 7 days) of the last dose of study treatment or can be performed on the date of discontinuation if that date is 
greater than 42 days from the last dose. FU visit 2 occurs approximately 100 days (± 7 days) from last dose of study treatment. See Section 5.1.3. Both follow- 
up visits should be conducted in person. 
b Not applicable per Protocol Amendment 01. Survival follow-up visits to occur every 3 months (± 14 days) from FU visit 2. Survival visit may be conducted in 
person or by telephone. Survival follow-up visits may coincide with efficacy follow-up visits (see below). BMS may request that survival data be collected on 
all treated participants outside of the 3-month specified window. At the time of such request, each participant will be contacted to determine their survival status 
unless the participant has withdrawn consent for all contact. 
c Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
33 
Approved v 21.0 
930143391 2.0 
 
 
3 
INTRODUCTION 
CA2097G8 is a randomized, double-blind, Phase 3 trial of nivolumab or nivolumab-placebo in 
combination with intravesical bacillus Calumette-Guerin (BCG) in participants with recurrent or 
persistent high-risk non-muscle-invasive bladder cancer (NMIBC) after treatment with BCG who 
are not BCG unresponsive. Nivolumab is an immuno-oncologic checkpoint inhibitor that enhances 
T-cell anti-tumor activity. BCG treatment results in tumor inflammation, with the potential result 
of improved response to the combination of BCG and nivolumab. 
The study aims to demonstrate that treatment with nivolumab in combination with intravesical 
BCG will improve event-free survival (EFS) vs intravesical BCG alone. Additional clinical 
endpoints include worsening-free survival (WFS), complete response rate (CRR) in participants 
with carcinoma in situ (CIS), and overall survival (OS). Additional objectives of the study include 
characterization of safety and tolerability, pharmacokinetics (PK), potential predictive biomarkers, 
and changes in patient-reported outcomes (PROs) for quality of life (QoL) assessment. 
3.1 
Study Rationale 
Individually targeting immune checkpoint receptors such as programmed cell death protein-1 
(PD-1) has demonstrated clinical activity across multiple tumor types, including advanced 
urothelial carcinoma (UC), for which several studies to date have demonstrated activity of 
therapeutic compounds aimed at the PD-1 receptor and its ligand, programmed cell death-ligand 
1 (PD-L1).1,2,3 
In high-risk NMIBC, the standard of care (SOC) is transurethral resection of the tumor followed 
by intravesical BCG treatment. As BCG results in tumor inflammation and nivolumab enhances 
T-cell activity within the tumor, combining BCG with nivolumab may result in the potential for 
improved response of the tumor to immunotherapy. 
3.1.1 
Changes per Protocol Amendment 01 
As of May-2021, the CA2097G8 study was behind its enrollment target. Bristol-Myers Squibb 
(BMS) undertook several mitigation actions to improve participant recruitment. Unfortunately, 
despite all efforts, the study was less than 5% of target enrollment since first patient first visit. 
Based on current timelines, the study would be unable to meet its scientific objectives in this 
evolving therapeutic landscape. As a result, a decision was made to close the study. It is important 
to note that there is no change to the understanding of the safety profile of nivolumab in 
combination with BCG for the participants with bladder cancer. 
As of 02-Jun-2021 (Dear Investigator Letter; Approved v1.0 930170267), the following measures 
were put into effect: 
• Enrollment for new participants was closed effective immediately. 
• Participants who signed study consent prior to this notification and were undergoing screening 
were permitted to be randomized to study treatment. 
• Participants on treatment were allowed to continue study treatment. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
34 
Approved v 21.0 
930143391 2.0 
 
 
• For participants currently on efficacy follow-up, it is at the discretion of the investigator and 
participant whether to continue the efficacy follow-up, until Protocol Amendment 01 is 
approved by the relevant Health Authorities and Ethics Committees/Institutional Review 
Boards (EC/IRBs) at the site. 
 
Protocol Amendment 01 describes the modification to study procedures. All participants must be 
re-consented upon approval and implementation of Protocol Amendment 01. These changes affect 
all participants and should be implemented when this Protocol Amendment 01is implemented at 
the site. 
Key changes in Protocol Amendment 01 include: 
• Details of closure of the study, with provision for participants currently on treatment to 
continue. 
• Clarification that all pharmacokinetic (PK), biomarker, patient-reported outcomes, and health 
care resource utilization assessments are no longer applicable per Protocol Amendment 01. 
• Clarification that study-related efficacy assessment and Pathology Review Committee (PRC) 
are no longer applicable per Protocol Amendment 01. Sites should continue efficacy 
assessment as per local standards of care. 
 
Additionally, dose modification criteria and immuno-oncology (I-O) agent management 
algorithms were updated per the current National Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI CTCAE) version (v5). 
The changes instituted in Protocol Amendment 01 should override any existing protocol 
requirements in the event of any apparent contraindications. 
3.1.2 
Study Hypothesis 
Not applicable per Protocol Amendment 01: 
Treatment of high-risk persistent or recurrent NMIBC that is not classified as BCG unresponsive 
with systemically administered nivolumab in combination with intravesical BCG will result in 
improvement in EFS when compared with intravesical BCG alone. 
3.2 
Background 
3.2.1 
Indication Background 
Bladder cancer is the ninth most common cancer worldwide, with nearly 430,000 new cases 
diagnosed in 2012.4,5 Bladder cancer ranks as the fifth most commonly diagnosed noncutaneous 
solid malignancy in the US, estimated to account for 79,000 new cases and almost 17,000 deaths 
in 2017.6 Bladder cancer is more common in men than in women, with a ratio of approximately 
3:1.6,7 The majority of cases are UC, with mixed or variant histologies (such as squamous cell 
carcinoma, adenocarcinoma, micropapillary carcinoma, or neuroendocrine carcinoma) comprising 
a smaller subset.8 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
35 
Approved v 21.0 
930143391 2.0 
 
 
Approximately 75% to 80% of all bladder cancers present as superficial, non-muscle-invasive 
disease, while the remaining 20% to 25% are muscle invasive or metastatic at the time of 
presentation.9 NMIBCs are confined to either the mucosal lining or lamina propria of the bladder, 
not yet having penetrated into the muscular bladder wall (muscularis propria).7 Initial treatment 
for patients with NMIBC includes transurethral resection of the bladder tumor (TURBT). This 
procedure is therapeutic in that the entire tumor is removed if feasible, and it is also prognostic in 
that it allows for accurate clinical staging and grading of the tumor. The need for subsequent 
therapy after TURBT is based on several well-described clinical and pathological risk factors for 
disease recurrence and progression that can be determined based on endoscopic examination of 
the bladder and pathologic evaluation of the tumor specimen. These risks factors include tumor 
grade, stage, size, multiplicity, recurrence rate, and the presence or absence of CIS.7 These risk 
factors have been used to create 3 clinical risk groupings (ie, low, intermediate, and high), which 
may assist clinicians and patients in determining prognosis and the need for additional therapy 
after TURBT. High-risk NMIBC includes any high-grade (HG) papillary Ta tumor (TaHG), any 
grade T1 tumor, and/or the presence of CIS.7 
Following the initial report of its successful use in bladder cancer patients,10 intravesical BCG 
became the SOC as adjuvant treatment for patients with high-risk NMIBC after TURBT. Multiple 
studies and meta-analyses have demonstrated that a 6-week induction course of intravesical BCG 
followed by maintenance treatment for 3 years of BCG treatment significantly decreases the risk 
of bladder tumor recurrence and progression in patients with high-risk NMIBC when compared 
with no additional treatment or treatment with intravesical chemotherapy.7,11,12,13,14,15 Despite the 
recognized benefit of BCG treatment in this patient population, tumor recurrence and progression 
within 5 years following BCG induction and maintenance is common, occurring in 40% to 80% 
(recurrence) and 25% to 45% (progression) of patients.16,17,18,19 While some patients will respond 
to a second induction course, for patients with persistent NMIBC, treatment with BCG beyond 2 
induction courses does not have any additional clinical benefit.20 
Treatment options for patients with recurrence after initial treatment for high-risk NMIBC with 
BCG therapy depend on a variety of factors, including timing of recurrence, amount of previous 
BCG exposure, and stage of disease. Recurrent NMIBC may be suitable for further treatment with 
BCG, or may be considered BCG unresponsive. 
A consensus definition of BCG unresponsive NMIBC has been developed to specifically define 
the population of patients who will no longer benefit from further BCG treatment (see Section 
6.2.1).21,22 Treatment for patients with high-risk NMIBC that is BCG unresponsive remains a 
challenge.  Therapeutic  options  include  radical  cystectomy  or  single/combination  agent 
chemotherapy. The prognosis of this group of patients remains poor, and ongoing studies23,24 are 
F 
2 
addressing this unmet need. 
The SOC for patients with high-risk NMIBC who have persistent or recurrent disease after BCG 
(either induction treatment alone or induction and maintenance treatment with BCG) that is not 
BCG unresponsive is TURBT followed by retreatment with BCG induction and maintenance. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
36 
Approved v 21.0 
930143391 2.0 
 
 
2
Patients with recurrence of high-risk NMIBC have a worse prognosis than those with a new 
diagnosis. 25 Outcomes of patients with persistent or recurrent disease that is not BCG 
unresponsive have not been studied specifically given the recent standardization of this diagnostic 
categorization. However, available evidence suggests the rate of recurrence in this group of 
patients may be estimated at approximately 40% at 24 months.26 
The natural history of NMIBC is that patients may have repeated episodes of disease recurrence 
and treatment with resection with or without intravesical treatment, dependent on the risk category. 
Repeated episodes of disease require tumor resection and intravesical therapy. Patients may 
become BCG unresponsive and require more aggressive surgery (radical cystectomy), or may 
progress to un-resectable/metastatic disease and require chemotherapy. 
The morbidity and mortality from radical cystectomy is significant, including a 31% perioperative 
complication rate, a 21% readmission rate, and a 1%-3% mortality rate following the procedure.27 
Despite this procedure’s potentially curative intent, radical cystectomy is not performed in 
approximately 50% of indicated patients due to reasons that include advanced age, comorbid 
conditions, or patient refusal28 and in those patients, treatment options are limited with significant 
unmet medical need. 
For patients who do progress to metastatic disease, the prognosis is poor, and responses to standard 
platinum based chemotherapy regimens generally are short-lived; the median survival of patients 
with metastatic disease is approximately 14 - 15 months.29 
Patients with persistent/recurrent high-risk NIMIBC after treatment with BCG are at higher risk 
of further recurrence/progression, and are therefore more frequently require radical cystectomy or 
progress to un-resectable/metastatic disease. New treatment options for persistent/recurrent high- 
risk NMIBC should reduce or delay subsequent recurrence or progression and therefore the 
requirement for cystectomy and the occurrence of metastatic disease. The addition of nivolumab 
with BCG may augment the immunological effect of BCG and provide additional clinical benefit 
vs BCG alone address this unmet need. 
3.2.2 
Nivolumab Mechanism of Action 
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human monoclonal 
antibody (HuMAb; immunoglobulin G4 [IgG4]-S228P) that targets the programmed death-1 
(PD- 1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative 
regulatory molecule expressed by activated T and B lymphocytes.30 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 (CHO) cells and is produced using 
standard mammalian cell cultivation and chromatographic purification technologies. The clinical 
study product is a sterile solution for parenteral administration. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
37 
Approved v 21.0 
930143391 2.0 
 
 
OPDIVOTM (nivolumab) is approved for the treatment of several types of cancer in multiple 
regions including the United States (US, Dec-2014), the European Union (EU, Jun-2015), and 
Japan (Jul-2014). 
3.2.3 
BCG Mechanism of Action 
Although the exact mechanism of action is unknown, the anti-tumor effects of BCG appear to be 
T-lymphocyte dependent. When administered intravesically to treat bladder cancer, BCG produces 
a local acute inflammatory reaction and a subacute granulomatous reaction that involves 
macrophage and lymphocyte infiltration in the mucosal bladder lining (urothelium) and lamina 
propria of the bladder. 
Evidence to date suggests that cells of the immune system, as well as bladder cancer cells 
themselves, have important roles in the anti-tumor effect of intravesical BCG.31 Requirements for 
effective BCG therapy include an intact immune system, live BCG, and close contact between 
cancer cells and BCG. BCG’s anti-tumor activity appears to be mediated through activation of the 
immune system and induction of an inflammatory response that includes an influx of immune cells 
into the bladder wall and release of a wide range of cytokines and chemokines that appear in the 
urine of BCG-treated patients. CD4+ cells predominate in the urine and bladder mucosa after BCG 
treatment. However, CD8+ cells are required for effective treatment and natural killer cells, 
granulocytes, and macrophages are also important constituents of the cellular response to BCG. 
BCG treatment results in a massive release of cytokines into the urine, including IL-1, IL-2, IL-5, 
IL-6, IL-8, IL-10, IL-12, IL-18, tumor necrosis factor (TNF), IFN-γ, granulocyte-macrophage 
colony-stimulating factor (GM-CSF) and TNF-related apoptosis-inducing ligand. Studies also 
support a role of BCG in the maturation of dendritic cells by signaling through toll-like receptors 
and secretion of inflammatory cytokines such as IL-12, IFN-γ, and TNF-α.32 
Both bladder cancer cells and benign urothelial cells appear to play a role in the initial recognition 
and processing of BCG.31 Bladder cancer cell attachment to BCG is mediated through fibronectin, 
leading to BCG internalization and subsequent secretion of immune-activating effectors by cancer 
cells including IL-6, IL-8, GM-CSF, and TNF. Bladder cancer cells also may function as antigen- 
presenting cells for BCG, and BCG may have direct cytotoxic effects on bladder cancer cells. 
For additional information on the mechanism of action of live BCG (intravesical), see the current 
prescribing information (Summary of Product Characteristics [SmPC], United States [US] 
Prescribing Information [USPI], or country-specific label). 
3.3 
Benefit/Risk Assessment 
There is significant unmet need in patients who have persistence or recurrence of high-risk NMIBC 
that is not BCG unresponsive. New therapies are required to reduce the rate of recurrence, 
cystectomy, and progression to metastatic disease. 
There is evidence for the efficacy of nivolumab in UC and proof of concept for PD-1 inhibition in 
NMIBC: 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
38 
Approved v 21.0 
930143391 2.0 
 
 
• In metastatic UC, nivolumab as monotherapy has received accelerated approval in the US for 
the treatment of patients with locally advanced or metastatic UC who have had disease 
progression during or following platinum-containing chemotherapy or who have had disease 
progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing 
chemotherapy. It has received approval in the EU for the treatment of locally advanced 
unresectable or metastatic UC in adults after failure of prior platinum-containing therapy. See 
the current prescribing information for nivolumab (Opdivo) for more information. 
• In NMIBC, preliminary evidence of clinical activity of PD-1 inhibition comes from study 
Keynote-057, a single-arm study of pembrolizumab in BCG-unresponsive NMIBC.26 In the 
interim analysis of this study, the response rate of CIS participants treated with pembrolizumab 
monotherapy was 39% at Month 3, with 80.2% of participants having a CR duration of ≥ 6 
month.33 The safety profile was consistent with the profile of pembrolizumab across tumor 
types. These data are clinically significant in a group of participants for whom there are no 
effective intravesical or systemic treatment options, and cystectomy is the SOC. 
 
In addition, the safety profile of both nivolumab and BCG are both well characterized. 
Extensive details on the safety profile of nivolumab are available in the Investigator’s Brochure 
(IB) and will not be repeated herein. 
Overall, the safety profile of nivolumab monotherapy is manageable and generally consistent 
across completed and ongoing clinical trials with no maximum tolerated dose (MTD) reached at 
any dose tested up to 10 mg/kg. Most adverse events (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-mediated AEs (IMAEs) has been defined, for which management algorithms 
have been developed; these are provided in 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 nivolumab IB. 
The incidence and pattern of BCG-related adverse effects are well characterized and are presented 
in the current prescribing information. 
The safety and tolerability of nivolumab in combination with intravesical BCG is currently 
unknown. BMS study CA2099UT23 is examining the combination of nivolumab with BCG in 
participants with BCG unresponsive high-risk NMIBC. At the time of protocol writing, the first 
8 participants treated with nivolumab plus BCG in study CA2099UT have passed the dose-limiting 
toxicity evaluation period and been reviewed by the Data Monitoring Committee (DMC) (data on 
file, May 2019). The study is continuing unchanged. 
To ensure an ongoing favorable benefit/risk assessment for participants enrolled into the present 
study, the following safety measures will be employed throughout the conduct of the study: 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
39 
Approved v 21.0 
930143391 2.0 
 
 
• Institution of an external DMC to provide independent oversight of safety, study conduct, and 
benefit/risk assessment of nivolumab in combination with BCG 
• Rigorous safety monitoring by BMS to ensure participants’ safety, including regular and 
systematic review of safety data, close follow-up of reported AEs, and intensive site and study 
investigator training/education on the implementation of the nivolumab and BCG toxicity 
management strategies 
 
4 
OBJECTIVES AND ENDPOINTS 
Objectives and endpoints are no longer applicable per Protocol Amendment 01. 
As of Protocol Amendment 01, only descriptive safety and investigator-assessed efficacy analyses 
will be conducted. No other analyses of efficacy, quality of life/patient-reported outcomes, PK, or 
health care resource utilization are planned. Previously collected biomarker samples may be 
analyzed, but no further collections are planned with Protocol Amendment 01. 
Table 4-1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• 
To compare the EFS per PRC of nivolumab plus 
BCG vs BCG alone in all randomized 
participants 
• 
EFS, defined as the time from randomization until any 
of the following events: recurrence (TaHG, T1 or CIS) 
or progression of disease, or death from any cause. For 
participants with CIS (+/- papillary disease) at study 
entry, a lack of complete response of the CIS 
component at the 13-week assessment will be 
considered an event. 
Secondary 
• 
To compare the WFS of nivolumab plus BCG vs 
BCG alone in all randomized participants 
• 
WFS, defined as the time from randomization to 
progression to muscle invasive disease, cystectomy, 
systemic chemotherapy, radiotherapy, or death from 
any cause. 
• 
To compare the OS of nivolumab plus BCG vs 
BCG alone in all randomized participants 
• 
OS, defined as the time from randomization to death 
from any cause. 
• 
To evaluate the CRR at first disease assessment 
(Week 13) in all randomized participants with 
CIS (+/- papillary disease) at study entry by 
treatment arm (nivolumab plus BCG and BCG 
alone) 
• 
CRR, defined as the proportion of participants with 
CIS (+/- papillary disease) at study entry who are 
disease free at the first disease assessment. 
• 
To evaluate the duration of response (DoR) in all 
randomized participants with CIS (+/- papillary 
disease) at study entry who achieved CRR at first 
disease assessment by treatment arm (nivolumab 
plus BCG and BCG alone) 
• 
DoR is restricted to participants with CIS (+/- 
papillary disease) at study entry who are disease free 
at the first disease assessment and is defined as the 
time between the date of the first CR to the date of 
first documented recurrence, progression, or death 
due to any cause. 
• 
To describe the safety and tolerability of 
nivolumab plus BCG and BCG alone in all 
treated participants 
• 
Overall safety and tolerability will be measured by the 
incidence 
of 
AEs, 
SAEs, 
AEs 
leading 
to 
discontinuation, IMAEs, deaths, and laboratory 
abnormalities and changes from baseline. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
40 
Approved v 21.0 
930143391 2.0 
 
 
Table 4-1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Tertiary/Exploratory 
• 
To evaluate the cystectomy-free survival (CFS) 
in all randomized participants by treatment arm 
(nivolumab plus BCG and BCG alone) 
• 
CFS, defined as the time from randomization to 
cystectomy or death from any cause 
• 
To evaluate the progression-free survival (PFS) 
per PRC in all randomized participants by 
treatment arm (nivolumab plus BCG and BCG 
alone) 
• 
PFS, defined as the time from randomization to 
progression to muscle invasive or metastatic disease 
(T2+) of disease or death from any cause 
• 
To evaluate disease specific survival (DSS) in all 
randomized participants by treatment arm 
(nivolumab plus BCG and BCG alone) 
• 
DSS, defined as the time from randomization to death 
from UC 
• 
To evaluate best overall CRR, as well as CRR 
at Week 26, at Week 52, and at Week 104 in all 
randomized participants with CIS (+/- papillary 
disease) at study entry by treatment arm 
(nivolumab plus BCG and BCG alone) 
• 
Best overall CRR, defined as the proportion of 
participants with CIS (+/- papillary disease) at study 
entry who achieve disease free at any disease 
assessment during study treatment. 
• 
CRR at different time points, defined as the 
proportion of participants with CIS (+/- papillary 
disease1) at study entry who are disease free at each 
of the specified disease assessment time points (ie, 
Week 26, Week 52, and Week 104). 
• 
To 
assess 
the 
participant’s 
cancer-related 
symptoms and quality of life 
• 
Change in subscales of the EORTC QLQ-C30 
• 
Change in subscales of the EORTC QLQ-NMIBC24 
• 
To evaluate the participant’s overall health status 
and utility for health 
• 
Change in scores in both the EQ-5D-5L visual analog 
scale and the utility index 
• 
To identify biomarkers that predict clinical 
efficacy 
• 
Correlation of selected biomarkers with (EFS and 
PFS) and safety (incidence of AEs) endpoints 
• 
To 
characterize 
nivolumab 
PK 
and 
immunogenicity in combination with BCG 
• 
PK parameters, immunogenicity, exposure-response 
(E-R) relationships between select PK measures of 
exposure and safety and efficacy endpoints, if 
applicable 
 
5 
STUDY DESIGN 
5.1 
Overall Design 
This is a Phase 3, randomized, double-blind, international, multicenter study of nivolumab in 
combination with BCG vs nivolumab-placebo with BCG in adult participants with high-risk 
NMIBC that is persistent or recurrent after treatment with BCG and does not qualify as BCG 
unresponsive.21 
The study design schematic is presented in Figure 5.1-1. 

