A Phase 1/2 Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers
Phase: PHASE1
Conditions: Cancer, Melanoma
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 1/2 Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in 
Advanced Cancers
NCT Number: NCT03400332
Document Date (Date in which document was last revised): 17 May 2024

Page:
1
Protocol Number:
CA027002
Date:
27-Oct-2017
Revised Date:
17-May-2024
CLINICAL PROTOCOL CA027002
A Phase 1/2 Study of BMS-986253 in Combination with Nivolumab or Nivolumab plus 
Ipilimumab in Advanced Cancers
Protocol Amendment Number: 07
Incorporates Administrative Letter 06
Clinical Scientist
Clinical Trial Physician/Medical Monitor
1000 Sierra Point Parkway
Brisbane, CA 94005
3033 Science Park Road
San Diego, CA 92121
Telephone (office): 
Telephone (office): 
Email: 
Email:
24-hr Emergency Telephone Number
USA:
International:
Bristol Myers Squibb Company
3401 Princeton Pike
Lawrenceville, NJ 08648
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
REGULATORY AGENCY IDENTIFIER NUMBER(S)
IND: 123274
EX-US: Non-IND
EU Trial Number: 2023-509061-20
NCT: NCT03400332
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Protocol Amendment No.: 07
Date: 17-May-2024
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).
© 2024 Bristol-Myers Squibb Company
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Protocol Amendment No.: 07
Date: 17-May-2024
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol 
Amendment 07
Global
17-May-2024
This amendment updates the primary analysis for Part 2. The population 
was changed from those with
 to all randomized 
participants, given additional analysis on baseline sIL-8 data suggesting
an association with tumor burden, thus decreasing the relevance of using 
sIL-8 as a selection biomarker. Further, to facilitate a timelier analysis, 
the primary endpoint was revised to objective response rate (from PFS). 
With these updates, the sample size was also updated. Approximately 
 participants (
 in each treatment arm) currently enrolled in Part 2 
will provide a sufficient sample size to analyze the new primary 
endpoint of objective response rate under a statistical framework.
Additional changes to simplify assessments are included to reduce
participant burden following the final analysis.
Administrative 
Letter 06
06-Nov-2023
Study personnel updated.
Protocol 
Amendment 06
Global
17-May-2023

Adds 
safety 
information 
about 
hemophagocytic 
lymphohistiocytosis.

Opens enrollment in Part 
 to participants with mismatch repair 
proficient colorectal cancer.


Identifies recommended Phase 2 dose for Part 2 as 3600 mg every 
2 weeks.
Protocol 
Amendment 05
Global
17-Feb-2022
Protocol Amendment 5 
 
 
Although there have been no such events to date, management 
guidelines for potential cytokine release syndrome (CRS) is added 
Inclusion criteria were updated to clarify prior 
therapies required for several indications
 
Criteria regarding prior use of targeted therapy in participants with 
 melanoma is also updated to accommodate 
prioritization of combination immunotherapy when appropriate.
Incorporates Administrative Letter 05. Appendix 6, Management 
Algorithms for Studies Under CTCAE Version 4.0, 
 
Administrative 
Letter 05
08-Feb-2021
The purpose of this administrative letter is to communicate the change 
of the Study Director/Medical Monitor and to clarify language 
regarding SARS-CoV-2 vaccines.
Protocol
Amendment 04
Global
23-Nov-2020
Based on interim analysis of data from Part 1 (as described in BMS-
986253 IB version 05, March 2020), the following study design 
revisions to the protocol were made:
Part 1: In Part 1B, the maximum administered dose of BMS-986253 
was increased from 2400 mg Q2W to 3600 mg Q2W, 
 
 
 Part 1C was added to assess the triplet combination of BMS-
986253 plus nivolumab plus ipilumumab.
Part 2: The study design was changed to a randomized, double-blind 
investigation of BMS-986253 plus nivolumab plus ipilimumab versus 
placebo plus nivolumab plus ipilimumab in advanced melanoma.
 
 
 
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Protocol Amendment No.: 07
Date: 17-May-2024
Document
Date of Issue
Summary of Change
The treatment period was also extended from 2 years to 3 years.
Administrative 
Letter 04
15-Oct-2019
The purpose of this administrative letter is to clarify observation 
periods after BMS-986253 and nivolumab infusions.
Revised 
Protocol 03
Global
10-Jul-2019
The purpose of this revised protocol is to expand enrollment in Part 1 
to allow further assessment of pharmacodynamic changes in the tumor 
microenvironment at a specific dosing regimen, if warranted. The 
maximum number of treated participants in Part 1 was increased from 
approximately 
 The presentation of the objectives and 
endpoints have been changed 
 
 Lastly, inclusion criteria for participants within Part 1 have 
been modified. The tumor types in Part 1 have not changed; however, 
modifications of the inclusion criteria define a more homogeneous 
population within those tumor types (restricted to participants who 
progressed on or within 3 months of anti-PD(L)1-based therapy) to aid 
in additional pharmacodynamic analysis. 
Administrative 
Letter 03
25-Feb-2019
The purpose of this administrative letter is to clarify acceptable methods 
for establishing HPV status in participants with oropharyngeal 
squamous cell carcinoma of the head and neck (SCCHN) and clarify 
instructions for PK time matched ECGs.
Revised 
Protocol 02
Global
02-Nov-2018
The study design is being modified for participants enrolling in Part 1B 
to provide flexibility to explore additional dosing regimens. In 
addition, revision is made to clarify and amend procedures related to 
collection of SAEs during the Pre-Screen Period. All participants will 
be entered into IRT and receive a unique subject ID after signing the 
Pre-Screen ICF. SAEs related to the pre-screen blood draw will be 
collected and followed until resolution or stabilization. The inclusion 
criteria are also being modified to allow certain PD-(L)1 naive 
participants with NSCLC, RCC, SCCHN, and UCC into the study. 
Lastly, this revised protocol includes guidance on palliative treatments 
that occur during the study period.
Revised 
Protocol 01
Global
13-Mar-2018
Incorporates Administrative Letters 01 and 02 and the following 
changes: 1) expands enrollment in Part 1 to include advanced 
Squamous cell carcinoma of the head and Neck (SCCHN) and 
Urothelial cancer (UCC) participants, 2) modifies eligibility criteria for 
participants with NSCLC, RCC, TNBC, HCC, CRC, and 3) modifies 
the sampling schedule for pharmacodynamic assessment.
Administrative 
Letter 02
07-Feb-2018
Correction to section 6.2, exclusion criteria numbering
Administrative 
Letter 01
29-Jan-2018
Correction to section 6.1, inclusion criteria numbering
Original 
Protocol
27-Oct-2017
Not applicable
 
 
 
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 07
This protocol amendment updates the primary analysis for the randomized assessment in Part 2.
Additional analysis on baseline serum IL-8 (sIL-8) data suggested an association with tumor 
burden, decreasing the relevance of using sIL-8 as a selection biomarker. Thus, the primary 
analysis population was changed from 
 to all randomized participants. To 
facilitate a timely analysis, the primary endpoint was further revised to objective response rate 
(ORR). Approximately
 participants (
 in each treatment arm) currently enrolled in Part 2 will 
provide a sufficient sample size to analyze the new primary endpoint of ORR under a statistical 
framework 
 
Additionally, for Part 2,
objectives and endpoints no longer considered essential for the study analysis have been 
reclassified as exploratory. 
Additional changes are made to simplify study procedures for participants following the final 
analysis. These changes aim to alleviate participant and site burden and remove sample collections
and study procedures that are no longer considered necessary. Assessments and procedures 
deemed necessary for monitoring the safety of the subjects remain unchanged.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 07
Section Number & Title
Description of Change
Brief Rationale
Title Page
Updated the clinical scientist and clinical 
trial physician/medical monitor 
information.
Administrative change.
Removed the EudraCT identifier and 
updated the European Union trial number.
The term “EudraCT” is obsolete, 
as it refers to the previous 
European legislation.
Section 1: Protocol Summary
Updated to reflect changes made in the 
body of the protocol.
To align with protocol updates.
Table 2-4: On-treatment 
Procedural Outline (Cohorts 
1B4 through 1B6 -
BMS-986253 Q2W and 
Nivolumab Q4W)
Table 2-6: On-treatment 
Procedural Outline (Part 1C 
and Part 2 - BMS-986253 Q2W 
and Nivolumab and Ipilimumab 
Q3W)
Table 2-7: Safety Follow-up 
Procedural Outline
Section 5.1.5.2: Response 
Follow-up Period
 
Section 7.11: Treatment After 
the End of the Study

Updated the body imaging 
requirements for on-treatment and 
follow-up visits to follow the standard 
of care and can stop when final 
analysis is completed.

Updated the electrocardiogram (ECG) 
requirements for Parts 1A, 1B, and 1C 
cohorts to be assessed by independent 
core laboratory until the final analysis.

Updated the requirement for treatment 
after the end of the study.

Updated the criteria for 
discontinuation from the study 
treatment. 

Noted that images will no longer be 
submitted to blinded independent 
central review (BICR) for evaluation 
and pharmacokinetic (PK), 
To remove unnecessary sample 
collections and study procedures 
after the final analysis is 
completed.
Protocol Amendment No.: 07
Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 07
Section Number & Title
Description of Change
Brief Rationale
Section 8.1: Discontinuation 
from Study Treatment 
Section 9.1.3: 
Electrocardiograms
Section 9.4: Efficacy 
Assessments
Section 9.4.1: Imaging 
Assessment for the Study
Section 9.4.2: BICR 
Confirmation of Progression 
(Part 2)
Section 9.5: Pharmacokinetics 
and Immunogenicity 
Assessments
Section 9.8: Biomarkers
immunogenicity, and biomarker 
samples will no longer be collected
following final analysis.
Table 2-6: On-treatment 
Procedural Outline (Part 1C 
and Part 2 - BMS-986253 Q2W 
and Nivolumab and Ipilimumab
Q3W)
Added that participants with no relevant 
changes to ECGs at 6 months of treatment 
may stop subsequent routine ECGs. 
To reduce participant and site 
burden.
Table 2-7: Safety Follow-up 
Procedural Outline
Section 5.1.5.1: Safety Follow-
up Period
Section 5.1.5.2: Response 
Follow-up Period
Section 5.1.5.3: Survival 
Follow-up Period
Section 8.1.2: Post Treatment 
Follow-up
 
 
 
 
 
 
 
 
 
 
 
 
 

Removed survival follow-up visits 
throughout the protocol.

Removed the 60-day safety follow-up 
visit.

Removed the assessment of 
participant survival status.
To simplify the procedures to 
reduce participant and site 
burden after the final analysis.
Protocol Amendment No.: 07
Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 07
Section Number & Title
Description of Change
Brief Rationale
 
 
 
 
 
 
 
 
 
 
Table 4-1: Objectives and 
Endpoints - Part 1
The secondary endpoint for median
duration of response per Response 
Evaluation Criteria in Solid Tumors
(RECIST) v1.1 was changed to duration of 
response per RECIST v1.1 per 
investigator.
Editorial change.
Table 4-2: Objectives and 
Endpoints - Part 2
Updated the primary objective for Part 2:

To compare ORR of BMS-986253 
plus nivolumab plus ipilimumab with 
placebo plus nivolumab and 
ipilimumab using RECIST v1.1. 
The primary endpoint for Part 2 was 
updated to ORR based on BICR 
assessments per RECIST v1.1 in all 
randomized participants.
The primary endpoint of Part 2 
was revised to ORR in all 
randomized participants 
regardless of baseline sIL-8 
level. The primary, secondary, 
 were 
updated to align with the revised 
endpoints of Part 2, 
 
 
 
Protocol Amendment No.: 07
Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 07
Section Number & Title
Description of Change
Brief Rationale
Section 5.1: Overall Design
Figure 5.1-3: Study Design 
Part 2
Section 5.2: Number of 
Participants
Section 5.4.3: Rationale for 
Selecting Participants Based on 
Serum IL-8
Section 7.4: Method of 
Treatment Assignment and 
Stratification
Section 7.5.2: Part 2
Section 10.1.3: Part 2
 
Table 10.3.1-2: Part 2 Efficacy 
Analysis
Former Section 10.3.8.2: Part 2 
Interim Analysis for Efficacy
Reduced the number of participants in 
Part 2 from approximately 
 
updated the total number of participants
and statistical considerations and analyses, 
and removed the requirement to enroll at 
least 51 participants with baseline 
 
in Part 2.
Updated the analysis plan according to the 
change in the primary endpoint for Part 2.
Reduced the number of 
participants to plan for a final 
analysis with the currently 
enrolled participants.
Removed the requirement for
to allow all 
participants to be included for
further analysis irrespective of 
their sIL-8 levels.
The statistical considerations for 
Part 2 were modified per 
updated objectives and 
endpoints.
Section 7.5.2: Part 2
Added a paragraph that Sponsor and 
Investigators will be unblinded to 
treatment assignments once database lock 
for the final analysis is completed.
To simplify the procedures and 
reduce participant burden after 
the final analysis.
Section 9.2.4: Regulatory 
Reporting Requirements for 
SAEs
Appendix 2: Study Governance 
Considerations
The legal framework has been updated 
from the European Directive 2001/20/EC 
to the European Regulation 536/2014.
To align with new European 
Union regulations.
All
Formatting and editorial corrections. 
Minor; therefore, have not been 
summarized.
Protocol Amendment No.: 07
Date: 17-May-2024
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY.............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 07 ............................. 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 07 ................ 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.2.1 BMS-986253 ............................................................................................ 
 
3.2.2 Nivolumab ................................................................................................ 
 
3.2.3 Ipilimumab ............................................................................................... 
 
3.2.4 Nivolumab plus Ipilimumab ..................................................................... 
 
 
 
3.3 Benefit/Risk Assessment .................................................................................. 
 
3.3.1 Safety Monitoring on Study Treatment .................................................... 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Pre-Screening Period (Applicable for Part 1 Only) ................................ 
 
5.1.2 Screening Period ...................................................................................... 
 
5.1.3 Treatment Period ..................................................................................... 
 
5.1.4 Window Visits........................................................................................... 
 
5.1.5 Follow-up ................................................................................................. 
 
5.1.5.1 Safety Follow-up Period ................................................................. 
 
5.1.5.2 Response Follow-up Period ............................................................ 
 
5.1.5.3 Survival Follow-up Period .............................................................. 
 
5.1.6 Data Monitoring Committee and Other External Committees ................ 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.4.1 Rationale for Targeting IL-8 in Cancer ................................................... 
 
5.4.2 Rationale for the Combination of BMS-986253 and Nivolumab ............. 
 
5.4.3 Rationale for Selecting Participants Based on Serum IL-8 ..................... 
 
5.4.4 Rationale for the Combination of BMS-986253, Nivolumab, and 
Ipilimumab .................................................................................................. 
 
5.4.5 Rationale for Testing Different Doses in Parallel in Part 1 .................... 
 
5.4.6 Rationale for Treatment Beyond Progression ......................................... 
 
5.4.7 Rationale for Tumor Selection ................................................................. 
 
5.4.8 Rationale for Treatment of Post-PD-(L)1 Melanoma in Part 2 .............. 
 
5.4.9 Rationale for Stratification in Part 2 ....................................................... 
 
5.4.10 Rationale for Treatment Duration ......................................................... 
 
 
 
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CA027002
Anti-IL-8
Protocol Amendment No.: 07
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5.5 Justification for Planned Dose Selection .......................................................... 
 
5.5.1 Rationale for Part 1A Dose Selection of BMS-986253 in Combination 
with Nivolumab. .......................................................................................... 
 
5.5.2 Rationale for Part 1B Dosing Schedules and Maximum Administered 
Dose ............................................................................................................ 
 
5.5.3 Rationale for Flat Dosing of BMS-986253 .............................................. 
 
5.5.4 Rationale for Nivolumab Dose Selection ................................................. 
 
5.5.5 Rationale for Ipilimumab Dose Selection ................................................ 
 
5.5.6 Rationale for Part 2 Dosing Schedules and Maximum Administered 
Dose/RP2D ................................................................................................. 
 
6 STUDY POPULATION ............................................................................................ 
 
6.1 Inclusion Criteria .............................................................................................. 
 
6.2 Exclusion Criteria ............................................................................................. 
 
6.3 Lifestyle Restrictions ........................................................................................ 
 
6.4 Screen Failures .................................................................................................. 
 
6.4.1 Retesting During Screening or Lead-In Period ....................................... 
 
7 TREATMENT ........................................................................................................... 
 
7.1 Treatments Administered .................................................................................. 
 
7.2 Handling and Dispensing .................................................................................. 
 
7.3 Schedule of Dose for Each Investigational Product ......................................... 
 
7.4 Method of Treatment Assignment and Stratification ........................................ 
 
7.5 Blinding............................................................................................................. 
 
7.5.1 Part 1 ....................................................................................................... 
 
7.5.2 Part 2 ....................................................................................................... 
 
7.6 Dosage Modification ......................................................................................... 
 
7.6.1 Dose-limiting Toxicities ........................................................................... 
 
 
 
 
 
 
 
 
 
 
 
7.6.2 Management Algorithms for Immuno-oncology Agents .......................... 
 
7.6.3 Dose Delays Due to Toxicity.................................................................... 
 
7.6.3.1 Criteria for Dose Delay Secondary to Changes in AST or ALT for 
Participants with HCC .......................................................................... 
 
7.6.3.2 Protocol-Specific Recommendation for Management of Hepatic 
Events in HCC Participants .................................................................. 
 
7.6.4 Criteria to Resume Treatment .................................................................. 
 
7.6.5 Exceptions to Permanent Discontinuation Criteria ................................. 
 
7.6.6 Management of Drug-related Infusion Reactions.................................... 
 
7.6.7 Management of Cytokine Release Syndrome (CRS) ................................ 
 
7.6.8 Hemophagocytic Lymphohistiocytosis (HLH) ......................................... 
 
7.6.8.1 HLH Management Approaches....................................................... 
 
7.7 Preparation/Handling/Storage/Accountability .................................................. 
 
7.7.1 Retained Samples for Bioavailability / Bioequivalence ........................... 
 
7.8 Treatment Compliance ...................................................................................... 
 
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CA027002
Anti-IL-8
Protocol Amendment No.: 07
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7.9 Concomitant Therapy........................................................................................ 
 
7.9.1 Prohibited and/or Restricted Treatments................................................. 
 
7.9.2 Other Restrictions and Precautions ......................................................... 
 
7.9.2.1 Imaging Restriction and Precautions ............................................. 
 
7.10 Permitted Therapy ........................................................................................... 
 
7.10.1 Palliative Local Therapy........................................................................ 
 
7.11 Treatment After the End of the Study ............................................................. 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation from Study Treatment ............................................................ 
 
8.1.1 Treatment Beyond Progression................................................................ 
 
8.1.2 Post Treatment Follow-up ....................................................................... 
 
8.2 Discontinuation from the Study ........................................................................ 
 
8.2.1 Study Termination .................................................................................... 
 
8.3 Lost to Follow-up .............................................................................................. 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Safety Assessment ............................................................................................ 
 
9.1.1 Physical Examinations ............................................................................. 
 
9.1.2 Vital signs................................................................................................. 
 
9.1.3 Electrocardiograms ................................................................................. 
 
9.1.4 Clinical Safety Laboratory Assessments .................................................. 
 
9.2 Adverse Events Assessments ............................................................................ 
 
9.2.1 Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information ......................................................................... 
 
9.2.2 Method of Detecting AEs and SAEs ......................................................... 
 
9.2.3 Follow-up of Adverse Events and Serious Adverse Events ...................... 
 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
 
9.2.5 Pregnancy ................................................................................................ 
 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
 
9.2.7 Immune-mediated Adverse Events ........................................................... 
 
9.2.8 Potential Drug-induced Liver Injury ....................................................... 
 
9.2.9 Other Safety Considerations .................................................................... 
 
9.3 Overdose ........................................................................................................... 
 
9.4 Efficacy Assessments........................................................................................ 
 
9.4.1 Imaging Assessment for the Study............................................................ 
 
9.4.2 BICR Confirmation of Progression (Part 2) ............................................ 
 
9.5 Pharmacokinetics and Immunogenicity Assessments ...................................... 
 
9.6 Pharmacodynamics ........................................................................................... 
 
9.7 Pharmacogenomics ........................................................................................... 
 
9.7.1 Absorption, Distribution, Metabolism, and Excretion Sampling ............. 
 
9.8 Biomarkers ........................................................................................................ 
 
9.8.1 Serum IL-8 Levels for Participant Selection ............................................ 
 
 
 
 
 
 
 
 
 
 
 
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CA027002
Anti-IL-8
Protocol Amendment No.: 07
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9.8.4 Additional Research Collection ............................................................... 
 
9.8.5 Methods to Detect HPV Status of SCCHN Originating in the Oropharynx
..................................................................................................................... 
 
9.9 Health Economics OR Medical Resource Utilization and Health Economics . 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Sample Size Determination............................................................................. 
 
10.1.1 Parts 1A and 1B ..................................................................................... 
 
10.1.2 Part 1C ................................................................................................... 
 
10.1.3 Part 2 ..................................................................................................... 
 
10.2 Populations for Analyses ................................................................................ 
 
10.3 Statistical Analyses ......................................................................................... 
 
10.3.1 Efficacy Analyses ................................................................................... 
 
10.3.2 Safety Analyses....................................................................................... 
 
10.3.3 Pharmacokinetic Analyses ..................................................................... 
 
10.3.4 Immunogenicity Analyses ....................................................................... 
 
10.3.5 Biomarker Analyses ............................................................................... 
 
10.3.6 ECG Analyses ........................................................................................ 
 
10.3.7 Other Analyses ....................................................................................... 
 
10.3.8 Interim Analyses..................................................................................... 
 
10.3.8.1 Part 1 ............................................................................................ 
 
 
 
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 ECOG PERFORMANCE STATUS ..................................................... 
 
APPENDIX 6 MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 4.0 ......................................................................................................... 
 
 
 
APPENDIX 8 RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS ........................ 
 
APPENDIX 9 CHILD-PUGH SCORE ........................................................................ 
 
APPENDIX 10 NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION ................................................................................................ 
 
APPENDIX 11 COUNTRY SPECIFIC AMENDMENTS .......................................... 
 
 
 
APPENDIX 13 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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Clinical Protocol
BMS-986253
CA027002
Anti-IL-8
Protocol Amendment No.: 07
Date: 17-May-2024
12
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8.0
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
1
PROTOCOL SUMMARY
Protocol Title: A Phase 1/2 Study of BMS-986253 in Combination with Nivolumab or 
Nivolumab plus Ipilimumab in Advanced Cancers 
Study Phase: 1/2 
Rationale:
BMS-986253 is a fully human-sequence immunoglobulin G1 kappa (IgG1κ) monoclonal antibody 
(mAb) directed against human interleukin-8 (IL-8). Development of BMS-986253 in cancer is 
supported by pre-clinical findings showing anti-IL-8 disruption of the IL-8: C-X-C chemokine 
receptor type 1/2 (CXCR1/2) signaling axis, which inhibits the recruitment of immunosuppressive 
myeloid derived suppressor cells (MDSC) to the tumor microenvironment, reduces cancer stem 
cell (CSC) renewal, reverses epithelial mesenchymal transition (EMT), and inhibits angiogenesis. 
These are all important mechanisms for cancer induced immunosuppression, recurrence, and 
metastasis. Moreover, emerging literature suggests a strong association between high IL-8 levels 
and both resistance to anti-programmed cell death (ligand) 1 (PD-[L]1) agents and overall poor 
survival. The present study will support the clinical development strategy for BMS-986253 as an 
anti-cancer agent in combination with nivolumab, or in combination with nivolumab and 
ipilimumab. It is hypothesized that inhibition of MDSC tumor infiltration, reduction of CSC 
renewal, and reversal of cancer cell EMT driven by BMS-986253 disruption of the IL-8: CXCR1/2 
signaling axis will further sensitize IL-8-producing tumors to immune checkpoint blockade.
Study Population:
Participants must be at least 18 years of age and have histologic or cytologic confirmation of a 
solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with radiographically 
measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, 
 
 For Parts 1A and 1B, participants must have 
 
 at baseline. For Parts 1C and 2, participants may have any baseline serum IL-8 level.
Objectives and Endpoints:
Table 1:
Objectives and Endpoints - Part 1
Objectives
Endpoints
Primary

To characterize safety, tolerability, and DLTs, and to 
determine the RP2D of BMS-986253 administered in 
combination with nivolumab, or in combination with 
nivolumab and ipilimumab in participants with 
advanced solid tumors.

Incidence of AEs, SAEs, AEs meeting protocol-
defined DLT criteria, and AEs leading to 
discontinuation, 
death, 
and 
laboratory 
abnormalities.
Secondary

To evaluate the preliminary efficacy of BMS-986253 
in combination with nivolumab in participants with 
advanced solid tumors using RECIST v1.1.

ORR and DOR per RECIST v1.1 per investigator.
Protocol Amendment No.: 07
Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 1:
Objectives and Endpoints - Part 1
Objectives
Endpoints

To characterize the PK and immunogenicity of 
BMS-986253 when administered in combination 
with nivolumab, or in combination with nivolumab 
and ipilimumab in participants with advanced solid 
tumors.

To assess serum IL-8 levels at baseline (ie, screening) 
and changes in IL-8 levels on treatment.

Summary measures of PK parameters and 
incidence of ADA to BMS-986253

Summary measures of IL-8 and change (or percent 
change) from baseline in IL-8 on treatment
Abbreviations: ADA, anti-drug antibody; AE, adverse event; BICR, blinded independent central review; 
DLT, 
dose-limiting 
toxicity; 
DOR, 
 
duration 
of 
response; 
ORR, objective 
response 
rate; 
PK, pharmacokinetic(s); RECIST, Response Evaluation Criteria in Solid Tumors; RP2D, recommended Phase 2 dose; 
SAE, serious adverse event.
Table 2:
Objectives and Endpoints - Part 2
Objectives
Endpoints
Primary

To compare
the ORR
of BMS-986253 plus 
nivolumab plus ipilimumab with placebo plus 
nivolumab and ipilimumab using RECIST v1.1. 

ORR 
based 
on 
BICR 
assessments 
per 
RECIST v1.1 in all randomized participants.
Secondary

To estimate the PFS of BMS-986253 plus nivolumab 
plus ipilimumab and placebo plus nivolumab and 
ipilimumab in participants with advanced melanoma 
using RECIST v1.1 (regardless of baseline serum 
IL-8 levels).

To compare the safety of BMS-986253 plus 
nivolumab plus ipilimumab with placebo plus 
nivolumab plus ipilimumab in participants with 
advanced melanoma.

mPFS and PFS hazard ratio based on BICR 
assessments per RECIST v1.1.

Incidence of AEs, SAEs, and AEs leading to 
discontinuation, 
death, 
and
laboratory 
abnormalities.
Abbreviations: AE, adverse event; BICR, blinded independent central review; ORR, objective response rate; mPFS, 
median progression-free survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid 
Tumors; SAE, serious adverse event. 
Overall Design:
This is a Phase 1/2 study of BMS-986253 administered in combination with nivolumab or in 
combination with nivolumab and ipilimumab in participants with advanced solid tumors. The 
study is comprised of 2 Parts. 
In Part 1, the safety of BMS-986253 in combination with nivolumab or in combination with 
nivolumab and ipilimumab will be evaluated in participants with advanced solid tumors. Part 1 is 
divided into 3 subsections: Part 1A (BMS-986253 plus nivolumab safety evaluation lead-in), Part 
1B (BMS-986253 plus nivolumab dose finding), and Part 1C (safety evaluation of BMS-986253 
in combination with nivolumab and ipilimumab). Parts 1A and 1B evaluate the doublet 
Protocol Amendment No.: 07
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
combination of BMS-986253 and nivolumab in participants with 
 
. Part 1C is a safety evaluation of the triplet combination of BMS-986253, nivolumab, 
and ipilimumab in participants with any baseline level of serum IL-8. Safety, pharmacokinetics 
(PK), and pharmacodynamics will be continuously evaluated throughout the study. The 
recommended Phase 2 dose (RP2D) will be determined based on the totality of the data in Part 1, 
to define the safe and most biologically active dose. 
Part 2 is a randomized, double-blind evaluation of BMS-986253 plus nivolumab plus ipilimumab 
versus placebo plus nivolumab plus ipilimumab in participants with melanoma who have 
progressed on anti-PD-(L)1 therapy.
The following tumor types will be enrolled as described in the inclusion criteria:

Parts 1A and 1B (must have 
): melanoma, renal cell carcinoma (RCC), 
urothelial cancer (UCC), squamous cell carcinoma of the head and neck (SCCHN), and non-
small cell lung cancer (NSCLC) (NSCLC cannot enroll in 1B6 
)

Part 1C: melanoma, UCC, hepatocellular carcinoma (HCC), and colorectal cancer (CRC)

Part 2: melanoma
Part 1A: Safety Evaluation Lead-in (already enrolled, 
 participants, per BMS-986253 IB)
The safety evaluation lead-in (Part 1A) will begin with a cohort of participants who will receive a 
2400 mg flat dose of BMS-986253 Q4W combined with 480 mg flat dose of nivolumab Q4W. A 
slightly higher dose (32 mg/kg or 2560 mg administered Q2W; yielding an overall dose of 
64 mg/kg or 5120 mg per month) of BMS-986253 monotherapy has been shown to be safe and 
well tolerated in BMS Study CA027001 (see BMS-986253 IB). 
 
 
After review of the clinical safety, 
including dose-limiting toxicities (DLTs) for the first 4 participants, the dose-finding phase 
(Part 1B) will open.
Part 1B: Dose-finding (participants enrolled in each cohort are per BMS-986253 IB)
In Part 1B, participants will be randomly assigned to receive 1 of 3 dosing regimens:

Cohort 1B1: 2400 mg of BMS-986253 Q4W and 480 mg of nivolumab Q4W 

Cohort 1B2: 1200 mg of BMS-986253 Q4W and 480 mg of nivolumab Q4W 

Cohort 1B3: 600 mg of BMS-986253 Q4W and 480 mg of nivolumab Q4W 
Assignment into any dosing regimen arm may be suspended 
 
 In addition, up to 4 new dosing regimens assessing the combination of 
BMS-986253 and nivolumab may be initiated 
 
Additional cohorts for alternate dosing regimens may include:
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8

Cohort 1B4: 2400 mg of BMS-986253 Q2W and 480 mg of nivolumab Q4W 

Cohort 1B5: 1200 mg of BMS-986253 Q2W and 480 mg of nivolumab Q4W 

Cohort 1B6: 3600 mg of BMS-986253 Q2W and 480 mg of nivolumab Q4W 
 
 
If analyses indicate further assessment of a dosing regimen is not warranted and/or assessment of 
an additional dosing regimen is indicated, then randomization will be stopped, and subsequent 
participants will be assigned sequentially to ongoing dosing regimens available at that time. 
Part 1C: Safety Evaluation of BMS-986253 in Combination with Nivolumab and Ipilimumab 
Part 1C is a safety evaluation of BMS-986253 in combination with nivolumab and ipilimumab. 
Part 1C will begin once the DLT period is completed for Cohort 1B6 (BMS-986253 3600 mg Q2W 
+ nivolumab 480 mg Q4W), and will enroll simultaneously with Part 1 Cohort 1B6. 
 
 
The higher-dose triplet combination Cohort 1C1 will enroll first. The safety and tolerability of this 
part will be evaluated 
 design to 
guide dose escalation decisions and the overall assessment 
 
In Part 1C, participants will initially be enrolled onto Cohort 1C1. For the first 12 weeks, 
participants will receive BMS-986253 3600 mg Q2W from Part 1B + nivolumab 1 mg/kg Q3W + 
ipilimumab 3 mg/kg Q3W. After 12 weeks, participants will receive BMS-986253 3600 mg Q2W 
from Part 1B and nivolumab 480 mg Q4W. 
 
 
 
 
 
 
 
 
 
 
 
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Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Part 2: Double-blind Randomized Evaluation of BMS-986253 plus Nivolumab plus Ipilimumab
versus Placebo plus Nivolumab plus Ipilimumab in Advanced Melanoma
Part 2 will begin after determination of the RP2D of BMS-986253 based on Part 1A and 1B data 
 and generation of safety data on the 
triplet combination of BMS-986253 plus nivolumab plus ipilimumab in Part 1C. 
 
 
Part 2 is a double-blind randomized evaluation of BMS-986253 plus nivolumab plus ipilimumab 
(2A) versus placebo plus nivolumab plus ipilimumab (2B) to evaluate the efficacy of BMS-986253 
in participants with advanced melanoma who are refractory to anti-PD-(L)1 therapy. 
This portion of the study will include participants with unresectable or metastatic melanoma (non-
ocular), who had progression on or after anti-PD-(L)1 therapy, but have not been treated with prior 
anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) therapy. Participants will be 
randomly assigned in a 1:1 ratio to 1 of 2 treatment arms: 
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8

2A: BMS-986253 + nivolumab + ipilimumab

2B: placebo + nivolumab + ipilimumab
During randomization, participants will be stratified by the following factors: screening serum 
IL-8 level, 
 and lactate dehydrogenase (LDH) 
levels.
The dose of nivolumab and ipilimumab will be determined by safety data from Part 1C, and the 
dose of BMS-986253 will be determined by the totality of Part 1 data. If safety is confirmed in 
Cohort 1C1, for the first 12 weeks, participants will receive ipilimumab 3 mg/kg Q3W 
intravenously (IV) (4 doses), nivolumab 1 mg/kg Q3W IV (4 doses), and BMS-986253 3600 mg 
Q2W or placebo IV (given at Q2W frequency for 6 doses). After 12 weeks, participants will be 
maintained on BMS-986253 3600 mg Q2W or placebo IV (Q2W) and nivolumab IV (480 mg 
Q4W). 
 
 
 
 
Approximately 
participants will be included in Part 2 and randomized in a 1:1 ratio to each 
arm.
The study design schemes are presented in Figures 1 and 2.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Figure 1:
Study Design: Part 1
Abbreviations: CRC, colorectal cancer; HCC, hepatocellular carcinoma; IL, interleukin; Ipi, ipilimumab; max, maximum; 
 
 Nivo, nivolumab; NSCLC, non-small cell lung cancer; QXW, every X weeks; R, randomized; RCC, renal cell carcinoma; S, sequential 
assignment; SCCHN, squamous cell carcinoma of the head and neck; UCC, urothelial cancer. 
a Once sequential enrollment begins, up to 4 additional cohorts may be evaluated in Part 1B.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Protocol Amendment No.: 07
Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Figure 2:
Study Design: Part 2
Abbreviations: BRAF, proto-oncogene B-Raf; CTLA, cytotoxic T-lymphocyte-associated protein; IL, interleukin, 
Ipi, ipilimumab; LDH, lactate dehydrogenase; Nivo, nivolumab; PD-(L)1, programmed cell death (ligand) 1; QXW, 
every X weeks. 
c After 12 weeks, nivolumab will be administered at 480 mg Q4W. 
The study will be divided into 4 periods: Pre-Screening, Screening, Treatment, and Follow-up.
Pre-Screening Period (applicable for Part 1 only):
Participants will provide consent for pre-screening to obtain a serum IL-8 level; further screening 
procedures will not be completed until the IL-8 level is resulted (except for participants with HCC 
and CRC). Depending on availability of cohorts at the time of enrollment, serum IL-8 results may 
determine eligibility and cohort assignment. 

Enrollment into Part 1B requires 

Enrollment into Part 1C does NOT require a minimum serum IL-8 level.

For participants with HCC and CRC: results of screening IL-8 are NOT required prior to 
signing the Main Informed Consent, since all HCC and CRC participants will be assigned to 
Part 1C (Part 1C does not require a minimum serum IL-8 level). Participants with HCC and 
CRC may enroll only when Part 1C is open. 

For participants with melanoma or UCC only being considered for Part 1C (for example, if 
Part 1B is not actively enrolling participants), results of screening IL-8 are NOT required prior 
to signing the Main Informed Consent.
Screening:
The screening period will be up to 28 days and begins by establishing the participant’s initial 
eligibility and signing of the informed consent form (ICF). In order to establish eligibility for this 
study, participants will undergo baseline physical examinations, vital signs and oxygen saturation 
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
measurements, 12-lead electrocardiogram (ECG), 
 
and clinical laboratory evaluations.
If a participant exceeds the 28-day screening period (eg, 
 
waiting for a laboratory value), the participant must be reconsented, but does not require a new 
participant identification number. The fewest number of procedures from the initial screening 
should be repeated to qualify the participant, while maintaining participant safety and eligibility. 
Repeat serum IL-8 testing will not be required if the previous sample was obtained within 42 days 
of study treatment initiation.
Assignment to a Study Part 1 (1A, 1B, or 1C) must be designated in the IRT system prior to the 
participant’s assignment to a dosing regimen. In Part 2, all participants will be randomly assigned 
to Arm 2A (BMS-986253 + nivolumab + ipilimumab) or 2B (placebo + nivolumab + ipilimumab). 
Prior to randomization in Part 2, screening laboratory test results for serum IL-8 and LDH must be 
received, and 
 must be entered in the electronic case report 
form (eCRF). Part 2 of the study is double-blind; the participant, Sponsor, and site staff (except as 
indicated) will not be aware of treatment/cohort assignment. 
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Treatment:
Table 3:
Dose, Frequency, Infusion Time, and Sequence of Ips
Cohort
BMS-986253 
Dose and 
Frequency
BMS-986253 
Infusion Time 
(min)
Nivolumab
Dose and 
Frequency
Nivolumab
Infusion Time 
(min)
Ipilimumab
Dose and 
Frequency
Ipilimumab
Infusion Time 
(min)
Order of Drug 
Administration
Part 1
1A a
2400 mg Q4W
480 mg Q4W
NA
1B1a
2400 mg Q4W
480 mg Q4W
NA
1B2a
1200 mg Q4W
480 mg Q4W
NA
1B3a
600 mg Q4W
480 mg Q4W
NA
1B4
2400 mg Q2W
480 mg Q4W
NA
1B5
1200 mg Q2W
480 mg Q4W
NA
1B6
3600 mg Q2W
480 mg Q4W
NA
1C1
3600 mg Q2W
1 mg/kg Q3W
(x 4 doses), 
followed by 
480 mg Q4W
3 mg/kg Q3W 
(x 4 doses)
Part 2
2A
3600 mg Q2W 
1 mg/kg Q3Wg
(x 4 doses), 
followed by 
480 mg Q4W
3 mg/kg Q3W 
(x 4 doses)
2B
Placebo 
Q2W 
1 mg/kg Q3Wg
(x 4 doses), 
followed by 
480 mg Q4W
3 mg/kg Q3W 
(x 4 doses)
Abbreviations: ’
 C, Cycle; D, Day; Ipi, ipilimumab; Nivo, nivolumab; QXW, every X weeks.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
a
 
Protocol Amendment No.: 07
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Follow-up:

Safety Follow-up Period: Upon completion of study therapy (or up to a maximum of 156 weeks 
if applicable), or once the decision is made to discontinue the participant from treatment, ie, at 
end of treatment (EOT), all participants will enter a safety follow-up period. For participants 
who complete all scheduled cycles of therapy, the EOT visit will be the same visit as the last 
scheduled and completed on-treatment visit, and will be the start of the safety follow-up period. 
For participants who do not complete all scheduled cycles of therapy, the EOT visit will be the 
next visit following the last study dose. If the EOT visit occurs 30 days or more after receipt 
of the last dose, then the EOT visit and Follow-up 1 visit can be completed at the same time. 
All participants will be evaluated for any new AEs for a minimum of 100 days after 
discontinuing study treatment. Follow-up visits should occur at Days 30 and 100 (7 days for 
all study visits) after the last dose. All participants will be required to complete the clinical 
safety follow-up visits, regardless of whether new anti-cancer therapy is started, except those 
participants who withdraw consent for study participation.

Response Follow-up Period: At the time of study treatment discontinuation, participants in Part 
1 will continue to have radiologic and clinical tumor assessments on the same schedule, every 
8 weeks (± 7 days), for the first 48 weeks after the first dose. After 48 weeks, radiological and 
clinical tumor assessments will occur every 12 weeks (± 7 days), until withdrawal of consent, 
death, final analysis, or initiation of another anti-cancer treatment, whichever occurs first, for 
up to 2 years after EOT. Participants in Part 2 will continue to have radiologic and clinical 
tumor assessments on the same schedule, every 8 weeks (± 7 days), starting from first dose for 
the first 48 weeks, then every 12 weeks (± 7 days), until blinded independent central review 
(BICR)-confirmed disease progression, final analysis, or treatment discontinuation (including 
treatment beyond progression), whichever occurs later. After the final analysis, radiological
assessments will be done per standard of care, at the discretion of the treating physician.
Number of Participants:
The maximum total number of participants will be approximately 
 Specifically, up to 
approximately 
 of these participants will be treated in Part 1, and approximately 
participants will be treated in Part 2. 
Study treatment: 
The study treatment is presented in Table 4.
Table 4:
Study Treatment
Product 
Description/
Class and Dosage 
Form
Potency
IP/Non-
IMP
Blinded or 
Open Label
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986253 
Injection
IP
Open labela
Vial
Refer to the label on
container and/or 
pharmacy manual
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 4:
Study Treatment
Product 
Description/
Class and Dosage 
Form
Potency
IP/Non-
IMP
Blinded or 
Open Label
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986253 
Injection
IP
Open labela
Vial
Refer to the label on
container and/or 
pharmacy manual
Nivolumab 
(BMS-936558) 
solution for injection
IP
Open labela
Vial
Refer to the label on
container and/or 
pharmacy manual
Ipilimumab
solution for injection
IP
Open labela
Vial 
Refer to the label on
container and/or 
pharmacy manual
Ipilimumab
solution for injection
IP
Open labela
Vial 
Refer to the label on
container and/or 
pharmacy manual
Normal saline
solution for 
injectionb
IP
Open label
Various (local 
commercial 
product)
Refer to the label on
container 
Dextrose 
solution for 
injectionb
IP
Open label
Various (local 
commercial 
product)
Refer to the label on
container 
Abbreviation: IP, Investigational Product.
a The term “open label” refers to the medication as it is upon receipt at the pharmacy. In Part 2 of this trial, BMS-
986253/placebo will be prepared, dispensed, and administered in a double-blinded fashion.
b This will be sourced by the investigative sites if permitted by local regulations.
Study Assessments and Analyses:
Safety Assessments: Safety assessments will be based on AE reports and the results of vital signs 
including oxygen saturation, ECGs, physical examinations, and clinical laboratory tests. AEs will 
be coded using the most current version of Medical Dictionary for Regulatory Activities and the 
incidence of observed AEs will be tabulated and reviewed for potential significance and clinical 
importance. AEs will be assessed continuously during the study and for a minimum of 100 days 
after the last dose of study treatment. A local laboratory will perform the clinical laboratory tests 
and will provide reference ranges for these tests. Both AEs and laboratory tests will be graded 
using the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03.
PK and Immunogenicity Assessments: Following the final analysis, PK and IMG samples will 
no longer be collected. 
PK and immunogenicity (IMG) assessment data for BMS-986253, nivolumab, and ipilimumab 
will be collected from study participants. All time points are relative to the start of the first drug 
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
administration on that day. All on-treatment time points are intended to align with days on which 
study drug is administered; if dosing occurs on a different day, the PK and IMG sampling should 
be adjusted accordingly. 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. All pre-
dose samples should be taken within 30 minutes before the start of any dose infusion. EOI samples 
should be taken immediately prior to completion of the infusion, preferably within 2 minutes. 
Blood samples should be drawn from a site other than the infusion site (ie, contralateral arm) on 
days of infusion.
PK of BMS-986253 will be derived, if feasible, from serum concentration versus time data 
following administration of BMS-986253 on Cycle 1 Day 1. Individual participant PK parameter 
values will be derived by non-compartmental methods using a validated PK analysis program (Part 
1 only). Actual times will be used for all formal analyses.
Sparse nivolumab and ipilimumab concentration-time data will be collected and may be used
in an integrated PPK or exposure response analysis along with data from other studies, which
will be the subject of a separate report. Separate samples will be collected for PK and IMG 
assessments.
Further details of sample collection, processing, and shipment will be provided in the laboratory 
procedures manual. Serum PK samples will be analyzed for BMS-986253, nivolumab, and 
ipilimumab by validated ligand-binding assays. In addition, serum samples will be archived for 
potential metabolite analysis, if the need arises and to the extent possible.
Immunogenicity samples will be analyzed for anti-nivolumab/anti-ipilimumab/anti-BMS-986253 
antibodies by validated IMG assays. IMG samples positive for anti-nivolumab, anti-ipilimumab, 
and anti-BMS-986253 may be analyzed for neutralizing antibodies by a validated method. 
 
 
 
 
For all PK and IMG plasma/serum samples, the date and actual time collected must be recorded. 
For participants whose only peripheral access is via a venous access device or peripherally inserted 
central catheter, refer to the Laboratory Manual for the proper technique to ensure undiluted whole 
blood for PK assessments.
Biomarker Assessments: Following the final analysis, biomarker samples will no longer be 
collected. 
Biomarker measures of baseline, on treatment, and upon disease progression 
 
 
 
 
 
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Efficacy Assessments: Following the database lock for the final analysis, efficacy will no longer 
be assessed. Imaging should be performed per standard of care at the discretion of the treating 
physician. 
Efficacy assessments for the anti-tumor activity of BMS-986253, in combination with nivolumab 
or in combination with nivolumab and ipilimumab, will use investigator assessed tumor 
measurements per RECIST v1.1. 
Assessment of partial response and complete response must be confirmed at least 4 weeks after 
initial response. Changes in tumor measurements and tumor responses will be assessed by the 
investigator per study design using RECIST v1.1 criteria. Investigators will also report the number 
and size of new lesions that appear while on study. The timepoint of tumor assessments will be 
reported on the eCRF based on the investigator’s assessment.
A BICR will be utilized in this study for determination of BICR-assessed endpoints. The BICR 
will review all available tumor assessment scans for all treated participants until the final analysis. 
Details of BICR responsibilities and procedures will be specified in the BICR charter.
A best overall response of SD requires a minimum of 49 days on study from the date of first dose 
to the date of the first imaging assessment.
 