 
Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Figure 5.1-1: 
CA2097G8 Study Design Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
41 
Approved v21.0 
930143391 2.0 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
42 
Approved v 21.0 
930143391 2.0 
 
 
The study will proceed through 3 phases: screening, treatment, and follow-up. 
As of 02-Jun-2021, enrollment into this study was closed. Protocol Amendment 01 removes the 
decision points and the efficacy follow-up along with other study procedures. As a result, initial 
benefit/risk assessment by the Data Monitoring Committee (DMC) and PRC will be removed. 
5.1.1 
Screening Phase 
As of 02-Jun-2021, enrollment into this study was closed. Therefore, the screening phase is no 
longer applicable per Protocol Amendment 01. 
Not applicable per Protocol Amendment 01: 
Screening begins by establishing the participant’s initial eligibility and signing of the informed 
consent form (ICF). All screening tests must be completed as per the inclusion criteria (Section 
6.1) and the time and events table (Section 2 Table 2-1). This includes complete excision of all 
papillary disease or CIS (if feasible) and biopsy of all suspicious lesions, urine cytology, and 
appropriate imaging of the chest, abdomen and pelvis. Screening tests that were performed as part 
of SOC do not need to be repeated. 
Representative diagnostic pathology slides, obtained at TURBT within 90 days prior to 
randomization, which can be used to confirm the diagnosis of high-risk NMIBC and exclude the 
presence of tumor invasion into the muscularis propria, must be available. Tumor tissue samples 
(1-10 hematoxylin and eosin [H&E] stained slides), with at least one slide containing muscularis 
propria, preferably from the area of the bladder with the greatest disease burden, must be sent to 
independent Pathology Review Committee (PRC) for review. Confirmation of diagnosis by the 
PRC is required for randomization. 
Sufficient, recent tumor tissue obtained within 90 days prior to randomization from the bladder 
tumor tissue obtained at TURBT (formalin-fixed paraffin-embedded block or 20 slides) will be 
submitted to the analytical laboratory for determination of PD-L1 expression and for biomarker 
studies. If less than 15 slides are available, please contact the Medical Monitor for discussion. 
Confirmation of receipt of acceptable tumor tissue by the analytical laboratory is required prior to 
randomization. 
If sufficient tissue is not available within 90 days prior to randomization, then the site will be asked 
for additional tissue or a repeat TURBT will be required. 
If tissue for diagnosis or biomarker assessment was obtained > 70 days prior to randomization, a 
repeat cystoscopy is required ≤ 70 days prior to randomization to ensure there is no recurrent 
disease. See Section 9.1.5 for further details. 
Participants may not have received any systemic or intravesical anticancer therapy after the date 
that the submitted tumor tissue was obtained, with the exception of a single dose of intravesical 
chemotherapy at the time of TURBT. For participants with CIS, bladder mapping must be 
performed with random biopsy or with florescence cystoscopy with biopsy of all areas suspicious 
for disease. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
43 
Approved v 21.0 
930143391 2.0 
 
 
Participants will be assessed for complete study eligibility prior to randomization as specified in 
Table 2-1. 
The screening phase ends with either confirmation of full eligibility and randomization of the 
participant or with the confirmation that the patient is a screen failure. This study permits 
reenrollment of a participant who discontinued the study as a pretreatment failure prior to 
randomization. If reenrolled, the participant must be reconsented. A new participant identification 
number will be assigned by the Interactive Response Technology (IRT) at the time of reenrollment. 
5.1.2 
Treatment Phase 
The treatment phase begins with the randomization of the participant in the IRT system. The 
participant is randomly assigned to 1 of the 2 treatment arms as noted in the study schematic. 
Stratification factors for randomization will include: disease status per PRC; time from last dose 
of BCG to recurrence per investigator; and intended BCG strain. Full details can be found in 
Section 5.2. 
During the treatment phase, participants will receive: 
• Arm A: Nivolumab 480 mg intravenous (IV) every 4 weeks (Q4W) for up to 24 months 
(104 weeks) and intravesical BCG (induction) weekly for 6 weeks followed by maintenance 
intravesical BCG weekly for 3 weeks at 3, 6, 12, 18, 24, 30, and 36 months (see Table 7.1.2- 
1) 
• Arm B: Nivolumab-placebo IV Q4W for up to 24 months (104 weeks) and intravesical BCG 
(induction) weekly for 6 weeks followed by maintenance intravesical BCG weekly for 3 weeks 
at 3, 6, 12, 18, 24, 30, and 36 months (see Table 7.1.2-1) 
 
For each arm, 1 treatment cycle equals 4 weeks. Day 1 of Cycle 1 will be the first dose of either 
study treatment. 
The dose of BCG used for each weekly intravesical treatment will be based on current prescribing 
information for the particular BCG strain and preparation administered. This may vary as BCG 
strain and/or preparation administered may vary based on geographic region in which the 
participant is receiving treatment. Sites are required to declare which BCG strain they intend to 
use during the screening period for the purposes of stratification. BCG will be given at full dose, 
unless the dose is reduced due to lower urinary tract symptoms whilst on study (see Section 7.4.2). 
For all participants, follow local standards of care for efficacy assessments. 
5.1.3 
Follow-up Phase 
The follow-up phase will begin when the decision to discontinue a participant from the last study 
treatment is made (no further study treatment) or when 3 years of study treatment has been 
completed (eg, a participant may be discontinued from nivolumab/nivolumab-placebo study 
treatment on or before 24 months but remains on maintenance BCG study treatment for 36 months 
[see Sections 5.4.4 and 5.4.5]). 
Participants must be followed for at least 100 days after last dose of last study treatment. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
44 
Approved v 21.0 
930143391 2.0 
 
 
• Follow-up (FU) visit 1 should occur 30 days from the last dose (± 7) days or can be performed 
on the date of discontinuation if that date is greater than 42 days from the last dose. 
• FU visit 2 occurs approximately 100 days (± 7 days) from last dose of study treatment. 
• Both visits should be conducted in person. 
 
 
Not applicable per Protocol Amendment 01: 
Survival follow-up begins after FU visit 2. 
• Survival follow-up visits occur every 3 months (± 14 days) until the end of the study. 
Not applicable per Protocol Amendment 01: 
Efficacy follow-up: 
• Efficacy assessments occur until disease recurrence (other than low-grade Ta) or progression, 
per PRC (based on a positive urinary cytology, bladder biopsy, or imaging), or treatment 
discontinuation, whichever is later. 
• For participants who have not had PRC confirmed progression or recurrence during the on- 
treatment period, efficacy assessments will continue as per Table 2-3 and Section 9.1.8. 
• Where scheduling allows, efficacy follow up and survival follow up can coincide. 
Treatment beyond disease recurrence/progression is not permitted except in the case of a low- 
grade papillary Ta tumor (TaLG) UC recurrence only, or for participants with CIS and/or Ta at 
Week 13 (see Section 8.1.4). 
5.1.4 
Data Monitoring Committee and Other External Committees 
Not applicable per Protocol Amendment 01: 
An independent, external DMC will be established to provide oversight of safety and efficacy 
considerations in this protocol and to provide advice to the Sponsor regarding actions the 
committee deems necessary for the continued protection of participants enrolled in the study. The 
DMC will be charged with assessing such actions in light of an acceptable benefit/risk profile for 
nivolumab and nivolumab-placebo plus BCG. The DMC will act in an advisory capacity to BMS 
and will monitor participant safety and evaluate the available efficacy data for the study. Data and 
summaries will be made available to the DMC. The BMS Oncology Clinical Development 
Department has primary responsibility for design and conduct of the study. 
Additional details concerning DMC oversight are provided in the DMC charter. 
Pathology Review Committee 
Not applicable per Protocol Amendment 01: 
An independent PRC will review cystoscopy reports, imaging reports, participant biopsy slides, 
and urinary cytology obtained prior to randomization to confirm the diagnosis of high-risk 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
45 
Approved v 21.0 
930143391 2.0 
 
 
NMIBC. Similarly, on-study cystoscopy and imaging reports, biopsies, and urine cytology will be 
submitted to the PRC to exclude or confirm recurrence or progression. 
Additional details concerning PRC responsibilities are provided in the PRC charter and in Section 
9.1.8. 
5.2 
Number of Participants 
Prior to Protocol Amendment 01, it was expected that approximately 700 participants would be 
randomized in a 1:1 ratio to receive nivolumab with BCG vs nivolumab-placebo with BCG and 
stratified by the following 3 factors: 
1. Disease status per PRC: 
a) CIS (+/- papillary disease)a 
b) T1 (+/- TaHG)a 
c) TaHG only 
2. Time from last dose of BCG until NMIBC high risk recurrence per investigator: 
a) early recurrence a (for participants enrolled with CIS, early recurrence is defined as any 
recurrence within 12 months after last BCG dose; for participants enrolled without CIS, 
early recurrence is defined as any recurrence within 6 months after last BCG dose) 
b) late recurrence (for participants enrolled with CIS, late recurrence is defined as any 
recurrence occurring more than 12 months after last BCG dose; for participants enrolled 
without CIS, late recurrence is defined as any recurrence occurring more than 6 months 
after last BCG dose) 
3. Intended BCG strain: 
a) TICE 
b) Other 
 
a Participants enrolled with T1 recurrence within 6 months of last BCG dose will be excluded from the randomization, 
per eligibility criteria 2d Section 6.1, as they are considered as BCG unresponsive (defined in Section 6.2.1). 
 
As of 02-Jun-2021, enrollment into this study was closed. 
Not applicable per Protocol Amendment 01: 
Assuming a 20% screen failure rate, it is estimated that approximately 875 participants with 
persistent or recurrent high-risk NMIBC after prior BCG treatment will be enrolled using the 
following enrollment assumptions: up to 3 randomized participants for the first 2 months, 
9 randomized participants per month for Month 3 and 4, 19 randomized participants per month for 
Month 5 and 6, 24 randomized participants per month for Month 7 and 8, 38 randomized 
participants per month for Month 9 and 10, 43 randomized participants per month for Month 11 
and 12, 48.5 randomized participants per month from Month 13 to 16, and 53 randomized 
participants per month thereafter. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
46 
Approved v 21.0 
930143391 2.0 
 
 
33
Based on the above information, it will take approximately 20.5 months to randomize 
700 participants in the study. 
Details regarding sample size calculation are found in Section 10.1. 
5.3 
End of Study Definition 
As of 02-Jun-2021, enrollment into this study was closed; therefore, study completion will be when 
all participants complete study procedures described in Section 2, including safety visits. 
The start of the trial is defined as the first participant’s first visit. End of trial is defined as the last 
participant’s last study visit or scheduled procedure shown in the Schedule of Activities. Primary 
completion is defined as the final date on which data for the primary endpoint was or is expected 
to be collected, if this is not the same. (Primary completion date is detailed in Section 10.1.) Study 
completion is defined as the final date on which data for the last efficacy analysis, as per 
hierarchical procedure defined in Sections 10.1 and 10.3.1, was or is expected to be collected, if 
this is not the same. 
5.4 
Scientific Rationale for Study Design 
5.4.1 
Rationale for the Combination of Nivolumab with BCG in NMIBC 
Immune checkpoint inhibitors such as nivolumab target pathways used by cancer cells to evade 
immune system attack. Such pathways may be important in recurrent NMIBC as evidenced by the 
association between PD-L1 expression and higher bladder cancer stage, and by the high levels of 
PD-L1 expression in the BCG granulomata of those failing prior BCG treatment. 34 Thus, elevated 
PD-L1 expression may be one possible mechanism by which bladder cancer cells evade treatment. 
Previous studies in participants with advanced UC suggest that tumors with an immune-inflamed 
(associated with high CD8+ infiltration) or immune-suppressed phenotype may have better 
response to immunotherapies, including checkpoint inhibitors, than tumors with an immune-desert 
phenotype.35 BCG appears to have a role in the recruitment of CD4+ and CD8+ lymphocytes into 
the bladder wall,31 augmenting the inflamed phenotype of a particular bladder tumor and 
potentially making it more susceptible to treatment with a checkpoint inhibitor such as nivolumab. 
These findings suggest that the balance between CD8+ cytotoxic T-cells and negative immune 
regulatory elements in the microenvironment of a bladder tumor may be critical in determining the 
host’s overall immune response and ultimate clinical outcome. An avid local immune response 
within the bladder that results from BCG treatment may improve response to anti-PD1 therapy, 
while anti-PD1 therapy with nivolumab may help to overcome tumor-associated 
immunosuppression that mitigates the effectiveness of BCG treatment in BCG-unresponsive 
tumors. This provides a strong rationale for combining nivolumab with BCG in patients with 
NMIBC. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
47 
Approved v 21.0 
930143391 2.0 
 
 
36
5.4.2 
Rationale for Event-free Survival as Primary Endpoint 
Not applicable per Protocol Amendment 01: 
EFS is the primary endpoint for this study, defined as the time from randomization until any of the 
following events: recurrence (TaHG, T1, or CIS) or progression of disease or death from any cause. 
For participants with CIS (with or without papillary disease) at baseline, a lack of complete 
response of the CIS component at the 13-week assessment will be considered an event. 
This endpoint has been selected in order that all participants in the study can be evaluated by 1 
single primary endpoint. Because of the frequent co-existence of CIS and papillary disease, a 
single primary endpoint ensures that the papillary component can be evaluated consistently in all 
study participants. As such, most clinical trials have evaluated high-risk participants with and 
without CIS together, and clinical practice treats high-risk recurrences similarly whether CIS or 
non-CIS.12,23 Given the demonstrated benefit of PD-1 inhibition in CIS NMIBC and in non-CIS 
metastatic UC26,33 it is reasonable to assume that benefit would be similar across histological 
subtypes. Evaluating the CIS and non-CIS population with 1 single endpoint is therefore 
appropriate. 
Although CIS can be removed in some participants by TURBT prior to study entry, it is not 
possible in all participants with CIS, unlike participants with papillary disease only where disease 
is expected to be completely removed by TURBT. Participants with CIS therefore pose a challenge 
with respect to a time-to-event endpoint in which the event is defined solely as recurrence of 
disease. 
Food and Drug Administration (FDA) guidance supports the use of EFS as an endpoint to support 
registration.36 In addition, a report from an FDA/American Urological Association (AUA) public 
workshop provides insight into trial design (including assessment of appropriate clinical 
endpoints) for the development of new therapies for patients with high-risk NMIBC. 37 This 
workshop supports the approach of including a mix of patients with CIS and non-CIS in the study 
population, and using a time-to-event endpoint including failure to achieve complete response 
(CR) in patients with CIS and recurrence in patients with CIS or papillary disease37 as events. 
These guidances support the definition of EFS and its use as a single primary endpoint in this 
study. 
5.4.3 
Rationale for Stratification Factors 
Patients with high-risk NMIBC have CIS, T1, or TaHG disease, or a combination of these. 
Although the high-risk category defines patients who are generally considered to be at higher risk 
for recurrence, the risk is not uniform within the group, and T stage is a key determinant of 
prognosis with CIS and T1 both having a significantly higher risk than TaHG.7,18 For this reason, 
tumor stage is included as a stratification factor. This approach also facilitates the analysis of CR 
in CIS patients as a secondary endpoint. 
The time from the initial diagnosis of high-risk NMIBC to recurrence is also an important predictor 
of future recurrence. Retrospective analysis of clinical trial data26 demonstrate that patients with a 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
48 
Approved v 21.0 
930143391 2.0 
 
 
shorter interval to recurrence have a higher risk for subsequent recurrence. The time limit which 
dichotomizes the population into lower and higher risk groups is tumor stage dependent, and 
defined as < 6 months or ≥ 6 months in patients with papillary disease only, and < 12 months or 
≥ 12 months in patients with CIS (with or without papillary disease). This classification aligns 
with the definition for BCG unresponsive disease (see Section 6.2.1), which is a central clinical 
concept on which this study is based. 
Different strains of BCG are used as SOC in varying regions, with some countries having more 
than one strain approved. There are no conclusive data showing a difference in efficacy or safety 
between available strains, although there is an ongoing non-inferiority trial comparing the TICE 
and Tokyo-172 strains in BCG-naive patients.38 As the TICE strain is widely used globally and is 
the only strain approved in many countries, stratification by BCG strain (TICE vs other) will be 
used to ensure balance between the arms. 
5.4.4 
Rationale for 2-year Duration of Treatment 
The optimal duration of immunotherapy in NMIBC is currently unknown. Because 
immunotherapy engages the immune system to control the tumor, continuous treatment as is 
required with targeted agents or cytotoxic therapy may not be necessary. 
In the adjuvant setting, the standard approach across the nivolumab development program is to 
treat with 1 year of nivolumab. This approach has demonstrated efficacy in the setting of advanced 
melanoma,39 where 1 year of treatment with adjuvant nivolumab following resection was superior 
to ipilimumab treatment. 
In this study, nivolumab is utilized to augment the immune response in the bladder of participants 
who have recurrence following BCG treatment. Participants are treated with up to 3 additional 
years of BCG (see Section 5.4.5) in accordance with evidence-based SOC. In order to increase the 
potential for synergy with BCG, nivolumab will therefore be given for 2 years with BCG. This 
will ensure that the susceptibility of the BCG inflamed phenotype to PD-1 inhibition is harnessed 
through a sufficient duration of the BCG course to optimize clinical benefit. 
5.4.5 
Rationale for Duration of BCG Treatment 
The SOC globally for high-risk NMIBC patients with recurrence of disease who are not bacillus 
Calumette-Guerin (BCG) unresponsive globally is induction and maintenance BCG therapy, given 
according to the SWOG 8507 protocol.12 This protocol forms the basis of guidance from the AUA7 
and European Association of Urology (EAU).18 
Participants in the study will receive 1 induction course of BCG (6 doses = 1 dose weekly for 
6 weeks) followed by maintenance BCG according to this schedule for a total of 3 years treatment. 
Maintenance dosing includes 3 doses of BCG at weekly intervals at Month 3, 6, 12, 18, 24, 30, 
and 36. This equals a total of 27 doses of BCG over 3 years. (See Section 7.1.2 and Table 7.1.2-1 
for dosing details.) 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
49 
Approved v 21.0 
930143391 2.0 
 
 
5.4.6 
Rationale for Double-blind Study Design 
The study will be double-blind and placebo controlled. This approach will minimize bias in 
evaluation of study endpoints, including the primary study endpoint of EFS, which is dependent 
on investigator-assessed findings at cystoscopy in addition to central PRC of urine cytology and 
histologic analysis of biopsy/excision specimens. Additionally, blinding is particularly important 
for accurately assessing quality of life with PROs, which is a key exploratory objective of the 
study. 
Participants in the control arm will be administered a placebo dose of nivolumab every 4 weeks. 
This will ensure that follow-up visits occur with equal frequency in the experimental and control 
arms, and hence minimize bias in the evaluation of AE frequency between arms. 
Individual participant unblinding is permitted upon documentation of recurrence or progression in 
order to make informed decisions about future treatment (see Section 7.3). 
5.5 
Justification for Dose 
5.5.1 
Justification for Nivolumab Dose 
A nivolumab dose of 480 mg given Q4W was selected for this study based on available PK, safety, 
and efficacy data. 
Nivolumab PK has been extensively studied in multiple tumor types, including melanoma, non- 
small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), classical Hodgkin lymphoma, 
SCCHN, colorectal cancer, and UC, and has been safely administered at doses up to 10 mg/kg 
every 2 weeks (Q2W). Nivolumab monotherapy was originally approved as a body-weight based 
dose of 3 mg/kg Q2W and was recently updated to 240 mg Q2W or 480 mg Q4W in multiple 
indications.40,41 Less frequent 480 mg Q4W dosing regimens can reduce the burden to patients of 
frequent, lengthy IV treatments and allow combination of nivolumab with other agents using 
alternative dosing regimens. 
The benefit/risk profiles of nivolumab 240 mg Q2W and 480 mg Q4W are predicted to be 
comparable to 3 mg/kg Q2W. This assessment is based on a comprehensive characterization of 
nivolumab PK, safety, efficacy, and exposure-response (E-R) relationships across indications. 
Population PK (PPK) analyses have shown that the PK of nivolumab is linear with proportional 
exposures over a dose range of 0.1 to 10 mg/kg; no clinically meaningful differences in PK across 
ethnicities and tumor types were observed. Using the PPK model, the exposures following 
administration of several dosing regimens of nivolumab administered as a flat dose were 
simulated, including 240 mg Q2W and 480 mg Q4W. The simulated average serum concentration 
at steady state following administration of nivolumab 480 mg Q4W are predicted to be similar to 
those following administration of nivolumab 240 mg Q2W and nivolumab 3 mg/kg Q2W 
administered to participants over a wide body weight range (34 to 180 kg) across tumor types. 
Extensive E-R analyses of multiple PK measures (maximum serum concentration at Day 1, 
average serum concentration at Day 28 [Cavg28], and trough serum concentration at Day 28 
[Cmin28]) and efficacy and safety endpoints indicated that the efficacy of the flat-dose 480 mg IV 
regimen are similar to that of 3 mg/kg Q2W IV regimen. In E-R efficacy analyses for OS and 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
50 
Approved v 21.0 
930143391 2.0 
 