Data Monitoring Committee: Yes, only for Part 2.
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Anti-IL-8
2
SCHEDULE OF ACTIVITIES 
Table 2-1:
Prescreening Procedural Outline (applicable for Part 1 only)
Procedure
Prescreening 
Visit 
Notes
Eligibility Assessments
Prescreen Informed Consent for Serum IL-8
X
Participants must sign the Pre-Screen Informed Consent prior to testing the 
screening serum IL-8 level. The pre-screen testing for serum IL-8 will occur 
before the 28-day screening window. Participants may not receive any systemic 
therapy after screening serum IL-8 is drawn.
Depending on availability of cohorts at the time of enrollment, serum IL-8 
results may determine eligibility and cohort assignment.
For participants with CRC and HCC: results of screening IL-8 are not required 
prior to signing the Main Informed Consent.
For participants with melanoma or UCC only being considered for Part 1C (for 
example, if Part 1B is not actively enrolling participants), results of screening 
IL-8 are NOT required prior to signing the Main Informed Consent.
IRT Assignment
X
To obtain participant identification number. This must be done prior to testing 
screening serum IL-8. 
Laboratory Test for Serum IL-8
X
Adverse Event Reporting
Monitor for Serious Adverse Events
X
All SAEs related to the blood draw must be collected from the date of 
participant’s written consent (Pre-screen ICF) and followed until resolution or 
stabilization of the SAE.
Abbreviations: CRC, colorectal cancer; HCC, hepatocellular cancer; IL-8, interleukin-8; IRT, Interactive Response Technologies; SAE, serious adverse event.
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Anti-IL-8
Table 2-2:
Screening Procedural Outline (All Study Phases)
Procedure
Screening
Visit
Day -28 to Day -1
Notes
Eligibility Assessments
Main Informed Consent
X
For participants in Part 1: eligible participants (as determined by serum IL-8 prescreen 
results and cohort availability) must sign the main informed consent within 1 week of 
serum IL-8 positive result by the central laboratory.
For Part 1 participants with CRC and HCC: results of screening IL-8 are not required 
prior to signing the Main Informed Consent. All CRC and HCC participants will be 
assigned to Part 1C, and may enroll only when Part 1C is open. 
ECOG Performance Status
X
Appendix 5
Inclusion/Exclusion Criteria
X
Medical History
X
All medical history relevant to the disease under study, and COVID-19 vaccines more 
than 30 days prior to first study treatment. 
Include any toxicities or allergy related to previous treatments.
Prior Cancer Therapies
X
Including all prior cancer treatment regimens and medications administered.
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Table 2-2:
Screening Procedural Outline (All Study Phases)
Procedure
Screening
Visit
Day -28 to Day -1
Notes
IRT Assignment
X
After completing all screening procedures, utilize IRT to either screen fail or obtain 
assignment information, as applicable. Assignment can occur up to 3 days prior to first 
dose.
Tumor Type Assessment
Body Imaging
X
Contrast enhanced CT/MRI of the chest, abdomen, pelvis, and all other known/suspected 
sites of disease. Images will be acquired within 28 days prior to the first treatment dose. 
Images acquired as part of care prior to signing the ICF, but within the 28-day limit, will be 
acceptable if there is no intervening treatment, and all required scanning acquisition 
parameters are met (if feasible per local regulations).
For participants with SCCHN, a CT or MRI of the neck is required.
For participants with HCC, imaging of the abdomen should include multi-phasic (at least 
three of the following four phases: precontrast, arterial, venous, delayed) CT or MRI of 
the liver.
See Section 9.4.1 for further details.
Brain Imaging
X
Part 1: At screening, MRI of the brain without and with contrast is required for 
participants with known or suspected brain metastases who have not had brain imaging 
within 28 days of anticipated first study drug administration. 
Part 2: MRI of the brain (without and with contrast) is required for ALL participants 
during screening to rule out evidence of progression for brain metastases within the 28 
days prior to treatment. 
CT of the Brain (without and with contrast) can be performed if MRI is contraindicated. 
See Section 9.4.1 for further details. Images will be acquired within 28 days prior to the 
first treatment dose. Images acquired as part of care prior to signing the ICF, but within 
the 28-day limit, will be acceptable if there is no intervening treatment, and all required 
scanning acquisition parameters are met (if feasible per local regulations).
Other Bone Scan
X
As clinically indicated per local standards. See Section 9.4.1 for further details.
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Table 2-2:
Screening Procedural Outline (All Study Phases)
Procedure
Screening
Visit
Day -28 to Day -1
Notes
Safety Assessments
Concomitant Medication Assessment
X
Collect and record concomitant medication up to 4 weeks prior to screening.
Collect and record vaccine use within 30 days prior to first study treatment.
ECG
X
ECGs should be recorded after the participant has been supine for at least 5 minutes. 
PE
X
If the screening PE is performed within 24 hours prior to dosing on Day 1 then a single 
exam may count as both the Screening and pre-dose evaluation.
Clinical Complaints
X
Clinical complaints related to the disease under study present 14 days prior to the first 
dose of study treatment must be collected.
Physical Measurements
X
Includes height, weight, and body mass index.
Vital Signs/Oxygen Saturation
X
Includes body temperature, respiratory rate, seated blood pressure, and heart rate. Blood 
pressure and heart rate should be measured after the participant has been resting quietly 
for at least 5 minutes. Consider alternate position(s) for vital sign collection. Obtain 
oxygen saturation at rest and exertion. 
Laboratory Tests
X
Includes blood and urine samples. 
FSH
X
Post-menopausal women < 55 years old. Refer to Appendix 4.
Pregnancy Test
X
For women of child-bearing potential only. Refer to Appendix 4.
Serology
X
Includes hepatitis B surface antigen, hepatitis C antibody, or a more complete panel for 
participants with hepatocellular carcinoma (see Table 9.1.4-1 for panel information).
Hematology
X
See Table 9.1.4-1 for panel information.
Serum chemistry
X
See Table 9.1.4-1 for panel information.
Other laboratory tests
X
Includes thyroid panel, amylase, lipase, etc (see Table 9.1.4-1 for panel information).
For HCC participants: AFP
IL-8 
X
Only for Part 2.
Urinalysis
X
See Table 9.1.4-1 for panel information.
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Table 2-2:
Screening Procedural Outline (All Study Phases)
Procedure
Screening
Visit
Day -28 to Day -1
Notes
HPV status of tumor for SCCHN of 
the oropharynx
X
HPV status for oropharyngeal cancers must be determined locally using p16 IHC or HPV 
PCR as described in Section 9.8.5. If HPV status was previously determined using an 
acceptable method listed in Section 9.8.5, re-testing is not necessary.
Stool Sample
X
A screening stool sample must be collected as per the supplemental laboratory manual.
Adverse Event Reporting
Monitor for Adverse Events
All SAEs must be collected from the time of signing the consent and for a minimum of 
100 days after discontinuing study treatment. 
Abbreviations: AFP, alpha fetoprotein; C, cycle; CRC, colorectal cancer; CT, computed tomography; D, day; ECG, electrocardiogram; ECOG, Eastern Cooperative 
Oncology Group; FSH, follicle stimulating hormone; HCC, hepatocellular carcinoma; HPV, human papillomavirus; ICF, informed consent form; IHC,
immunohistochemistry; IL-8, interleukin-8; IRT, Interactive Response Technologies; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PE,
physical examination; SAE, serious adverse event; SCCHN, squamous cell carcinoma of the head and neck.
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Anti-IL-8
Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
Safety Assessmentsd
ECOG Performance 
Status
X
X
X
X
X
Appendix 5
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
X
X
X
X
Assess concomitant 
treatment during the 
study duration.
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Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
ECG
X
X
X
X
X
X
12-lead ECGs should 
be recorded after 
participant has been 
supine for at least 5 
minutes. 
 
 
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Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
 
 
 
 
 
 
 
 
Laboratory Testing
Xe
X
X
X
X
X
X
X
See Section 9.1.4.
Physical 
Examination 
(Complete)
X
X
X
X
X
X
X
X
X
X
Physical Examination 
(Complete)
Pregnancy Test 
(WOCBP)
X
X
X
X
X
X
Serum or urine 
pregnancy test must be 
performed (urine 
pregnancy test: 
minimum sensitivity 
25 IU/L or equivalent 
units of hCG) within 
24 hours prior to 
administration of study 
drug.
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Anti-IL-8
Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
Thyroid Function 
Tests (TSH)
X
X
X*
X
*TSH to be done every 
3rd cycle starting at 
Cycle 7. If TSH is 
abnormal. Free T3 and 
Free T4 should be 
collected. Results 
should be examined by 
the investigator or 
appropriate designee 
within 48 hours of dose 
administration.
Weight
X
X
X
X
X
X
Vital Signs and 
Oxygen Saturations
X*
X
X
X
X
X*
X
X*
X*
X
X
Includes body 
temperature, respiratory 
rate, seated blood 
pressure, and heart rate. 
Blood pressure and 
heart rate should be 
measured after the 
participant has been 
resting quietly for at 
least 5 minutes. 
Consider alternate 
position(s) for vital sign 
collection. Obtain 
oxygen saturation at 
rest. *Pre- and post-
dose vital signs on 
Day 1 of each cycle. 
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Anti-IL-8
Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
Note: post dose vital 
signs are to be taken 
after BMS-986253 
infusion AND after 
Nivolumab infusion.
Adverse Event Reporting
Monitor for 
Nonserious 
Adverse Events
Nonserious AEs must be collected starting with the first dose of study drug and for a minimum of 100 days 
after discontinuing study treatment.
Monitor for Serious 
Adverse Events
All SAEs must be collected from the time of signing the consent and for a minimum of 100 days after 
discontinuing study treatment. Death due to disease progression within 100 days of discontinuation of study 
treatment must be reported as an SAE.
PK Assessments
See Section 9.5 for further details
Immunogenicity 
Assessments
See Section 9.5 for further details
Biomarker 
Assessments
See Section 9.8
Additional 
Research Sampling
See Section 9.8.4
Efficacy 
Assessments
See Section 9.4
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BMS-986253
Anti-IL-8
Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
Body Imaging
Contrast enhanced CT/MRI of the chest, abdomen, pelvis, and all other known/suspected sites of disease 
should occur every 8 weeks (7 days), starting from first dose for the first 48 weeks, then every 12 weeks 
(7 days) until withdrawal of consent, death, or initiation of another anti-cancer treatment, whichever occurs 
first. See Section 9.4.1
For participants with SCCHN, a CT or MRI of the neck is required.
For HCC participants, contrast-enhanced triphasic CT of the liver is required. See Section 9.4.1 for further 
details.
Brain Imaging
Participants with a history of brain metastasis should have surveillance MRI as clinically indicated at the 
discretion of the investigator. See Section 9.4.1.
Other: Bone Scan
As clinically indicated per local standards. See Section 9.4.1
Clinical Supplies
IRT Assignment
X
Once eligibility has 
been confirmed, IRT 
assignment may be 
performed up to 3 days 
prior to study drug 
administration.
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BMS-986253
Anti-IL-8
Table 2-3:
On-treatment Procedural Outline (Part 1A and Cohorts 1B1 through 1B3 - BMS-986253 Q4W and 
Nivolumab Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 
5+ 
(28 d)
EOT
a,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D1c
D2c
D8c
D15c
D22c
D1c
Study Drug Administration
Details regarding 
preparation and 
administration are 
provided in the 
pharmacy manual or 
training materials.
BMS-986253 
Administration
X
X
X
X
X
See Section 7.1 for 
BMS-986253 dose 
administration.
Nivolumab 
Administration
X
X
X
X
X
See Section 7.1 for 
nivolumab dose 
administration.
Abbreviations: AE, adverse event, BMS, Bristol Myers Squibb; CBC, complete blood count; C, Cycle; CT, computed tomography; d, days; D, Day; 
ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EDC, Electronic Data Capture; EOI, end of infusion; EOT, end of treatment; HCC, 
hepatocellular carcinoma; hCG, human chorionic gonadotropin; IL-8, interleukin-8; IRT, Interactive Response Technologies; MRI, magnetic resonance imaging; 
PCR, polymerase chain reaction; 
 PK, pharmacokinetic(s); Q4W, every 4 weeks; SAE, serious adverse event; SCCHN, squamous cell 
carcinoma of the head and neck; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; WOCBP, women of childbearing potential.
a For participants who complete all scheduled cycles of therapy, the EOT visit will be the same visit as last scheduled and completed on-treatment visit and the 
start of the Week 1 Clinical/Safety Follow-up visit.
b For participants who do not complete all scheduled cycles of therapy, the EOT visit will be the next visit following the last study dose. If the EOT visit occurs 
30 days or more after receipt of the last dose, then the EOT visit and Follow-up 1 visit can be completed at the same time.
c 3-day window
d If multiple procedures are required at a single timepoint, safety assessments (ECGs, vital signs, and pulse oximetry) are a higher priority than PK/Immunogenicity 
sampling.
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BMS-986253
Anti-IL-8
e In addition to pre-treatment laboratory tests, CBC with differential will be collected with the last PK laboratory draw on C1D1 
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CA027002
BMS-986253
Anti-IL-8
Table 2-4:
On-treatment Procedural Outline (Cohorts 1B4 through 1B6 - BMS-986253 Q2W and Nivolumab 
Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 5 
+ (28 d)
EOTa,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D15c
D1c
D2c
D8c
D15c
D22c
D1c
D15
Safety Assessmentsd
ECOG 
Performance Status
X
X
X
X
X
X
X
Appendix 5
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assess concomitant 
treatment during the 
study duration.
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CA027002
BMS-986253
Anti-IL-8
Table 2-4:
On-treatment Procedural Outline (Cohorts 1B4 through 1B6 - BMS-986253 Q2W and Nivolumab 
Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 5 
+ (28 d)
EOTa,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D15c
D1c
D2c
D8c
D15c
D22c
D1c
D15
ECG
X
X
X
X
X
X
X
X
12-lead ECGs should 
be recorded after 
participant has been 
supine for at least 
5 minutes. 
 
 
 
 
 
 
 
 
 
 
 
 
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CA027002
BMS-986253
Anti-IL-8
Table 2-4:
On-treatment Procedural Outline (Cohorts 1B4 through 1B6 - BMS-986253 Q2W and Nivolumab 
Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 5 
+ (28 d)
EOTa,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D15c
D1c
D2c
D8c
D15c
D22c
D1c
D15
 
 
Laboratory Testing
Xe
X
X
X
X
X
X
X
See Section 9.1.4
Physical 
Examination 
(Complete)
X
X
X
X
X
X
X
X
X
X
Physical Examination 
(Complete)
Pregnancy Test 
(WOCBP)
X
X
X
X
X
Serum or urine 
pregnancy test must 
be performed (urine 
pregnancy test: 
minimum sensitivity 
25 IU/L or equivalent 
units of hCG) within 
24 hours prior to 
administration of 
study drug.
Thyroid Function 
Tests (TSH)
X*
X*
X*
X
*TSH to be done 
every 3rd cycle, ie, 
C1D1, C4D1, C7D1, 
etc. If TSH is 
abnormal, T3 and 
free T4 should be 
collected. Results 
should be examined 
by the investigator or 
appropriate designee 
within 48 hours of 
dose administration.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-4:
On-treatment Procedural Outline (Cohorts 1B4 through 1B6 - BMS-986253 Q2W and Nivolumab 
Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 5 
+ (28 d)
EOTa,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D15c
D1c
D2c
D8c
D15c
D22c
D1c
D15
Weight
X
X
X
X
X
X
Vital Signs and 
Oxygen 
Saturations
X*
X
X
X
X
X*
X
X*
X
X*
X
X
X
X
Includes body 
temperature, 
respiratory rate, 
seated blood 
pressure, and heart 
rate. Blood pressure 
and heart rate should 
be measured after the 
participant has been 
resting quietly for at 
least 5 minutes. 
Consider alternate 
position(s) for vital 
sign collection. 
Obtain oxygen 
saturation at rest. 
*Pre- and post-dose 
vital signs on Day 1 
of each cycle. Note: 
post dose vital signs 
are to be taken after 
BMS-986253 
infusion AND after 
Nivolumab infusion.
Adverse Event Reporting
Monitor for 
Nonserious 
Adverse Events
Nonserious AEs must be collected starting with the first dose of study drug and for a minimum of 100 days 
after discontinuing study treatment.
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CA027002
BMS-986253
Anti-IL-8
Table 2-4:
On-treatment Procedural Outline (Cohorts 1B4 through 1B6 - BMS-986253 Q2W and Nivolumab 
Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 5 
+ (28 d)
EOTa,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D15c
D1c
D2c
D8c
D15c
D22c
D1c
D15
Monitor for 
Serious Adverse 
Events
All SAEs must be collected from the date of participant’s written consent and for a minimum of 100 days after 
discontinuing study treatment. Death due to disease progression within 100 days of discontinuation of study 
treatment must be reported as an SAE.
PK Assessments
See Section 9.5 for further details
Immunogenicity 
Assessments
See Section 9.5 for further details
Biomarker 
Assessments
See Section 9.8
Additional 
Research Sampling
See Section 9.8.4
Efficacy 
Assessments
See Section 9.4
Body Imaging
Contrast enhanced CT/MRI of the chest, abdomen, pelvis, and all other known/suspected sites of disease should 
occur every 8 weeks (7 days), starting from first dose for the first 48 weeks, then every 12 weeks (7 days) 
until withdrawal of consent, death, initiation of another anti-cancer treatment, or final analysis, whichever 
occurs first. See Section 9.4.1. For participants with SCCHN, a CT or MRI of the neck is required.
Brain Imaging
Participants with a history of brain metastasis should have surveillance MRI as clinically indicated at the 
discretion of the investigator. See Section 9.4.1.
Other: Bone Scan
As clinically indicated per local standards. See Section 9.4.1
Clinical Supplies
IRT Assignment
X
Once eligibility has 
been confirmed, IRT 
assignment may be 
performed up to 
3 days prior to study 
drug administration.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-4:
On-treatment Procedural Outline (Cohorts 1B4 through 1B6 - BMS-986253 Q2W and Nivolumab 
Q4W)
Procedure
Cycle 1
(28 d)
Cycle 2
(28 d)
Cycle 3
(28 d)
Cycle 4
(28 d)
Cycle 5 
+ (28 d)
EOTa,b
Notes
D1
D2
D8c
D15c
D22c
D1c
D2c
D8
D15c
D1c
D15c
D1c
D2c
D8c
D15c
D22c
D1c
D15
Study Drug Administration
Details regarding 
preparation and 
administration are 
provided in the 
pharmacy manual or 
training materials.
BMS-986253 
Administration
X
X
X
X
X
X
X
X
X
X
BMS-986253 will be 
administered on day 
1 and 15 of ALL 
cycles. 
See Section 7.1 for 
BMS-986253 dose 
administration.
Nivolumab 
Administration
X
X
X
X
X
See Section 7.1 for 
Nivolumab dose 
administration.
Abbreviations: AE, adverse event; BMS, Bristol Myers Squibb; C, Cycle; CBC, complete blood count; CT, computed tomography; d, days; D, Day; 
ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EDC, Electronic Data Capture; EOI, end of infusion; EOT, end of treatment; HCC, 
hepatocellular carcinoma; hCG, human chorionic gonadotropin; IL-8, interleukin-8; IRT, Interactive Response Technologies; MRI, magnetic resonance imaging; 
; PK, pharmacokinetic(s); Q2W, every 2 weeks; Q4W, every 4 weeks; SAE, serious adverse event; SCCHN, squamous cell carcinoma 
of the head and neck; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; WOCBP, women of childbearing potential.
a For participants who complete all scheduled cycles of therapy, the EOT visit will be the same visit as the last scheduled and completed on-treatment visit and the 
start of the Week 1 Clinical/Safety Follow-up visit.
b For participants who do not complete all scheduled cycles of therapy, the EOT visit will be the next visit following the last study dose. If the EOT visit occurs 30 
days or more after receipt of the last dose, then the EOT visit and Follow-up 1 visit can be completed at the same time.
c 3-day window
d If multiple procedures are required at a single timepoint, safety assessments (ECGs, vital signs, and pulse oximetry) are a higher priority than PK/Immunogenicity 
sampling.
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Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
e In addition to pre-treatment laboratory tests, CBC with differential will be collected with the last PK laboratory draw on C1D1 
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CA027002
BMS-986253
Anti-IL-8
Table 2-5:
On-treatment Procedural Outline 
Procedure
Cycle 1
Cycle 2
EOTa,b
Notes
 and Beyond
D1
D1
D8
Safety Assessmentsc
Vital Signs and 
Oxygen 
Saturations
X*
X*
X
Includes body temperature, respiratory rate, seated blood pressure, and heart rate. 
Blood pressure and heart rate should be measured after the participant has been 
resting quietly for at least 5 minutes. Consider alternate position(s) for vital sign 
collection. Obtain oxygen saturation at rest. 
*Pre- and post-dose vital signs on Day 1 of each cycle. 
Note: Post dose vital signs are to be taken after BMS-986253 infusion AND after 
nivolumab infusion.
Weight
X
X
X
Physical 
Examination 
(Complete)
X
X
X
Physical Examination (Complete)
ECOG 
Performance 
Status
X
X
Appendix 5
Concomitant 
Medication 
Assessments
X
X
X
Assess concomitant treatment during the study duration.
ECG
X
X
X
12-lead ECGs should be recorded after participant has been supine for at least 
5 minutes. 
 