 
4
objective response rate (ORR) conducted in melanoma, RCC, and NSCLC using Cavg28 as the 
exposure measure, probabilities of achieving a response and survival probabilities at 1 year and 
2 years for IV 480 mg Q4W were similar to that of IV 3 mg/kg Q2W. In E-R safety analyses, it 
was demonstrated that the exposure margins for safety are maintained following nivolumab 
480 mg Q4W, and the predicted risks of discontinuations due to AEs or death, AE Grade 3+, and 
IMAEs. Grade 2+ are similar following nivolumab 480 mg Q4W relative to nivolumab 3 mg/kg 
Q2W across tumor types. In addition, nivolumab exposures with 240 mg Q2W and 480 mg Q4W 
flat-dose IV regimens across tumor types are maintained well below the corresponding exposures 
observed with the well-tolerated 10 mg/kg IV nivolumab Q2W dose regimen. 
Additional details on nivolumab posologies and benefit/risk can be found in the IB. 
5.5.2 
Justification for BCG Dose 
The appropriate dose and dosing schedule of BCG in combination with systemic immuno- 
oncology (I-O) agents in BCG relapse is unknown. In this study, BCG is being administered to 
augment the local immune response in the bladder and to work synergistically with nivolumab in 
order to overcome potential immune inhibitory mechanisms used by bladder cancer cells to evade 
the local immune response induced by BCG. 
BCG strains used in routine clinical practice vary by geographic location, with different strains 
currently being utilized in the United States, Europe, and Japan. 42 The dose used for each weekly 
intravesical BCG treatment will be based on current prescribing information for the particular BCG 
strain. 
6 
STUDY POPULATION 
As of 02-Jun-2021, enrollment into this study was closed. Male participants continuing treatment 
should follow the updated contraceptive guidance in Appendix 4. 
For entry into the study, the following criteria MUST be met. 
6.1 
Inclusion Criteria 
1) Signed Written Informed Consent 
a) Prior to study participation, written informed consent from participants, guardians, or 
legally acceptable representatives must be obtained according to local laws and regulations 
(Appendix 2). 
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory testing, and other requirements of the study. 
2) Type of Participant and Target Disease Characteristics 
a) Histologically confirmed persistent or recurrent high-risk non-muscle-invasive UC (TaHG 
and/or T1 and/or CIS) 
b) Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma 
c) Treated with at least 1 adequate course of induction BCG therapy (at least 5 out of 6 doses) 
d) Persistent or recurrent disease ≤ 24 months of last BCG dose, but not classified as BCG 
unresponsive (definition in Section 6.2.1) 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
51 
Approved v 21.0 
930143391 2.0 
 
 
e) Sufficient tissue for both biomarker analysis and central PRC confirmation of diagnosis 
(Section 5.1.1) 
f) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 (Appendix 6) 
g) Participants with multiple prior diagnoses of NMIBC which may have been treated with 
BCG or other intravesical therapy, that preceded the qualifying episode and associated 
recurrence, are permitted 
h) Must have undergone each of the following procedures within 90 days of randomization. 
If these procedures are performed as part of the participant’s routine care, they do not need 
to be repeated provided that they were performed within the required time period: 
i) Complete excision of all papillary disease (T1/TaHG). For participants with T1 lesions, 
a restaging TURBT must be performed within 8 weeks after the initial TURBT to 
ensure papillary disease is fully resected, and the pathology specimen must contain 
muscularis propria that is free of invasive tumor per PRC. 
ii) Resection or fulguration of all detectable CIS, if feasible. Fluorescence-guided 
cystoscopy is encouraged but not mandated. It is understood that due to the nature of 
this disease, complete resection of CIS cannot be assured. 
iii) The presence of any suspicious lesions must be recorded and these lesions will be 
biopsied. 
iv) Urine cytology must be obtained from a voided specimen (except from the first 
morning urination) or by bladder wash. Recognizing the possibility of occult CIS, 
cytology at screening does not need to be negative for study participation. 
v) Computed tomography (CT) scan of the chest and CT or MRI of the abdomen, pelvis, 
and all other areas of suspected disease to exclude locally advanced or metastatic 
bladder cancer or synchronous UC in the upper urinary tracts within 90 days prior to 
randomization. 
vi) Pelvic examination, preferably under anesthesia to exclude locally advanced disease. 
3) Age and Reproductive Status 
a) Males and females, ages 18 or age of majority, and older 
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) WOCBP must agree to follow instructions for method(s) of contraception (see Appendix 
4) for the duration of treatment with study treatment(s) and for 5 months after the last dose 
of study treatment (ie, 30 days [duration of ovulatory cycle] plus the time required for 
nivolumab to undergo approximately 5 half-lives). 
d)  Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception and fetal protection (see Appendix 4) for the duration of 
treatment with study treatment(s) and 7 months after the last dose of study treatment (ie, 
90 days [duration of sperm turnover] plus the time required for nivolumab to undergo 
approximately 5 half-lives). In addition, male participants must be willing to refrain from 
sperm donation during this time. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
52 
Approved v 21.0 
930143391 2.0 
 
 
e) WOCBP who are continuously not heterosexually active are also exempt from 
contraceptive requirements, and still must undergo pregnancy testing as described in this 
section. 
Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy and 
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 shall advise on the use of highly effective methods of contraception 
(Appendix 4) which have a failure rate of < 1% when used consistently and correctly. 
6.2 
Exclusion Criteria 
1) Medical Conditions 
a) Woman who are breastfeeding 
b) Prior malignancy active within the previous 3 years except for locally curable cancers that 
have been apparently cured or not requiring treatment, such as basal or squamous cell skin 
cancer, prostate cancer with evidence of undetectable prostate specific antigen, low-risk 
prostate cancer or renal cell cancer < 3 cm under surveillance, or carcinoma in situ of the 
cervix or breast 
c) Patients with serious or uncontrolled medical disorders 
d) Participants with an active, known, or suspected autoimmune disease 
e) 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. 
f) Participants with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 
14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement 
steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active 
autoimmune disease. 
g) UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 
24 months of enrollment 
h) UC and/or CIS in the prostatic urethra within 12 months of enrollment 
i) Previous or concurrent muscle invasive, locally advanced, or disseminated/metastatic UC 
j) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cytotoxic T- 
lymphocyte-associated protein 4 antibody, or any other antibody or drug specifically 
targeting T-cell costimulation or checkpoint pathways 
k) Recurrent high-risk NMIBC that is classified as BCG unresponsive: 
• Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary 
disease/tumor invades the subepithelial connective tissue) disease within 12 months of 
completion of adequate BCG therapy** 
• Recurrent TaHG/any T1 disease within 6 months of completion of adequate BCG 
therapy** 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
53 
Approved v 21.0 
930143391 2.0 
 
 
• T1HG disease < 6 months following an induction BCG course (at least 5 of 6 induction 
doses) 
** Adequate BCG treatment is defined as at least 2 courses of BCG. This can include 
2 induction courses (at least 5 of 6 doses of an initial induction course plus at least 2 of 
6 doses of a second induction course) or 1 induction course (at least 5 of 6 induction 
doses) and at least 2 of 3 doses of a maintenance cycle (“5+2”). 
l) New York Heart Association (NYHA) functional Classification of Heart Failure: Class III 
or Class IV 
m) Has any contraindication to intravesical BCG therapy, including evidence of active 
tuberculosis 
2) Prior/Concomitant Therapy 
a) Prior systemic chemotherapy or immunotherapy for UC. Intravesical chemotherapy and/or 
interferon administered prior to the current recurrence or as a single dose at the time of 
TURBT is permitted. 
b) Prior radiation therapy for bladder cancer 
c) Prior surgery for bladder cancer other than TURBT and/or bladder biopsies 
d) Use of an investigational agent within 4 weeks of randomization 
e) Participants who have received a live /attenuated vaccine within 30 days of first treatment 
f) Treatment with botanical preparations (eg, herbal supplements or traditional Chinese 
medicines) intended for general health support or to treat the disease under study within 
2 weeks prior to randomization/treatment. Refer to Section 7.7.1 for prohibited therapies. 
3) Physical and Laboratory Test Findings 
a) White blood cells (WBC) < 2000/μL 
b) Neutrophils < 1500/μL 
c) Platelets < 100*103/μL 
d) Hemoglobin < 9.0 g/dL 
e) Serum creatinine > 1.5x upper limit of normal (ULN), unless creatinine clearance 
≥ 40 mL/min (measured or calculated using the Cockroft-Gault formula) 
f) Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT): > 3.0x ULN 
g) Total bilirubin > 1.5x ULN (except participants with Gilbert syndrome who must have a 
total bilirubin level of < 3.0x ULN) 
h) Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of 
virus, eg, Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C 
antibody (anti-HCV) positive (except if HCV-RNA negative). 
i) Known history of positive test for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed 
at sites where mandated locally (Appendix 7). 
4) Allergies and Adverse Drug Reaction 
a) History of allergy or hypersensitivity to study drug components 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
54 
Approved v 21.0 
930143391 2.0 
 
 
5) Other Exclusion Criteria 
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply and BMS approval is required.) 
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness 
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria. 
6.2.1 
BCG Unresponsive Definition and Patient Eligibility 
Patients are eligible for this study if they have persistent or recurrent high-risk NMIBC after 
treatment with at least 1 induction course of BCG (Section 6.1 [2c]). The recurrence must be ≤ 24 
months after the last dose of BCG and not meet the criteria to be classified as BCG unresponsive 
(Section 6.1 [2d]). 
In order to assess a participant’s eligibility for the study, the NMIBC recurrence must not meet the 
Food and Drug Administration (FDA) definition for BCG-unresponsive disease below:21 
• Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor 
invades the subepithelial connective tissue) disease within 12 months of completion of 
adequate BCG therapy** 
• Recurrent TaHG/any T1 disease within 6 months of completion of adequate BCG therapy** 
• T1HG disease at the first evaluation following an induction BCG course (at least 5 of 
6 induction doses) 
 
**Adequate BCG treatment is defined as at least 2 courses of BCG. This can include 2 
induction courses (at least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses 
of a second induction course) or 1 induction course (at least 5 of 6 induction doses) and at least 
2 of 3 doses of a maintenance cycle (“5+2”). 
This definition includes patients who have T1 disease at the first evaluation following induction 
BCG. The timing of the first disease evaluation following induction BCG may vary due to 
differences in local clinical practice and individual patient factors. To ensure a consistent approach 
in this study, the eligibility criteria exclude all patients with T1 disease within 6 months following 
induction BCG (see Section 6.2). 
Patients who have received less than adequate BCG as defined here (ie, only 1 course of induction 
BCG ± 1 additional BCG dose) cannot be considered BCG unresponsive (except patients with 
disease within 6 months of induction BCG therapy). T1 patients are eligible for the study if they 
have recurrence 6-24 months after the last BCG dose. 
6.3 
Lifestyle Restrictions 
Not applicable. No restrictions are required. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
55 
Approved v 21.0 
930143391 2.0 
 
 
6.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently randomized in the study/included in the analysis population. A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements, as applicable, and to respond to queries from regulatory authorities. Minimal 
information includes date of consent, demography, screen failure details, eligibility criteria, and 
any serious AEs (SAEs). 
6.4.1 
Retesting During Screening or Lead-In Period 
Participant reenrollment: This study permits the reenrollment of a participant who has discontinued 
the study as a pretreatment failure (ie, has not been treated). If reenrolled, the participant must be 
reconsented. 
Retesting of laboratory parameters and/or other assessments within any single screening or lead- 
in period will be permitted (in addition to any parameters that require a confirmatory value). 
The most current result prior to Randomization is the value by which study inclusion will be 
assessed, as it represents the participant’s most current, clinical state. 
Laboratory parameters and/or assessments that are included in Table 2-1, Screening Procedural 
Outline, may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant. 
7 
TREATMENT 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo or 
medical device intended to be administered to a study participant according to the study 
randomization or treatment allocation. 
Study 
treatment 
includes 
both 
Investigational 
[Medicinal] 
Product 
(IP/IMP) 
and 
Noninvestigational [Medicinal] Product (Non-IP/Non-IMP) and can consist of the following: 
• Nivolumab 
• Nivolumab-placebo, and 
• BCG. 
An investigational product, also known as investigational medicinal product in some regions, is 
defined 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- 
investigational products. 

 
Clinical Protocol 
CA2097G8 
BMS-936558 
Nivolumab 
 
Table 7-1: 
Study Treatments for CA2097G8 
 
Product Description/ 
Class and Dosage 
Form 
Potency 
IP/Non-IMP 
Blinded or Open 
Label 
Packaging/ 
Appearance 
Storage Conditions 
(per label) 
BMS-936558 
(Nivolumab) Solution 
for Injection 
10 mg/mL 
IP 
Open Labela 
Vials 
Refer to the label on 
container and/or 
Pharmacy Manual 
BCGb 
Various per BCG strain 
IP 
Open Labela 
Various per BCG strain 
As per package insert 
0.9% Sodium Chloride 
for Injection 
n/a 
IP 
Open Labela 
Various (local 
commercial product) 
As per package insert 
5% Dextrose for 
Injection 
n/a 
IP 
Open Labela 
Various (local 
commercial product) 
As per package insert 
a The term “open label” refers to the medication as it is upon receipt at the pharmacy. The trial will be conducted in a double-blinded fashion with respect to the 
nivolumab/nivolumab-placebo. 
b This product may be obtained by the investigational sites as local commercial product in certain countries as allowed by local regulations. These products should 
be prepared/stored/administered in accordance with the package insert or SmPC. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
56 
Approved v21.0 
930143391 2.0 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
57 
Approved v 21.0 
930143391 2.0 
 
 
7.1 
Treatments Administered 
The selection and timing of dose for each participant is as follows: 
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/ 
Nivolumab- 
placebo 
480 mg 
(n/a for placebo) 
Solution for injection 
administered every 4 weeks, max 
treatment duration is 2 years 
IV 
BCG 
Dose according to prescribing 
information for BCG strain 
Refer to Table 2-2 
Intravesical 
 
7.1.1 
Nivolumab Dosing 
Participants should receive nivolumab at a dose of 480 mg as an approximately 30-minute infusion 
on Day 1 of each treatment cycle until recurrence or progression, unacceptable toxicity, withdrawal 
of consent, completion of 24 months of treatment, or the study ends, whichever occurs first. If 
needed, flush the intravenous line with an appropriate amount of diluent (eg, 0.9% Sodium 
Chloride or 5% Dextrose in water) to ensure that the complete dose is administered over 
approximately 30 minutes. For participants with CIS and/or TaHG at Week 13 assessment, see 
Section 8.1.4. 
Participants should begin study treatment within 3 calendar days of randomization but no earlier 
than ≥ 14 days following last TURBT/bladder biopsy. Nivolumab/nivolumab-placebo and BCG 
should begin concurrently or within 3 days of each other. Cycle 1 will begin at the time of the first 
dose of study treatment. 
There should be a minimum of 26 days between nivolumab/nivolumab-placebo doses. There will 
be no dose escalations or reductions of nivolumab/nivolumab-placebo allowed. For Q4W dosing 
cycles, participants may be dosed within a ± 3 day window. Premedications are not recommended 
for the first dose of nivolumab/nivolumab-placebo. 
Participants should be carefully monitored for infusion reactions during nivolumab administration. 
If an acute infusion reaction is noted, participants should be managed according to Section 7.7.4. 
Doses of nivolumab/ nivolumab-placebo 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 Investigator Brochure and/or Pharmacy Manual for further details 
regarding storage, preparation, and administration of nivolumab. 
Care must be taken to assure sterility of the prepared solution as the product does not contain any 
antimicrobial preservative or bacteriostatic agent. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
58 
Approved v 21.0 
930143391 2.0 
 
 
7.1.2 
BCG Dosing 
Participants should begin study treatment within 3 calendar days of randomization but no earlier 
than ≥ 14 days following last TURBT/bladder biopsy. BCG and nivolumab/nivolumab-placebo 
should begin concurrently or within 3 days of each other. Cycle 1 will begin at the time of the first 
dose of study treatment. 
Participants should receive an intravesical instillation of BCG weekly for 6 weeks starting on Day 
1 of BCG treatment (induction period) and then weekly for 3 weeks at 3, 6, 12, 18, 24, 30 and 36 
months after the first BCG dose (maintenance period) (see Table 7.1.2-1). 
Table 7.1.2-1: 
Timing of Intravesical BCG Maintenance Dose 
 
Time 
Weekly BCG Dose (Days)a for 3 Weeks 
Months 
Week (Wk) 
Days to Dose 
3 
13 
Wk 14 (D1), Wk 15 (D1), Wk 16 (D1) 
6 
26 
Wk 27 (D1), Wk 28 (D1), Wk 29 (D1) 
12 
52 
Wk 53 (D1), Wk 54 (D1), Wk 55 (D1) 
18 
78 
Wk 79 (D1), Wk 80 (D1), Wk 81 (D1) 
24 
104 
Wk 105 (D1), Wk 106 (D1), Wk 107 (D1) 
30 
130 
Wk 131 (D1), Wk 132 (D1), Wk 133 (D1) 
36 
156 
Wk 157 (D1), Wk 158 (D1), Wk 159 (D1)b 
a Must be a minimum of 5 days between BCG doses. 
b Treatment will complete after 3 years and 15 days (± 3 days). 
 
The BCG dose should be prepared and administered according to the package insert. BCG may 
be obtained by the investigational sites, where possible/allowed by local regulations, as local 
commercial product in certain countries. These products should be prepared/stored/ 
administered in accordance with the package insert or SmPC and local practice. 
Typical procedure is as follows: 
• A urethral catheter will be inserted into the bladder by a qualified medical professional under 
aseptic conditions. The bladder will then be drained, after which the BCG suspension will be 
instilled slowly, under gravity. The catheter will then be withdrawn. BCG should not be given 
if the urethra is traumatized during catheter insertion or if there is gross hematuria. 
• The participant should retain the BCG suspension for as long as possible for up to 2 hours. The 
participant should lie prone during the first 15 minutes following instillation, after which the 
participant is allowed to be in the upright position. At the end of 2 hours, the participant should 
void in the seated position. The participant will be instructed to maintain adequate fluid intake 
in the hours following BCG treatment to flush the bladder. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
59 
Approved v 21.0 
930143391 2.0 
 
 
Participants should receive BCG until recurrence, progression, unacceptable toxicity, withdrawal 
of consent by the participant, or completion of 3 years of treatment, whichever occurs first. For 
participants with CIS and/or TaHG at Week 13 assessment, see Section 8.1.4. 
Participants should begin study treatment within 3 calendar days of randomization and at least 14 
days after the last bladder tumor resection or bladder biopsy, whichever occurs later (if local 
standard clinical practice requires longer than 14 days between biopsy and initiation of BCG, this 
is acceptable). If BCG treatment after the first dose is delayed for any reason, 
nivolumab/nivolumab-placebo should continue as scheduled, unless the participant has study drug 
toxicity meeting nivolumab dose delay criteria. If nivolumab is delayed for any reason, BCG 
treatment should continue as scheduled, unless the participant meets BCG dose delay criteria (eg, 
study drug toxicity or other reasons including traumatic catheterization/gross hematuria). 
For details on prepared drug storage, preparation, and administration, please see the BCG package 
insert. 
7.2 
Method of Treatment Assignment 
All participants will be centrally randomized using an IRT. Before the study is initiated, each user 
will receive log-in information and directions on how to access the IRT. After the participant’s 
initial eligibility is established and informed consent has been obtained, the participant must be 
enrolled into the study by accessing an IRT to obtain the participant number. Every participant 
who signs the informed consent form must be assigned a participant number in IRT. The 
investigator or designee will register the participant for enrollment by following the enrollment 
procedures established by BMS. The following information is required for enrollment: 
• Whether informed consent was obtained 
• Year of birth 
• Gender at birth 
 
Once enrolled in IRT, enrolled participants who have met all eligibility criteria will be ready to be 
randomized through the IRT. Disease status data will be transferred directly from the PRC. 
Confirmation of receipt of acceptable tumor tissue for biomarker analysis will be provided by the 
analytical laboratory. The following information is required for participant randomization: 
• Participant number 
• Year of birth 
• Disease status based on PRC assessment: 
o Presence of CISa (Yes vs No) 
o Presence of T1a,b (Yes vs No) 
o Presence of TaHGa,b,c (Yes vs No) 
• Time from last received BCG dose until high-risk NMIBC recurrencea,b,c (≤ 6 months after 
last BCG dose vs between 6 and ≤ 12 months after last BCG dose vs > 12 months after last 
BCG dose) 
• Intended BCG strain for study treatment (TICE vs other) 
• Confirmation of receipt of acceptable tumor tissue by the analytical laboratory 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
60 
Approved v 21.0 
930143391 2.0 
 
 
 
a Participants enrolled with CIS (+/- TaHG) will be considered as early recurrence if they have recurrence ≤ 6 months 
or between 6 and ≤ 12 months after last BCG dose, and will be considered as late recurrence if they have recurrence 
> 12 months after last BCG dose. Participants enrolled with CIS + T1 will be considered as early recurrence if they 
have recurrence between 6 and ≤ 12 months after last BCG dose, late recurrence if they have recurrence > 12 months 
after last BCG dose, and are not eligible if they have recurrence ≤ 6 months after last BCG dose (see also note b). 
b Participants enrolled with T1 (+/- TaHG) recurrence occurring ≤ 6 months after last BCG dose received will be 
excluded from the randomization, per eligibility criteria 2d Section 6.1, as they are considered as BCG unresponsive 
(defined in Section 6.2.1), and will be considered as late recurrence if they have recurrence between 6 and ≤ 12 
months or > 12 months after last BCG dose. 
c Participants enrolled with TaHG only will be considered as early recurrence if they have recurrence ≤ 6 months 
after last BCG dose, and will be considered as late recurrence if they have a recurrence between 6 and ≤ 12 months 
or > 12 months after last BCG dose. 
 
Study treatment will be dispensed at the study visits as listed in Schedule of Activities (Section 2). 
See Sections 5.1 and 5.1.2 for a description of treatment assignment during the treatment phase of 
the study. 
The exact details for using the IRT will be detailed in the IRT manual. 
7.3 
Blinding 
As of Protocol Amendment 01, it has been determined that blinding is not required. In both 
scenarios where the investigators may break the blind in the best interest of the participant or in 
case of accidental unblinding, IRT instructions should be followed along with a notification to the 
Medical Monitor. 
This is a randomized, double-blind study. Access to treatment codes will be restricted from all 
participants and site and BMS personnel prior to final database lock, with exceptions as specified 
below. Each investigative site must assign an unblinded pharmacist/designee, and an unblinded 
site monitor will be assigned to provide oversight of drug supply and other unblinded study 
documentation. 
To further minimize bias, the investigative clinical site staff is masked to results from PD-L1 
analysis. 
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual participant in which knowledge of the 
investigational product is critical to the participant's management, the blind for that participant 
may be broken by the investigator. The participant’s safety takes priority over any other 
considerations in determining if a treatment assignment should be unblinded. 
Before breaking the blind of an individual participant's treatment, the investigator should 
determine that the unblinded information is necessary, ie, that it will alter the participant's 
immediate management. In many cases, particularly when the emergency is clearly not related to 
the investigational product, the problem may be properly managed by assuming that the participant 
is receiving active product. It is highly desirable that the decision to unblind treatment assignment 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
61 
Approved v 21.0 
930143391 2.0 
 
 
be discussed with the Medical Monitor, but the investigator always has ultimate authority for the 
decision to unblind. The actual TASK of unblinding can be delegated by the investigator to a 
designee assigned the task on the Delegation of Authority. The Principal Investigator or appointed 
designee should only call in for emergency unblinding AFTER the decision to unblind the 
participant has been documented. 
For this study, the method of unblinding for emergency purposes is through the IRT. For 
information on how to unblind in an emergency, consult the IRT manual. 
In case of an emergency, the investigator(s) has unrestricted access to randomization information 
via the IRT and is capable of breaking the blind through the IRT system without prior approval 
from sponsor. Following the unblinding, the Investigator shall notify the Medical Monitor and/or 
designee. 
In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt is made 
to preserve the blind. 
Any request to unblind a participant for nonemergency purposes should be discussed with the 
Medical Monitor. 
Designated staff of BMS Research & Development (R&D) may be unblinded (obtain the 
randomization codes) prior to database lock to facilitate the bioanalytical analysis of PK samples 
and immunogenicity. A bioanalytical scientist in the Bioanalytical Sciences department of BMS 
R&D (or a designee in the external central bioanalytical laboratory) will be unblinded to (may 
obtain) the randomized treatment assignments in order to minimize unnecessary bioanalytical 
analysis of samples. 
7.4 
Dosage Modification 
AE criteria for delaying, resuming, and discontinuing study treatment is provided in Table 7.4-1. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 7.4-1: 
Adverse Event Criteria for Delay, Resume, and Discontinuation of Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
62 
Approved v21.0 
930143391 2.0 
 
 
 
 
Drug-related AE per NCI CTCAE v5 
Severity 
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
Gastrointestinal 
Colitis or Diarrhea 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to baseline 
Grade 3 
Nivolumab monotherapy: 
Delay dose 
Dosing may resume when AE resolves to baseline 
Grade 4 
Permanently discontinue 
Renal 
Serum Creatinine Increased 
Grade 2 or 3 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value 
Grade 4 
Permanently discontinue 
Pulmonary 
Pneumonitis 
Grade 2 
Delay dose 
Dosing may resume after pneumonitis has resolved 
to ≤ Grade 1 
Grade 3 or 4 
Permanently discontinue 
Hepatic 
AST, ALT, or TBili increased 
AST or ALT > 3× and ≤ 5× 
ULN or TBili > 1.5× and ≤ 
3× ULN, regardless of 
baseline value 
Delay dose 
Dosing may resume when laboratory values return to 
baseline after discussion with the Medical Monitor 
AST or ALT > 5× ULN or 
TBili > 3× ULN, regardless 
of baseline value 
Delay dose or 
permanently discontinue 
In most cases of AST or ALT > 5× ULN, study 
treatment will be permanently discontinued. If the 
investigator determines a possible favorable 
benefit/risk ratio that warrants continuation of study 
treatment, a discussion between the investigator and 
the Medical Monitor/designee must occur and 
approval must be obtained from Medical Monitor 
prior to resuming therapy 
Concurrent AST or ALT > 
3× ULN and TBili > 2× 
Permanently discontinue 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 7.4-1: 
Adverse Event Criteria for Delay, Resume, and Discontinuation of Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
63 
Approved v21.0 
930143391 2.0 
 
 
 
 
Drug-related AE per NCI CTCAE v5 
Severity 
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
ULN, regardless of baseline 
value 
Endocrinopathy 
Adrenal Insufficiency 
Grade 2 adrenal insufficiency 
Delay dose 
Dosing may resume after adequately controlled with 
hormone replacement 
Grade 3 or 4 adrenal 
insufficiency or adrenal crisis 
Delay dose or 
permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If adrenal insufficiency resolves or is adequately 
controlled with physiologic hormone replacement, 
participant may not require discontinuation of study 
drug 
Hyperglycemia 
Hyperglycemia requiring 
initiation or change in daily 
management (Grade 2 or 3) 
Delay dose 
Dosing may resume if hyperglycemia resolves to 
Grade ≤ 1 or baseline value or is adequately 
controlled with glucose-controlling agents 
Grade 4 
Delay dose or 
permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If hyperglycemia resolves or is adequately controlled 
with glucose-controlling agents, participant may not 
require discontinuation of study drug 
Hypophysitis/Hypopituitarism 
Symptomatic Grade 1-3 that 
is also associated with 
corresponding abnormal 
laboratory value and/or 
pituitary scan 
Delay dose 
Dosing may resume if endocrinopathy resolves to be 
asymptomatic or is adequately controlled with only 
physiologic hormone replacement 
Grade 4 
Delay dose or 
permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If endocrinopathy resolves or is adequately 
controlled with physiologic hormone replacement, 
participant may not require discontinuation of study 
drug 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 7.4-1: 
Adverse Event Criteria for Delay, Resume, and Discontinuation of Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
64 
Approved v21.0 
930143391 2.0 
 
 
 
 
Drug-related AE per NCI CTCAE v5 
Severity 
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
Hyperthyroidism or Hypothyroidism 
Grade 2 or 3 
Delay dose 
Dosing may resume if endocrinopathy resolves to be 
asymptomatic or is adequately controlled with only 
physiologic hormone replacement or other medical 
management 
Grade 4 
Delay dose or 
permanently discontinue 
Mandatory discussion with and approval from the 
Medical Monitor needed prior to resuming therapy. 
If endocrinopathy resolves or is adequately 
controlled with physiologic hormone replacement or 
other medical management, participant may not 
require discontinuation of study drug 
Skin 
Rash 
Grade 2 rash covering > 30% 
body surface area or Grade 3 
rash 
Delay dose 
Dosing may resume when rash reduces to ≤ 10% 
body surface area 
Suspected Stevens-Johnson 
syndrome (SJS), toxic 
epidermal necrolysis (TEN), 
or drug reaction with 
eosinophilia and systemic 
symptoms (DRESS) 
Delay dose 
Dosing may resume if SJS, TEN, or DRESS is ruled 
out and rash reduces to ≤ 10% body surface area 
Grade 4 rash or confirmed 
SJS, TEN, or DRESS 
Permanently discontinue 
Neurological 
Guillain-Barre Syndrome (GBS) 
Any Grade 
Permanently discontinue 
Myasthenia Gravis (MG) 
Any Grade 
Permanently discontinue 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 7.4-1: 
Adverse Event Criteria for Delay, Resume, and Discontinuation of Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
65 
Approved v21.0 
930143391 2.0 
 
 
 
 
Drug-related AE per NCI CTCAE v5 
Severity 
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
Encephalitis 
Any Grade encephalitis 
Delay dose 
After workup for differential diagnosis (ie, infection, 
tumor related), if encephalitis is not drug related, 
then dosing may resume when AE resolves 
Any Grade drug-related 
encephalitis 
Permanently discontinue 
Myelitis 
Any Grade myelitis 
Delay dose 
After workup for differential diagnosis (ie, infection, 
tumor related), if myelitis is not drug related, then 
dosing may resume when AE resolves 
Any Grade drug-related 
myelitis 
Permanently discontinue 
Neurological (other than GBS, MG, 
encephalitis, or myelitis) 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to baseline 
Grade 3 or 4 
Permanently discontinue 
Myocarditis 
Myocarditis 
Symptoms induced from 
mild to moderate activity or 
exertion 
Delay dose 
Dosing may resume after myocarditis has resolved 
Severe or life-threatening, 
with symptoms at rest or with 
minimal activity or exertion 
and/or where intervention 
indicated 
Permanently discontinue 
Other Clinical AEs 
Pancreatitis: 
Amylase or Lipase Increased 
Grade 3 with symptoms 
Delay dose 
Note: Grade 3 increased amylase or lipase without 
signs or symptoms of pancreatitis does not require 
dose delay 
Dosing may resume when participant becomes 
asymptomatic 
Grade 4 
Permanently discontinue 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 7.4-1: 
Adverse Event Criteria for Delay, Resume, and Discontinuation of Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
66 
Approved v21.0 
930143391 2.0 
 
 
 
 
Drug-related AE per NCI CTCAE v5 
Severity 
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
Uveitis 
Grade 2 uveitis 
Delay dose 
Dosing may resume if uveitis responds to topical 
therapy (eye drops) and after uveitis resolves to 
Grade ≤ 1 or baseline. If participant requires oral 
steroids for uveitis, then permanently discontinue 
study drug 
Grade 3 or 4 uveitis 
Permanently discontinue 
Other Drug-related AE 
(not listed above) 
Grade 2 non-skin AE, except 
fatigue 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value 
Grade 3 AE - First 
occurrence lasting ≤ 7 days 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value 
Grade 3 AE - First 
occurrence lasting > 7 days 
Permanently discontinue 
Recurrence of Grade 3 AE of 
any duration 
Permanently discontinue 
Grade 4 or life-threatening 
adverse reaction 
Permanently discontinue 
Other Laboratory Abnormalities 
Other Drug-related Laboratory 
Abnormality (not listed above) 
Grade 3 
Delay dose 
Exceptions: 
No delay required for: Grade 3 lymphopenia 
Permanent discontinuation for: Grade 3 
thrombocytopenia > 7 days or associated with 
bleeding 
Grade 4 
Permanently discontinue 
Exceptions: The following events do not require 
discontinuation of study drug: 
• 
Grade 4 neutropenia ≤ 7 days 
• 
Grade 4 lymphopenia or leukopenia 
• 
Grade 4 isolated electrolyte 
imbalances/abnormalities that are not associated 
with clinical sequelae and are responding to 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Table 7.4-1: 
Adverse Event Criteria for Delay, Resume, and Discontinuation of Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
67 
Approved v21.0 
930143391 2.0 
 
 
 
 
Drug-related AE per NCI CTCAE v5 
Severity 
Action Taken 
Clarifications, Exceptions, and Resume Criteria 
supplementation/appropriate management within 
72 hours of their onset 
Infusion Reactions 
(Manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other allergic-like reactions) 
Hypersensitivity Reaction or Infusion 
Reaction 
Grade 3 or 4 
Permanently discontinue 
See Section 7.7.4 (Treatment of Infusion-related 
Reactions) 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DRESS, drug reaction with eosinophilia and systemic symptoms; 
GBS, Guillain-Barre syndrome; MG, myasthenia gravis; NCI CTCAE v5, National Cancer Institute Common Terminology Criteria for Adverse Events version 5; 
SJS, Stevens-Johnson syndrome; TBili, total bilirubin; TEN, toxic epidermal necrolysis; ULN, upper limit of normal. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
68 
Approved v 21.0 
930143391 2.0 
 
 
7.4.1 
Nivolumab/Nivolumab-placebo Dose Modifications 
No dose modifications are permitted for nivolumab/nivolumab-placebo. 
7.4.2 
BCG Dose Modifications 
BCG dose modification due to BCG toxicity (such as dysuria, urinary frequency, urinary urgency, 
cystitis, and hematuria) is allowed according to local guidelines and standard clinical 
practice.43,44,45,46 
documented in the case report form (CRF). 
7.4.3 
Dose Delay Criteria 
7.4.3.1 
Nivolumab/Nivolumab-placebo Dose Delay Criteria 
Dose delay criteria apply for all drug-related AEs, regardless of whether the event is attributed to 
nivolumab, placebo, or both. Delay administration of both nivolumab and placebo if any of the 
delay criteria in Table 7.4-1 are met. Delay nivolumab and placebo dosing for any AE, laboratory 
abnormality, or intercurrent illness which, in the judgement of the investigator, warrants delaying 
the dose of study medication. 
Delay administration of both nivolumab and placebo in case of severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infection, either confirmed or suspected. 
For participants who require delay of nivolumab/nivolumab-placebo, re-evaluate weekly, or more 
frequently, if clinically indicated and resume dosing when criteria to resume treatment are met (see 
Section 7.4.4). Continue tumor assessments per protocol even if dosing is delayed. 
Administration of BCG should not be delayed if nivolumab/nivolumab-placebo treatment is 
delayed. 
7.4.3.2 
BCG Dose Delay Criteria 
Administration of BCG should be delayed if the participant develops a concurrent febrile illness, 
a urinary tract infection (UTI), or gross hematuria during the treatment period and for 14 days after 
traumatic urinary catheterization or bladder biopsy. In addition, investigators may delay BCG in 
accordance with clinical judgment and standard local practice. The reason for dose delay must be 
clearly documented. 
Administration of nivolumab/nivolumab-placebo should not be delayed if BCG treatment is 
delayed. 
7.4.4 
Criteria to Resume Treatment 
7.4.4.1 
Nivolumab/Nivolumab-placebo Criteria to Resume Treatment 
Participants may resume study treatment if they have completed AE management (ie, corticosteroid taper) or 
are on ≤ 10 mg prednisone or equivalent and meet the requirements per Table 7.4-1. 
• Prior to re-initiating treatment in a participant with a dosing delay lasting > 10 weeks, the 
Medical Monitor (or designee) must be consulted. Continue tumor assessments per protocol 
The reason for dose reduction, and the change of dose, must be clearly 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
69 
Approved v 21.0 
930143391 2.0 
 
 
even if dosing is delayed. Continue periodic study visits to assess safety and laboratory studies 
every 4 weeks or more frequently if clinically indicated during such dosing delays. 
• Participants with SARS-CoV-2 infection (either confirmed or suspected) may resume 
treatment if all of the following are met: 
− At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive test result (eg, RT-PCR or viral antigen); and 
− Resolution of acute symptoms (including at least 24 hours has passed since last fever 
without fever reducing medications); and 
− 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 with the Medical Monitor or designee. For suspected cases, treatment may 
also resume if SARS-CoV-2 infection is ruled out and other criteria to resume treatment 
are met. 
 
7.4.4.2 
BCG Criteria to Resume Treatment 
BCG administration can resume when the concurrent febrile illness, UTI, or gross hematuria 
resolve and antibiotic treatment has ended. For other dose delay reasons, BCG can resume in 
accordance with clinical judgment and standard local practice. 
• Participants with SARS-CoV-2 infection (either confirmed or suspected) may resume 
treatment if all of the following are met: 
− At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive test result (eg, RT-PCR or viral antigen); and 
− Resolution of acute symptoms (including at least 24 hours has passed since last fever 
without fever reducing medications); and 
− 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 with the Medical Monitor or designee. For suspected cases, treatment may 
also resume if SARS-CoV-2 infection is ruled out and other criteria to resume treatment 
are met. 
 
7.4.5 
Management Algorithms for Immuno-oncology Agents 
I-O agents are associated with AEs that can differ in severity and duration than AEs caused by 
other therapeutic classes. Nivolumab is considered as the I-O agent in this protocol. Early 
recognition and management of AEs associated with I-O agents may mitigate severe toxicity. 
Management algorithms have been developed to assist investigators in assessing and managing 
the following groups of AEs: 
• Gastrointestinal 
• Renal 
• Pulmonary (For participants with dyspnea, complete blood count (CBC) and methemoglobin 
should be measured.) 
• Hepatic 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
70 
Approved v 21.0 
930143391 2.0 
 
 
• Endocrinopathy 
• Skin 
• Neurological (For participants with confusion, methemoglobin should be measured.) 
• Myocarditis 
The above algorithms are found in the Appendix 5 of this protocol. 
7.5 
Preparation/Handling/Storage/Accountability 
For nivolumab, refer to the current version of the IB and/or Pharmacy Manual for complete 
storage, handling, dispensing, and infusion information. 
For BCG, refer to the current prescribing information for complete storage, handling, and 
dispensing information. 
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 contact BMS immediately. 
Study treatment not supplied by BMS will be stored in accordance with the package insert. 
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets). 
Further guidance and information for final disposition of unused study treatment are provided in 
Appendix 2. 
7.5.1 
Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
Not applicable. 
7.6 
Treatment Compliance 
Study treatment compliance will be periodically monitored by drug accountability, as well as the 
participant’s medical record and electronic case report form. Drug accountability should be 
reviewed by the site study staff at each visit to confirm treatment compliance. Sites should discuss 
discrepancies with the participant at each on-treatment study visit. 
7.7 
Concomitant Therapy 
Concomitant medications are recorded at baseline and throughout the treatment phase of the study 
in the appropriate section of the CRF. All medications (prescriptions or over-the-counter 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
71 
Approved v 21.0 
930143391 2.0 
 
 
medications) continued at the start of the study or started during the study and different from the 
study treatment must be documented in the concomitant therapy section of the CRF. 
Coronavirus disease 2019 (COVID-19) vaccines that are NOT live are allowed and should be 
handled in the same manner as other vaccines. Administration may occur during the study, 
including during the administration of the BMS study treatment and after the last administration 
of the BMS study treatment. Non-live 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 nivolumab, with or without intravesical BCG, 
is unknown. 
7.7.1 
Prohibited and/or Restricted Treatments 
The following medications are prohibited during the study until recurrence or progression (unless 
utilized to treat a drug-related AE): 
• Immunosuppressive agents 
• Immunosuppressive doses of systemic corticosteroids (except as stated in Section 7.7.3) 
• Any concurrent antineoplastic therapy (ie, chemotherapy, hormonal therapy, immunotherapy, 
extensive, nonpalliative radiation therapy, or standard or investigational agents for treatment 
of NMIBC) 
• Any complementary medications (eg, herbal supplements, traditional Chinese medicines, 
marijuana and its derivatives) intended to treat the disease under study. Such medications are 
permitted if they are used as supportive care. Approval from BMS-Medical Monitor (or 
designee) is required prior to concurrent use. 
• Any live/attenuated vaccine (eg, varicella; zoster; yellow fever; rotavirus; oral polio; and 
measles, mumps, rubella) during treatment and until 100 days post last dose. 
 
7.7.2 
Other Restrictions and Precautions 
Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg 
daily prednisone equivalent) or other immunosuppressive medications within 14 days of 
randomization are excluded. Inhaled or topical steroids, and adrenal replacement steroid 
doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune 
disease. 
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 for each participant. Imaging contraindications and contrast risks should be considered in 
this assessment. Participants with renal insufficiency should be assessed as to whether or not they 
should receive contrast and, if so, what type and dose of contrast is appropriate. Specific to MRI, 
participants with severe renal insufficiency (ie, estimated glomerular filtration rate [eGFR] 
< 30 mL/min/1.73 m2) are at increased risk of nephrogenic systemic fibrosis. MRI contrast should 
not be given to this participant population. In addition, participants may be excluded from MRI if 
they have tattoos, metallic implants, pacemakers, etc. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
72 
Approved v 21.0 
930143391 2.0 
 
 
Gentle hydration before and after IV contrast should follow local SOC. The ultimate decision to 
perform MRI in an individual participant in this study rests with the site radiologist, the 
investigator, and the standards set by the local Ethics Committee. 
7.7.3 
Permitted Therapy 
Participants are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses > 10 mg 
daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for 
prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune conditions (eg, delayed- 
type hypersensitivity reaction caused by a contact allergen) is permitted. 
7.7.4 
Treatment of Infusion-related Reactions 
If an infusion-related reaction should occur, it might manifest with fever, chills, rigors, headache, 
rash, pruritus, arthralgias, hypotension, hypertension, bronchospasm, or other allergic-like 
reactions. All Grade 3 or 4 infusion reactions should be reported within 24 hours to the study 
Medical Monitor/designee and reported as an SAE if it meets the criteria. Infusion reactions should 
be graded according to National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE; Version 5.0) guidelines. 
Treatment recommendations are provided below and may be modified based on local treatment 
standards and guidelines, as appropriate: 
For Grade 1 symptoms (mild reaction; infusion interruption not indicated; intervention not 
indicated): 
• Remain at bedside and monitor participant until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg at least 30 minutes before 
additional nivolumab administrations. 
 
For Grade 2 symptoms (moderate reaction required therapy or infusion interruption but responds 
promptly to symptomatic treatment [eg, antihistamines, nonsteroidal anti-inflammatory drugs, 
narcotics, corticosteroids, bronchodilators, IV fluids]); prophylactic medications indicated for 
≤ 24 hours): 
• Stop the study treatment infusion, begin an IV infusion of normal saline, and treat the 
participant 
with 
diphenhydramine 
50 
mg 
IV 
(or 
equivalent) 
and/or 
acetaminophen/paracetamol 325 to 1000 mg; remain at bedside and monitor participant until 
resolution of symptoms. Corticosteroid and/or bronchodilator therapy may also be 
administered as appropriate. If the infusion is interrupted, then restart the infusion at 50% of 
the original infusion rate when symptoms resolve; if no further complications ensue after 
30 minutes, the rate may be increased to 100% of the original infusion rate. Monitor participant 
closely. If symptoms recur, then no further study treatment will be administered at that visit. 
• For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
73 
Approved v 21.0 
930143391 2.0 
 
 
should be administered at least 30 minutes before nivolumab infusion. If necessary, 
corticosteroids (up to 25 mg of hydrocortisone or equivalent) may be used. 
 
For Grade 3 or 4 symptoms (severe reaction, Grade 3: prolonged [ie, not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following 
initial improvement; hospitalization indicated for other clinical sequelae [eg, renal impairment, 
pulmonary infiltrates]). Grade 4: Life-threatening; pressor or ventilatory support indicated): 
• Immediately discontinue infusion of study treatment. Begin an IV infusion of normal saline 
and treat the participant as follows: Recommend bronchodilators, epinephrine 0.2 to 1 mg of a 
1:1000 solution for subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution 
injected slowly for IV administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed. Participant should be monitored 
until the investigator is comfortable that the symptoms will not recur. Study treatment will be 
permanently discontinued. Investigators should follow their institutional guidelines for the 
treatment of anaphylaxis. Remain at bedside and monitor participant until recovery of the 
symptoms. 
 
In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine or corticosteroids). 
7.8 
Treatment After the End of the Study 
At the end of the treatment period as defined in Section 7.1, BMS will not continue to provide 
BMS-supplied study treatment to participants/investigators unless BMS chooses to extend the 
study. The investigator should ensure that the participant receives appropriate SOC to treat the 
condition under study. 
8 
DISCONTINUATION CRITERIA 
8.1 
Discontinuation From Study Treatment 
Participants MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons: 
• Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information 
• Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the best 
interest of the participant 
• Termination of the study by BMS 
• Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
74 
Approved v 21.0 
930143391 2.0 
 
 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply and 
BMS approval is required.) 
• Additional protocol-specified reasons for discontinuation (Sections 8.1.1 and 8.1.2) 
• Disease progression or recurrence locally diagnosed. 
 
Refer to the Schedule of Activities, 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, the investigator must immediately, within 24 hours of awareness of the 
pregnancy, notify the BMS Medical Monitor/designee of this event. In most cases, the study 
treatment will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for participant safety). Refer to Section 9.2.5. 
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 (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness). 
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page. 
8.1.1 
Nivolumab/Nivolumab-placebo Dose Discontinuation 
Nivolumab/nivolumab-placebo treatment must be permanently discontinued per criteria in Table 
7.4-1 in Section 7.4. Discontinue nivolumab for 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. 
• 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 adverse events 
are allowed. 
− Dosing delays lasting > 6 weeks from the previous dose that occur for non-drug-related 
reasons may be allowed if approved by the BMS Medical Monitor (or designee). 
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 every 6 weeks or more frequently if clinically indicated during such dosing 
delays. 
Any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of the 
Investigator, presents a substantial clinical risk to the participant with continued nivolumab dosing. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
75 
Approved v 21.0 
930143391 2.0 
 
 
8.1.2 
Discontinuation of BCG 
BCG treatment should be permanently discontinued for the following: 
• Any event requiring discontinuation of nivolumab/nivolumab-placebo as in Section 8.1.1 
• Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
investigator, presents a substantial clinical risk to the participant with continued BCG dosing 
• Systemic BCG reaction (see current BCG prescribing information for description) 
• BCG infection (see current BCG prescribing information for description) 
 
Participant may continue nivolumab/nivolumab-placebo treatment if BCG is discontinued. 
The duration of treatment with BCG is based on global standard evidence-based guidelines 
(Section 5.4.5). Every effort should be made to treat participants with the full course of BCG as 
defined in the protocol, although if the participant and investigator agree that it is in the 
participant’s best interests to discontinue BCG treatment, the participant should be counselled 
appropriately and the reason for discontinuation should be documented in the CRF. 
8.1.3 
Post Study Treatment Study Follow-up 
Per Protocol Amendment 01, efficacy follow-up is not required. Participants on efficacy follow- 
up at the time of Protocol Amendment 01 implementation at each site will conclude efficacy 
follow-up. Local standard of care assessments should be followed. 
Participants will be followed for assessment of safety through 100 days post last dose of study 
treatment. 
Not applicable per Protocol Amendment 01: 
In this study, EFS is a key endpoint of the study. Post study follow-up is of critical importance and 
is essential to preserving participant safety and the integrity of the study. Participants who 
discontinue study treatment must continue to be followed (in this study or a rollover study) for 
collection of outcome and/or survival follow-up data as required and in line with Section 5 until 
death or the conclusion of the study. 
BMS may request that survival data be collected on all treated/randomized participants outside of 
the protocol-defined window (Section 2, Table 2-3). At the time of this request, each participant 
will be contacted to determine his/her survival status unless the participant has withdrawn consent 
for all contacts or is lost to follow-up. 
8.1.4 
CIS and/or TaHG at Week 13: Continued Treatment 
Participants should continue treatment with nivolumab/nivolumab-placebo and BCG until disease 
recurrence, progression, unacceptable toxicity, treatment discontinuation, or until the end of the 
defined treatment periods. 
In participants with CIS (with or without papillary disease) at baseline, the presence of CIS and/or 
a positive cytology at the first disease assessment (Week 13) is defined as an EFS event and is 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
76 
Approved v 21.0 
930143391 2.0 
 
 
considered equivalent to recurrence. The presence of TaHG is considered recurrence and also 
defined as an EFS event (see Section 9.1.1). 
Evidence from the BCG-naïve setting suggests47 that with continued BCG exposure, many 
participants with CIS at the first disease assessment respond to continued BCG treatment after the 
first disease assessment (Week 13) and by the second disease assessment (Week 26). For this 
reason, study participants who have CIS at Week 13 (either positive cytology, cystoscopy and 
biopsy findings, or both) may continue treatment until Week 26. Similarly, participants with TaHG 
at Week 13 may also derive delayed benefit from continued treatment, and may also continue on 
study treatment until Week 26. TaHG at Week 13 should be treated with TURBT as appropriate 
in line with SOC. 
Participants with CIS and/or TaHG at Week 13 must have no other evidence of recurrence or 
progression to continue treatment. It is at the investigator’s discretion to continue treating such 
participants based on their clinical assessment of the best interests of the participant and 
appropriate patient counselling and documented consent, including consideration of alternative 
treatment options such as cystectomy. 
In participants who have CIS and/or TaHG disease at Week 13 and who are treated beyond Week 
13, subsequent CIS or recurrent TaHG a will require permanent discontinuation. 
8.2 
Discontinuation from the Study 
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol specified follow-up procedures. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 
• Participants should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible. 
• The withdrawal of consent should be explained in detail in the medical records by the 
investigator, as to whether the withdrawal is from further treatment with study treatment only 
or also from study procedures and/or post treatment study follow-up, and entered on the 
appropriate CRF page. 
• In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law. 
• If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
8.3 
Lost to Follow-up 
• All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant. 
• Lost to follow-up is defined by the inability to reach the participant after a minimum of three 
documented phone calls, faxes, or emails as well as lack of response by participant to one 
registered mail letter. All attempts should be documented in the participant’s medical records. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
77 
Approved v 21.0 
930143391 2.0 
 
 
• 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. 
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 randomization. The investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in the Schedule of Activities. 
 