 
 
Table 9.5-5 for timing.
Procedures
Laboratory 
Testing
X
X
X
See Section 9.1.4
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-5:
On-treatment Procedural Outline 
Procedure
Cycle 1
Cycle 2
EOTa,b
Notes
 and Beyond
D1
D1
D8
Pregnancy Test 
(WOCBP)
X
X
X
Serum or urine pregnancy test must be performed (urine pregnancy test: minimum 
sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug.
Thyroid Function 
Tests (TSH)
X*
X*
X
*TSH to be done every 4 cycles, ie, C1D1, C5D1, C9D1, etc. If TSH is abnormal, 
T3 and free T4 should be collected. Results should be examined by the 
investigator or appropriate designee within 48 hours of dose administration.
Adverse Event Reporting
Monitor for 
Nonserious 
Adverse Events
All nonserious adverse events must be collected starting with the first dose of study drug and for a minimum of 100 days after 
discontinuing study treatment 
Monitor for 
Serious Adverse 
Events
All SAEs must be collected from the time of signing the consent and for a minimum of 100 days after discontinuing study treatment. 
Death due to disease progression within 100 days of discontinuation of study treatment must be reported as an SAE.
Additional Assessments
PK Assessments
See Section 9.5 for further details
Immunogenicity 
Assessments
See Section 9.5 for further details
Biomarker 
Assessments
See Section 9.8
Additional 
Research 
Sampling
See Section 9.8.5
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-5:
On-treatment Procedural Outline 
Procedure
Cycle 1
Cycle 2
EOTa,b
Notes
 and Beyond
D1
D1
D8
Efficacy 
Assessments
See Section 9.4
Body Imaging
Contrast-enhanced CT/MRI of the chest, abdomen, pelvis, and all other known/suspected sites of disease should occur every 8 weeks 
(7 days), starting from first dose for the first 48 weeks, then every 12 weeks (7 days) until withdrawal of consent, death, or initiation of 
another anti-cancer treatment, whichever occurs first. See Section 9.4.1.
For participants with SCCHN, a CT or MRI of the neck is required.
Brain Imaging
Participants with a history of brain metastasis should have surveillance MRI as clinically indicated at the discretion of the investigator. See 
Section 9.4.1.
Other: Bone 
Scan
As clinically indicated per local standards. See Section 9.4.1.
Clinical Supplies
IRT Assignment
X
Once eligibility has been confirmed, IRT assignment may be performed up to 
3 days prior to study drug administration.
Study Drug Administration
Details regarding preparation and administration are provided in the pharmacy 
manual or training materials.
Abbreviations: C, Cycle; CT, computed tomography; d, days; D, Day; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EDC, Electronic 
Data Capture; EOI, end of infusion; EOT, end of treatment; hCG, human chorionic gonadotropin; IRT, Interactive Response Technologies; MRI, magnetic 
resonance imaging; PK, pharmacokinetic(s); 
 SAE, serious adverse event; T3, triiodothyronine; T4, thyroxine; TSH, thyroid stimulating 
hormone; WOCBP, women of childbearing potential.
a For participants who complete all scheduled cycles of therapy, the EOT visit will be the same visit as the last scheduled and completed on-treatment visit and the 
start of the Week 1 Clinical/Safety Follow-up visit.
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CA027002
BMS-986253
Anti-IL-8
b For participants who do not complete all scheduled cycles of therapy, the EOT visit will be the next visit following the last study dose. If the EOT visit occurs 30 
days or more after receipt of the last dose, then the EOT visit and Follow-up 1 visit can be completed at the same time.
c If multiple procedures are required at a single timepoint, safety assessments (ECGs, vital signs, and pulse oximetry) are a higher priority than PK/immunogenicity 
sampling.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-6:
On-treatment Procedural Outline (Part 1C and Part 2 - BMS-986253 Q2W and Nivolumab and 
Ipilimumab Q3W)
Procedure
Cycle 1 and 2
(42 d)
Cycle 3 and 
Beyond
(28 d)
EOTa,b
Notes
D1
D15
D22
D29
D36
D1
D15
Safety Assessmentsc
Vital Signs and 
Oxygen 
Saturations
X
X
X
X
X
X
Includes body temperature, respiratory rate, seated blood pressure, and 
heart rate. Blood pressure and heart rate should be measured after the 
participant has been resting quietly for at least 5 minutes. Consider 
alternate position(s) for vital sign collection. Obtain oxygen saturation at 
rest. *Pre- and post-dose vital signs on Day 1 of each cycle. Note: Post 
dose vital signs are to be taken after nivolumab infusion, ipilimumab 
infusion and BMS-986253 or placebo infusion.
Weight
X
X
X
X
Physical 
Examination 
(Complete)
X
X
X
X
Physical Examination (Complete)
ECOG 
Performance 
Status
X
X
X
Appendix 5
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
Assess concomitant treatment during the study duration.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-6:
On-treatment Procedural Outline (Part 1C and Part 2 - BMS-986253 Q2W and Nivolumab and 
Ipilimumab Q3W)
Procedure
Cycle 1 and 2
(42 d)
Cycle 3 and 
Beyond
(28 d)
EOTa,b
Notes
D1
D15
D22
D29
D36
D1
D15
ECG
X
X*
X
X
12-lead ECGs should be recorded after participant has been supine for at 
least 5 minutes. 
 
 
 
 
Participants with no clinically relevant changes on ECGs at 6 months on 
treatment may discontinue routine ECGs. 
See 
 of ECGs.
* Required for Part 1C only.
Laboratory 
Testing
X
X
X
X
See Section 9.1.4
Only applicable for Part 1C: For HCC participants AFP
Pregnancy Test 
(WOCBP)
X
X
X
Serum or urine pregnancy test must be performed (urine pregnancy test: 
minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours 
prior to administration of study drug.
Thyroid 
Function Tests 
(TSH)
X
X
X*
*TSH to be done on C3D1, C4D1, C5D1, and C6D1. TSH to be done 
every other cycle, after C6D1 (ie, C8D1, C10D1, etc). If TSH is 
abnormal, T3 and free T4 should be collected. Results should be 
examined by the investigator or appropriate designee within 48 hours of 
dose administration.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-6:
On-treatment Procedural Outline (Part 1C and Part 2 - BMS-986253 Q2W and Nivolumab and 
Ipilimumab Q3W)
Procedure
Cycle 1 and 2
(42 d)
Cycle 3 and 
Beyond
(28 d)
EOTa,b
Notes
D1
D15
D22
D29
D36
D1
D15
Adverse Event Reporting
Monitor for 
Nonserious 
Adverse Events
All nonserious adverse events must be collected starting with the first dose of study drug and for a minimum of 100 days after 
discontinuing study treatment.
Monitor for 
Serious Adverse 
Events
All SAEs must be collected from the date of participant’s written consent and for a minimum of 100 days after discontinuing study 
treatment. Death due to disease progression within 100 days of discontinuation of study treatment must be reported as an SAE.
Other Assessments
PK Assessments
See Section 9.5 for further details
Immunogenicity 
Assessments
See Section 9.5 for further details
Biomarker 
Assessments
See Section 9.8
Additional 
Research 
Sampling
See Section 9.8.4
Efficacy 
Assessments
See Section 9.4
Body Imaging
For Part 1C: Contrast-enhanced CT/MRI of the chest, abdomen, pelvis, and all other known/suspected sites of disease should occur every 
8 weeks (7 days), starting from first dose for the first 48 weeks, then every 12 weeks (7 days) until withdrawal of consent, death, or 
Protocol Amendment No.: 07
Date: 17-May-2024
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8.0
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v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-6:
On-treatment Procedural Outline (Part 1C and Part 2 - BMS-986253 Q2W and Nivolumab and 
Ipilimumab Q3W)
Procedure
Cycle 1 and 2
(42 d)
Cycle 3 and 
Beyond
(28 d)
EOTa,b
Notes
D1
D15
D22
D29
D36
D1
D15
initiation of another anti-cancer treatment, whichever occurs first. For HCC participants, contrast-enhanced triphasic CT of the liver is 
required. See Section 9.4.1.
For Part 2: Timing of scans should be based on date of first treatment, which is considered Week 1. Contrast-enhanced CT/MRI of the chest, 
abdomen, pelvis, and all other known/suspected sites of disease should occur every 8 weeks (7 days), starting from first dose for the first 
48 weeks, then every 12 weeks (7 days). Tumor assessments should continue until BICR-confirmed disease progression, final analysis, or
treatment discontinuation (including treatment beyond progression), whichever occurs later. See Section 9.4.1.
Brain Imaging
Participants with a history of brain metastasis should have surveillance MRI as clinically indicated at the discretion of the investigator. See 
Section 9.4.1.
Other: Bone 
Scan
As clinically indicated per local standards. See Section 9.4.1.
Clinical Supplies
IRT Assignment
X
Once eligibility has been confirmed, IRT assignment may be performed 
up to 3 days prior to study drug administration.
Study Drug Administration
Nivolumab 
Administration
X
X
X
Nivolumab will be administered every 3 weeks for the first 2 cycles 
(4 doses) and then every 4 weeks for Cycle 3 and beyond. See 
Section 7.1 for nivolumab dose administration.
Ipilimumab 
Administration
X
X
Ipilimumab will be administered every 3 weeks on Cycles 1 and 2 
(4 doses) ONLY. See Section 7.1 for ipilimumab dose administration.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Abbreviations: AFP, alpha fetoprotein; BICR, blinded independent central review; C, Cycle; CT, computed tomography; d, days; D, day; ECG, electrocardiogram; 
ECOG, Eastern Cooperative Oncology Group; EDC, Electronic Data Capture; EOT, end of treatment; HCC, hepatocellular carcinoma; hCG, human chorionic 
gonadotropin; IRT, Interactive Response Technologies; MRI, magnetic resonance imaging; PK, pharmacokinetic(s); QXW, every X weeks; SAE, serious adverse 
event; T3, triiodothyronine; T4, thyroxine; TSH, thyroid stimulating hormone; WOCBP, women of childbearing potential.
a For participants who complete all scheduled cycles of therapy, the EOT visit will be the same visit as the last scheduled and completed on-treatment visit and the 
start of the Week 1 Clinical/Safety Follow-up visit.
b For participants who do not complete all scheduled cycles of therapy, the EOT visit will be the next visit following the last study dose. If the EOT visit occurs 30 
days or more after receipt of the last dose, then the EOT visit and Follow-up 1 visit can be completed at the same time.
c If multiple procedures are required at a single timepoint, safety assessments (ECGs, vital signs, and pulse oximetry) are a higher priority than PK/immunogenicity 
sampling.
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Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-7:
Safety Follow-up Procedural Outline
Procedure
FU 1
30 Days (7 Days)
FU 3
100 Days (7 Days)
Response Follow-up 
(Q12W)
Notes
Safety Assessments
Concomitant Medications
X
X
ECOG Performance Status 
X
X
Appendix 5
Physical Examination
X
X
Vital Signs/Oxygen 
Saturation and Weight
X
X
Including weight, body temperature, 
respiratory rate, pulse oximetry, 
seated BP, and heart rate.
Laboratory Tests
Hematology and Serum 
Chemistry
X
X
See Section 9.1.4
Only applicable for Part 1C: For 
HCC participants: AFP
Pregnancy testing (WOCBP)
X
X
Pharmacokinetic Assessment
PK / Immunogenicity 
Sampling
See Section 9.5 for further details
Adverse Event Reporting
AEs reported during this time 
period should be followed until 
resolved to baseline, stabilized, or 
deemed irreversible.
Monitor for Nonserious AEs
All nonserious adverse events must be collected starting with the first dose of the study 
and for a minimum of 100 days after discontinuing study treatment.
Monitor for SAEs
All SAEs must be collected from the time of signing the consent and for a minimum of 
100 days after discontinuing study treatment. Death due to disease progression within 
100 days of discontinuation of dosing must be reported as an SAE.
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Date: 17-May-2024
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Table 2-7:
Safety Follow-up Procedural Outline
Procedure
FU 1
30 Days (7 Days)
FU 3
100 Days (7 Days)
Response Follow-up 
(Q12W)
Notes
Efficacy Assessments
New and Subsequent Anti-
cancer Therapy
X
X
New anti-cancer therapy including 
radiotherapy, surgery, and systemic 
therapy
Tumor Type Assessment
Body Imaging
Part 1: See Section 9.4.1. After EOT, participants should continue tumor assessment 
on the same schedule, every 8 weeks (± 7 days), starting from first dose for the first 48 
weeks, then every 12 weeks (± 7 days), until withdrawal of consent, death, initiation of 
another anti-cancer treatment, final analysis, or for up to a maximum of 2 years, 
whichever occurs first.
Part 2: Timing of scans should be based on date of first treatment, which is considered 
Week 1.
See Section 9.4.1. After EOT, participants in Part 2 will continue to have radiologic 
and clinical tumor assessments on the same schedule, every 8 weeks (± 7 days), 
starting from the first dose for the first 48 weeks, then every 12 weeks (± 7 days), until 
BICR-confirmed disease progression, final analysis, or treatment discontinuation 
(including treatment beyond progression), whichever occurs later. 
For participants with SCCHN, a CT or MRI of the neck is required. For HCC 
participants, contrast-enhanced triphasic CT of the liver is required. See Section 9.4.1
for further details.
Brain Imaging
See Section 9.4.1. Participants with a history of brain metastasis should have 
surveillance MRI as clinically indicated at the discretion of the investigator.
Other Bone Scan
See Section 9.4.1. As clinical indicated per local standards.
Abbreviations: AE, adverse event; AFP, alpha fetoprotein; BICR, blinded independent central review; BP, blood pressure; CT, computed tomography; ECOG, 
Eastern Cooperative Oncology Group; EOT, end of treatment; FU, follow-up; HCC, hepatocellular carcinoma; IgG, immunoglobulin G; MRI, magnetic resonance 
imaging; PK, pharmacokinetic(s); Q12W, every 12 weeks; SAE, serious adverse event; SCCHN, squamous cell carcinoma of the head and neck; WOCBP, women 
of childbearing potential.
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
3
INTRODUCTION
This is a study of BMS-986253, a monoclonal antibody (mAb) against human interleukin-8 (IL-8), 
conducted in humans with advanced solid tumors. This study will evaluate the safety profile, 
tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of 
BMS-986253 in combination with nivolumab (Parts 1A and 1B) or in combination with nivolumab
and ipilimumab (Parts 1C and 2) in participants with advanced solid tumors. 
Parts 1A and 1B will evaluate the safety, tolerability, PK, and pharmacodynamics of different 
doses of BMS-986253 in combination with nivolumab in participants with non-small cell lung 
cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN), urothelial 
cancer (UCC) and renal cell carcinoma (RCC), who have 
 
Part 1C will evaluate the safety and tolerability of BMS-986253 in combination with nivolumab 
and ipilimumab in participants with melanoma, colorectal cancer (CRC), hepatocellular cancer 
(HCC), and UCC, who may have any serum IL-8 level. Part 2 is a randomized, double-blind 
evaluation to assess efficacy of BMS-986253 in combination with nivolumab and ipilimumab 
versus placebo plus nivolumab and ipilimumab in participants with unresectable or metastatic 
melanoma. 
3.1
Study Rationale
Immuno-oncology (I-O) drugs, which harness the immune system to fight cancer, have emerged 
as a major advancement in cancer treatment.1
Current approaches include blocking 
immunosuppressive signals, such as programmed cell death 1 (PD-1) or cytotoxic T-lymphocyte-
associated protein 4 (CTLA-4) with antagonistic antibodies and stimulating immunity with 
agonistic antibodies. Despite recent progress, in many cases resistance to the immunotherapy 
occurs due to the interplay of various mechanisms of immune suppression.2 Thus, new 
combination strategies are needed to target these multiple mechanisms of immune suppression to 
overcome the resistance and to extend the breadth of current immune therapies. 
There is growing evidence that IL-8 (also called CXCL8) plays an important role in 
immunosuppression.3 IL-8 belongs to the CXC chemokine subfamily that includes several 
molecules involved in the activation and chemoattraction of various leukocytes.4 IL-8 expression 
is highly regulated in healthy individuals with serum IL-8 concentrations at very low or 
undetectable levels 
5,6 However, IL-8 serum concentrations are often 
elevated in cancer patients.3,7,8,9,10 IL-8 may be produced by a variety of cells, including cancer 
cells, leukocytes, endothelial cells, and fibroblasts. IL-8 binds to two receptors, CXCR1 and 
CXCR2,11 and promotes recruitment of myeloid derived suppressor cells (MDSCs) to the tumor 
microenvironment (TME), and suppress T-cell function. 12,13 IL-8 has also been shown to play a 
pro-tumoral role in the TME, and promote the epithelial mesenchymal transition (EMT),14 cancer 
stem cell (CSC) renewal,15,16 and angiogenesis.17,18
In many types of advanced cancer, high levels of IL-8 correlate with worse prognosis as well as 
resistance to therapeutic approaches, including anti PD-1 and anti-CTLA-4 therapy.3,19,20,21,25 One 
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hypothesis that can explain this resistance is IL-8-dependent recruitment of immunosuppressive 
MDSC into the tumor.22 Preliminary analysis of several clinical trials containing nivolumab-based 
therapy confirm recent observations made by other groups, that high levels of IL-8 are associated 
with resistance to anti-PD-L1-based therapy in advanced NSCLC, melanoma, and RCC (see 
Section 5.4.3).21,23 Thus, blocking IL-8 with an antagonist antibody in combination with 
nivolumab or nivolumab plus ipilimumab represents an approach with the potential to extend I-O 
benefits to patients not adequately served by existing anti-PD-(L)1 therapies alone. 
Pharmacological inhibition of IL-8 is a rational approach to disrupt not only immunosuppression 
associated with MDSCs, but also pro-tumorigenic mechanisms of CSC maintenance, EMT, and 
angiogenesis.
3.2
Background
3.2.1
BMS-986253
BMS-986253 is a fully human-sequence IgG1κ mAb directed against IL-8. 
 
 
 The antibody will thus antagonize the IL-8 mediated 
signals and may increase the anti-tumor response through distinct mechanisms of action: 

blocking the recruitment of immunosuppressive MDSC to the tumor

disrupting angiogenesis

inhibition of invasive EMT

affecting the CSC phenotype
Furthermore, relieving the immunosuppression by reducing MDSCs in the tumor 
microenvironment has the potential to increase the activation of Effector CD8 T cells in synergy 
with PD-1 blockade by nivolumab. This study will, in part, evaluate this hypothesis in participants 
with NSCLC, melanoma, RCC, UCC, or SCCHN that progress on or after anti-PD-(L)1 therapy 
and which have a detectable level of IL-8 in the serum.
Previous data on treatment with BMS-986253 monotherapy in humans, demonstrated a safe and 
tolerable profile (see BMS-986253 Investigator’s Brochure [IB]).24 The highest dose tested in 
humans was administered in the CA027001 Study, in which multiple ascending doses of 
BMS-986253 were found to be safe and well tolerated across the dose range of 4 to 32 mg/kg 
every 2 weeks (Q2W) in 15 participants with advanced tumors.25 This was equivalent to a 2560 mg 
flat dose for 80 kg body weight Q2W or a 5120 mg total accumulative dose Q4W. No serious 
adverse events (SAEs) were considered related to BMS-986253 monotherapy. There was no 
increase in the frequency of adverse events (AEs) with increased doses. There were no deaths or 
discontinuations due to AEs in this study. The maximum tolerated dose (MTD) was not reached.
The current study will evaluate the safety, tolerability, and preliminary efficacy of intravenous 
(IV) doses of BMS-986253, administered in combination with nivolumab or in combination with 
nivolumab and ipilimumab in participants with advanced solid tumors, and is expected to 
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determine the recommended Phase 2 dose(s) (RP2D) of the combination to be used in future 
studies.
It is anticipated that anti-IL-8 mAb (BMS-986253) administered in combination with anti-PD-1 
mAb (nivolumab) or in combination with nivolumab and anti-CTLA-4 mAb (ipilimumab), will 
demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile to support 
further clinical testing.
The scientific rationale for the study design is discussed in greater detail in Section 5.3. Additional 
details such as BMS-986253 Nonclinical/Clinical Pharmacology, Nonclinical/Clinical PK/ 
pharmacodynamics, Nonclinical Toxicology and clinical safety are summarized in the 
BMS-986253 IB.24
3.2.2
Nivolumab
Nivolumab is a fully human, IgG4 (kappa) isotype mAb that binds to PD-1 with nanomolar affinity 
(dissociation constant, 3.06 nM) and a high degree of specificity. Nivolumab blocks binding of 
PD-1 to its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2). 
Nonclinical in vitro testing of nivolumab demonstrated that binding to PD-1 results in enhanced 
T-cell proliferation and release of interferon gamma in vitro in mixed lymphocyte reaction and 
cytomegalovirus assays.
The nonclinical safety of nivolumab was evaluated in a comprehensive toxicology program in 
mice and monkeys and was submitted as part of Biologics License Application 125554. Details of 
the in vitro and in vivo nonclinical pharmacology studies conducted to support the development 
of nivolumab can be found in Section 4.1 of the nivolumab IB.
While nivolumab was well tolerated in cynomolgus monkeys, there is a potential for enhanced 
toxicity when combined with other immunostimulatory agents. However, nonclinical studies with 
nivolumab did not predict clinically relevant adverse effects (eg, no evidence of immune-mediated 
adverse effects was observed in nonclinical toxicology studies with nivolumab). Therefore, 
combination nonclinical toxicology studies with BMS-986253 and nivolumab have not been 
conducted and are not required by the International Conference on Harmonisation S9 Note for 
Guidance on Nonclinical Evaluation for Anticancer Pharmaceuticals. The safety of the 
combination will be carefully monitored in the planned clinical trial. 
The overall safety experience with nivolumab, as either monotherapy or in combination with other 
therapeutics, is based on experience in approximately 26,400 subjects (see nivolumab IB).26
Nivolumab has been approved by the United States (US) Food and Drug Administration (FDA) 
for various indications, including unresectable or metastatic melanoma (as a single agent and in 
combination with ipilimumab), metastatic NSCLC (as a single agent and in combination with 
ipilimumab), advanced RCC (as a single agent and in combination with ipilimumab), recurrent or 
metastatic squamous cell carcinoma of the head and neck with disease progression on or after a 
platinum-based therapy, advanced or metastatic urothelial carcinoma with disease progression on 
or after a platinum-based therapy, and MSI-H CRC (as a single agent or in combination with 
ipilimumab).
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For nivolumab monotherapy, the safety profile is similar across tumor types. The only exception 
is pulmonary inflammation AEs, which may be numerically greater in participants with NSCLC. 
In participants with NSCLC, it can be difficult to distinguish between nivolumab-related and 
unrelated causes of pulmonary symptoms and radiographic changes. There is no relationship 
between the incidence, severity, or causality of AEs and the nivolumab dose level. The safety of 
nivolumab in combination with other therapeutics such as ipilimumab, cytotoxic chemotherapy, 
anti-angiogenics, and targeted therapies is being explored in several ongoing clinical trials. The 
safety profile of nivolumab combination therapy varies with the agent combined with nivolumab, 
but is generally consistent with the safety profiles observed with either agent alone and, in some 
cases, both frequency and severity of AEs were greater than that observed with either agent alone. 
Additional details on the safety profile of nivolumab, including results from other clinical studies, 
are summarized in the nivolumab IB.26
3.2.3
Ipilimumab
Ipilimumab is a fully human IgG1 (kappa) monoclonal antibody that binds to human cytotoxic T-
lymphocyte antigen 4 (CTLA-4) with nanomolar affinity (dissociation constant 5.25 nM) and a 
high degree of specificity. CTLA-4 is expressed on a subset of activated T-cells on which it acts 
as a negative regulator of T-cell activity. Ipilimumab is a mAb that binds to CTLA-4 and blocks 
the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to 
augment T-cell activation and proliferation, including the activation and proliferation of tumor 
infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce Treg function, which 
may contribute to a general increase in T-cell responsiveness, including the anti-tumor response.
The overall safety experience of ipilimumab as either monotherapy or in combination with other 
therapeutics is based on experience in over 30,000 subjects. Additional details on the safety profile 
of ipilimumab, including results from other clinical studies, are summarized in the ipilimumab 
IB.27
Ipilimumab has been approved by the US FDA for the treatment of several cancers, including 
unresectable or metastatic melanoma (single agent or combined with nivolumab), intermediate- or 
poor-risk RCC (in combination with nivolumab), MSI-H CRC that has progressed after 
chemotherapy (in combination with nivolumab), HCC that has previously been treated with 
sorafenib (in combination with nivolumab), and first-line NSCLC with PD-L1 ≥1% (in 
combination with nivolumab). 
3.2.4
Nivolumab plus Ipilimumab
The combination of nivolumab and ipilimumab has been approved by the US FDA for the 
treatment of patients across a variety of cancers, including melanoma, intermediate-/poor-risk-
RCC, NSCLC, MSI-H CRC, and HCC (as indicated in Section 3.2.3). The safety profile of 
nivolumab plus ipilimumab is characterized by immune-related toxicities, such as diarrhea, rash, 
pneumonitis, liver toxicity, and endocrinopathies. The frequencies and intensities of these events 
in the combination are variable and depend on the specific doses and schedule used. Additional 
details on the safety profile on the combination of nivolumab and ipilimumab, are summarized in 
the nivolumab IB.26
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3.3
Benefit/Risk Assessment
Patients who have advanced solid tumors including metastatic/unresectable melanoma, NSCLC, 
SCCHN, RCC, UCC, HCC, or CRC, that progress after at least 1 line of standard systemic therapy 
have a poor prognosis and no curative options.
The safety of BMS-986253 as monotherapy has been established in earlier studies in healthy 
volunteers, participants with inflammatory skin disease (Palmoplantar Pustulosis), and in 
participants with advanced malignancies. BMS-986253 monotherapy has been administered to 
participants with advanced malignancies 
 