Additional measures, including non-study required laboratory tests, should be performed as 
clinically indicated or to comply with local regulations. Laboratory toxicities (eg, suspected drug 
induced liver enzyme evaluations) will be monitored during the follow-up phase via on-site/local 
labs until all study drug-related toxicities resolve, return to baseline, or are deemed irreversible. 
Evaluate participant immediately to rule out cardiac or pulmonary toxicity if participant shows 
cardiac or pulmonary-related signs (hypoxia, abnormal heart rate, or changes from baseline) or 
symptoms (eg, dyspnea, cough, chest pain, fatigue, palpitations). 
Some of the assessments referred to in this section may not be captured as data in the CRF. They 
are intended to be used as safety monitoring by the treating physician. Additional testing or 
assessments may be performed as clinically necessary or where required by institutional or local 
regulations. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
78 
Approved v 21.0 
930143391 2.0 
 
 
9.1 
Efficacy Assessments 
Per Protocol Amendment 01, efficacy assessments will be conducted per the local standards of 
care. 
Not applicable per Protocol Amendment 01: 
Efficacy assessments occur until disease recurrence (other than TaLG) or progression, per PRC 
(based on a positive urinary cytology, bladder biopsy, or imaging), or until treatment 
discontinuation, whichever occurs later (Table 2-2 and Table 2-3). 
9.1.1 
Event-free Survival Evaluation 
Not applicable per Protocol Amendment 01: 
The following events, included in the EFS definition, will be assessed by the PRC per its charter 
and by the investigator throughout the duration of the study (see below): 
• CR in CIS participants 
• Persistent CIS (Week 13) in CIS participants 
• Recurrence 
• Progression 
 
If the PRC is no longer active during the follow-up phase, events will be assessed by the 
investigator. 
9.1.2 
Complete Response Assessment in CIS Participants 
Not applicable per Protocol Amendment 01: 
Determination of CR in CIS participants will be based on results of: 
• Cystoscopy and urinary cytology (Sections 9.1.3 and 9.1.4) at all time points 
• Bladder biopsy (Section 9.1.5) at the Week 26 time point and at any time point where 
biopsy is done for cause 
• Imaging assessments (Section 9.1.7) 
CIS participants are those with CIS +/- papillary disease prior to study entry. 
9.1.2.1 
Complete Response at First On-study Assessment (Week 13) 
Not applicable per Protocol Amendment 01: 
A CIS participant will be classified as having a CR at the first on-study assessment (Week 13) if 
the participant has a normal cystoscopy with a negative (including atypical) urinary cytology. 
In case of abnormal cystoscopy, a biopsy of the abnormal area(s) in the bladder (Section 9.1.5) is 
required. Participants will be classified as having a CR at the first on-study assessment if biopsies 
are free of TaHG or ≥ T1 UC or CIS. The biopsy may show TaLG UC only. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
79 
Approved v 21.0 
930143391 2.0 
 
 
In the case of suspicious cytology and no abnormalities or TaLG UC only on biopsy, see Section 
9.1.4.2. For details on positive/suspicious cytology with a normal biopsy and the assessment of 
CR, see Sections 9.1.4.1 and 9.1.4.2. 
9.1.2.2 
Persistent CIS at First On-study Assessment (Week 13) 
Not applicable per Protocol Amendment 01: 
CIS participants with persistent CIS at Week 13 who develop a concurrent TaHG or T1 papillary 
tumor at the first on-study evaluation, or biopsy-confirmed stage ≥ T1 will be classified as disease 
recurrence and/or progression as appropriate (see Table 9.1.2.4-1). 
CIS participants with persistent CIS at Week 13 who do not develop a concurrent TaHG or T1 
papillary tumor, or biopsy-confirmed stage ≥ T1 will be classified as persistent CIS. This will be 
classified as an EFS event. 
For details on positive/suspicious cytology with a normal biopsy and the assessment of CR, see 
Sections 9.1.4.1 and 9.1.4.2. 
9.1.2.3 
Complete Response After First On-study Assessment in Participants 
with Persistent CIS at First Assessment 
Not applicable per Protocol Amendment 01: 
Participants with CIS at the first disease assessment will be permitted to continue on study 
treatment until Week 26 (see Section 8.1.4), based on the clinical judgment of the investigator. 
Such participants may have a CR at the Week 26 assessment. 
CIS participants with persistent CIS only at the first on-study evaluation can be classified as having 
a CR at the Week 26 assessment if the following criteria are met: cystoscopic examination of the 
bladder must either be normal based on investigator report or, if any abnormality is seen, biopsy 
of the abnormal area(s) must not demonstrate TaHG UC, any ≥ T1 UC, or CIS. Participants with 
only TaLG UC will be classified as having CR. 
For details on positive/suspicious cytology with a normal biopsy and the assessment of CR, see 
Sections 9.1.4.1 and 9.1.4.2. 
The primary endpoint of EFS and the secondary endpoint of CR rate will be based on the Week 
13 CR assessment only. DoR will include the Week 13 assessment and subsequent assessments. 
Exploratory endpoints will examine CR at additional time points (see Section 4). 
9.1.2.4 
Disease Recurrence/Progression 
Per Protocol Amendment 01, disease recurrence and progression will be determined in all 
participants throughout the duration of the study by the investigator according to local standards 
of care. 
Not applicable per Protocol Amendment 01: 
This determination of recurrence or progression will be based on evaluation of urinary cytology 
and tissue obtained at bladder biopsy, whether the biopsy is performed for cause or as required by 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
80 
Approved v 21.0 
930143391 2.0 
 
 
the protocol. Any abnormality in any participant (CIS or non-CIS) discovered on cystoscopic 
examination of the bladder that is suspicious for recurrent papillary tumor or CIS must be biopsied 
and evaluated. This biopsy is in addition to the required biopsies in screening and at Week 26 in 
CIS participants. Protocol-defined or off-schedule imaging may also inform a diagnosis of 
progression. 
Recurrence is defined as the presence of high-risk bladder lesions, including TaHG or T1 UC or 
CIS in the bladder biopsy specimen. Participants with only TaLG UC on bladder biopsy will not 
be classified as having a recurrence, per PRC. 
Recurrence is also defined as a positive (malignant) urinary cytology, per PRC. A positive urinary 
cytology should be investigated as detailed in Section 9.1.4.1. 
A suspicious urine cytology must be evaluated as described in Sections 9.1.4.1 and 9.1.4.2. A 
suspicious cytology alone does not define recurrence. Participants with an initial suspicious 
cytology who are found to have a positive (malignant) cytology on repeat testing, high-risk disease 
on for-cause or random biopsies from the bladder or prostatic urethra (CIS, TaHG, ≥ T1), or an 
upper tract lesion on imaging will be classified as having recurrence/progression on the date of the 
original suspicious cytology result. 
CIS participants with CIS only +/- positive cytology at Week 13 will be classified as having 
persistent disease. This is considered equivalent to recurrence. 
Participants with CIS and/or Ta at Week 13 may continue treatment, irrespective of disease stage 
at screening. Participants with Ta who continue treatment must have resection (TURBT) of disease 
in accordance with SOC (see Section 8.1.4). 
Progression is defined as any tumor invasion into the muscularis propria of the bladder (ie, 
progression of any high-risk NMIBC to MIBC [Stage T2 or greater]) or the development of 
extravesical or disseminated disease based on cross-sectional imaging and/or clinical examination, 
whichever occurs first. Although not required, progression detected by imaging and/or clinical 
examination should be confirmed histologically, if feasible. 
The classification of recurrence and progression is summarized in Table 9.1.2.4-1. 

 
Clinical Protocol 
CA2097G8 
BMS-936558 
Nivolumab 
 
Table 9.1.2.4-1: 
Determination of Recurrent/Progression of High-risk NIMBC 
 
Baselinea 
On-treatment (All visits) 
TaLGb 
TaHGc 
T1 
CISd 
Positive Cytology 
Onlyd 
Muscle-invasive 
(>=T2)/Locoregional (Extra 
Vesical)/Regional Node/ 
Metastasis/Upper Urinary Tract 
Tumor 
(1) Non-CIS TaHG 
(2) CIS Alone 
(3) CIS with TaLG 
(4) CIS with TaHG 
(5) Non-CIS T1 
(6) CIS with T1 
No event 
Recurrence 
Recurrence 
Recurrence 
Recurrence 
Progression 
a Arranged from lowest to highest severity. 
b Participants with TaLG alone at baseline are not eligible for the study. 
c Participants with TaHG at Week 13 may continue treatment after TURBT. Please see Section 8.1.4. 
d Participants with CIS and/or positive cytology only at Week 13 may continue treatment, and may be considered to have persistent disease rather than recurrence. 
(see Section 8.1.4). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
81 
Approved v21.0 
930143391 2.0 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
82 
Approved v 21.0 
930143391 2.0 
 
 
9.1.3 
Cystoscopy 
Per Protocol Amendment 01, efficacy assessments will be conducted per the local standards of 
care. 
Not applicable per Protocol Amendment 01: 
Cystoscopic examination of the urinary bladder and urethra will be performed within 90 days of 
randomization (Table 2-2). Fluorescence-guided cystoscopy may also be used but is not required. 
However, the same method of assessment used at baseline (prior to randomization) should be 
employed throughout the entire study period where possible. 
The entire urethra and bladder mucosa should be visualized during each cystoscopic examination. 
Investigators are required to completely document all findings on the study CRF, including 
presence/absence of papillary tumors, number and size of tumors, and abnormal areas of erythema 
or other abnormalities possibly consistent with CIS. The location of tumors or abnormalities 
should be clearly documented on the CRF. Other bladder pathology, including, but not limited to, 
bladder diverticula, stones, and trabeculation, should also be documented. This documentation will 
be submitted to PRC to aid in their evaluation of urinary cytology and bladder biopsies. 
Cystoscopy examination will continue per AUA7 and EAU18 guidelines for 5 years following 
randomization, regardless of early discontinuation of study treatment, until documented PRC 
assessed recurrence or progression. Cystoscopy examinations will take place at Week 13 (± 1 
week) and at 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months (± 4 weeks) (3 months = 13 
weeks); see Table 9.1.4-1. After 5 years, cystoscopy will be every year (± 1 month). 
9.1.4 
Urine Cytology 
Not applicable per Protocol Amendment 01: 
A voided (except from the first morning urination) or bladder wash specimen for urinary cytology 
will be obtained, reviewed by the investigator, and sent to the PRC for review within 90 days prior 
to randomization. Urine cytology will be performed with cystoscopy at the following time points: 
Week 13 (± 1 week) and 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, and 60 months (± 4 weeks) (3 
months = 13 weeks) (see Table 9.1.4-1) until PRC assessed recurrence or progression. 
Urine cytology may be repeated if read by the PRC as suspicious (see Sections 9.1.4.2 and 9.1.4.3). 
If a bladder wash specimen is obtained, the bladder will be emptied, and the bladder wash sample 
will be obtained by rinsing the bladder at least twice with 50 cc of normal saline, either through 
the cystoscope or through a urinary catheter. The material will be placed in a urine collection 
specimen cup. 
Urine cytology tests will continue per AUA7 and EAU18 guidelines for 5 years following 
randomization, regardless of early discontinuation of study treatment, until documented PRC 
assessed recurrence or progression. After 5 years, urine cytology will be every year (± 1 month). 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
83 
Approved v 21.0 
930143391 2.0 
 
 
Table 9.1.4-1: 
Timing of Cystoscopy and Urine Cytology 
 
Months 
Week 
Assessment Daya 
(± 4 weeks) 
3 
13 
Week 14, Day 1b 
6 
26 
Week 27, Day 1 
9 
39 
Week 40, Day 1 
12 
52 
Week 53, Day 1 
15 
65 
Week 66, Day 1 
18 
78 
Week 79, Day 1 
21 
91 
Week 92, Day 1 
24 
104 
Week 105, Day 1 
30 
130 
Week 131, Day 1 
36 
156 
Week 157, Day 1 
42 
182 
Week 183, Day 1 
48 
208 
Week 209, Day 1 
60c 
260 
Week 261, Day 1 
a Should not occur < 6 weeks after most recent dose of BCG. 
b Window is ± 1 week at Week 13. 
c After 5 years, cystoscopy and urine cytology will be every year (± 1 month). 
 
9.1.4.1 
Positive Cytology with Normal Cystoscopy 
Not applicable per Protocol Amendment 01: 
If the cytology is positive (defined by the presence of malignant cells), the source of the positive 
cytology should be investigated with: 
1) Cystoscopic examination of the bladder 
2) Biopsies targeted to any visually abnormal areas of the bladder, 
3) Random bladder biopsies and a biopsy of the prostatic urethra (in male participants) if no 
visually abnormal areas are seen on cystoscopy, and 
4) Contrast studies of the upper urinary tracts if the source of the positive cytology cannot be 
localized to the lower urinary tract. 
Split urinary cytology specimens from the upper and lower urinary tracts are encouraged, but not 
required, to isolate the source of the positive cytology from the upper tracts. 
Complete response requires a negative (including atypical) urinary cytology per PRC. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
84 
Approved v 21.0 
930143391 2.0 
 
 
9.1.4.2 
Suspicious Cytology with Normal Cystoscopy 
Not applicable per Protocol Amendment 01: 
A suspicious urine cytology with a negative cystoscopy poses a particular challenge as there are 
currently no guidelines available to assist clinicians with decisions including whether to perform 
additional testing, what type of additional testing to perform, or whether to change surveillance 
strategies.48 A suspicious cytology in combination with a negative cystoscopy at any efficacy 
evaluation requires a repeat urine cytology 4 weeks after the initial suspicious cytology result. If 
the repeat cytology is negative (including atypical), the participant will be classified as having a 
CR on the date of the original suspicious cytology. If the repeat cytology is positive (malignant), 
the participant will be classified as having recurrence/progression on the date of the original 
suspicious cytology and the source of the positive cytology should be evaluated as described in 
Section 9.1.4.1. 
If the repeat cytology is again suspicious, random bladder biopsies (left bladder wall, right bladder 
wall, posterior bladder wall, bladder dome, trigone) and biopsy of the prostatic urethra (in male 
participants) must be performed. Such random biopsies can be done in combination with required 
biopsies from areas of prior papillary tumor/CIS based on prior examination and bladder mapping 
if the suspicious cytology result was obtained during the 26 week evaluation in CIS participants. 
Alternatively, random biopsies should be done as a separate procedure at any other evaluation. 
Contrast studies of the upper urinary tracts must also be performed if the repeat cytology is 
suspicious, with the study being performed (CT, MRI, retrograde pyelograms) left to the discretion 
of the investigator. 
If high-risk disease is identified in the random biopsies from the bladder or in the prostatic urethra 
(CIS, TaHG, any ≥ T1), or if an upper tract lesion is identified on imaging, the participant will be 
classified as having recurrence/progression on the date of the original suspicious cytology. If no 
cause for the suspicious cytology is found, or if the participant is found to have TaLG disease in 
the bladder or prostatic urethra, the participant will be classified as having a CR on the date of the 
original suspicious cytology and treatment/evaluations will proceed as per protocol. 
9.1.4.3 
Suspicious Cytology, Abnormal Cystoscopy 
Not applicable per Protocol Amendment 01: 
A participant (CIS or non-CIS) with a suspicious cytology and an abnormal cystoscopy must be 
evaluated with bladder biopsy as specified in Section 9.1.5. If biopsies obtained from the 
cystoscopically abnormal area(s) demonstrate TaHG, ≥ T1 UC, or CIS, the participant will be 
classified as having recurrence/progression. If biopsies obtained from the cystoscopically 
abnormal areas demonstrate only benign tissue or TaLG UC, the participant will be considered 
free of recurrence/progression and, in the case of a CIS participant, as CR. The need for upper tract 
imaging, in addition to bladder biopsy, will be left to the judgment of the investigator but will not 
be required for classification as no recurrence/progression or CR. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
85 
Approved v 21.0 
930143391 2.0 
 
 
Bladder biopsy, whether for cause or as required at the Week 26 time point, must be free of high- 
risk disease (CIS, TaHG, any ≥ T1) per PRC for the participant to be classified as having a CR. 
Participants with only TaLG UC on bladder biopsy will be classified as having a CR. 
9.1.5 
Bladder Biopsy 
Per Protocol Amendment 01, efficacy assessments will be conducted per the local standards of 
care. 
Complete resection of all papillary disease (Ta/T1) is required for all participants within 90 days 
prior to randomization. At least one slide must contain musclaris propria, preferably from the area 
of most significant disease. For participants with clinical stage T1 disease, a repeat TURBT is 
required within 8 weeks after the initial TURBT to confirm complete resection of disease and to 
ensure that no tumor has invaded the muscularis propria of the bladder prior to randomization. The 
location, number, and size of each bladder tumor should be documented in the screening CRF. 
Any areas of abnormality consistent with possible CIS (such as erythema) must be biopsied and/or 
resected prior to randomization. The location of the abnormality should be documented in the CRF. 
If the tumor tissue was obtained > 70 days prior to the anticipated randomization date, a repeat 
cystoscopy is required prior to randomization to ensure the participant does not have recurrent 
disease. The repeat cystoscopy must be completed ≤ 70 days prior to randomization. If there is 
papillary NMIBC on the repeat cystoscopy, the participant’s eligibility needs to be reassessed and 
the tissue must be submitted to the PRC for assessment. The disease stage should be updated to 
take account of all TURBT findings. Bladder mapping in all CIS participants to identify occult 
disease should be performed at baseline, using one of the following techniques: 
• Random sampling of the bladder mucosa (in which case, biopsies should be obtained from the 
bladder dome, right and left lateral walls, posterior wall, trigone, and prostatic urethra [in male 
participants]) 
• Fluorescence cystoscopy with biopsy of all abnormal areas 
 
 
In participants in whom it is not feasible to perform bladder mapping at baseline, it is acceptable 
to defer this procedure until Week 26 (± 5 weeks). 
Not applicable per Protocol Amendment 01: 
Any abnormality in any participant (CIS or non-CIS) discovered on cystoscopic examination of 
the bladder that is suspicious for recurrent papillary tumor or CIS must be biopsied and evaluated. 
All papillary lesions identified on surveillance cystoscopy must be fully resected, if feasible. The 
location, number, and size of these lesions should be recorded in the CRF. 
In addition, on-study biopsy is required at 26 (± 5) weeks following randomization in CIS 
participants, even if the bladder is normal on visual inspection (see Table 2-2). In such cases, areas 
of prior papillary tumor and/or CIS, based on prior examination and bladder mapping must be 
biopsied even if these areas are normal to visual inspection. Bladder mapping is required in CIS 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
86 
Approved v 21.0 
930143391 2.0 
 
 
participants at 26 weeks if not performed prior to randomization. If any of these areas are biopsied 
at 26 weeks based on the presence of an abnormality on cystoscopy, or due to the presence of 
tumor on prior examination as described above, an additional random biopsy from the area is not 
required. 
To the extent feasible, all papillary tumors and abnormalities consistent with possible CIS should 
be fully resected or biopsied during the follow-up period after the participant completes all on- 
study evaluations. The location, number, and size of these lesions should be documented on the 
CRF. 
During the treatment and follow-up periods, biopsy specimens will be evaluated by the investigator 
and by the PRC per its charter, or by the investigator if the PRC is no longer active. 
9.1.6 
Patient-reported Outcomes 
Not applicable per Protocol Amendment 01: 
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. 
Additionally, generic health-related QoL measures provide data needed for calculating utility 
values to inform health economic models. 
Participants will be asked to complete the European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire - Cancer (EORTC QLQ-C30), the European Organization 
for Research and Treatment of Cancer Quality of Life Questionnaire - Non-muscle-invasive 
Bladder Cancer (EORTC QLQ-NMIBC24), and the EuroQoL Group’s 5-level version of the 
EQ-5D (EQ-5D-5L) in the participant’s preferred language when available. Participants will 
complete all measures on Day 1 of every dosing cycle at the site while on treatment and during 
FU visits 1 and 2. In addition, the EORTC QLQ-C30 and EQ-5D-5L will be administered at some 
survival follow-up visits. The QLQ-C30 and EQ-5D-5L may be administered by telephone using 
standardized scripts. When survival visits coincide with efficacy visits, assessments can be 
collected at the efficacy visits. 
Table 2-2 and Table 2-3 provide information regarding the timing of PRO assessments. 
9.1.6.1 
EORTC QLQ-C30 
Not applicable per Protocol Amendment 01: 
The EORTC QLQ-C3049 is the most commonly used QoL instrument in oncology trials. The 
instrument’s 30 items are divided among 5 functional scales (physical, role, cognitive, emotional, 
and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, 
constipation, diarrhea, and financial difficulties), and a global health/QoL scale. With the 
exception of 2 items included in the global health/QoL scale, for which responses range from 1 
(Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores 
for the QLQ-C30 are transformed to a 0 to 100 metric such that higher values indicate better 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
87 
Approved v 21.0 
930143391 2.0 
 