 
and was demonstrated to be safe and tolerable. 
The safety profile of nivolumab monotherapy is well defined and is based on experience with 
greater than 15,000 participants evaluated in clinical trials. The frequency and types of immune-
mediated adverse reactions (IMARs) are similar across multiple types of tumors and are described 
in the Reference Safety Information (RSI) in the current nivolumab IB. Management algorithms 
for nivolumab-induced AEs involving gastrointestinal, renal, pulmonary, hepatic, endocrinopathy, 
skin, and neurologic systems are included in the protocol (Appendix 5).
The safety profile of ipilimumab monotherapy is well defined and is based on experience with 
greater than 7,300 participants evaluated in clinical trials. The frequency and types of IMARs are 
similar across multiple types of tumors and are described in the RSI in the current ipilimumab 
IB.27
Management 
algorithms 
for 
ipilimumab-induced 
AEs 
involving 
myocarditis, 
gastrointestinal, renal, pulmonary, hepatic, endocrinopathy, skin, and neurologic systems are 
included in the protocol (Appendix 6). 
In combination with nivolumab, the risk that BMS-986253 may potentiate immune-mediated 
adverse reactions should be low as blocking IL-8 does not directly activate T-cells. Blocking IL-8 
may, in fact, reduce the inflammatory process by reducing the neutrophil recruitment in the 
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damaged tissue. Available safety data from trials using I-O combination strategies with nivolumab 
have shown that the safety profile varies depending on the agent being combined with nivolumab, 
but is generally consistent with the safety profiles observed with either agent alone and, in some 
cases, both the frequency and severity of AEs were greater than that observed with either agent 
alone. The safety of the combination of BMS-986253 with nivolumab will be carefully monitored 
in the study.
 
 
 
 Overall, 
 participants experienced Grade ≥ 3 related AEs, and 
 
participants discontinued study treatment because of AEs related to the study drugs (less than or 
similar to that expected with nivolumab monotherapy in an I-O naïve population). There were no 
deaths related to the study drugs, and there were no dose-dependent AEs identified. Based on these 
data, an increase in IMARs with the combination of BMS-986253 and nivolumab compared with 
nivolumab monotherapy is not expected.24
The triplet combination of BMS-986253, nivolumab, and ipilimumab has not been previously 
evaluated. However, based on the safety data generated on the combination of BMS-986253 and 
nivolumab, and the combination of nivolumab and ipilimumab, the triplet combination is expected 
to have a tolerable safety profile. For similar reasons, as stated in the previous paragraph (mainly 
that blocking IL-8 may reduce the inflammatory process and safety data generated on the 
combination of BMS-986253 and nivolumab), BMS-986253 is not expected to increase the rate 
of IMARs observed with the combination of nivolumab and ipilimumab. 
 
 
 
 
 
 
 
 
Continuous safety assessments will be utilized by the investigators and Bristol Myers Squibb 
(BMS) to determine whether dose modification, additional safety measures, or termination of the 
study is required at any time. In addition, AEs and SAEs will be reviewed on an ongoing basis by 
the BMS Medical Monitor and Global Pharmacovigilance and Epidemiology representatives to 
monitor for any safety signals or trends. Additionally, in Part 2 of the study, an independent safety 
or Data Monitoring Committee (DMC) will be used 
 
 As BMS-986253 is an experimental agent, it is possible 
that unforeseen, unknown, or unanticipated reactions may occur. The protocol was developed 
while carefully balancing risks and benefits of treatment of a novel treatment in this patient 
population.
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3.3.1
Safety Monitoring on Study Treatment
Frequent safety assessments will be carried out by the Sponsor/BMS Medical Monitor (or 
designee) and investigators throughout the study to determine whether dose modification, 
additional safety measures, or termination of the study treatment combination arm is required at 
any time. In addition, AEs and SAEs will be reviewed regularly by the BMS Medical Monitor (or 
designee) and the Pharmacovigilance group to look for trends and potential safety signals. 
Treatment of AEs will follow institutional guidelines and recommended management algorithms, 
as listed in the IBs and prescribing information, as applicable, for each combination agent, and 
provided as appendices to this protocol. Specific algorithms for the management of immune-
related adverse events (irAEs) are provided in Appendix 6 and are applicable to irAEs for all I-O 
study treatment combinations.
The global coronavirus disease 2019 (COVID-19) pandemic has been identified as a potential risk 
to clinical trial participants in general. Whether BMS-986253 in combination with nivolumab or 
in combination with nivolumab and ipilimumab administration increases the risk for contracting 
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or increases the severity 
or duration of symptoms is currently unknown. This unknown risk must be considered when 
enrolling a participant.
No additional safety monitoring or routine screening tests will be required due to the SARS-CoV-2 
pandemic. Participants with a recent or acute infection will be excluded or delay start of treatment 
as defined in Section 6.2. If a participant has a confirmed SARS-CoV-2 infection while on study 
treatment, dose delay or interruption of study treatment is required as described in Section 7.6.3. 
The study has been designed with study visits that allow for close monitoring of participants’ safety 
throughout the clinical trial (Section 9.1), and participants are encouraged to contact the 
investigator if an intercurrent illness develops between study visits. Testing for COVID-19 to 
inform decisions about clinical care during the study should follow local standard practice.
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 BMS-986253 in combination with nivolumab or in combination with 
nivolumab and ipilimumab is unknown.
Additionally, in Part 2 of this study, an independent DMC will provide oversight. The DMC will 
act in an advisory capacity to BMS and will monitor participant safety and evaluate the available 
efficacy data for the study. They will advise the Sponsor regarding actions the committee deems 
necessary for the continuing protection of participants enrolled in the study and those yet to be 
recruited to the trial as well as for the continuing validity and scientific merit of the study results.
The DMC is charged with assessing such actions in light of an acceptable benefit-risk profile for 
BMS-986253.
 
 The oncology therapeutic area of BMS has primary responsibility for 
design and conduct of the study.
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4
OBJECTIVES AND ENDPOINTS
Table 4-1:
Objectives and Endpoints - Part 1
Objectives
Endpoints
Primary

To characterize safety, tolerability, and DLTs, and
to
determine
the
RP2D
of
BMS-986253
administered in combination with nivolumab, or in 
combination with nivolumab and ipilimumab in
participants with advanced solid tumors.

Incidence of AEs, SAEs, AEs meeting protocol-
defined DLT criteria, and AEs leading to 
discontinuation, 
death, 
and 
laboratory 
abnormalities.
Secondary

To evaluate the preliminary efficacy of BMS-986253 
in combination with nivolumab in participants with 
advanced solid tumors using RECIST v1.1.

To characterize the PK and immunogenicity of BMS-
986253 when administered in combination with 
nivolumab, or in combination with nivolumab and 
ipilimumab in participants with advanced solid 
tumors.

To assess serum IL-8 levels at baseline (ie, screening) 
and changes in IL-8 levels on treatment.

ORR and DOR per RECIST v1.1 per investigator.

Summary measures of PK parameters and 
incidence of ADA to BMS-986253.

Summary measures of IL-8 and change (or percent 
change) from baseline in IL-8 on treatment.
Abbreviations: ADA, anti-drug antibody; AE, adverse event; DLT, dose-limiting toxicity; DOR, duration of response; 
 EOT, end of treatment; ORR, objective response rate; PK, pharmacokinetic(s); 
 
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 RECIST, Response 
Evaluation Criteria in Solid Tumors; RP2D, recommended Phase 2 dose; SAE, serious adverse event.
Table 4-2:
Objectives and Endpoints - Part 2
Objectives
Endpoints
Primary

To compare the ORR
of BMS-986253 plus 
nivolumab plus ipilimumab with placebo plus 
nivolumab and ipilimumab using RECIST v1.1. 

ORR 
based 
on 
BICR 
assessments 
per 
RECIST v1.1 in all randomized participants.
Secondary

To estimate PFS of BMS-986253 plus nivolumab 
plus ipilimumab and placebo plus nivolumab and 
ipilimumab in participants with advanced melanoma 
using RECIST v1.1 (regardless of baseline serum 
IL-8 levels).

To compare the safety of BMS-986253 plus 
nivolumab plus ipilimumab with placebo plus 
nivolumab plus ipilimumab in participants with 
advanced melanoma. 

mPFS and PFS hazard ratio based on BICR 
assessments per RECIST v1.1.

Incidence of AEs, SAEs, and AEs leading to 
discontinuation, 
death, 
and 
laboratory 
abnormalities.
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Table 4-2:
Objectives and Endpoints - Part 2
Abbreviations: ADA, anti-drug antibody; AE, adverse event; BICR, blinded independent central review;
CI, confidence interval; DOR, duration of response; 
; IL-8, interleukin 8; 
 
 
 ORR, objective response rate; 
 mPFS, median progression free 
survival; PFS, progression-free survival; 
 PMN, 
polymorphonuclear neutrophil; QTcF, QT interval corrected by the Fridericia correction formula; RECIST, Response 
Evaluation Criteria in Solid Tumors; SAE, serious adverse event; 
5
STUDY DESIGN
5.1
Overall Design
This is a Phase 1/2 study of BMS-986253 administered in combination with nivolumab or in 
combination with nivolumab and ipilimumab in participants with advanced solid tumors. The 
study is comprised of 2 parts: Part 1 and Part 2. 
In Part 1, the safety of BMS-986253 in combination with nivolumab, or in combination with 
nivolumab and ipilimumab will be evaluated in participants with advanced solid tumors. Part 1 is 
divided into 3 subsections: Part 1A (BMS-986253 plus nivolumab safety evaluation lead-in), Part 
1B (BMS-986253 plus nivolumab dose finding), and Part 1C (safety evaluation of BMS-986253 
in combination with nivolumab and ipilimumab). Parts 1A and 1B evaluate the doublet 
combination of BMS-986253 and nivolumab in participants with 
 
 Part 1C is a safety evaluation of the triplet combination of BMS-986253, nivolumab, 
and ipilimumab, in participants with any baseline level of serum IL-8 (see Figure 5.1-2).
 
 The RP2D will 
be determined based on the totality of the data in Part 1, to define the safe and most biologically 
active dose. The following tumor types will be enrolled onto Part 1 as described in the inclusion 
criteria:

Parts 1A and 1B 
: melanoma, RCC, UCC, SCCHN, and 
NSCLC 

Part 1C: melanoma, UCC, HCC, and CRC
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Part 2 is a randomized, double-blind evaluation of BMS-986253 plus nivolumab plus ipilimumab 
versus placebo plus nivolumab plus ipilimumab in melanoma. The study design schematic is 
presented in Figure 5.1-3.
Part 1A: Safety Evaluation Lead-in (already enrolled,
 participants, per BMS-986253 IB24)
The safety evaluation lead-in (Part 1A) will begin with a cohort of participants who will receive a 
2400 mg flat dose of BMS-986253 Q4W combined with 480 mg flat dose of nivolumab Q4W. A 
slightly higher dose (32 mg/kg or 2560 mg administered Q2W; yielding an overall dose of 
64 mg/kg or 5120 mg per month) of BMS-986253 monotherapy has been shown to be safe and 
well tolerated in BMS Study CA027001 (see BMS-986253 IB24). 
 
 
After review of the clinical safety, 
including dose-limiting toxicities (DLTs) for the first 4 participants, the dose-finding phase 
(Part 1B) will open. 
Part 1B: Dose-finding (participants enrolled in each cohort are per BMS-986253 IB24)
In Part 1B, participants will be randomly assigned to receive one of the following dosing regimens:

Cohort 1B1: 2400 mg of BMS-986253 Q4W and 480 mg of nivolumab Q4W 

Cohort 1B2: 1200 mg of BMS-986253 Q4W and 480 mg of nivolumab Q4W 

Cohort 1B3: 600 mg of BMS-986253 Q4W and 480 mg of nivolumab Q4W 
Assignment into any dosing regimen arm may be suspended
 
 In addition, up to 4 new dosing regimens assessing the combination of 
BMS-986253 and nivolumab may be initiated 
 
Additional cohorts for alternate dosing regimens may include:

Cohort 1B4: 2400 mg of BMS-986253 Q2W and 480 mg of nivolumab Q4W 

Cohort 1B5: 1200 mg of BMS-986253 Q2W and 480 mg of nivolumab Q4W 

Cohort 1B6: 3600 mg of BMS-986253 Q2W and 480 mg of nivolumab Q4W 
 
 
For any dosing regimen evaluating a higher dose of BMS-986253 than previously explored, an 
initial 4-participant safety-lead with a 28-day DLT period will be required. Approximately 
 
participants will be dosed in the treatment arms. Additional exploration of a specific dosing 
regimen may be warranted in Part 1B, in which case additional participants will be assigned to that 
dosing regimen,
 
 A maximum of approximately 
 participants will be 
dosed in Part 1A and Part 1B. 
 
 
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Part 1C: Safety Evaluation of BMS-986253 in Combination with Nivolumab and Ipilimumab 
Part 1C is a safety evaluation of BMS-986253 in combination with nivolumab and ipilimumab. 
Part 1C will begin once the DLT period is completed for Cohort 1B6 (BMS-986253 3600 mg Q2W 
+ nivolumab 480 mg Q4W), and will enroll simultaneously with Part 1 Cohort 1B6. 
 
 
The higher-dose triplet combination Cohort 1C1 will enroll first. The safety and tolerability of this 
part will be evaluated 
 to 
guide dose escalation decisions
 and the overall assessment 
 
In Part 1C, participants will initially be enrolled onto Cohort 1C1. For the first 12 weeks, 
participants will receive BMS-986253 3600 mg Q2W from Part 1B + nivolumab 1 mg/kg Q3W + 
ipilimumab 3 mg/kg Q3W. After 12 weeks, participants will receive BMS-986253 3600 mg Q2W 
from Part 1B and nivolumab 480 mg Q4W. 
 
 
 
 
 
 
 
 
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Part 2: Double-blind Randomized Evaluation of BMS-986253 plus Nivolumab plus Ipilimumab
versus Placebo plus Nivolumab plus Ipilimumab in Advanced Melanoma
Part 2 will begin after determination of the RP2D of BMS-986253 based on Part 1A and 1B data 
 and generation of safety data on the 
triplet combination of BMS-986253 plus nivolumab plus ipilimumab in Part 1C. 
 
Part 2 is a double-blind randomized evaluation of BMS-986253 plus nivolumab plus ipilimumab 
(2A) versus placebo plus nivolumab plus ipilimumab (2B) to evaluate the efficacy of BMS-986253 
in participants with advanced melanoma who are refractory to anti-PD-(L)1 therapy. 
This portion of the study will include participants with unresectable or metastatic melanoma (non-
ocular), who had progression on or after anti-PD-(L)1 therapy, but have not been treated with prior 
anti-CTLA-4 therapy (see Section 6.1). Participants will be randomly assigned in a 1:1 ratio to 1 
of 2 treatment arms: 

2A: BMS-986253 + nivolumab + ipilimumab

2B: placebo + nivolumab + ipilimumab
During randomization, participants will be stratified by the following factors as described in 
Section 7.4: screening serum IL-8 level, 
 and lactate 
dehydrogenase (LDH) levels.
The dose of nivolumab and ipilimumab will be determined by safety data from Part 1C, and the 
dose of BMS-986253 will be determined by the totality of Part 1 data. If safety is confirmed in 
Cohort 1C1, for the first 12 weeks, participants will receive ipilimumab 3 mg/kg Q3W IV 
(4 doses), nivolumab 1 mg/kg Q3W IV (4 doses), and BMS-986253 3600 mg Q2W or placebo IV 
(given at Q2W frequency for 6 doses). After 12 weeks, participants will be maintained on BMS-
986253 3600 mg Q2W or placebo IV (Q2W) and nivolumab IV (480 mg Q4W). 
 
 
 
 
 
Approximately 
participants will be included in Part 2 and randomized in a 1:1 ratio to each 
arm.
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Figure 5.1-2:Study Design Part 1
Abbreviations: CRC, colorectal cancer; HCC, hepatocellular carcinoma; IL, interleukin; Ipi, ipilimumab; max, maximum; 
 
 
 Nivo, nivolumab; NSCLC, non-small cell lung cancer; QXW, every X weeks; R, randomized; RCC, renal cell carcinoma; S, sequential 
assignment; SCCHN, squamous cell carcinoma of the head and neck; UCC, urothelial cancer. 
a Once sequential enrollment begins, up to 4 additional cohorts may be evaluated in Part 1B.
 
 
 
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Figure 5.1-3:Study Design Part 2
Abbreviations: BRAF, proto-oncogene B-Raf; CTLA, cytotoxic T-lymphocyte-associated protein; IL, interleukin, 
Ipi, ipilimumab; LDH, lactate dehydrogenase; Nivo, nivolumab; PD-(L)1, programmed cell death (ligand) 1; QXW, 
every X weeks. 
c After 12 weeks, nivolumab will be administered at 480 mg Q4W. 
5.1.1
Pre-Screening Period (Applicable for Part 1 Only)
Participants will provide consent for pre-screening to obtain a serum IL-8 level; further screening 
procedures will not be completed until the IL-8 level is resulted (except for participants with HCC 
and CRC). Depending on availability of cohorts at the time of enrollment, serum IL-8 results may 
determine eligibility and cohort assignment. 

Enrollment into Part 1B requires 

Enrollment into Part 1C does NOT require a minimum serum IL-8 level.

For participants with HCC and CRC: results of screening IL-8 are NOT required prior to 
signing the Main Informed Consent, since all HCC and CRC participants will be assigned to 
Part 1C (Part 1C does not require a minimum serum IL-8 level). Participants with HCC and 
CRC may enroll only when Part 1C is open. 

For participants with melanoma or UCC only being considered for Part 1C (for example, if 
Part 1B is not actively enrolling participants), results of screening IL-8 are NOT required prior 
to signing the Main Informed Consent.
If the participant meets pre-screening criterion for study entry, the Main Informed Consent must 
be signed within 1 week of serum IL-8 positive result by the central laboratory. Participants will 
be enrolled using Interactive Response Technology (IRT) during Pre-Screening and will be 
assigned a designated subject identification number. 
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5.1.2
Screening Period
The screening period will be up to 28 days and begins by establishing the participant’s initial 
eligibility and signing of the informed consent form (ICF). In order to establish eligibility for this 
study, participants will undergo baseline physical examinations, vital signs and oxygen saturation 
measurements, 12-lead electrocardiogram (ECG), 
 
 and clinical laboratory evaluations.
If a participant exceeds the 28-day screening period (eg, 
 
waiting for a laboratory value), the participant must be reconsented, but does not require a new 
participant identification number. The fewest number of procedures from the initial screening 
should be repeated to qualify the participant, while maintaining participant safety and eligibility. 
Repeat serum IL-8 testing will not be required if the previous sample was obtained within 42 days 
of study treatment initiation.
Assignment to a Study Part 1 (1A, 1B, or 1C) must be designated in the IRT system prior to the 
participant’s assignment to a dosing regimen. In Part 2, all participants will be randomly assigned 
to Arm 2A (BMS-986253 + nivolumab + ipilimumab) or 2B (placebo + nivolumab + ipilimumab). 
Prior to randomization in Part 2, screening laboratory test results for serum IL-8 and LDH must be 
received, and 
 must be entered in the electronic case report 
form (eCRF). Part 2 of the study is double-blind; the participant, Sponsor, and site staff (except as 
indicated in Section 7.5) will not be aware of treatment/cohort assignment, as described in 
Section 7.4. 
5.1.3
Treatment Period
Physical examinations, vital sign or pulse oximetry measurements, 12-lead ECGs, and clinical 
laboratory evaluations will be performed at selected times throughout the study (see Section 2). 
 
 
 
 
Participants will be closely monitored for AEs throughout the study. Blood samples will be 
collected at selected times for PK and pharmacodynamic analysis as per Section 9.8,
 In Part 1, stool will be collected during screening, on treatment, and at 
progression to evaluate pharmacodynamic effect in relation to the gut microbiota (per Section 9.8,
 In Part 2, stool will be collected during screening only (per 
Section 9.8,
All participants will be treated for up to 3 calendar years from first dose or until disease 
progression, intolerance to treatment, meeting discontinuation criteria, or withdrawal of consent. 
Participants enrolled in the safety evaluation lead-in period (Part 1A), will start with a 4-week DLT 
evaluation following the first dose (corresponding to the first cycle of the treatment period). A 
sentinel participant approach will be used with a 5-day interval between the treatment initiation of 
the first participant and the treatment of subsequent participants at each dose level that will be 
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tested in Part 1A. Participants enrolled in the dose-finding (Part 1B), in the triplet safety assessment 
(Part 1C), and in Part 2 of the study will start their treatment period at the dose regimen according 
to their assigned cohort, respectively. Additional cohorts in Part 1 may start with a safety lead-in 
(4-week DLT evaluation) as previously described.
Study visits and samples collections will vary based on cohort assignment as per Sections 9.5
and 9.8. 
5.1.4
Window Visits
A 3-day window is permitted to accommodate study participants and schedules between 
treatment visits.  
 
 
5.1.5
Follow-up
5.1.5.1
Safety Follow-up Period
Upon completion of study therapy (or up to a maximum of 156 weeks if applicable), or once the 
decision is made to discontinue the participant from treatment, ie, at end of treatment (EOT), all 
participants will enter a safety follow-up period.
For participants who complete all scheduled cycles of therapy, the EOT visit will be the same visit 
as the last scheduled and completed on-treatment visit, and will be the start of the safety follow-
up period. For participants who do not complete all scheduled cycles of therapy, the EOT visit will 
be the next visit following the last study dose. If the EOT visit occurs 30 days or more after receipt 
of the last dose, then the EOT visit and Follow-up 1 visit can be completed at the same time.
All participants will be evaluated for any new AEs for a minimum of 100 days after discontinuing 
study treatment. Follow-up visits should occur at Days 30 and 100 (7 days for all study visits) 
after the last dose. All participants will be required to complete the 3 clinical safety follow-up 
visits, regardless of whether new anti-cancer therapy is started, except those participants who 
withdraw consent for study participation.
5.1.5.2
Response Follow-up Period
At the time of study treatment discontinuation, participants in Part 1 will continue to have 
radiologic and clinical tumor assessments on the same schedule, every 8 weeks (± 7 days), for the 
first 48 weeks after the first dose. After 48 weeks, radiological and clinical tumor assessments will 
occur every 12 weeks (± 7 days), until withdrawal of consent, death, or initiation of another anti-
cancer treatment, whichever occurs first, for up to 2 years after EOT. 
Participants in Part 2 will continue to have radiologic and clinical tumor assessments on the same 
schedule, every 8 weeks (± 7 days), starting from first dose for the first 48 weeks, then every 12 
weeks (± 7 days), until blinded independent central review (BICR)-confirmed disease progression, 
final analysis, or treatment discontinuation (including treatment beyond progression), whichever 
occurs later.
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5.1.5.3
Survival Follow-up Period
As of Protocol Amendment 07 Global, survival follow-up will no longer be performed. 
All participants will begin survival follow-up after completion of safety follow-up every 12 weeks 
(± 2 weeks) until 2 years after last dose of study treatment. All participants will be followed-up by 
either a clinic visit or telephone contact Q12W (from completion of safety follow-up) for 2 years 
or until death, lost to follow-up, withdrawal of consent, or conclusion of the study, whichever 
comes first. Participants will have both the Response Follow-up Period and Survival Follow-up 
Period occur simultaneously during the 2-year follow-up period. The duration of this follow-up is 
up to 2 years after completion of safety follow-up, although a longer follow-up period could be 
considered in selected cases if an efficacy signal is apparent. New and subsequent cancer therapies 
will also be recorded in this Survival Follow-up Period. 
5.1.6
Data Monitoring Committee and Other External Committees
For Part 1 of this study, BMS has elected not to use a DMC. In addition to the comprehensive 
safety monitoring plan outlined below, the following key points were considered for this decision:

This is an open-label study.

Participants will be observed frequently for clinical evaluation and blood counts during the 
study.

The eligibility criteria exclude participants with disease characteristics that could predispose 
them to a higher risk of morbidity.

Exclusion of participants with known autoimmunity (as per Section 6.2 exclusion criteria) also 
applies as they could be at risk for exacerbation of their current condition.

Well-defined discontinuation criteria are established in the protocol for individual participants 
for both safety and treatment futility with clear criteria for treatment discontinuation, dose 
delay, and toxicity management. 
BMS has in place a multi-layered process for ensuring participant safety through close 
collaboration of study site investigators, the BMS study team, and the BMS Worldwide Patient 
Safety (WWPS)-led Safety Management Team (SMT). This collaborative process constitutes the 
Data Safety Monitoring Plan for the study as detailed below:
Study safety is evaluated continuously by representatives of BMS WWPS, who operate 
independently from the clinical team and monitor safety across all BMS protocols. AEs are 
monitored continuously by WWPS. Signal detection is performed at least monthly and ad hoc 
throughout the study by the SMT composed, at a minimum, of the WWPS medical safety 
assessment physician (Chair of the SMT) and WWPS single case review physician, the study 
Medical Monitor(s), the study biostatistician, and epidemiologist. The SMT monitors actual or 
potential issues related to participant safety that could result in a significant change in the medical 
risk-benefit balance associated with the use of study treatments. Furthermore, investigators will be 
kept updated of important safety information, such as DLTs, during teleconferences between 
investigators and the BMS clinical team that will be held at least Q4W during dose escalation and 
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at least monthly during dose expansion. If appropriate, select safety issues may be escalated to a 
senior level, multidisciplinary, BMS-wide Medical Review Group for further evaluation and 
action.
To support safety oversight, BMS has established ongoing processes for collection, review, 
analysis, and submission of individual AE reports and their aggregate analyses. Because this is an 
open-label part, the BMS Medical Monitor and the investigators will have access to all data 
necessary for safety evaluation.
For Part 2 of this study (a randomized, double-blind evaluation of BMS-986253 plus nivolumab 
plus ipilimumab vs placebo plus nivolumab plus ipilimumab), an independent DMC will provide 
oversight. The DMC will act in an advisory capacity to BMS and will monitor participant safety 
and evaluate the available efficacy data for the study. They will advise the sponsor regarding 
actions the committee deems necessary for the continuing protection of participants enrolled in the 
study and those yet to be recruited to the trial as well as for the continuing validity and scientific 
merit of the study results. The DMC is charged with assessing such actions in light of an acceptable 
benefit-risk profile for BMS-986253. Details of DMC responsibilities and tasks are specified in 
the DMC charter.
 
 The oncology therapeutic area of BMS has primary responsibility for design 
and conduct of the study. 
In addition, a BICR will be utilized in Part 2 for determination of BICR-assessed endpoints.
The BICR will review all available tumor assessment scans for all treated participants. Details of 
BICR responsibilities and procedures will be specified in the BICR charter. 
5.2
Number of Participants
The maximum total number of participants will be approximately 
 Specifically, up to 
approximately 
 of these participants will be treated in Part 1, and approximately 
participants will be treated in Part 2. 
5.3
End of Study Definition
The date the first participant signs a study-specific ICF will be defined as the start of the study. A 
participant is considered enrolled when the study-specific ICF is signed. The date the last 
participant completes discharge procedures or last follow up visit will be defined as the end of the 
study.
5.4
Scientific Rationale for Study Design
BMS-986253 is being investigated in humans with advanced solid tumors in combination with 
nivolumab, and in combination with nivolumab and ipilimumab.
5.4.1
Rationale for Targeting IL-8 in Cancer
IL-8 (CXCL8) is a chemokine whose main physiologic function is the attraction of a 
polymorphonuclear inflammatory leukocyte infiltrate acting on CXCR1/2. Recently, it has been 
found that tumors frequently produce IL-8, which exerts different pro-tumoral functions, including 
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angiogenesis, provide growth factors and survival signaling for CSCs as well as the attraction of 
immunosuppressive myeloid cells endowed with the ability to dampen anti-tumor immunity. In 
the tumor, IL-8 is mainly produced by cancer cells themselves. IL-8 serum concentration has been 
shown to correlate with cumulative tumor size, stage, and prognosis in numerous cancer 
types.28,29,30,31 Because of a short 
 concentrations closely follow in time the 
changes occurring in IL-8-producing cells. Recent data strongly support a correlation between 
serum IL-8 levels and tumor burden as well as clinical stage in patients with melanoma, RCC, 
NSCLC, and HCC.3,21,23 In fact, patients with higher serum IL-8 levels had worse overall survival
(OS).3,21,23 Because of the roles that IL-8 plays in favoring tumor progression through several 
mechanism such as modulating chemotaxis, resistance to therapy, angiogenesis, and metastasis, 
therapeutic strategies aiming to interfere with IL-8 has the potential to alleviate these functions, 
thereby diminishing the risk of (further) metastatic spread and recurrent disease in these patients. 
Anti-IL-8 neutralizing antibody (HuMax-IL-8) was shown to decrease IL-8-induced neutrophil 
activation and migration in vitro resulting in beneficial anti-inflammatory responses in patients 
with palmoplantar pustulosis32 which also provided support to test this antibody in cancer patients.
5.4.2
Rationale for the Combination of BMS-986253 and Nivolumab
Recent reports have shown that changes in serum IL-8 levels accurately correlate with tumor 
burden changes in metastatic melanoma and NSCLC patients during treatment with anti-PD-(L)1 
mAbs and in metastatic melanoma patients during treatment with anti-PD-(L)1 plus anti-CTLA-4 
mAbs.20
In fact, increased expression of IL-8 by cancer cells could contribute to 
immuno-resistance by promoting the recruitment of immunosuppressive myeloid derived cells.12
These cells are well known to dampen the cytotoxic ability of T-Cells by various mechanism.33,34
Preliminary data, from multiple trials with nivolumab, show that a high level of serum IL-8 at 
baseline that persists or increases throughout therapy correlates with decreased response and 
survival in melanoma, NSCLC and RCC (see BMS-986253 IB24). In the preclinical models, the 
combination of a PD-(L)1 inhibitor and an IL-8 axis inhibitor was better at reducing tumor growth 
than either agent given as monotherapy suggesting a specific immunosuppressive role for IL-8.35,36
IL-8 produced in the tumor attracts MDSCs into the tumor microenvironment and these cells can 
in turn inhibit the immunological response to the tumor by T-lymphocytes; further confirming that 
IL-8 signaling is involved in tumor immunosuppression.12
Based on these data, the combination of nivolumab with BMS-986253 could demonstrate a 
synergetic anti-tumor activity. IL-8 serum levels may be used to guide choice of dose in pivotal 
efficacy trials of BMS-986253 in advanced cancer participants with resistance to anti-PD-L1 
therapies.
5.4.3
Rationale for Selecting Participants Based on Serum IL-8
In healthy subjects, IL-8 is not typically present in the serum; however, it can be found in the 
serum of patients with various cancer types. 
 
 
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Parts 1A and 1B will select participants with 
 for the following 
reasons: 1) these participants may be more likely to benefit from IL-8 blockade since higher IL-8 
levels correlate with worse prognosis; 2) to allow for assessment of target engagement (reduction 
in IL-8) in the blood, which will in part be used to inform RP2D dose selection. 
In Part 1C and in Part 2, participants will not be selected based on serum IL-8. The main purpose 
of Part 1C will be generation of safety data on the combination of BMS-986253 plus nivolumab 
plus ipilimumab, to support a randomized evaluation of BMS-986253 plus nivolumab plus 
ipilimumab versus placebo plus nivolumab plus ipilimumab in Part 2. In Part 2, the primary 
endpoints will be in all randomized participants regardless of baseline serum IL-8 level. 
 
 
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5.4.4
Rationale for the Combination of BMS-986253, Nivolumab, and 
Ipilimumab
Combining immunotherapeutic agents with different mechanisms of action offers the possibility 
of synergistic response. Preclinical data indicate that the combination of PD-1 and CTLA-4 
receptor blockade may improve antitumor activity. In vitro combinations of nivolumab plus 
ipilimumab increase IFN-γ production 2- to 7-fold over either agent alone in a mixed lymphocyte 
reaction. In a murine melanoma vaccine model, dual blockade with anti-CTLA-4 and anti-PD-1 
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antibodies increased tumor infiltration of T effector cells and decreased intratumoral T regulatory 
cells to a greater extent than either agent alone.37 Furthermore, clinical trial data has led to FDA 
approval of the combination of nivolumab and ipilimumab in several cancers, including RCC, 
melanoma, NSCLC, and MSI-high CRC.
Baseline serum IL-8 levels correlate with prognosis in patients treated with anti-PD-1 therapy, 
including melanoma patients treated with a combination of nivolumab and ipilimumab on 
CA209067. Adding BMS-986253, a fully human mAb against IL-8, to nivolumab plus ipilimumab 
could improve clinical outcomes.23
Although the triplet combination of BMS-986253, ipilimumab, and nivolumab has not been 
previously evaluated, based on the safety data generated on the combination of BMS-986253 and 
nivolumab, and the combination of nivolumab and ipilimumab, the triplet combination is expected 
to have a tolerable safety profile. 
5.4.5
Rationale for Testing Different Doses in Parallel in Part 1 
In the CA027001 first-in-cancer study, treatment with BMS-986253 monotherapy was determined 
to be safe and well tolerated across the dose range of 4 to 32 mg/kg Q2W in 15 participants with 
advanced tumors (equivalent to 2560 mg flat dose for 80 kg body weight Q2W; and 5120 mg total 
accumulative dose Q4W). In this study, it was not possible to determine the dose which achieve a 
sustained neutralization of IL-8 to block its intratumoral- activity. Therefore, after the preliminary 
safety of the combination of 2400 mg BMS-986253 Q4W with 480 mg nivolumab Q4W is 
established in Part 1A, Part 1B will evaluate different doses and dosing frequencies of 
BMS-986253 combined with 480 mg of nivolumab Q4W. If a cohort in Part 1B evaluates a higher 
dose of BMS-986253 than previously assessed (maximum dose to be assessed BMS-986253 
3600 mg Q2W or 5400 mg Q3W), a safety-lead in will be required for that cohort. 
In addition, cohorts in 1C (triplet combinations of BMS-986253 + nivolumab + ipilimumab) may
be evaluated simultaneously with cohorts in Part 1B, as long as initial safety data for the BMS-
986253 dose used in Part 1C has been established in combination with nivolumab in Part 1B. 
The totality of data from Part 1 
 
will further determine the RP2D of BMS-986253 in combination with nivolumab, or in 
combination with nivolumab plus ipilimumab.
5.4.6
Rationale for Treatment Beyond Progression
Immunotherapeutic agents produce atypical clinical response patterns that are not usually observed 
with conventional chemotherapy. Accumulating clinical evidence indicates that some participants 
treated with immune system stimulating agents may develop disease progression by the 
conventional response criteria before demonstrating clinical overall responses and/or stable 
disease.
Two distinct nonconventional patterns have been reported: 1) a reduction in target tumor burden 
despite the appearance of new lesion(s), and 2) a transient increase in target tumor burden in an 
initial phase, followed by subsequent tumor shrinkage.
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These phenomena were observed in the Phase 2 Study (CA209003) of nivolumab in participants 
with solid tumors. Two hypotheses potentially explain these phenomena. First, enhanced 
inflammation within tumors could lead to an increase in tumor size, which would appear as 
enlarged index lesions and as newly visible small non-index lesions. Over time, both the malignant 
and inflammatory portions of the mass may then decrease, leading to overt signs of clinical 
improvement. Alternatively, in some individuals, the kinetics of tumor growth may initially 
outpace anti-tumor immune activity. With sufficient time, the anti-tumor activity will dominate 
and become clinically apparent. Therefore, it is important to avoid premature discontinuation of 
the study drug that might induce a nonconventional response pattern in some participants.
The decision to continue treatment beyond investigator-assessed progression should be discussed 
with the BMS Medical Monitor and documented in the study records. The assessment of clinical 
benefit should take into account whether the participant is clinically deteriorating and unlikely to 
receive further benefit from continued treatment.
5.4.7
Rationale for Tumor Selection
Part 1
Melanoma, RCC, and NSCLC were selected based on recent literature19,20 and on retrospective 
preliminary analysis from nivolumab studies (see Section 5.4.3 and BMS-986253 IB24), showing 
a high level of serum IL-8 at baseline that persists or increases throughout therapy correlates with 
decreased response and survival in these tumor types, independently from baseline tumor burden. 
These tumor types were selected to explore the activity of neutralizing IL-8 in combination with 
nivolumab in participants resistant to anti-PD-L1 therapy. Additional tumor types (UCC, SCCHN, 
HCC, and CRC) were selected based on reports showing the role of IL-8 in tumor 
progression38,39,40,41,42,43,44 high levels of MDSC,45
 
 IL-8 correlating with outcome,21,23 and suboptimal activity 
of nivolumab as single therapy46 to determine if interfering with IL-8 and MDSC recruitment could 
sensitize these tumors to nivolumab therapy.
Part 2
Part 2 is a double-blind, randomized evaluation of BMS-986253 plus nivolumab plus ipilimumab
versus placebo plus nivolumab plus ipilimumab in participants with melanoma who progressed on 
prior PD-(L)1 therapy. 
 
 
 
 
5.4.8
Rationale for Treatment of Post-PD-(L)1 Melanoma in Part 2
Part 2 is a randomized, double-blind evaluation of BMS-986253 plus nivolumab plus ipilimumab 
vs placebo plus nivolumab plus ipilimumab in participants with melanoma who have progressed 
on anti-PD-(L)1 therapy. Rationale for evaluation of the BMS-986253 plus nivolumab plus 
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ipilimumab is provided in Section 5.4.4. Rationale for selection of melanoma in Part 2 is provided 
in Section 5.4.7. 
Patients with unresectable or metastatic melanoma who have progressed on prior anti-PD-(L)1 
therapy have a poor prognosis. This is a patient population with a high unmet medical need and 
optimal treatment is not well defined. Ipilimumab is approved for the treatment of melanoma in 
the adjuvant and advanced/metastatic settings. In the advanced/metastatic setting, ipilimumab had 
been shown to lead to durable responses and improved OS in combination with nivolumab. 
For melanoma patients whose cancer progressed on anti-PD-1 therapy, addition of ipilimumab to 
anti-PD-(L)1 therapy may lead to meaningful clinical activity. Olson et al performed a prospective 
study evaluating pembrolizumab plus ipilimumab in 70 patients with melanoma that previously 
progressed on anti-PD-(L)1 as the immediate prior therapy. The ORR was 29% by irRECIST and 
the median duration of response was 16.6 months.47 Da Silva et al performed a multicenter, 
retrospective cohort study of 193 patients with metastatic melanoma resistant to anti-PD(L)1 who 
went on to receive ipilimumab plus anti-PD-(L)1 at centers in Australia, Europe, and USA. The 
overall objective response rate to combination treatment with 31% and median OS was 20.4 
months.48
Thus the treatment of patients that have previously progressed on anti-PD(L)1 monotherapy with 
the combination of anti-PD-(L)1 with ipilimumab is an appropriate treatment option supported by 
widely utilized guidelines endorsed by the National Comprehensive Cancer Network (NCCN)49
and the European Society for Medical Oncology (ESMO).50 For patients with BRAF-mutated 
melanoma, the optimal timing of targeted therapy with respect to immunotherapy is not defined 
and may be based on individualized decision making. When these patients are treated with anti-
PD-(L)1 monotherapy therapy prior to targeted therapy, use of targeted therapy or the combination 
of ipilimumab plus anti-PD-1 blockade as next therapy are both considered appropriate options 
supported by guidelines.49
Based on the aforementioned data, the combination of nivolumab and ipilimumab was chosen as 
the control arm in this patient population. Participants with BRAF-mutated melanoma must have 
either been previously treated with BRAF-targeted therapy, not be a candidate for such therapy, or 
declined targeted therapy after having been provided adequate information to make an informed 
decision as part of an individualized decision-making process. To reduce bias, the randomized 
evaluation will be double-blind, and participants in the control arm will receive placebo in place 
of BMS-986253. 
5.4.9
Rationale for Stratification in Part 2
In order to minimize the potential for imbalance of factors that may impact efficacy endpoints, the 
following stratification factors will be used in the Part 2 randomized evaluation: 
 
 and peripheral 
LDH (≤ ULN or > ULN). Higher levels of serum IL-8 correlate with worse prognosis in melanoma 
(Section 5.4.3). 
 
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 Lastly, elevated LDH 
is poor prognostic factor in melanoma patients treated with ICI.51,52,53,54
5.4.10
Rationale for Treatment Duration
Despite recent advances in immunotherapies for the treatment of cancer, the ideal treatment 
duration to achieve and perpetuate good durable response is still an area of ongoing investigation. 
Current clinical data on the time to response suggest that most I-O- naïve patients who show a 
response when treated with nivolumab do so within the first 24 weeks on therapy, but interruption 
of nivolumab after the first year of therapy might be deleterious compared with prolonged therapy 
until 2 years.55
In this study participants are treated with BMS-986253 combined with either nivolumab, or 
nivolumab plus ipilimumab. BMS-986253 is an antibody that blocks the cytokine IL-8, which is 
continuously produced by the tumor and other immune cells. The optimal duration of 
BMS-986253 treatment is unknown, and continuous treatment may be required. This study also 
primarily consists of patients who have progressed on or after anti-PD-1 or anti-PD-L1 therapy, 
and the optimal duration of nivolumab treatment in this setting is also unknown. Ipilimumab will 
be administered for a maximum of 4 doses or 12 weeks. Treatment on this study will be limited to 
3 calendar years.
5.5
Justification for Planned Dose Selection
5.5.1
Rationale for Part 1A Dose Selection of BMS-986253 in Combination 
with Nivolumab.
Based on 
 from the single ascending dose and multiple 
ascending dose studies described in the BMS-986253 IB,24 a combination of a flat dose of 2400 mg 
Q4W BMS-986253 with a flat dose of 480 mg nivolumab Q4W was selected as the starting dose 
for initial testing in this study. 
There are several sources of data which support the choice of a 2400 mg Q4W flat dose of 
BMS-986253 as a rationale and safe starting dose:
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4) Based on the known biology of IL-8, depletion of IL-8 is not expected to exacerbate nivolumab 
immune related AEs. Rather, it is anticipated (and supported by pre-clinical models) that 
depletion of IL-8 may lessen immune suppression of anti-tumor T-cells. 
5.5.2
Rationale for Part 1B Dosing Schedules and Maximum Administered 
Dose
The dosing schedule for each part of Study CA027002 is summarized in Table 7.3-1 and Section 2, 
and the rationale for dose is presented in the following sections.
The rationale for including the option to explore Q2W dosing regimens of BMS-986253 was based 
on preliminary serum-free IL-8 data from the first 3 participants in this study. Based on these data, 
by C2D1 following Q4W dosing, a rise in serum IL-8 was observed, which may be prevented with 
Q2W dosing of BMS-986253. Preliminary safety data demonstrated that BMS-986253 Q2W 
monotherapy as well as the combination of 2400 mg BMS-986253 Q4W and 480 mg nivolumab 
Q4W was tolerable.24
 
 
 
 
The rationale for the maximum administered dose of BMS-986253 was based on interim analysis 
of safety and serum IL-8 data from Part 1 (as described in BMS-986253 IB),24 and PK/
pharmacodynamic modeling. Based on safety data from Cohorts 1A and 1B1 through 1B5, BMS-
986253 plus nivolumab was well tolerated at BMS-986253 2400 mg Q2W + nivolumab 480 mg 
Q4W (Cohort 1B4), and dose-dependent AEs were not identified based on available data. 
Furthermore, dose- and frequency-dependent-free serum IL-8 suppression was observed, with 
robust suppression at 2400 mg Q2W + nivolumab 480 mg Q4W. 
 