 
52
functioning or QoL or a higher level of symptoms. A score difference of 10 is used as an estimate 
of the minimally important difference (MID) for the subscales of the EORTC QLQ-C30.50 
9.1.6.2 
EORTC QLQ-NMIBC24 
Not applicable per Protocol Amendment 01: 
The EORTC QLQ-NMIBC24 is a bladder cancer-specific questionnaire designed to evaluate 
symptoms and problems associated with NMIBC.51 The QLQ-NMIBC24 includes 9 symptom and 
2 functional scales/items assessing multiple domains, including urinary symptoms, intravesical 
treatment issues, future worries, malaise, abdominal bloating and flatulence, and sexual 
functioning. 
9.1.6.3 
EQ-5D-5L 
Not applicable per Protocol Amendment 01: 
The EQ-5D-5L is a standardized instrument used to measure self-reports of general health 
status.52 The instrument has 2 components: a descriptive system and a visual analog scale (VAS). 
The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression. Each dimension has 5 levels, reflecting no problems, 
slight problems, moderate problems, severe problems, and extreme problems. A dimension for 
which there are no problems is said to be at level 1, while a dimension for which there are extreme 
problems is said to be at level 5. Thus, the vectors 11111 and 55555 represent the best and the 
worst health state, respectively. Altogether, the instrument describes 3,125 different health states. 
Empirically derived weights can be applied to an individual’s responses to the EQ-5D-5L 
descriptive system to generate a utility index measuring the value to society of his or her current 
health. 53 
The EQ-5D-5L VAS allows subjects to rate their own current health on a 0 to 100 point scale 
ranging from “the worst health you can imagine” to the “best health you can imagine,” 
respectively. The MID for the EQ-5D-5L VAS is a 7-point change in score.54 
The EQ-5D-5L uses a recall period of “today.” 
9.1.7 
Imaging Assessment for the Study 
Not applicable per Protocol Amendment 01: 
Imaging will be performed every 52 weeks (± 4 weeks) from randomization. 
At the Sponsor’s discretion, scans may be submitted to an imaging core lab and may be reviewed 
by a Blinded Independent Central Review at a later date, or at any time during the study. 
Tumor imaging is performed during screening to confirm the staging of the disease and to exclude 
synchronous UC in the upper urinary tracts. Imaging may also be performed at the discretion of 
the investigator due to symptoms, to exclude disease progression, or to exclude UC in the upper 
urinary tracts. Documentation of the results of imaging studies obtained during screening will be 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
88 
Approved v 21.0 
930143391 2.0 
 
 
submitted to PRC to confirm participant eligibility. Documentation of the results of imaging 
studies obtained during treatment will be submitted to PRC to aid in the evaluation of progression. 
Contrast-enhanced CT of the chest, CT or MRI of the abdomen and pelvis, including excretory 
imaging, and all other suspected sites of disease should be performed during screening and as 
clinically indicated. 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. 
Should a participant have contraindication for CT IV contrast, a noncontrast CT of the chest and a 
contrast-enhanced MRI of the abdomen and pelvis, including excretory imaging, and other 
suspected sites of disease should be obtained. 
For participants in whom there is a documented contraindication to both CT and MRI IV contrasts, 
noncontrast enhancing CT of the chest and noncontrast enhancing CT/MRI of the abdomen and 
pelvis is acceptable. Imaging of the upper urinary tracts must be appropriately performed using 
appropriate alternative techniques per local SOC (eg, retrograde studies or endosocopy). Please 
consult with the medical monitor. 
MRI of brain (without and with contrast) is required for participants with known or suspected brain 
metastases, unless participant has completed an imaging study of the brain within 28 days of study 
drug administration. CT of the brain (without and with contrast) can be performed if MRI is 
contraindicated. 
9.1.8 
Clinical and Pathology Review Committee Review of Efficacy 
Assessments 
Not applicable per Protocol Amendment 01: 
The primary endpoint of this study is based upon the PRC evaluation of CR, recurrence, and/or 
progression. Accordingly, all relevant diagnostic tests completed (per Table 2-2 and Table 2-3) at 
any time point must submitted to the PRC until such a time as the PRC determine 
recurrence/progression. This includes repeat tests such as those outlined in Sections 9.1.4.1 and 
9.1.4.2. 
The criteria for determining CR, recurrence, and/or progression are the same for the investigator 
and the PRC (see Section 9.1.1). The interpretation of individual tests may be different at the 
investigator’s site and at the PRC, and as a consequence the determination of 
recurrence/progression may be different. 
All clinical decisions on patient care including the discontinuation of study drug will be based on 
the investigator’s assessment of study diagnostic tests and clinical information, and should be 
independent of PRC. The results of the PRC assessment will be available to sites, although 
investigators should make clinical decisions on the basis of their assessment of all the information 
available to them, including the cytology, cystoscopy, biopsy, and imaging findings locally. 
If the investigator determines recurrence/progression but the PRC do not, the participant can stop 
study treatment in accordance with the protocol. In this situation, efficacy assessments should 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
89 
Approved v 21.0 
930143391 2.0 
 
 
continue at the protocol defined schedule and be submitted to the PRC until the PRC determine 
recurrence/progression or until the patient starts a subsequent line of treatment for UC (including 
intravesical treatment, cystectomy, or radiotherapy). 
If the PRC determines recurrence/progression but the investigator does not, the participant should 
continue with treatment in accordance with the protocol until the investigator makes a 
determination of recurrence/progression. In such a situation, efficacy assessments should continue 
in accordance with the protocol defined schedule, including submission to PRC. Please discuss 
such cases with the medical monitor. 
If urinary cytology findings at the site are negative and the PRC’s findings of the same time point 
urine sample is suspicious or positive and the cystoscopy findings are negative, the site should 
perform additional tests to identify the source of the positive/suspicious cytology as outlined in 
Sections 9.1.4.1 and 9.1.4.3. 
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. 
Contacts for SAE reporting specified in Appendix 3. 
IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component 
for which noninflammatory etiologies (eg, infection or tumor progression) have been ruled out. 
IMAEs can include events with an alternate etiology that 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 
Sections 5.6.1 and 5.6.2 in the IB represent the Reference Safety Information to determine 
expectedness of SAE for expedited reporting. 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 randomized/assigned to treatment and 
never treated with study drug, SAEs should be collected for 30 days from the date of 
randomization. 
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure, (eg, a follow-up skin biopsy). 
• Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the CRF module. 
• All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
90 
Approved v 21.0 
930143391 2.0 
 
 
• The investigator will submit any updated SAE data to the sponsor or designee within 24 hours 
of updated information being available. 
 
All AEs (SAEs and non-serious AEs) associated with confirmed or suspected SARS-CoV-2 
infection must be collected from the date of the participant’s written consent until 100 days 
following discontinuation of dosing. 
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the investigator must promptly notify the Sponsor. 
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3. 
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 judgment in the context of known 
adverse events, when appropriate for the program or protocol. 
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. 
Every AE must be assessed by the investigator with regard to whether it is considered immune- 
mediated. For events which are potentially immune-mediated, additional information will be 
collected on the participant’s CRF. 
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 nonserious AEs of special interest (as defined in 
Section 9.2) 
AEs (SAEs and non-serious AEs) associated with confirmed or suspected SARS-CoV-2 infection 
will be followed until resolution, until the condition stabilizes, until the event is otherwise 
explained, the event is deemed irreversible, or until the participant is lost to follow-up (as defined 
in Section 8.3), or for suspected cases, until SARS-CoV-2 infection is ruled out. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
91 
Approved v 21.0 
930143391 2.0 
 
 
Further information on follow-up procedures is given in Appendix 3. 
9.2.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
product under clinical investigation are met. 
• An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements. 
Sponsor or designee will be reporting adverse events to regulatory authorities and ethics 
committees according to local applicable laws including European Directive 2001/20/EC and FDA 
Code of Federal Regulations (CFR) 21 CFR Parts 312 and 320. A SUSAR (Suspected, Unexpected 
Serious Adverse Reaction) is a subset of SAEs and will be reported to the appropriate regulatory 
authorities and investigators following local and global guidelines and requirements. 
9.2.5 
Pregnancy 
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives after product administration, the investigator must immediately notify the BMS 
Medical Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form 
to BMS Designee within 24 hours of awareness of the event and in accordance with SAE reporting 
procedures described in Appendix 3. 
If the investigator determines a possible favorable benefit/risk ratio that warrants continuation of 
study treatment, or re-initiation of study treatment, a discussion between the investigator and the 
BMS Medical Monitor/designee must occur. If, for whatever reason, the pregnancy has ended, 
confirmed by negative serum pregnancy test, treatment may be resumed (at least 3 weeks and not 
greater than 6 weeks after the pregnancy has ended), following approvals of participant/sponsor/ 
IRB/EC, as applicable. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form. 
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
Sponsor or designee. In order for Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an informed consent form for 
disclosure of this information. Information on this pregnancy will be collected on the Pregnancy 
Surveillance Form. 
In cases where a study drug can be present in seminal fluid at exposures sufficient to potentially 
cause fetal toxicity, and if any sexual activity (eg, vaginal, anal, oral) has occurred between a male 
participant and a pregnant WOCBP partner(s), the information should be reported to the Sponsor 
or designee, even if the male participant has undergone a successful vasectomy. In order for 
Sponsor or designee to collect any pregnancy surveillance information from the female partner, 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
92 
Approved v 21.0 
930143391 2.0 
 
 
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 SAE Report Form electronic, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning. 
• Any laboratory test result that is clinically significant or meets the definition of an SAE 
• Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted 
• Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy 
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value). 
9.2.7 
Potential Drug-induced Liver Injury 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential drug induced liver injury (DILI) event. All occurrences 
of potential DILIs meeting the defined criteria must be reported as SAEs (see Section 9.2 and 
Appendix 3 for reporting details). 
Potential drug induced liver injury is defined as: 
1) Aminotransferase (AT) (ALT or AST) elevation > 3x ULN 
AND 
2) Total bilirubin > 2x ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase), 
AND 
3) No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic. 
9.2.8 
Other Safety Considerations 
Any significant worsening noted during interim or final physical examinations, electrocardiogram, 
x-ray filming, any other potential safety assessment required or not required by protocol should 
also be recorded as a nonserious or serious AE, as appropriate, and reported accordingly. 
9.3 
Overdose 
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as SAEs (see Section 9.2.1 for reporting details). 
For this study, an overdose is defined as any study drug administration that is greater than 125% 
of the intended, protocol-defined dose 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
93 
Approved v 21.0 
930143391 2.0 
 
 
9.4 
Safety 
Planned time points for all safety assessments are listed in the Schedule of Activities. 
9.4.1 
Physical Examinations 
Refer to Schedule of Activities. 
9.4.2 
Vital Signs 
Refer to Schedule of Activities. 
9.4.3 
Electrocardiograms 
Refer to Schedule of Activities. 
9.4.4 
Clinical Safety Laboratory Assessments 
Investigators must document their review of each laboratory safety report. 
 
Hematology - CBC 
Hemoglobin 
Hematocrit 
Total leukocyte count, including differential 
Platelet count 
Chemistry 
AST 
ALT 
Total bilirubin 
Alkaline phosphatase 
Lactate dehydrogenase 
Creatinine 
Blood urea nitrogen or serum urea 
Glucose 
Albumin - screening only 
Sodium 
Potassium 
Chloride 
Calcium 
Phosphorus 
TSH, free T3 and free T4 - screening 
TSH, with reflexive fT3 and fT4 if TSH is 
abnormal - on treatment 
Creatine kinase 
Creatinine clearance - screening only 
Urinalysis (at screening) 
Protein 
Glucose 
Blood 
Leukocyte esterase 
Specific gravity 
pH 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
94 
Approved v 21.0 
930143391 2.0 
 
 
 
Urinalysis (performed prior to dosing at visits when BCG is administered) 
Protein 
Glucose 
Blood 
Leukocyte esterase and/or WBC 
Specific gravity 
pH 
Microscopic analysis required for abnormal dipstick urinalysis or clinical symptoms 
suggestive of urinary tract infection. 
Presence of WBCs, red blood cells, or bacteria 
Serology 
Hepatitis B/C, (HBV sAG, HCV antibody or HCV RNA) - screening only 
Other Analyses 
Pregnancy test (WOCBP only: minimum sensitivity 25 IU/L or equivalent units of HCG) 
Follicle stimulating hormone (FSH) screening - only required to confirm menopause in women 
< age 55 (Appendix 4) 
 
9.4.5 
Imaging Safety Assessment 
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the study investigator as per standard 
medical/clinical judgment. 
9.5 
Pharmacokinetics 
Per Protocol Amendment 01, PK will not be evaluated. 
Not applicable per Protocol Amendment 01: 
Samples for PK and immunogenicity (antidrug antibody [ADA]) assessment will be collected for 
participants at the time points indicated in Table 9.5-1 for both randomized arms. PK and ADA 
samples collected for the BCG arm will not be analyzed. 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 is collected but the dose is subsequently delayed, an additional 
predose sample should not be collected. 
Further details of sample collection, processing, and shipment will be provided in the laboratory 
procedures manual. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
95 
Approved v 21.0 
930143391 2.0 
 
 
Table 9.5-1: 
Pharmacokinetic Sampling Schedule for All Participants 
 
Study Day of 
Sample Collectiona 
(1 Cycle = 4 Weeks) 
Event 
Time Relative to 
Nivolumab Dose 
Hour: Min 
Nivolumab 
Pharmacokinetic 
Serum Sample 
Nivolumab 
Immunogenicity 
Serum Sample 
Cycle 1 Day 1 
Predoseb 
00:00 
X 
X 
EOIc 
00:30 
X 
Cycle 2 Day 1 
Predoseb 
00:00 
X 
X 
Cycle 3 Day 1 
Predoseb 
00:00 
X 
X 
Cycle 4 Day 1 
Predoseb 
00:00 
X 
X 
Cycle 5 Day 1 
Predoseb 
00:00 
X 
X 
EOIc 
00:30 
X 
Every 4 Cycles 
Starting at Cycle 6 
Day 1 Until EOT 
Predoseb 
00:00 
X 
X 
Follow-up Period 
Follow-up 30 Day 
X 
X 
Follow-up 100 Day 
X 
X 
Abbreviations: EOI, end of infusion; EOT, end of treatment 
a If a participant discontinues study drug treatment during the treatment/sampling period, they will move to sampling 
at the follow-up visits. 
b Predose samples should be collected just before the administration of the drug (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 End of infusion (EOI) sample should be taken immediately prior to the stopping of nivolumab infusion, preferably 
within 2 minutes prior to the end of infusion. If the end of infusion is delayed beyond the nominal infusion duration, 
the collection of this sample should also be delayed accordingly. EOI samples may not be collected from the same 
IV access as the drug was administered. 
 
9.6 
Pharmacodynamics 
Per Protocol Amendment 01, pharmacodynamics will not be evaluated. 
9.7 
Pharmacogenomics 
Not applicable. 
9.8 
Biomarkers 
Per Protocol Amendment 01, biomarkers will not be evaluated. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
96 
Approved v 21.0 
930143391 2.0 
 
 
Not applicable per Protocol Amendment 01: 
A variety of factors that could potentially predict clinical response and incidence of AEs to 
nivolumab combination treatments will be investigated in peripheral blood, urine, and tumor 
specimens taken from all participants prior to treatment. Data from these investigations will be 
evaluated for associations with EFS, WFS, OS, CRR and DOR data. In addition, analyses of 
markers between the treatment arms will provide the necessary data to identify biomarkers with 
predictive or prognostic value. All samples collected may also be used for future exploratory 
analyses (unless restricted by local requirements and/or institutional policies) to assess biomarkers 
associated with bladder cancer or immunotherapy treatment. Complete instructions on the 
collection, processing, handling and shipment of all samples described herein will be provided in 
a separate procedure manual. 
Table 9.8-1: 
Biomarker Sampling Schedule: All Participants 
 
Study Day 
of Sample 
Collectiona 
(1 Cycle = 
4 Weeks) 
Tum 
or 
Biops 
y 
Serum 
Soluble 
Factors 
MDSCs 
Whole 
Blood 
(Gene 
Express 
ion) 
PBMCs 
Plasma 
ctDNA 
Whole 
Blood 
DNA 
Urine 
Markers 
b 
Stool 
Microbi 
ome 
(optiona 
l) 
Screening 
X 
X 
Cycle 1 
Day 1 
X 
X 
X 
X 
X 
X 
X 
Cycle 2 
Day 1 
X 
X 
X 
X 
Cycle 3 
Day 1 
X 
X 
Cycle 4 
Day 1 
X 
X 
Cycle 6 
Day 1 
Xc 
X 
X 
X 
X 
Cycle 9 
Day 1 
X 
X 
X 
Cycle 13 
Day 1 
X 
X 
X 
Cycle 18 
Day 1 
X 
X 
X 
Cycle 24 
Day 1 
X 
X 
X 
X 
Upon 
Recurrence 
X 
Xd 
Xd 
Xd 
Xd 
Xd 
X 
a Biomarker sampling occurs prior to dosing of study drug and can occur ± 5 days from the scheduled time, except 
for C1D1. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
97 
Approved v 21.0 
930143391 2.0 
 
 
b Urine samples will be collected in the US and Canada sites only before nivolumab infusion and 1 hour after the 
infusion. However, do not collect after BCG administration on the same day. If BCG will be given before nivolumab 
on C1D1, collect the C1D1 urine markers sample before BCG administration. 
c This is a transurethral resection of the bladder tumor (TURBT) biopsy performed at 26 weeks in CIS participants. 
BCG must not be given for at least 14 days after biopsy. 
d Peripheral blood biomarker collections are optional. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
98 
Approved v 21.0 
930143391 2.0 
 
 
 
9.8.2 
Immunogenicity Assessments 
Immunogenicity blood collections are discontinued with Protocol Amendment 01 and will not be 
evaluated. 
Not applicable per Protocol Amendment 01: 
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 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 IMAEs. 
9.8.3 
Other Assessments 
9.8.3.1 
Tumor Tissue Specimens 
Per Protocol Amendment 01, tumor tissue specimens will not be collected. 
Not applicable per Protocol Amendment 01: 
Pretreatment tumor tissue specimens in the form of a paraffin-embedded block or 20 unstained 
slides will be submitted to an analytical laboratory for biomarker analysis. Confirmation of receipt 
of acceptable tissue for biomarker analysis is needed prior to randomization. If < 15 unstained 
slides are available, please discuss with the medical monitor prior to patient enrollment. 
Participants must provide a fresh tumor biopsy from the disease site. Archived tissue from prior 
biopsies or from prior surgical resection (obtained > 90 days prior to randomization) will not be 
accepted. If a radical cystectomy is performed post-treatment, a tissue block or at least 20 slides 
should be provided for biomarker analysis. For PD-L1 analysis, the PD-L1 stained tissue sections 
will be assessed by a pathologist and membranous PD-L1 expression will be scored in tumor cells 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
99 
Approved v 21.0 
930143391 2.0 
 
 
if a minimum of 100 evaluable tumor cells are present. Tumor samples containing less than 100 
tumor cells per tissue section will be classified as not evaluable. 
In addition to PD-L1 testing, the tumor samples may be used to assess other putative predictive 
biomarkers of nivolumab combination efficacy and/or to better characterize the tumor-immune 
microenvironment. Various molecular markers with potential predictive value for the treatment of 
bladder cancer with nivolumab and other immunotherapies are currently under investigation and 
may be assessed in this study. These tumor tissue biomarkers include, but are not limited to, 
immunohistochemistry (IHC) for PD-1, PD-L2, tumor-infiltrating lymphocytes (TILs) or 
subpopulations of TILs, and DNA/RNA sequencing to assess mutational data and gene expression 
signatures. These tumor samples may also be used to further characterize the tumor-immune 
microenvironment through assessment of markers that may be associated with the efficacy of 
nivolumab combination treatment, including, but not limited to, other T-cell checkpoint receptors 
and ligands (eg, Lag-3, Tim-3), and intra-tumoral immune cell subsets, including macrophages, 
natural killer (NK) cells, dendritic cells (DCs), and B-cells. 
Collection of on-treatment biopsy samples is required in CIS participants at approximately 
26 weeks following the first dose of study treatment, and 1 biopsy sample should be obtained in 
case of recurrence or progression in all participants (see Table 2-2 and Table 2-3). These on- 
treatment and recurrence biopsies are needed to understand the reasons for disease recurrence, the 
mechanism of action of nivolumab combinations, and how to benefit patients with optimal 
treatment strategies. They may be used for the assessment of markers implicated in resistance to 
immunotherapeutic agents, including, but not limited to, other T-cell checkpoint receptors and 
ligands (eg, Lag-3, Tim-3) and intratumoral immune cell subsets, including, but not limited to, T- 
cells, DCs, NK cells, B-cells, macrophages, and myeloid-derived suppressor cells (MDSCs). These 
samples may also be used to investigate the effect of nivolumab combinations on the expression 
of potentially relevant predictive and/or prognostic bladder cancer biomarkers. Both the pre- and 
on-treatment tumor samples and the sample collected upon recurrence may be retrospectively 
profiled for gene expression/mutation status (using whole genome/exome DNA and RNA 
sequencing), as well as for the expression of other immune or bladder cancer-related genes, RNAs, 
microRNA and proteins, or for the presence of immune cell populations using a variety of 
methodologies inclusive of, but not limited to, IHC, quantitative reverse transcription polymerase 
chain reaction (qRT-PCR), mass spectrometry, and fluorescent in-situ hybridization (FISH). 
9.8.3.2 
Peripheral Blood Markers 
Per Protocol Amendment 01, peripheral blood markers will not be evaluated. 
Not applicable per Protocol Amendment 01: 
A variety of factors that may impact the immunomodulatory properties and efficacy of nivolumab 
combination treatments will be investigated in peripheral blood specimens taken from all 
participants prior to or during treatment. Data from these investigations will be evaluated for 
associations with response, survival, and/or safety (AE) data. Several analyses will be completed 
and are described briefly below. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
100 
Approved v 21.0 
930143391 2.0 
 