 
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Based on the analysis of the totality of data from Part 1 Cohorts 1B1 through 1B6 and Part 1C, the 
BMS-986253 RP2D was selected for Part 2, where the additional clinical benefit of BMS-986253 
in combination with nivolumab and ipilimumab, as compared with nivolumab and ipilimumab 
combination in melanoma patients will be evaluated. 
 
 
 
 
 
Table 5.5.2-1:
Dose and Schedule by Study Part
Part
Dose and Schedule 
BMS-986253
Dose and Schedule 
Nivolumab
Dose and Schedule 
Ipilimumab
Part 1A: Safety 
Evaluation Lead-in
2400 mg Q4Wa
480 mg Q4W
Part 1B: Dose-findingb
1B1
1B2
1B3
1B4 (safety lead-in)
1B5
1B6 (safety lead-in)
2400 mg Q4W
1200 mg Q4W
600 mg Q4W
2400 mg Q2W
1200 mg Q2W
3600 mg Q2W
480 mg Q4W
480 mg Q4W
480 mg Q4W
480 mg Q4W
480 mg Q4W
480 mg Q4W
Part 1C: Safety Triplet 
Combination 
1C1 (safety lead-in)
3600 mq Q2W
1 mg/kg Q3Wc
3 mg/kg Q3W (4 doses)
Part 2: Double-blind 
Randomized Study in 
Melanoma Post PD-1
Cohort 2A
Cohort 2B 
3600 mg Q2W 
(Placebo) Q2W 
1 mg/kg Q3Wc
1 mg/kg Q3Wc
3 mg/kg Q3W (4 doses)
3 mg/kg Q3W (4 doses)
Abbreviations: BMS, Bristol Myers Squibb; QXW, every X weeks.
a If safety is not confirmed at 2400 mg, a lower dose will be evaluated prior to opening the Part 1B: randomized 
dose-finding phase.
b Up to 4 additional dosing regimens may be explored in Part 1B. If any dosing regimen evaluates a higher dose of 
BMS-986253 than previously explored, an initial 4 participant safety-lead with a 28-day DLT period will be 
required.
c After 12 weeks of treatment, nivolumab will be administered 480 mg Q4W.
 
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5.5.3
Rationale for Flat Dosing of BMS-986253
A flat dose (mg) of BMS-986253 will be used in this study instead of a body size-based 
(ie, body weight or body surface area) dose. Therapeutic mAb doses have been routinely 
calculated on a body size basis. This practice assumes that dosing by body size significantly 
reduces variability in therapeutic mAb- exposure.60 However, recent analyses of marketed and 
experimental mAbs have demonstrated that body size-based dosing did not always offer 
advantages over flat dosing in reducing exposure variability. Many mAbs are target-specific with 
a relatively large therapeutic window that increases the tolerability of exposure variability. 
Additionally, participant-specific, disease-specific, and physiologic characteristics often 
contribute to exposure variability, resulting in a generally smaller contribution of body size. 
Therefore, the dosing paradigm for mAbs should be assessed in the context of all of these unique 
characteristics.
With either dosing strategy, bias with respect to exposure is expected to occur in the extremes of 
the body weight distribution. In general, body size-based dosing could result in higher mAb 
concentrations in the heaviest participants (eg, 90th percentile), whereas flat dosing could lead to 
higher mAb concentrations in the lightest participants (eg, 10th percentile). Body weight 
distribution data from a clinical trial database of over 2,500 adults with solid or hematologic 
cancers suggested a log-normal distribution of body weight with median, 10th, and 90th percentiles 
of 78 kg, 56 kg, and 112 kg, respectively.61 To minimize the potential risk of higher exposures in 
the lowest body weight participants, the flat doses of BMS-986253 will be based on a body weight 
of 70 kg.
In addition to the above rationale, flat dosing offers practical advantages over body size-based 
dosing, including a convenient approach with respect to pharmacy preparation and clinical 
administration, and is also more likely to reduce the potential for dosing errors related to body 
size-based calculations. Since the magnitude of the impact of body size on the human PK of 
BMS-986253 is not yet determined, the PK and safety data from the Phase 1/2 study will be 
evaluated to validate the flat dosing approach. If appropriate, based on the totality of the data, the 
Sponsor will consider a revision of the flat dosing strategy. BMS-986253 will be administered 
Q4W. However, the alternate dosing frequencies (with the most frequent dosing frequency of 
Q2W) may be explored based on continuous evaluation of the totality of safety, pharmacodynamic, 
and PK data. 
 
5.5.4
Rationale for Nivolumab Dose Selection
Nivolumab monotherapy has been extensively studied in multiple tumor types, including 
melanoma, NSCLC, RCC, SCCHN, and urothelial carcinoma, using body weight-normalized 
dosing (mg/kg), and has been safely administered at doses up to 10 mg/kg Q2W. Nivolumab is 
currently approved for the treatment of various tumor types with a monotherapy regimen of 
240 mg Q2W, 3 mg/kg Q2W, or 480 mg Q4W across multiple markets.
In addition, nivolumab is approved in combination with ipilimumab or ipilimumab plus 
chemotherapy for the treatment of various cancers with dosing regimen of 1 mg/kg Q3W (in 
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melanoma and HCC), 
 360 mg Q3W or 3 mg/kg Q2W (in 
NSCLC).
In Parts 1A and 1B, given a wide therapeutic window and quantitative clinical pharmacology 
understanding, nivolumab 480 mg Q4W or 360 mg Q3W infused over approximately 30 minutes 
is selected in combination with BMS-986253 to allow for aligning doses frequency in combination 
treatment.
In Part 1C, the safety of BMS-986253 3600 mg Q2W in combination with nivolumab and 
ipilimumab will be evaluated before starting Part 2. Since our primary efficacy evaluation in Part 2 
will be in participants with advanced/metastatic melanoma, we will prioritize evaluation of the 
approved regimen of nivolumab 1 mg/kg Q3W infused over approximately 30 minutes (in 
combination with ipilimumab 3 mg/kg Q3W) for up to 4 combination doses for the first 12 weeks 
of treatment. 
 
 In Part 1C, after the first 12 weeks, the 
dose/frequency of nivolumab will be flat dose, 480 mg Q4W.
For Part 2, we will be using the approved doses of nivolumab and ipilimumab in 
advanced/metastatic melanoma: 
 
 
 
 
 
5.5.5
Rationale for Ipilimumab Dose Selection
Ipilimumab is approved as monotherapy for the treatment of advanced melanoma and adjuvant 
melanoma with 3 mg/kg Q3W for 4 doses and 10 mg/kg Q3W for 4 doses followed by maintenance 
dose, respectively. Ipilimumab 3 mg/kg Q3W (in combination with nivolumab 1 mg/kg Q3W) for 
up to 4 combination doses, followed by nivolumab monotherapy is approved for the treatment of 
melanoma and HCC. Ipilimumab 
 
for up to 4 combination doses, followed by nivolumab monotherapy is approved for the treatment 
of RCC and CRC.
The safety of BMS-986253 3600 mg Q2W in combination with nivolumab and ipilimumab will 
be evaluated in Part 1C before starting Part 2. Since our primary efficacy evaluation in Part 2 will 
be in participants with advanced/metastatic melanoma, we will prioritize evaluation of the 
approved regimen of ipilimumab 3 mg/kg Q3W infused over approximately 30 minutes 
 
 
 
For Part 2, we will be using the approved doses of nivolumab and ipilimumab in 
advanced/metastatic melanoma: 
 
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5.5.6
Rationale for Part 2 Dosing Schedules and Maximum Administered 
Dose/RP2D
6
STUDY POPULATION
For entry into the study, the following criteria MUST be met prior to dosing on Day 1. No 
exceptions will be granted. This study permits the re-enrollment of a participant that has 
discontinued the study as a pretreatment failure. If re-enrolled, the participant must be 
re- consented and meet all inclusion/exclusion criteria.
6.1
Inclusion Criteria
1) Signed Written Informed Consent
a) The participant must sign the ICF prior to the performance of any study-related procedures 
that are not considered part of standard of care.
2) Type of Participant and Target Disease Characteristics
a) Participants must be at least 18 years old and have histologic or cytologic confirmation of 
a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with 
radiographically measurable disease per RECIST v1.1 (Appendix 8) (Medical photos are
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not allowed). 
 
 
 
 
 
 
 
 
 
i)
Participants with lesions in a previously irradiated field as the sole site of measurable 
disease will be permitted to enroll provided the lesion(s) have demonstrated clear 
progression and can be measured accurately. 
b) Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 
or 1 (Appendix 5).
c) The following tumor histologies will be permitted except for participants with CNS 
metastases as the only site of active disease. All participants must have received, and then 
progressed, relapsed, or been intolerant to at least 1 standard treatment regimen in the 
advanced or metastatic setting according to tumor type. Part 1 will include participants with 
RCC, SCCHN, melanoma, UCC, NSCLC, HCC, and CRC. Part 2 will include participants 
with melanoma. Separate inclusion criteria are listed for participants with melanoma in 
Part 1 and Part 2. 
i)
Non-Small Cell Lung Carcinoma (Only Part 1A and Part 1 Cohorts 1B1 through 1B5 
[enrolled through Revised Protocol 03]. Participants with NSCLC will not be allowed 
in Parts 1B6, 
 and 1C as per Protocol Amendment 04).
(1) Not applicable as per Protocol Amendment 04
(2) Not applicable as per Revised Protocol 02
(3) Not applicable as per Protocol Amendment 04
(4) Not applicable as per Revised Protocol 02
(5) Not applicable as per Protocol Amendment 04
(6) Not applicable as per Revised Protocol 03 
(7) Not applicable as per Protocol Amendment 04
(8) Not applicable as per Revised Protocol 03
(9) Not applicable as per Protocol Amendment 04
ii) Renal Cell Carcinoma with a clear cell component.
(1) Not applicable as per Revised Protocol 02
(2) Participants in Part 1: Must have received and progressed/been intolerant of (or not 
be a candidate for) an anti-angiogenic therapy (eg, including but limited to 
bevacizumab, axitinib, cabozantinib, pazopanib, sorafenib, sunitinib and 
tivozanib). 
(3) Not applicable as per Protocol Amendment 04
(4) Not applicable as per Revised Protocol 03
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(5) Participants in Part 1: Must have documented progressive or recurrent disease on 
or within 3 months of discontinuation of anti-PD-(L)1 therapy (administered as 
monotherapy or as part of a combination) as per RECIST 1.1 criteria. 
(a) Prior anti-PD-(L)1 based therapy must be the most recent treatment.
iii) Melanoma in Part 1
(1) Histologically confirmed, unresectable Stage III or Stage IV melanoma, as 
specified in the American Joint Committee on Cancer staging system. 
(a) Participants with ocular or uveal melanoma are ineligible. 
(2) PD-L1 status must be documented if available. 
 
(3) Not applicable as per Revised Protocol 03
(4)
 Both BRAF mutated and wild-type 
participants are permitted in this cohort.
(a) If participant has 
 they must have received (or not be 
a candidate for) BRAF inhibitor treatment, or declined targeted therapy after 
having been provided adequate information to make an informed decision.
(5) Must have documented progressive or recurrent disease on or within 3 months of 
discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as part of 
a combination) as per RECIST 1.1 criteria:
(a) Prior anti-PD-(L)1 based therapy must be the most recent treatment 
iv) Not applicable as per Revised Protocol 02: Expansion Cohort only
v) Not applicable as per Protocol Amendment 04: Triple negative breast cancer
vi) Microsatellite Stable Colorectal cancer (Part 1C only)
(1) Histologically documented, locally advanced, unresectable, or metastatic MSS 
CRC.
(2) Microsatellite instability status (MSI) and/or mismatch repair status must be 
documented. Only MSS or pMMR participants are permitted in this cohort. Note: 
pMMR is defined as expression of MLH1, MSH2, MSH6, and PMS2 by 
immunohistochemistry (IHC) and MSS is defined by the absence of instability in 
microsatellite markers by polymerase chain reaction (PCR) as determined by a 
local laboratory. If the MSI molecular test and mismatch repair IHC test results 
are both available, then both MSS and pMMR will be required for study entry. 
Patients with MSI high or MSI-low or mismatch repair deficiency will not be 
eligible.
(3) Participants must have received and progressed on, or been intolerant to (not 
candidates for) a fluoropyrimidine, oxaliplatin, and irinotecan.
(4) Participants with epidermal growth factor receptor (EGFR)-expressing RAS 
wildtype tumors must have received (or not be a candidate for) EGFR-directed 
therapy (eg, cetuximab).
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vii) Not applicable as per Protocol Amendment 04: Pancreatic ductal adenocarcinoma
viii)
Hepatocellular carcinoma (Part 1C only)
(1) Participants cannot be eligible for liver transplant at the time of inclusion. For 
participants who progressed after locoregional therapy, locoregional therapy for 
HCC must be completed at least 4 weeks prior to the baseline scan. All acute toxic 
effects of any prior local treatment must have resolved to National Cancer Institute 
(NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade 
> 1 or been deemed irreversible. 
(2) Participants may either have histologically or radiologically confirmed HCC. 
Participants with a radiological diagnosis may be enrolled for screening in the study 
but histological confirmation is mandatory prior to initiation of study therapy.
(3) Participants must have received and progressed/been intolerant of (or not be a 
candidate for) at least 1 line of therapy, including anti-PD-(L)1-based therapy.
(a) Prior anti-PD-(L)1-based therapy must be the most recent treatment 
(4) Must be Child-Pugh Class A (6 points or less) (Appendix 9);
(5) Must have results of testing for hepatitis B surface antigen, hepatitis B surface 
antibody, hepatitis B core antibody, hepatitis B deoxyribonucleic acid (DNA) PCR, 
hepatitis C antibody and hepatitis C ribonucleic acid (RNA) PCR;
(6) For participants with hepatitis B infection, hepatitis B DNA viral load must be 
< 500 IU/mL and the participant must be on anti-viral therapy per institutional 
guidelines.
(a) If the participant is receiving anti-viral therapy, the anti-viral therapy must have 
been started at least 4 weeks prior to screening. 
(7) Participants with hepatitis B infection cannot have a co-infection with hepatitis C 
or hepatitis D (must obtain hepatitis D antibody testing).
(8) Participants with active hepatitis C virus (HCV), infection, as defined by any 
detectable HCV RNA and positive antibody titer, can be enrolled provided they are 
on anti-viral therapy. Participants with resolved HCV infection, as evidenced by 
undetectable HCV RNA and positive antibody titer, can be enrolled. Participants 
on antiviral therapy for HCV should continue treatment during the study. 
Participants with active HCV who are not on antiviral therapy at screening cannot 
be enrolled in the study.
(a) If the participant is receiving anti-viral therapy, the anti-viral therapy must have 
been started at least 4 weeks prior to screening.
ix) Other tumor types could be considered at the time of expansion based on scientific 
rationale and be added to the study by subsequent amendment.
x) Urothelial carcinoma (UCC)
(1) Histologically confirmed, advanced (ie, unresectable or metastatic) transitional cell 
carcinoma of the urothelium involving the bladder, urethra, ureter, or renal pelvis. 
(2) Not applicable as per Revised Protocol 02 
(3) PD-L1 status must be documented if available. 
 
 
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(4) Participants must have received and progressed/been intolerant of (or not be a 
candidate for) standard of care chemotherapy (eg, platinum-based regimen) in the 
recurrent or metastatic setting.
(5) Not applicable as per Revised Protocol 03
(6) Must have documented progressive or recurrent disease on or within 3 months of 
discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as part of 
a combination) as per RECIST 1.1 criteria.
(a) Prior anti-PD-(L)1 based therapy must be the most recent treatment.
xi) Squamous Cell Carcinoma of the Head and Neck (SCCHN) (Only Part 1A and Part 
1B. Participants with SCCHN will not be allowed in Part 1C.)
(1) Histologically confirmed, advanced (ie, unresectable or metastatic) squamous cell 
carcinoma of the Oral Cavity, Pharynx, Larynx.
(2) Not applicable as per Revised Protocol 02
(3) PD-L1 status must be documented if available. 
 
 
(4) Participants must have received and progressed/been intolerant of (or not be a 
candidate for) standard of care chemotherapy (eg, platinum-based regimen) in the 
recurrent or metastatic setting.
(5) For SCC of the oropharynx, HPV status must be documented. Both HPV-positive 
or HPV-negative participants are permitted in this cohort. 
(6) Not applicable as per Revised Protocol 03
(7) Must have documented progressive or recurrent disease on or within 3 months of 
discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as part of 
a combination) as per RECIST 1.1 criteria.
(a) Prior anti-PD-(L)1 based therapy must be the most recent treatment.
xii)Melanoma in Part 2
(1) Histologically confirmed, unresectable Stage III or Stage IV melanoma, as 
specified in the American Joint Committee on Cancer staging system. 
(a) Participants with ocular or uveal melanoma are ineligible. 
(2) PD-L1 status must be documented if available. PD-L1 status will also be re-tested 
using tissue acquired from the pre-treatment biopsy (if provided).
(3)
 Both BRAF-mutated and wild-type 
participants are permitted in this cohort.
(a) If participant has 
 they must have received (or not be 
a candidate for) BRAF inhibitor treatment, or declined targeted therapy after 
having been provided adequate information to make an informed decision.
(4) Must have documented progressive or recurrent disease on or after discontinuation 
of anti-PD-(L)1 therapy (administered as monotherapy or as part of a combination) 
as per RECIST 1.1 criteria:
(a) Prior anti-PD-(L)1-based therapy (with at least 6 weeks of exposure) must be 
the most recent treatment. If the participant received palliative radiation after 
discontinuation of anti-PD-(L)1 therapy: 
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(i) The participant meets this criteria if the documented progressive/recurrent 
disease included sites outside the radiation field. 
(ii) The participant does not meet this criteria if all the sites of 
progressive/recurrent disease were limited to the field that was subsequently 
irradiated. 
(b) Participants who received anti-PD-(L)1 in the advanced/metastatic setting, 
must have documented progressive or recurrent disease on or within 3 months 
of discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as 
part of a combination) as per RECIST 1.1 criteria.
(c) Participants who received anti-PD-(L)1 in the adjuvant setting must have 
documented progressive or recurrent disease on or within 6 months of 
discontinuation of anti-PD-(L)1 therapy (administered as monotherapy or as 
part of a combination) as per RECIST 1.1 criteria. 
(d) Confirmation of radiographic progression on prior anti-PD-(L)1 therapy is 
required with a scan confirming progression at least 4 weeks after the initial 
progression. Screening scans can be used as the confirmation of progression.
(5) Must not have received prior anti-CTLA-4 therapy.
3) Physical and Laboratory Test Findings
Participants must have:
a) Baseline 
 (only required for Part 1A and Part 1B)
b) Adequate hematologic function as defined by the following:
i)
Neutrophils ≥1,500 L
ii) Platelets ≥80 × 103/L (transfusion to achieve this level is not permitted within 
2 weeks of first study treatment administration)
iii) Hemoglobin ≥8 g/dL (transfusion to achieve this level is not permitted within 2 weeks 
of first study treatment administration)
c) Adequate hepatic function
i)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper 
limit of normal (ULN)
ii) Total bilirubin ≤1.5× ULN (except participants with Gilbert’s Syndrome who must 
have normal direct bilirubin)
iii) Specifically for participants with HCC:
(1) Prothrombin time-international normalized ratio ≤2.3 or prothrombin time 
≤6 seconds above control
(2) Adequate hepatic function as documented by
(a) Serum albumin 2.8 g/dL (transfusion to meet this requirement is not 
permitted)
(b) Total bilirubin 3 mg/dL
(c) AST and ALT 5× the institutional ULN
d) Normal thyroid function or stable on hormone supplementation per investigator assessment
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e) Serum creatinine ≤1.5× ULN or creatinine clearance (CrCl) ≥ 40 mL/min (measured using 
the Cockcroft-Gault formula below):
Female CrCl = [(140 - age in years) × weight in kg × 0.85]/(72 × serum creatinine in 
mg/dL);
Male CrCl = [(140 - age in years) × weight in kg]/(72 × serum creatinine in mg/dL);
f)
Ability to comply with treatment, PK and pharmacodynamic sample collection, and 
required study follow-up periods.
4) Age and Reproductive Status
a) Males and females, aged at least 18 years old.
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) within 24 hours prior to the start of study treatment. An extension up to 72 
hours prior to the start of study treatment is permissible in situations where results cannot 
be obtained within the standard 24-hour window. Additional requirements for pregnancy 
testing during and after study intervention are located in Section 2, Schedule of 
assessments.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception (Appendix 4) 
and included in the ICF. WOCBP are permitted to use hormonal contraception methods (as 
described in Appendix 4).
e) WOCBP who are continuously not heterosexually active are also exempt from 
contraceptive requirements but should still undergo pregnancy testing as described in this 
section.
f)
Not applicable as per Protocol Amendment 04 
g) Not applicable as per Revised Protocol 03
h) Women who are not of childbearing potential are exempt from contraceptive requirements.
i)
Women participants must have documented proof that they are not of childbearing 
potential.
j)
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
k) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:
(1) Is not a WOCBP
OR
(2) Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), with low user dependency, as described in Appendix 
4 during the intervention period and for at least 5 months and agrees not to donate 
eggs (ova, oocytes) for the purpose of reproduction for the same time period
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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. 
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) Target Disease Exclusions
a) Participants with primary CNS malignancies, or tumors with CNS metastases as the only 
site of disease, will be excluded. Participants with controlled brain metastases; however, 
will be allowed to enroll. Controlled brain metastases are defined as no radiographic 
progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks 
of observation if no intervention is clinically indicated), and no longer taking steroids for 
at least 2 weeks prior to first dose of study treatment, and with no new or progressive 
neurological signs and symptoms.
b) Participants with leptomeningeal metastases will be excluded.
2) Prohibited Treatments
a) Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer 
therapy and initiation of study therapy.
b) Non-cytotoxic agents, unless at least 4 weeks or 5 half-lives (whichever is shorter) have 
elapsed from the last dose of prior anti-cancer therapy and the initiation of study therapy. 
If 5 half-lives are shorter than 4 weeks, agreement with the Sponsor/Medical Monitor is 
mandatory.
c) Prior participation in an anti-IL-8 clinical study.
3) Medical History and Concurrent Diseases
a) Participants with concomitant second malignancies (except adequately treated 
non-melanomas skin cancers or in situ urothelial, breast, or cervical cancers) are excluded 
unless a complete remission was achieved at least 2 years prior to study entry, and no 
additional therapy is required or anticipated to be required during the study period.
b) Participants with other active malignancy requiring concurrent intervention
c) Prior organ allograft
d) Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless 
the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
i)
Any active neuropathy > Grade 2 (NCI CTCAE v4.03)
e) Participants with the following:
i)
Active, known, or suspected autoimmune disease:
(1) Participants with well controlled asthma and/or mild allergic rhinitis (seasonal 
allergies) are eligible
(2) Participants with the following disease conditions are also eligible:
(a) Vitiligo
(b) Type 1 diabetes mellitus
(c) Residual hypothyroidism due to autoimmune condition only requiring hormone 
replacement
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(d) Euthyroid participants with a history of Grave’s disease (participants with 
suspected autoimmune thyroid disorders must be negative for thyroglobulin and 
thyroid peroxidase antibodies and thyroid stimulating immunoglobulin (Ig) 
prior to the first dose of study treatment)
(e) Psoriasis not requiring systemic treatment, or conditions not expected to recur 
in the absence of an external trigger are permitted to enroll
ii) History of life-threatening toxicity related to prior immune therapy or any toxicity that 
resulted in permanent discontinuation from prior immune therapy (eg, anti-CTLA-4 or 
anti-PD-(L)1 treatment or any other mAb or drug specifically targeting T-cell 
co-stimulation or immune checkpoint pathways) except those that are unlikely to 
re-occur with standard countermeasures (eg, hormone replacement after adrenal crisis).
iii) Conditions requiring systemic treatment with either corticosteroids > 10 mg daily 
prednisone equivalents or other immunosuppressive medications within 14 days of 
study treatment administration. Participants requiring adrenal replacement steroid 
doses >10 mg daily prednisone equivalent in the absence of active autoimmune disease 
are allowed.
(1) Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating 
study treatment is permitted.
iv) Uncontrolled or significant cardiovascular disease including, but not limited, to any of 
the following:
(1) Myocardial infarction or stroke/transient ischemic attack within the past 6 months
(2) Uncontrolled angina within the past 3 months
(3) Any history of clinically significant arrhythmias (such as ventricular tachycardia, 
ventricular fibrillation, or torsade de pointes)
(4) History of other clinically significant heart disease (eg, cardiomyopathy, congestive 
heart failure with New York Heart Association functional classification III to IV 
[Appendix 10], pericarditis, or significant pericardial effusion)
(5) History of myocarditis, regardless of etiology
(6) Cardiovascular disease-related requirement for daily supplemental oxygen therapy;
 