 
9.8.3.2.1 Serum-soluble Factors 
Per Protocol Amendment 01, serum-soluble factors will not be evaluated. 
Not applicable per Protocol Amendment 01: 
Blood samples for exploratory serum biomarker analyses will be drawn at specified time points. 
Additionally, serum samples will be collected when clinically safe and feasible, upon occurrence 
of drug-related SAEs of a Grade 3 or higher, and/or any laboratory abnormality regarded as a drug- 
related SAE. Serum samples may be assessed by enzyme-linked immunosorbent assay, seromics, 
microRNA profiling, circulating tumor DNA measurements, metabolomics, and/or other relevant 
multiplex-based protein assay methods for immune-related factors that will predict for nivolumab 
combination benefits or correlate with treatment-related AEs. Numerous potential serum/plasma- 
based biomarkers are currently under investigation for their potential to predict or correlate with 
safety or efficacy to nivolumab combinations or other immunotherapies, including, but not limited 
to, levels of soluble PD-L1, antitumor antibodies, cytokines, chemokines, inflammatory factors, 
NKG2D ligands (eg, soluble MICA), circulating tumor DNA (ctDNA), and microRNAs 
(including, but not limited to, miR-513 and miR19b). 
9.8.3.2.2 Myeloid-derived Suppressor Cells 
Per Protocol Amendment 01, myeloid derived suppressor cells will not be evaluated. 
Not applicable per Protocol Amendment 01: 
MDSCs are an immune cell population capable of suppressing T-cell activation and proliferation. 
Low pretreatment MDSC levels in peripheral blood may be associated with better OS in bladder 
cancer participants treated with nivolumab combinations. MDSCs will be measured at baseline 
and on-treatment to assess pharmacodynamic (PD) changes or associations with outcome. 
9.8.3.2.3 Whole Blood Gene Expression 
Per Protocol Amendment 01, whole blood gene expression will not be evaluated. 
Not applicable per Protocol Amendment 01: 
The expression level of genes related to response to nivolumab combination therapies will be 
quantified using molecular methods such as Affymetrix by microarray, RNA seq and qRT-PCR 
analysis in whole blood samples. Analysis may include, but are not necessarily limited to, genes 
associated with immune-related pathways, such as T-cell activation and antigen processing and 
presentation. 
9.8.3.2.4 Peripheral Blood Mononuclear Cells 
Per Protocol Amendment 01, peripheral blood mononuclear cell samples will not be collected. 
Not applicable per Protocol Amendment 01: 
Peripheral blood samples will be taken prior to initiation of study therapy and at designated time 
points on-treatment for PBMC preparation. Samples must be shipped within 48 hours to a BMS- 
designated analytical laboratory for processing. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
101 
Approved v 21.0 
930143391 2.0 
 
 
These PBMC samples may be used for immunophenotyping or characterization of the immune 
cell subsets in the periphery, including, but not limited to, T-cells, B cells, NK cells, or 
subpopulations of the aforementioned immune cell types. These samples may also be used to 
assess immune cell function or antigen specific T-cell proliferation or activation pending emerging 
information from other nivolumab combination studies. 
9.8.3.2.5 Plasma-circulating Tumor DNA 
Per Protocol Amendment 01, plasma ctDNA will not be measured. 
Not applicable per Protocol Amendment 01: 
The presence of cell-free DNA in circulating blood is a well-documented phenomenon. Fragments 
of DNA are shed into the blood stream from dividing cells during cell proliferation or cell death. 
In participants with cancer, a fraction of this DNA is tumor derived and is termed ctDNA. Albeit 
small, fragments of DNA average between 180 to 200 base pairs and specific genomic regions can 
be amplified with polymerase chain reaction. Moreover, several studies have detected mutations 
in ctDNA that exactly correspond to mutations from the parent tumor. Using tissue and plasma, 
BEAMing or similar technology will be utilized to measure cell-free DNA and the 
presence/frequency of mutations in circulation. 
9.8.3.2.6 Whole Blood DNA 
Per Protocol Amendment 01, whole blood DNA will not be collected. 
Not applicable per Protocol Amendment 01: 
Whole blood will be collected from all participants prior to treatment to generate genomic DNA 
for Single Nucleotide Polymorphism (SNP) analyses. These analyses will focus on SNPs within 
genes associated with PD-1 and other immunoregulatory signaling pathways to determine if 
natural variation within those genes is associated with response to nivolumab combinations and/or 
with AEs during treatment. Sequencing of the blood genomic DNA will also serve as a control to 
determine the tumor mutational burden (TMB). 
9.8.3.3 
Urine Markers 
Per Protocol Amendment 01, urine markers will not be evaluated. 
Not applicable per Protocol Amendment 01: 
A variety of immune-related factors that may predict response to treatment have been identified in 
the urine of bladder cancer patients treated with intravesical BCG. These factors include, but are 
not limited to, the urinary immune cell infiltrate and urinary cytokine profile after intravesical 
treatment.55 The association between these and other urinary factors with response and/or toxicity 
(AEs) in BCG unresponsive patients undergoing treatment with systemic I-O therapy, with or 
without intravesical BCG, is currently unknown. 
Voided urine specimens will be collected at baseline and during treatment for a subgroup of 
participants in the current study. Factors that may be associated with treatment outcome and/or 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
102 
Approved v 21.0 
930143391 2.0 
 
 
toxicity will be investigated. Data from these investigations will be evaluated for associations with 
CR, EFS, and safety (AE) data. 
9.8.3.4 
Microbiome Analysis 
Per Protocol Amendment 01, microbiome analysis will not be conducted. 
Not applicable per Protocol Amendment 01: 
The potential influence of the gut microbiome on bladder cancer treatment outcome is not known. 
The microbiome is known to affect treatment of certain cancer types (ie, colorectal cancer) through 
several mechanisms, including promotion of disease via induction of chronic inflammation or 
catabolism of polyamines on other carcinogenic digestible material. In addition, the innate and 
adaptive immune system activation state and repertoire may be altered based on local microbiota, 
leading to differential activity of nivolumab in cancer participants. DNA will be extracted from 
fecal samples taken prior to therapy and on-treatment (Table 9.8-1). A gene sequencing approach 
will be utilized to survey microbial species in the gut in order to define microbiota as a function 
of efficacy and safety. Overall changes in the gut microbiota will also be characterized in 
individual participants that receive therapy. 
9.9 
Health Care Resource Utilization and Health Economics 
Per Protocol Amendment 01, health care resource utilization and health economics parameters will 
not be evaluated. 
Not applicable per Protocol Amendment 01: 
Health care 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) 
 
10 
STATISTICAL CONSIDERATIONS 
Per Protocol Amendment 01, only descriptive safety and limited investigator-assessed efficacy 
analyses will be conducted. 
10.1 
Sample Size Determination 
Per Protocol Amendment 01, sample size will be limited to the participants enrolled as of 
02-Jun-2021. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
103 
Approved v 21.0 
930143391 2.0 
 
 
Not applicable per Protocol Amendment 01: 
The sample size for this study is based on a comparison of the EFS distribution between 
participants randomized to receive nivolumab plus BCG and participants randomized to receive 
nivolumab-placebo plus BCG (“BCG alone”). 
EFS distribution for the control arm (“BCG alone”) has been derived from Steinberg et al data.26 
The BCG alone arm is assumed to be a 2-pieces exponential distribution with a 17 months median 
EFS, 80% EFS rate at first disease assessment (Week 13), and 40% EFS rate at 24 months. 
The number of events and power of this primary objective were calculated assuming a proportional 
hazard model. Approximately 335 events (ie, recurrence, progression, death from any cause) 
observed among the 700 randomized participants will provides around 90% power to detect a 
constant hazard ratio (HR) of 0.7 with an overall type 1 error of 0.05 (2-sided), see Table 10.1-1. 
The sample size takes into account a 5% drop out for EFS analysis (exponential 10% by Month 24 
in each treatment arm). 
An HR of 0.7 corresponds to a 52% increase in median EFS (from 17 months in BCG alone vs 26 
months in nivolumab plus BCG), a 5.5% absolute EFS rate increase after first disease assessment 
(from 80% in BCG alone vs 85.5% in nivolumab plus BCG), and a 12.6% absolute EFS rate 
increase at 24 months (from 40% EFS at 24 months in the BCG alone vs 52.6% EFS at 24 months 
in nivolumab plus BCG). 
Under the above criteria, the critical HR (cHR) would be 0.8, which corresponds to a 30% increase 
in median EFS (from 17 months in BCG alone vs 22 months in nivolumab plus BCG). 
Table 10.1-1: 
Summary of EFS Assumptions (BCG Alone vs Nivolumab Plus 
BCG) 
 
Periods 
Hazard rates in 
BCG alone 
Hazard rates in 
Nivolumab plus BCG 
Hazard ratio 
0 - 3 months 
0.0744 
0.0521 
0.7 
> 3 months 
0.0330 
0.0231 
0.7 
 
The accrual will take about 20.5 months (see Section 5.2) to randomize approximately 
700 participants. 
Final analysis of the primary endpoint (primary completion) will occur when at least 335 EFS 
events are observed, and a minimum of 12 months follow-up have been reached in all randomized 
participants and is projected to occur approximately 34 months after the start of the study (20.5 
months of accrual and 13.5 months of follow-up). 
If the required number of EFS events is not reached and all randomized participants have achieved 
at least 24 months follow-up, the final EFS analysis will be conducted, the statistical characteristics 
of the design will be recalculated according to the observed number of EFS events at the time of 
the analysis. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
104 
Approved v 21.0 
930143391 2.0 
 
 
No interim analysis of EFS is planned in this study. 
The key secondary endpoints of WFS and OS will be formally compared in all randomized 
participants using a hierarchical procedure with a fixed sequence approach as summarized in 
Figure 10.1-1. 
Figure 10.1-1: 
Efficacy Analyses and Timing 
 
 
 
 
WFS could be formally compared only if the primary endpoint of EFS was successful. Given the 
sample size, approximately 335 WFS events in all randomized subjects will provide approximately 
90% power to detect an HR of 0.7 with an overall type I error of 5% (2-sided). This corresponds 
to a median WFS increase from 5 years to 7.1 years under exponential assumption. The calculation 
accounts for approximately 14% drop out for WFS analysis (exponential with 20% by 60 months). 
One interim WFS analysis is planned using Lan-DeMets alpha spending function with the 
O’Brien-Fleming type of boundary after approximately 250 WFS events are observed (about 75% 
of targeted number of WFS events) and is expected to occur approximately 3.4 years after the end 
of accrual (about 62 months after FPFV). If the interim WFS analysis is performed exactly at 250 
events, the boundary in terms of statistical significance for declaring superiority would be 0.019 
(cHR = 0.74). 
The boundary for declaring superiority in terms of statistical significance for the final WFS 
analysis after 335 events would be 0.044 (cHR = 0.80). The final analysis of WFS is projected to 
occur approximately 87 months after the start of the study (approximately 20.5 months accrual and 
66.5 months follow-up). 
OS could be formally compared only if EFS and WFS were successful. Given the sample size, 
approximately 299 deaths in all randomized subjects will provide approximately 70% power to 
detect an HR of 0.75 with an overall type I error of 5% (2-sided). This corresponds to a median 
OS increase from 9.7 years to 13.0 years under exponential assumption. The final analysis of OS 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
105 
Approved v 21.0 
930143391 2.0 
 
 
is projected to occur approximately 128 months after the start of the study (approximately 20.5 
months accrual and 108 months follow-up). Under the above criteria, the critical HR would be 
0.79. 
If the required number of OS events is not reached and all randomized participants have achieved 
at least 10 years follow-up, the final OS analysis will be conducted, the statistical characteristics 
of the design will be recalculated according to the observed number of OS events at the time of 
the analysis. 
East version 6.4 was used for sample size/power computations. 
10.2 
Populations for Analyses 
Per Protocol Amendment 01, only safety assessments will be conducted. 
For purposes of analysis per Protocol Amendment 01, the following populations are defined: 
 
Population 
Description 
Enrolled 
All participants who signed informed consent form and were registered into 
IRT 
Randomized 
All enrolled participants randomized via IRT 
Treated 
All participants who take at least 1 dose of study treatment 
 
Unless otherwise specified, the safety analyses will be conducted in all treated participants. 
Unless otherwise specified, the investigator-assessed efficacy analyses will be conducted in all 
randomized participants. 
Not applicable per Protocol Amendment 01: 
For purposes of analysis, the following populations are defined: 
 
Population 
Description 
Enrolled 
All participants who sign informed consent and were registered into IRT 
Randomized 
All enrolled participants randomized via IRT 
Randomized CIS 
All randomized participants with CIS (with or without papillary disease) per 
PRC at baseline 
Randomized non-CIS 
All randomized participants without CIS per PRC at baseline 
Treated 
All participants who take at least 1 dose of study treatment 
PK 
All participants with available serum time-concentration data from 
randomized participants dosed with nivolumab 
Immunogenicity 
All participants with available data from randomized participants dosed with 
nivolumab 
Immunogenicity evaluable 
All treated participants with baseline and at least 1 post-baseline 
immunogenicity assessment 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
106 
Approved v 21.0 
930143391 2.0 
 
 
 
HEOR 
All treated participants who have an assessment at baseline and at least 1 
subsequent assessment. 
Biomarker 
All randomized participants with available biomarker data (PD-L1 expression 
status and other assays) 
 
Unless otherwise specified, the safety analyses will be conducted in all treated subjects. 
Unless otherwise specified, the efficacy analyses will be conducted in all randomized subjects. 
10.3 
Statistical Analyses 
The Statistical Analysis Plan (SAP) will be developed and finalized before the first database lock 
and will describe the selection of participants to be included in the analyses and procedures for 
accounting for missing, unused, and spurious data. Below is a summary of planned statistical 
analyses of the primary and secondary endpoints. 
A description of the participant population will be included in a statistical output report, including 
subgroups of age, gender, and race. 
10.3.1 
Efficacy Analyses 
Per Protocol Amendment 01, descriptive analyses of investigator-assessed efficacy will be collated 
as listings. 
Not applicable per Protocol Amendment 01: 
 
Endpoint 
Statistical Analysis Methods 
Primary 
EFS per PRC of nivolumab plus BCG vs “BCG alone” 
The primary definition of EFS is defined as the time 
between the date of randomization and the date of first 
documented event or death due to any cause, whichever 
occurs first. Events include recurrence of disease (TaHG, 
T1, or CIS) and progression of disease. For participants 
with CIS (with or without papillary disease) at study 
entry, lack of CR at Week 13 assessment will be 
considered an event. 
Participants who die without a reported 
progression/disease recurrence will be considered to have 
experienced an event on the date of their death. 
Participants who did not report progression or recurrence 
of disease or die will be censored on the date of their last 
evaluable tumor assessment. 
Participants who did not have any on- study tumor 
assessments and did not die will be censored on their date 
of randomization. 
The primary definition of EFS accounts for subsequent 
therapy by censoring at the last evaluable disease 
assessment on or prior to the date of subsequent therapy. 
EFS will be analyzed in all randomized participants 
and will be compared between the 2 treatment arms 
using a stratified 2-sided log rank test with an overall 
5% alpha. 
The HR and the corresponding 2-sided 95% 
confidence interval (CI) will be estimated in a 
stratified Cox proportional hazard model using the 
randomized arm as a single covariate, stratified by 
the stratification factors, corresponding to the 
comparison of EFS. 
The EFS curves for each randomized arm will be 
estimated using the Kaplan-Meier (KM) product- 
limit method. In addition, EFS rates at specific time 
points will be estimated using KM estimates on the 
EFS curve for each randomized arm. Associated 2- 
sided 95% CIs will be calculated using the 
Greenwood formula (using log-log transformation). 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
107 
Approved v 21.0 
930143391 2.0 
 
 
 
Endpoint 
Statistical Analysis Methods 
Further details on the censoring rules for consideration of 
subsequent therapies will be described in the Statistical 
Analysis Plan (SAP). 
Secondary 
WFS of nivolumab plus BCG vs “BCG alone” 
WFS is defined as the time from randomization to 
progression to muscle-invasive disease (ie, T2), 
cystectomy, systemic chemotherapy, radiotherapy, or 
death from any cause. 
The hypothesis testing will only be performed if the 
higher hierarchical endpoint (eg, EFS) is met, as 
described in the SAP. 
WFS will be analyzed in all randomized participants 
and will be compared between the 2 treatment arms 
using a stratified 2-sided log rank test with an overall 
5% alpha. 
The HR and the corresponding 2-sided (100-adjusted 
alpha)% confidence interval (CI) will be estimated in 
a stratified Cox proportional hazard model using the 
randomized arm as a single covariate, stratified by 
the stratification factors, corresponding to the 
comparison of WFS. 
The WFS curves for each randomized arm will be 
estimated using the KM product-limit method. In 
addition, WFS rates at specific time points will be 
estimated using KM estimates on the WFS curve for 
each randomized arm. Associated 2-sided 95% CIs 
will be calculated using the Greenwood formula. 
OS of nivolumab plus BCG vs “BCG alone” 
OS is defined as the time between the date of 
randomization and the date of death due to any cause. For 
participants still alive, OS is censored at the last date the 
participant is known to be alive. 
The hypothesis testing will only be performed if the 
higher hierarchical endpoints (EFS and WFS) are 
met, as described in the SAP. 
OS will be analyzed in all randomized participants 
and will be compared between the 2 treatment arms 
using a stratified 2-sided log rank test with an overall 
5% alpha. 
The HR and the corresponding 2-sided 95% 
confidence interval (CI) will be estimated in a 
stratified Cox proportional hazard model using the 
randomized arm as a single covariate, stratified by 
the stratification factors, corresponding to the 
comparison of OS. 
The OS curves for each randomized arm will be 
estimated using the KM product-limit method. In 
addition, OS rates at specific time points will be 
estimated using KM estimates on the OS curve for 
each randomized arm. Associated 2-sided 95% CIs 
will be calculated using the Greenwood formula. 
CRR at Week 13 
CRR is defined as the proportion of participants with CIS 
(+/- TaHG/T1) per PRC at randomization who are 
disease free at the first disease assessment (Week 13). 
CRR will be analyzed in all randomized participants 
with CIS (with or without papillary disease) per PRC 
at baseline with disease assessment at Week 13. 
Estimates of response rate, along with its exact 2- 
sided 95% CI by Clopper and Pearson, 56 will be 
55F 
presented by treatment group. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
108 
Approved v 21.0 
930143391 2.0 
 
 
 
Endpoint 
Statistical Analysis Methods 
Duration of Response (DoR) 
DoR is defined as the time between the date of the first 
CR to the date of first documented recurrence, 
progression, or death due to any cause. 
DoR will be analyzed in all randomized participants 
with CIS (with or without papillary disease) per PRC 
at baseline and achieved CR at first disease 
assessment (ie, Week 13). 
The DoR for each treatment group will be estimated 
using the KM product limit method and will be 
displayed graphically. A table will be produced 
presenting number of events, number of subjects 
involved, medians, and 95% CIs for the medians. 
Median values of DoR, along with 2-sided 95% CI in 
each treatment group will be computed based on a 
log-log transformation method. 
Exploratory 
Exploratory efficacy endpoints definitions and analysis methods will be described in the SAP finalized before 
first database lock 
 
Additional sensitivity analyses for primary and secondary endpoints will also be performed, details 
will be included in the SAP. 
10.3.2 
Safety Analyses 
Limited safety analysis will be performed in all treated participants and will be described in the 
SAP. 
 
Endpoint 
Statistical Analysis Methods 
Secondary 
Safety 
Descriptive statistics of safety will be presented using NCI CTCAE version 5.0 by treatment group. 
All on-study AEs, treatment-related AEs, AEs leading to discontinuation, IMAEs, SAEs, and 
treatment-related SAEs, and deaths will be tabulated using worst grade per NCI CTCAE version 
5.0 criteria by system organ class and preferred term. 
On-study laboratory parameters including hematology, chemistry, liver function, and renal 
function will be summarized using worst grade NCI CTCAE version 5.0 criteria. 
Events reported from the first dose up to and including 100 days following the last dose of study 
treatment could be included in estimating this incidence rate. 
 
10.3.3 
Other Analyses 
Not applicable per Protocol Amendment 01: 
Outcome research, PK, PD, immunogenicity, and biomarker exploratory analyses will be 
described in the SAP finalized before first database lock. The PPK and PD analyses will be 
presented separately from the main clinical study report. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
109 
Approved v 21.0 
930143391 2.0 
 
 
10.3.3.1 
Pharmacokinetic Analyses 
Not applicable per Protocol Amendment 01: 
The nivolumab concentration data obtained in this study may be combined with data from other 
studies in the clinical development program to develop PPK 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 E-R analyses of selected efficacy 
and safety endpoints. If the analyses are conducted, the results of PPK and E-R analyses will be 
reported separately. 
10.3.3.2 
Immunogenicity Analyses 
Not applicable per Protocol Amendment 01: 
Methodology for analysis of immunogenicity will be described in the SAP. 
10.3.3.3 
Outcomes Research Analyses 
Not applicable per Protocol Amendment 01: 
PRO measures include EORTC QLQ-C30, EORTC 
QLQ-NMIBC24, and EQ-5D-5L. 
Methodology for analysis of PROs will be described in the SAP. 
10.3.4 
Interim Analyses 
Not applicable per Protocol Amendment 01: 
No interim analysis is planned for the primary endpoint of EFS. 
One interim analysis is planned for the first secondary endpoint of WFS at 75% information 
fraction, as described in Section 10.1, Sample Size Determination. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
110 
Approved v 21.0 
930143391 2.0 
 
 
11 
REFERENCES 
 
1 Bellmunt J, de Wit R, Vaughn Dj, et al. Pembrolizumab as second-line therapy for advanced 
urothelial carcinoma. N Engl J Med 2017;376:1015-26. 
2  Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after 
platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 
2017;18:312-22. 
3 Rosenberg JE, Hoffman-Censits J, Powles, et al. Atezolizumab in patients with locally 
advanced and metastatic urothelial carcinoma who have progressed following treatment with 
platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 
2016;387:1909-20. 
4 Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: A global 
overview and recent trends. Eur Urol 2017;17:96-108. 
5 Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin 
2015;65:87-108. 
6 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017;67:7-30. 
7  Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder 
cancer: AUA/SUO guideline. J Urol 2016;196:1021-9. 
8 
Kamat AM, Hahn NM, Efstathiou JA, et al. Bladder cancer. Lancet 2016;388:2796-2810. 
9  Nielsen ME, Smith AB, Meyer AM, et al. Trends in stage-specific incidence rates for urothelial 
carcinoma of the bladder in the United States: 1988 to 2006. Cancer 2014;120:86-95. 
10 Morales A, Eidinger D, Bruce AW. Intracavitary bacillus Calmette-Guerin in the treatment of 
superficial bladder tumors. J Urol 1976;116:180-3. 
11 Chou R, Buckley D, Fu R, et al. Emerging approaches to diagnosis and treatment of non- 
muscle-invasive bladder cancer [Internet]. Rockville (MD): Agency for Healthcare Research 
and Quality (US): 2015. Report No.: 15(16)-EHC017-EF. AHRQ Comparative Effectiveness 
Reviews. 
12 Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Guerin 
immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the 
bladder: a randomized Southwest Oncology Group Study. J Urol 2000;163:1124-9. 
13 Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Guerin reduces 
the risk of progression in patients with superficial bladder cancer: a meta-analysis of the 
published results of randomized clinical trials. J Urol 2002;168:1964-70. 
14 Shelley MD, Kynaston H, Court J, et al. A systematic review of intravesical bacillus Calmette- 
Guerin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder 
cancer. BJU Int 2001;88:209-16. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
111 
Approved v 21.0 
930143391 2.0 
 
 
 
15 Han RF, Pan JG. Can intravesical bacillus Calmette-Guerin reduce recurrence in patients with 
superficial bladder cancer? A meta-analysis of randomized trials. Urology 2006;67:1216-23. 
16 Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU cancers group 
randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta, 
T1 papillary carcinoma of the urinary bladder; one-third dose versus full dose and 1 year versus 
3 years of maintenance. Eur Urol 2013;63:462-72. 
17 Sylvester RJ, Brausi MA, Kirkels WJ, et al. Long-term efficacy results of EORTC genito- 
urinary group randomized phase 3 study 30911 comparing intraveical instillations of 
epirubicin, bacillus Calmette-Guerin, and bacillus Calmette-Guerin plus isoniazid in patients 
with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder. Eur Urol 
2010;57:766-73. 
18 Babjuk M, Oosterlinck W, Sylvester R, et al. EAU guidelines on non-muscle-invasive 
urothelial carcinoma of the bladder, the 2011 update. Eur Urol 2011;59:997-1008. 
19 Fernandez-Gomez J, Madero R, Solsona E, et al. Predicting nonmuscle invasive bladder cancer 
recurrence and progression in patients treated with bacillus Calmette-Guerin: The CUETO 
scoring model. J Urol 2009;182:2195-203. 
20 Catalona WJ, Hudson MA, Gillen DP, et al. Risks and benefits of repeated courses of 
intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol 
1987;137:220-4. 
21 US Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research, Center for Biologics Evaluation and Research. BCG- 
unresponsive non-muscle invasive bladder cancer: Developing drugs and biologics for 
treatment guidance for industry. February 2018. 
22 Lerner SP, Dinney C, Kamat A, et al. Clarification of bladder cancer disease states following 
treatment of patients with intravesical BCG. Bladder Cancer 2015;1:29-30. 
23 BMS-936558: A Phase 2, Randomized, Open-label Study of Nivolumab or Nivolumab/BMS- 
986205 Alone or Combined with Intravesical BCG in Participants with BCG-Unresponsive, 
High-Risk, Non-Muscle Invasive Bladder Cancer. (Study CA2099UT). Bristol-Myers Squibb 
Company; 2017. Document Control No. 930120285. 
24 Li R, Spiess PE, Kamat AM. Treatment Options for Patients with Recurrent Tumors After 
BCG Therapy: Are We Ignoring the Obvious? European Urology [22 Apr 2018, 74(4):405- 
408] 
25 Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression 
in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined 
analysis of 2596 patients from seven EORTC trials. Eur Urol 2006;49(3):466-5. 
26 Steinberg RL, Thomas LJ1, Mott SL, O’Donnell MA. Bacillus Calmette-Guérin (BCG) 
treatment failures with non-muscle invasive bladder cancer: A data-driven definition for BCG 
unresponsive disease. Bladder Cancer 2016;2(2):215-24. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
112 
Approved v 21.0 
930143391 2.0 
 
 
 
27 Johnson SC, Smith ZL, Golan S, et al. Temporal trends in perioperative morbidity for radical 
cystectomy using the National Surgical Quality Improvement Program database. Urol Oncol 
2017;Aug 1. doi; 10.1016/j.urolonc.2017.07.013. [Epub ahead of print] 
28 Gore JL, Litwin MS, Lai J, et al. Use of radical cystectomy for patients with invasive bladder 
cancer. J Natl Cancer Inst 2010;102:802-11. 
29 von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus 
methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: 
results of a large, randomized, multinational, multicenter, Phase 3 study. J Clin Oncol 
2000;18:3068-77. 
30 Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev Immunol. 
2003;21:807-39. 
31 Redelman-Sidi G, Glickman MS, Bochner BH. The mechanism of action of BCG therapy for 
bladder cancer—a current perspective. Nat Rev Urol 2014;11:153-62. 
32 Tsuji S, Matsumoto M, Takeuchi O, et al. Maturation of human dendritic cells by cell wall 
skeleton of Mycobacterium bovis bacillus Calmette-Guerin: Involvement of toll-like receptors. 
Infect Immun 2000;68:6883-90. 
33 Balar AV, Kulkarni GS, Uchio EM, et al. Keynote 057: Phase II trial of pembrolizumab 
(pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) 
unresponsive to bacillus Calmette-Guérin (BCG). J Clin Oncol 2019;37(7 suppl):350. 
34 Inman BA, Sebo TJ, Frigola X, et al. PD-L1 (B7-H1) expression by urothelial carcinoma of 
the bladder and BCG-induced granulomata: associations with localized stage progression. 
Cancer 2007;109:1499-1505. 
35 Farina MS, Lundgren KT, Bellmunt J. Immunotherapy in urothelial cancer: Recent results and 
future perspectives. Drugs 2017;77:1077-89. 
36 Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics: Guidance for 
Industry. December 2018. https://www.fda.gov/regulatory-information/search-fda-guidance- 
documents/clinical-trial-endpoints-approval-cancer-drugs-and-biologics (Accessed July 2, 
2019) 
37 Jarow JP, Lerner SP, Kluetz PG, et al. Clinical trial design for the development of new 
therapies for nonmuscle-invasive bladder cancer: Report of a Food and Drug Administration 
and American Urological Association public workshop. Urology 2014;83(2):262-4. 
38 Svatek RS, Tangen C, Delacroix S, et al. Background and Update for S1602 “A Phase III 
Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming 
with Intradermal BCG Before Intravesical Therapy for BCG-naïve High-grade Non-muscle- 
invasive Bladder Cancer. Eur Urol Focus 4(2018):522-524. 
39 Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected 
stage III or IV melanoma. N Engl J Med 2017;377(19):1824-35. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
113 
Approved v 21.0 
930143391 2.0 
 
 
 
40 OPDIVO (nivolumab) US Prescribing Information. Bristol-Myers Squibb, Princeton, NJ. 
February 2018. 
41 Opdivo. Annex I Summary of Product Characteristics. Bristol-Myers Squibb Company. 2018. 
42 Witjes JA, Dalbagni G, Karnes RJ, et al. The efficacy of BCG TICE and BCG Connaught in a 
cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer. Urol Oncol 
2016;34:484. 
43 Gandhi NM, Morales A, Lamm DL. Bacillus Calmette-Guérin immunotherapy for 
genitourinary 
cancer. 
BJU 
Int. 
2013 
Aug;112(3):288-97. 
doi 
10.1111/j.1464- 
410X.2012.11754.x. Epub 2013 Mar 20. 
44 Sylvester RJ. Bacillus Calmette-Guérin treatment of non-muscle invasive bladder cancer. Int 
J Urol. 2011 Feb;18(2):113-20. doi: 10.1111/j.1442-2042.2010.02678.x. Epub 2010 Nov 22. 
45 Ashton A, Murthy Kusuma VR, Crew J2, Mostafid AH. BCG therapy in NMIBC: How much 
and for how long? Arch Esp Urol. 2018 May;71(4):342-348. 
46 Cheng CW, Ng MT, Chan SY, Sun WH. Low dose BCG as adjuvant therapy for superficial 
bladder cancer and literature review. ANZ J Surg. 2004 Jul;74(7):569-72. 
47 Kamat AM, Sylvester RJ, Böhle A, Palou J, Lamm DL, Brausi M, Soloway M, Persad R, 
Buckley R, Colombel M, Witjes JA. Definitions, End Points, and Clinical Trial Designs for 
Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder 
Cancer Group. J Clin Oncol. 2016 Jun 1;34(16):1935-44. doi: 10.1200/JCO.2015.64.4070. 
Epub 2016 Jan 25. 
48 Kim PH, Sukhu R, Cordon BH, et al. Reflex fluorescence in situ hybridization assay for 
suspicious urinary cytology in patients with bladder cancer with negative surveillance 
cystoscopy. BJU Int 2014;114(3):354-9. 
49 Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and 
Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical 
trials in oncology. J Natl Cancer Inst 1993;85(5):365-76. 
50 Osoba D, Rodrigues G, Myles J, et al. Interpreting the significance of changes in health-related 
quality of life scores. J Clin Oncol 1998;16:139-44. 
51 Blazeby JM, Hall E, Aaronson NK, et al. Validation and reliability testing of the EORTC QLQ- 
NMIBC24 questionnaire module to assess patient-reported outcomes in non-muscle invasive 
bladder cancer. Eur Urol 2014;66:1148-56. 
52 Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five- 
level version of EQ-5D (EQ-5D-5L). Qual Life Res 2011;20(10):1727-36. 
53 van Hout B, Janssen MF, Feng YS, et al. Interim scoring for the EQ-5D-5L: Mapping the EQ- 
5D-5L to EQ-5D-3L value sets. Value Health 2012;15(5):708-15. 
54 Pickard AS, Neary MP, Cella D. Estimation of minimally important differences in EQ-5D 
utility and VAS scores in cancer. Health Qual Life Outcomes 2007;5(1):70. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
114 
Approved v 21.0 
930143391 2.0 
 
 
 
55 Kamat AM, Li R, O’Donnell MA, et al. Predicting response to intravesical bacillus Calmette- 
Guérin immunotherapy: Are we there yet? A systematic review. Eur Urol 2018;73(5):738-48. 
56 Clopper C, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial. Biometrika 1934;26:404-13. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
115 
Approved v 21.0 
930143391 2.0 
 
 
12 
APPENDICES 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
116 
Approved v 21.0 
930143391 2.0 
 
 
APPENDIX 1 
ABBREVIATIONS AND TRADEMARKS 
 
Term 
Definition 
ADA 
anti-drug antibody 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AT 
aminotransaminases 
AUA 
American Urological Association 
BCG 
bacillus Calumette-Guerin 
BMS 
Bristol-Myers Squibb 
Cavg 
average concentration 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CFS 
cystectomy-free survival 
cHR 
critical hazard ratio 
CI 
confidence interval 
CIS 
carcinoma in situ 
Cmin 
minimum observed concentration 
CMV 
cytomegalovirus 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CRF 
case report form, paper or electronic 
CRR 
complete response rate 
CT 
computed tomography 
CTAg 
clinical trial agreement 
ctDNA 
circulating tumor DNA 
CTLA-4 
cytotoxic T-lymphocyte-associated protein-4 
DC 
dendritic cell 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
117 
Approved v 21.0 
930143391 2.0 
 
 
 
Term 
Definition 
DILI 
drug-induced liver injury 
DMC 
Data Monitoring Committee 
DOR 
duration of response 
DRESS 
drug reaction with eosinophilia and systemic symptoms 
DSS 
disease specific survival 
EAU 
European Association of Urology 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
EFS 
event-free survival 
ELISA 
enzyme-linked immunosorbent assay 
EOI 
end of infusion 
EORTC-QLQ- 
C30 
European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire - Cancer 
EORTC QLQ- 
NMIBC24 
European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire - Non-muscle-invasive Bladder Cancer 
EOT 
end of treatment 
EQ-5D-3L 
EuroQoL 5-dimensions 3-levels (quality of life questionnaire) 
EQ-5D-5L 
EuroQoL 5-dimensions 5-levels (quality of life questionnaire) 
E-R 
exposure-response 
FDA 
Food and Drug Administration 
FISH 
fluorescent in-situ hybridization 
FSH 
follicle stimulating hormone 
FPFV 
first patient, first visit 
FU 
follow-up 
GBS 
Guillain-Barre Syndrome 
GM-CSF 
granulocyte-macrophage colony-stimulating factor 
GFR 
glomerular filtration rate 
H&E 
hematoxylin and eosin 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
118 
Approved v 21.0 
930143391 2.0 
 
 
 
Term 
Definition 
HCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
HG 
high-grade 
HIPAA 
Health Insurance Portability and Accountability Act (US) 
HIV 
Human Immunodeficiency Virus 
HR 
hazard ratio 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
IFN 
interferon 
IHC 
immunohistochemistry 
IMAEs 
immune-mediated AEs 
IMP 
investigational medicinal products 
I-O 
immuno-oncology(ic) 
IP 
investigational product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IV 
intravenous 
KM 
Kaplan-Meier 
MDSC 
myeloid-derived suppressor cell 
MG 
myasthenia gravis 
MID 
minimal important difference 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
N/A 
not applicable 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NK 
natural killer 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
119 
Approved v 21.0 
930143391 2.0 
 
 
 
Term 
Definition 
NMIBC 
non-muscle invasive bladder cancer 
Non-IMP 
noninvestigational medicinal product 
Non-IP 
noninvestigational product 
NSCLC 
non-small cell lung cancers 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell 
PD 
pharmacodynamic 
PD-1 
programmed cell death protein-1 
PD-LI, PD-L2 
programmed cell death-ligand 1, programmed cell death-ligand 2 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PPK 
population pharmacokinetics 
PRC 
Pathology Review Committee 
PROs 
patient-reported outcomes 
PS 
Performance Status 
Q2W, Q3W, Q4W 
quaque (every) 2 weeks, quaque (every) 3 weeks, quaque (every) 4 weeks 
QoL 
quality of life 
qRT-PCR 
quantitative reverse transcription polymerase chain reaction 
R&D 
Research and Development 
RBC 
red blood cell 
RCC 
renal cell carcinoma 
RT-PCR 
reverse transcriptase polymerase chain reaction 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SCCHN 
squamous cell carcinoma of the head and neck 
SJS 
Stevens-Johnson syndrome 
SmPC 
Summary of Product Characteristics 
SNP 
single nucleotide polymorphism 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
120 
Approved v 21.0 
930143391 2.0 
 
 
 
Term 
Definition 
SOC 
standard of care 
SOP 
Standard Operating Procedures 
SUSAR 
suspected unexpected serious adverse reaction 
TaHG 
high-grade papillary Ta tumor 
TaLG 
low-grade papillary Ta tumor 
TBili 
total bilirubin 
TEN 
toxic epidermal necrolysis 
TILs 
tumor-infiltrating lymphocytes 
TNF 
tumor necrosis factor 
TURBT 
transurethral resection of the bladder tumor 
UC 
urothelial carcinoma 
ULN 
upper limit of normal 
US 
United States 
USPI 
US Prescribing Information 
UTI 
urinary tract infection 
VAS 
visual analog scale 
WBC 
white blood cell 
WFS 
worsening-free survival 
WOCBP 
women of childbearing potential 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
121 
Approved v 21.0 
930143391 2.0 
 
 
APPENDIX 2 
STUDY GOVERNANCE CONSIDERATIONS 
The term “participant” is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term “subject” used in the case report form (CRF) is intended 
to refer to a person (participant) who has consented to participate in the clinical research study. 
REGULATORY AND ETHICAL CONSIDERATIONS 
GOOD CLINICAL PRACTICE 
This study will be conducted in accordance with: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines Good Clinical Practice (GCP), 
• as defined by the International Council on Harmonisation (ICH) 
• in accordance with the ethical principles underlying European Union Directive 2001/20/EC, 
• United States Code of Federal Regulations, Title 21, Part 50 (21CFR50), and 
• 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 (IRB)/Independent Ethics Committee (IEC), and regulatory authorities according 
to applicable local regulations prior to initiation of the study. 
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to 
affect, to a significant degree one or more of the following: (1) the physical, safety or mental 
integrity of one or more subjects/participants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s). 
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks. 
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, participant recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects/participants. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator’s Brochure 
(IB) or product labeling information to be provided to subjects/participants and any updates. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
122 
Approved v 21.0 
930143391 2.0 
 
 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures. 
COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS 
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and, if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects/participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s), the deviation or change will be submitted as soon 
as possible to: 
• IRB/IEC 
• Regulatory Authority(ies), if applicable by local regulations (per national requirements) 
 
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS. 
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
subjects/participants currently enrolled in the study if they are affected by the amendment; and (3) 
the new form must be used to obtain consent from new subjects/participants prior to enrollment. 
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s). 
FINANCIAL DISCLOSURE 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 
INFORMED CONSENT PROCESS 
Investigators must ensure that subjects/participants are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer 
to participate. 
In situations where consent cannot be given by subjects/participants, their legally acceptable 
representatives (as per country guidelines) are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which the participant 
volunteers to participate. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
123 
Approved v 21.0 
930143391 2.0 
 
 
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form which will include all elements required by ICH, GCP and applicable 
regulatory requirements. The sample informed consent form will adhere to the ethical principles 
that have their origin in the Declaration of Helsinki. 
Investigators must: 
• Provide a copy of the consent form and written information about the study in the language in 
which the participant is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 
• Allow time necessary for participant or participant's legally acceptable representative to 
inquire about the details of the study. 
• Obtain an informed consent signed and personally dated by the participant or the participant's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 
• Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects/participants, prior to the beginning of 
the study, and after any revisions are completed for new information. 
 
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant. 
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects’/participants’ signed ICF and, in the US, the subjects’/participants’ signed HIPAA 
Authorization. 
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
The rights, safety, and well-being of the study subjects/participants are the most important 
considerations and should prevail over interests of science and society. 
SOURCE DOCUMENTS 
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
124 
Approved v 21.0 
930143391 2.0 
 
 
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, including investigational and no-investigational products (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 by BMS (or its vendors): 
Records or logs must comply with applicable 
regulations and guidelines and should include: 
• amount received and placed in storage area 
• amount currently in storage area 
• label identification number or batch number 
• amount dispensed to and returned by each 
participant, including unique participant 
identifiers 
• amount transferred to another area/site for 
dispensing or storage 
• nonstudy disposition (eg, lost, wasted) 
• amount destroyed at study site, if applicable 
• amount returned to BMS 
• retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 
• dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form. 
Sourced by site, and not supplied by 
BMS or its vendors (examples include IP 
sourced 
from 
the 
sites 
stock 
or 
The investigator or designee accepts responsibility 
for documenting traceability and study treatment 
integrity in accordance with requirements applicable 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
125 
Approved v 21.0 
930143391 2.0 
 
 
 
If 
Then 
commercial supply, or a specialty 
pharmacy) 
under law and the SOPs/standards of the sourcing 
pharmacy. 
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements. 
CASE REPORT FORMS 
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study. 
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules in accordance with the applicable regulatory 
requirement(s). 
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a 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 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
126 
Approved v 21.0 
930143391 2.0 
 
 
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. 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, including investigational and non-investigational products (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 
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
127 
Approved v 21.0 
930143391 2.0 
 
 
 
If 
Then 
or 
commercial 
supply, 
or 
a 
specialty according to the institutional guidelines and 
pharmacy) 
procedures. 
 
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met: 
• On-site disposal practices must not expose humans to risks from the drug. 
• On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances. 
• Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request. 
• Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented. 
• Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period. 
 
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. 
DISSEMINATION OF CLINICAL STUDY DATA 
In order to benefit potential study participants, patients, healthcare providers and researchers, and 
to help BMS honor its commitments to study participants, BMS will make information about 
clinical research studies and a summary of their results available to the public as per regulatory 
and BMS requirements. BMS will post study information on local, national or regional databases 
in compliance with national and international standards for disclosure. BMS may also voluntarily 
disclose information to applicable databases. 
CLINICAL STUDY REPORT 
A Signatory Investigator must be selected to sign the clinical study report. 
For each CSR related to this protocol, the following criteria will be used to select the signatory 
investigator: 
• External Principal Investigator designated at protocol development 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
128 
Approved v 21.0 
930143391 2.0 
 
 
• National Coordinating Investigator 
• Study Steering Committee chair or their designee 
• Participant recruitment (eg, among the top quartile of enrollers) 
• Involvement in trial design 
• Regional representation (eg, among top quartile of enrollers from a specified region or country) 
• Other criteria (as determined by the study team) 
SCIENTIFIC PUBLICATIONS 
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTAg) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTAg. 
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
principal investigator, sub-investigator or any other member of the study staff without the prior 
written consent of the Sponsor. 
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship: 
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights and conclusion); AND 
2) Drafting the work or revising it critically for important intellectual content; AND 
3) Final approval of the version to be published; AND 
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
 
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered. 
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
129 
Approved v 21.0 
930143391 2.0 
 
 
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, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and 
should specify "intentional overdose" as the verbatim term 
Events NOT Meeting the AE Definition 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
DEFINITION OF SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
130 
Approved v 21.0 
930143391 2.0 
 
 
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 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
131 
Approved v 21.0 
930143391 2.0 
 
 
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 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 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
132 
Approved v 21.0 
930143391 2.0 
 
 
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 (EDC) system is unavailable/not functioning for transmission of the eCRF 
to BMS (or designee). 
♦ In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission 
♦ When paper forms are used, the original paper forms are to remain on site 
• Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission. 
SAE Email Address: Refer to Contact Information list. 
SAE Facsimile Number: Refer to Contact Information list. 
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
133 
Approved v 21.0 
930143391 2.0 
 
 
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 postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
• Postmenopausal female 
− A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle stimulating hormone (FSH) level 
> 40 mIU/mL to confirm menopause. 
 
CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILDBEARING 
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 ovulation/or implantation (These methods of contraception cannot be used by 
WOCBP participants in studies where hormonal contraception is prohibited)b 
− oral (birth control pills) 
− intravaginal (vaginal birth control suppositories, rings, creams, gels) 
− transdermal 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
134 
Approved v 21.0 
930143391 2.0 
 
 
 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulationb 
− oral 
− injectable 
Highly Effective Methods That Are User Independent 
• 
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited)b 
• 
Intrauterine hormone-releasing system (IUS)(This method of contraception cannot be used 
by WOCBP participants in studies where hormonal contraception is prohibited)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 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
135 
Approved v 21.0 
930143391 2.0 
 
 
 
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. 
 
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S) OF 
CHILD BEARING POTENTIAL. 
• Given that nivolumab is not a genotoxic agent, and that relevant systemic concentrations 
sufficient to produce a risk of fetal toxicity are not expected in WOCBP partners from exposure 
to a male participant’s seminal fluid, male study participants will not be required to use 
contraceptive measures and/or a latex or other synthetic condom during sexual activity with a 
WOCBP partner. 
 
COLLECTION OF PREGNANCY INFORMATION 
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
136 
Approved v 21.0 
930143391 2.0 
 
 
APPENDIX 5 
MANAGEMENT ALGORITHMS 
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens. 
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated. 
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The oral 
equivalent of the recommended IV doses may be considered for ambulatory patients with low- 
grade toxicity. The lower bioavailability of oral corticosteroids should be taken into account when 
switching to the equivalent dose of oral corticosteroids. 
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended. 
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
137 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
138 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
139 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
140 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
141 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
142 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
143 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
144 
Approved v21.0 
930143391 2.0 
 
 
 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
145 
Approved v 21.0 
930143391 2.0 
 
 
APPENDIX 6 
ECOG PERFORMANCE STATUS SCALE 
 
ECOG PERFORMANCE STATUSa 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead 
a Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, and Carbone PP. Toxicity and Response 
Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649-655. 

Clinical Protocol 
BMS-936558 
CA2097G8 
Nivolumab 
Protocol Amendment No.: 01 
Date: 11-Oct-2021 
146 
Approved v 21.0 
930143391 2.0 
 
 
APPENDIX 7 
COUNTRY SPECIFIC REQUIREMENTS 
Criteria for exclusion of HIV-positive participants in Argentina, Czech Republic, Germany, 
and any other countries where exclusion of HIV-positive participants is locally mandated 
 
 
Protocol Section 
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 3 (i) 
“Known history of testing positive for human immunodeficiency virus 
(HIV) or known acquired immunodeficiency syndrome (AIDS)”to be 
replaced with “Positive test for HIV”