v) History of chronic hepatitis as evidenced by the following:
(1) Positive test for hepatitis B surface antigen
(2) Positive test for qualitative hepatitis C viral load by PCR
(a) Participants with positive hepatitis C antibody and negative quantitative 
hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection 
is not an exclusion criterion.
(b) Additional testing or substitute testing per institutional guidelines to rule out 
infection is permitted.
(3) Specific exclusions for participants with HCC:
(a) Active coinfection with both hepatitis B and C
(b) Hepatitis D infection in participants with hepatitis B
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(c) Clinically significant ascites (prior ascites that required treatment and require 
on-going prophylaxis OR current ascites requiring treatment)
(4) Presence of portal hypertension with history of bleeding due to esophageal or 
gastric varices within 6 months prior to randomization
(5) Episodes of hepatic encephalopathy (≥ Grade 2) within 12 months prior to 
randomization
vi) Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal 
therapy ≤7 days prior to the first dose of study treatment (except for viral infections 
that are presumed to be associated with the underlying tumor type required for study
entry).
vii)Known history of testing positive for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at 
sites where mandated by local requirements.
viii)
Any major surgery within 4 weeks of the first dose of study treatment. Participants
must have recovered from the effects of major surgery or significant traumatic injury 
at least 14 days before the first dose of study treatment.
ix) Receipt of a live/attenuated vaccine within 30 days of first treatment
(1) The use of inactivated seasonal influenza vaccines, eg, Fluzone, will be permitted 
on study without restriction.
x) Receipt of packed red blood cells or platelet transfusion within 2 weeks of the first dose 
of study treatment
xi) Any known or underlying medical, psychiatric condition and/or social reason that, in 
the opinion of the investigator or Sponsor, could make the administration of study 
treatment hazardous to the participants or could adversely affect the ability of the 
participant to comply with or tolerate the study.
f)
WOCBP who are pregnant or breastfeeding.
g) Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 
days for severe/critical illness prior to C1D1. 
i)
Acute symptoms must have resolved and based on investigator assessment in 
consultation with the Medical Monitor, there are no sequelae that would place the 
participant at a higher risk of receiving study treatment.
h) Previous SARS-CoV-2 vaccine within 14 days of C1D1.
i)
History of hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome 
(MAS) 
j)
A history of disease related to chronic Epstein-Barr virus (EBV) infection including post-
transplant lymphoproliferative disorders, Hodgkin’s lymphoma, extranodal natural killer 
(NK)/T-cell lymphoma (nasal type), Burkitt’s lymphoma, and chronic active EBV 
infection. 
4) Allergies and Adverse Drug Reaction
a) History of allergy to study treatment(s), combination of study treatments or any of its 
components
b) History of severe hypersensitivity reaction to any mAb
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5) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated (Note: under certain specific 
circumstances and only in countries where local regulation permit a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply and BMS approval is required).
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
There are no lifestyle restrictions applicable for this study given that the participants will receive 
the study investigational products (IPs) IV.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently randomized/entered in the study/included in the analysis population. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, as applicable, and to respond to queries from regulatory authorities. 
Minimal information includes date of consent, demography, screen failure details, eligibility 
criteria, and any serious AEs.
6.4.1
Retesting During Screening or Lead-In Period
This study permits the re-enrollment of a participant that has discontinued the study as a 
pretreatment failure (ie, participant has not been randomized/has not been treated). If re-enrolled, 
the participant must be re-consented.
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 2-2, may be repeated in an 
effort to find all possible well-qualified participants. Consultation with the Medical Monitor may 
be needed to identify whether repeat testing of any particular parameter is clinically relevant.
Testing for asymptomatic SARS-CoV-2 infection by RT-PCR or viral antigen is not required. 
However, some participants may develop suspected or confirmed symptomatic SARS-CoV-2 
infection, or be discovered to have asymptomatic SARS-CoV-2 infection during the screening 
period. In such cases, subjects may be considered eligible for the study after meeting all 
inclusion/exclusion criteria related to active infection, and after meeting the following criteria: 
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
At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive RT-PCR or viral antigen test result, and

At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and

Acute symptoms (eg, cough, shortness of breath) have resolved, and 

In the opinion of the investigator, there are no SARS-CoV-2 infection sequelae that may place 
the participant at a higher risk of receiving investigational treatment.
In the instance of a SARS-CoV-2 infection during screening, the screening period may be extended 
beyond the protocol-specified timeframe with MM approval.
Any screening tests already performed which could potentially be affected by the SARS-CoV-2 
infection or its complications on an individual basis and agreed upon with the MM (eg, safety 
laboratory tests, SpO2, chest CT scan) should be repeated.
7
TREATMENT
7.1
Treatments Administered
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 only the Investigational [Medicinal] Product (IP/IMP) and consist of the 
following:

BMS-986253

Nivolumab

Ipilimumab

Placebo for BMS-986253 (
 sodium chloride for injection or 
 dextrose for injection)
An IP, also known as IMP in some regions, is defined as a pharmaceutical form of an active 
substance or placebo being tested or used as a reference in a clinical study, including products 
already with a marketing authorization but used or assembled (formulated or packaged) differently 
than the authorized form, or used for an unauthorized indication, or when used to gain further 
information about the authorized form.
All drugs used in this study qualify as IPs, as per previous text, and their description and storage 
information are described in Table 7.1-1.
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, are considered as 
Non-investigational [Medicinal] Product (Non-IP/Non-IMP).
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Table 7.1-1:
Study Treatments for CA027002
Product 
Description/
Class and Dosage 
Form
Potency
IP/
Non-IMP
Blinded or 
Open Label
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986253 
Injection
IP
Open labela
Vial
Refer to the label on
container and/or pharmacy 
manual
BMS-986253 
Injection
IP
Open labela
Vial
Refer to the label on
container and/or pharmacy 
manual
Nivolumab 
(BMS-936558) 
solution for injection
IP
Open labela
Vial
Refer to the label on
container and/or pharmacy 
manual
Ipilimumab
solution for injection
IP
Open labela
Vial 
Refer to the label on
container and/or pharmacy 
manual
Ipilimumab
solution for injection
IP
Open labela
Vial 
Refer to the label on
container and/or pharmacy 
manual
Normal saline
solution for 
injectionb
IP
Open label
Various 
(local 
commercial 
product)
Refer to the label on
container 
Dextrose 
solution for 
injectionb
IP
Open label
Various 
(local 
commercial 
product)
Refer to the label on
container 
Abbreviation: IP, Investigational Product.
a The term “open label” refers to the medication as it is upon receipt at the pharmacy. In Part 2 of this trial, BMS-
986253/placebo will be prepared, dispensed, and administered in a double-blinded fashion.
b This will be sourced by the investigative sites if permitted by local regulations.
7.2
Handling and Dispensing
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and BMS should be contacted immediately.
IP documentation must be maintained that includes all processes required to ensure drug is 
accurately administered. This includes documentation of drug storage, administration and, as 
applicable, storage temperatures, reconstitution, and use of required processes (eg, required 
diluents, administration sets).
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Infusion-related supplies (eg, IV bags, in-line filters, and 
 sodium chloride solution) will not 
be supplied by the Sponsor and should be purchased locally if permitted by local regulations.
Placebo in Part 2 must be handled/dispensed/infused in an identical fashion as BMS-986253 in 
order to maintain the blind.
Please refer to the current version of the IB and/or pharmacy manual for complete storage, 
handling, dispensing, and infusion information for BMS-986253, placebo, nivolumab, and 
ipilimumab.
7.3
Schedule of Dose for Each Investigational Product
The dosing schedule for each IP is detailed below in Table 7.3-1 and Section 2 for all study parts. 
For BMS-986253, nivolumab, and ipilimumab, participants may be dosed within a ± 3-day 
window. Premedications are not recommended on Cycle 1 Day 1. Additional information can be 
found in the pharmacy manual.
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Table 7.3-1:
Dose, Frequency, Infusion Time, and Sequence of IPs
Cohort
BMS-986253 
Dose and 
Frequency
BMS-986253 
Infusion Time 
(min
Nivolumab
Dose and 
Frequency
Nivolumab
Infusion Time 
(min
Ipilimumab
Dose and 
Frequency
Ipilimumab
Infusion Time 
(min)
Order of Drug 
Administration
Part 1
1Aa
2400 mg Q4W
480 mg Q4W
30 min
NA
1B1a
2400 mg Q4W
480 mg Q4W
30 min
NA
1B2a
1200 mg Q4W
480 mg Q4W
30 min
NA
1B3a
600 mg Q4W
480 mg Q4W
30 min
NA
1B4
2400 mg Q2W
480 mg Q4W
30 min
NA
1B5
1200 mg Q2W
480 mg Q4W
30 min
NA
1B6
3600 mg Q2W
480 mg Q4W
30 min
NA
1C1
3600 mg Q2W
1 mg/kg Q3W
(x 4 doses), 
followed by 
480 mg Q4W
30 min
3 mg/kg Q3W 
(x 4 doses)
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Table 7.3-1:
Dose, Frequency, Infusion Time, and Sequence of IPs
Cohort
BMS-986253 
Dose and 
Frequency
BMS-986253 
Infusion Time 
(min)h
Nivolumab
Dose and 
Frequency
Nivolumab
Infusion Time 
(min)h
Ipilimumab
Dose and 
Frequency
Ipilimumab
Infusion Time 
(min)h
Order of Drug 
Administration
Part 2
2A
3600 mg Q2W 
1 mg/kg Q3Wg
(x 4 doses), 
followed by 
480 mg Q4W
3 mg/kg Q3W 
(x 4 doses)
2B
Placebo 
Q2W 
1 mg/kg Q3Wg
(x 4 doses) 
followed by 
480 mg Q4W
3 mg/kg Q3W 
(x 4 doses)
Abbreviations: 
 C, Cycle; D, Day; Ipi, ipilimumab; Nivo, nivolumab; QXW, every X weeks.
a
 
 
 
 
 
 
 
 
 
 
 
 
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7.4
Method of Treatment Assignment and Stratification
During the pre-screening visit, the investigative site will enroll the participant in IRT for 
assignment of a unique 5-digit participant number designated by BMS. Enrolled participants, 
including those not dosed, will be assigned sequential participant numbers starting with 
 
 The participant identifier number (PID) will ultimately be 
comprised of the site number and participant number. For example, the first participant screened 
(ie, enrolled) at site number 1, will have a PID of 
. To distinguish Part 1 and Part 2 
participants, the first digit of the participant number will always be a 2 for Part 2 participants 
 
 Once it is determined that the participant meets the eligibility criteria following the 
screening visit, the investigative site will utilize the IRT to centrally assign the participant into the 
open dose panel (Part 1) or blinded treatment arm (Part 2). Study treatment will be dispensed at 
the study visits as listed in Schedule of Activities (Section 2).
Part 1
provides a summary of treatment assignment in Part 1. The safety evaluation lead-in 
(Part 1A) will start with a cohort of participants dosed at 2400 mg of BMS-986253 combined with 
480 mg of nivolumab Q4W. 
 
After the review of clinical safety 
assessment of the first 4 participants, the DLT, and the totality of available data, up to 
approximately 
additional participants will be enrolled in the dose-finding phase (Part 1B). 
Participants will be randomly assigned in an approximately 1:1:1 ratio to Cohorts 1B1, 1B2, and 
1B3. Randomization will be performed using an equal randomization with each cohort capped at 
approximately 
participants, such that corresponding entries for capped cohort in the 
randomization list will be skipped.
In the event that the safety lead-in evaluation recommends to evaluate a lower dose of 
BMS-986253 (1200 mg) prior to start of the randomized dose-finding phase (Part 1B), a cohort of 
4 participants will be treated in combination with 480 mg of nivolumab. If there are no safety 
concerns after the clinical safety assessment, then participants will be randomized in a similar 
fashion in approximately 1:1 ratio to Cohorts 1B2 and 1B3.
If PK, pharmacodynamic, and/or safety analyses indicate further assessment of a dosing regimen 
is not warranted and/or assessment of additional dosing regimens is indicated, then randomization 
will be stopped, and subsequent participants will be assigned sequentially to dosing regimens 
available at that time. If any dosing regimen evaluates a higher dose of BMS-986253 than 
previously explored, an initial 4-participant safety lead-in with a 28-day DLT period will be 
required. Approximately 
participants will be dosed in the dosing regimen(s) of interest. 
Additional exploration of a specific dosing regimen may be warranted, in which case a maximum 
of approximately 
additional participants will be assigned to a dosing regimen of interest in Part 
1B. A maximum of approximately 
participants will be dosed in Part 1B.
Part 1C is a safety evaluation of BMS-986253 in combination with nivolumab and ipilimumab. 
Part 1C will begin once the DLT period is completed for Cohort 1B6 (BMS-986253 3600 mg Q2W 
+ nivolumab 480 mg Q4W), and will enroll simultaneously with Part 1B. In Part 1C, participants 
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will be enrolled onto Cohort 1C1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Part 2
Part 2 will begin after determination of the RP2D from Part 1 and generating safety data on the 
triplet combination of BMS-986253 plus nivolumab plus ipilimumab in Part 1C. Part 2 is a double-
blind randomized evaluation of BMS-986253 plus nivolumab plus ipilimumab versus placebo plus 
nivolumab plus ipilimumab and will be conducted to evaluate the efficacy of BMS-986253 in 
participants who are refractory to anti-PD-(L)1 therapy. 
IRT will be used to track the enrollment number.
Once assigned a subject ID in IRT, participants that have met all eligibility criteria will be 
randomized through IRT (up to 3 days prior to C1D1). The following information is required prior 
to participant randomization:

Participant subject ID

Date of birth

Gender

Screening serum IL-8 level 
 

Screening LDH 
Participants will be randomized in a 1:1 ratio to treatment and control arms. Three stratification 
factors will be used during randomization: screening 
 
 
and screening LDH (≤ ULN or > ULN). Screening serum IL-8 data will be transferred directly 
from the analyzing laboratory to IRT. BRAF status and screening LDH must be entered in eCRF 
by the site. 
Approximately 
participants will be randomized in Part 2.
The exact procedures for using the IRT will be detailed in the IRT manual.
7.5
Blinding
7.5.1
Part 1
Part 1 of this study is open label, with randomized and non-randomized portions. Data emerging 
from this portion of the study may be necessary to inform timely decisions for adjusting procedures 
in subsequent portions of the study, including early termination of the study, requiring access to 
IRT treatment codes in either the randomized or non-randomized portions of the study. 
Additionally, treatment assignments may facilitate optimization of the bioanalytical analysis of 
samples.
Designated members of the study team, as well as the Bioanalytical and/or clinical pharmacology 
groups of the Sponsor can access IRT treatment codes prior to the formal locking of the study 
database for these purposes. This access to the treatment codes will not impact the data integrity 
of the study.
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7.5.2
Part 2
Part 2 of the study will be conducted as a double-blind study. The Sponsor, participants, 
investigator, and site staff will be blinded to the study therapy administered. Each investigative 
site must assign an unblinded pharmacist/designee, and an unblinded site monitor will be assigned 
by Sponsor to provide oversight of drug supply and other unblinded study documentation.
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 
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 via the IRT system. For 
information on how to unblind in an emergency, consult the IRT manual.
In cases of accidental unblinding, contact the BMS Study Director/Medical Monitor (or designee) 
and ensure every attempt is made to preserve the blind.
Any request to unblind a participant for non-emergency purposes should be discussed with the 
BMS Study Director/Medical Monitor (or designee).
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 
study director.
Designated staff of Bristol-Myers Squibb Company may be unblinded prior to database lock to 
facilitate the bioanalytical analysis of pharmacokinetic samples and immunogenicity. 
Bioanalytical scientists in the Bioanalytical Sciences department of Bristol-Myers Squibb 
Company (or a designee in the external central bioanalytical laboratory) may be unblinded to (may 
obtain) the randomized treatment assignments in order to minimize unnecessary bioanalytical 
analysis of samples.
If a participant is assessed by the investigator to have disease progression, and unblinding is 
considered necessary to inform the appropriate subsequent anti-cancer therapy, the study treatment 
assignment for the participant can be obtained by the investigator through IRT for non-emergency 
unblinding. The investigator should follow the procedures outlined in the IRT manual to obtain 
the participant’s study treatment assignment. The BMS central study team (including but not 
limited to clinical, statistics, data management) will remain blinded to treatment assignment.
The study will remain blinded until the database lock for 
as described 
in the statistical analysis plan. If an interim analysis is conducted, the Sponsor may be unblinded 
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to the results after accrual to the study has completed and if the primary endpoint is met (as per 
Section 10).
Once the database lock for the final analysis is completed, the Sponsor and Investigators will be 
unblinded to treatment assignments; participants on the control arm will no longer receive placebo 
and will no longer have study visits on Day 15 of each cycle. Similarly, if BMS-986253 is 
discontinued for any participants (in accordance with Sections 7.6.1, 7.6.4, or 8.1), they will no 
longer have study visits on Day 15 of each cycle.
7.6
Dosage Modification
 
 
7.6.1
Dose-limiting Toxicities
DLTs will be defined based on the incidence, intensity, and duration of AEs that are possibly 
related to study treatment. The DLT period will be 4 weeks (28 days). Any toxicities that occur 
beyond the DLT period will be accounted for in making final dose level decisions.
Participants that experience a DLT or are discontinued due to a DLT in the 4-week combination 
treatment DLT period, will be considered as DLT-evaluable participants for the safety evaluation 
period. Participants who withdraw from the study during the DLT evaluation period, for reasons 
other than a DLT, will not be considered as DLT-evaluable participants and may be replaced with 
a new participant at the same dose level. All participants who receive treatment will be included 
in the evaluation, regardless of whether they are DLT evaluable or not.
The incidence of DLT(s) during the 4-week DLT evaluation period will be used in the dose 
decisions for rest of the study, including in the dose-finding phase to define the RP2D or MTD. 
AEs occurring after the DLT period will be considered for the purposes of defining the RP2D upon 
agreement between the Sponsor, Medical Monitor, and investigators.
Participants experiencing a DLT will not be re-treated with study treatment, and will enter the 
safety follow-up period of the study, unless the investigator determines that one of the agents must 
be discontinued due to a DLT attributed to that agent alone.
AEs will be graded according to the NCI CTCAE v4.03.
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7.6.2
Management Algorithms for Immuno-oncology Agents
I-O agents are associated with irAEs that can differ in severity and duration from AEs caused by 
other therapeutic classes. BMS-986253, nivolumab, and ipilimumab are considered I-O agents in 
this protocol. Early recognition and management of irAEs associated with I-O agents may mitigate 
severe toxicity. Management algorithms have been developed from extensive experience with 
nivolumab to assist investigators in assessing and managing the following groups of irAEs:

Gastrointestinal

Renal

Pulmonary

Hepatic

Endocrinopathies
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
Skin

Neurological

Myocarditis
The clinical nature of AEs noted with BMS-986253 will determine the role of the algorithms for 
use in toxicities related to its use in this study. The algorithms recommended for the management 
of irAEs in this protocol are in Appendix 6.
7.6.3
Dose Delays Due to Toxicity
Dose delay criteria apply for all drug-related AEs, regardless of whether the event is attributed to 
BMS-986253 (or placebo), nivolumab, or ipilimumab. Delay administration of all study drugs if 
any of the delay criteria listed below are met. 

Potential DLTs, until DLT relatedness is defined.

Select AEs and laboratory abnormalities:

≥Grade 2 pneumonitis.

≥Grade 2 abnormality in AST, ALT, or total bilirubin.

≥Grade 2 creatinine.

≥Grade 2 diarrhea or colitis.

≥Grade 2 neurological AE.

AE, laboratory abnormality, or concurrent illness that, in the judgment of the investigator, 
warrants delaying study treatment administration.

Confirmed SARS-CoV-2 infection.
For participants who require delay, re-evaluate weekly, or more frequently, if clinically indicated 
and resume dosing when criteria to resume treatment are met (see Section 7.6.4). Continue tumor 
assessments per protocol even if dosing is delayed.
Criteria for participants who are required to permanently discontinue study treatments is listed in 
Section 8.1. Participants not meeting guidelines for permanent discontinuation will be permitted 
to resume therapy based on the criteria specified below in Section 7.6.4. Participants eligible to 
resume study therapy will resume study therapy at the nominal treatment visit following their last 
received study medication dose.
The end of cycle tumor assessments, such as CT, MRI, or positive emission tomography (PET), 
will continue on an every 8 weeks (Q8W) schedule relative to the participant’s first dose, 
regardless of any treatment delay incurred.
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7.6.3.1
Criteria for Dose Delay Secondary to Changes in AST or ALT for 
Participants with HCC
Participants with HCC who experience the following must have the study drug delayed:

If a participant has a baseline AST or ALT that is within normal limits, delay dosing for 
drug-related > Grade 2 toxicity (2 grade shift). If a participant has baseline AST or ALT within 
the Grade 1 toxicity range, delay dosing for drug-related > Grade 3 toxicity (2 grade shift)

If a participant has baseline AST or ALT within the Grade 2 toxicity range, delay dosing for a 
2-fold drug-related increase in AST or ALT or for AST or ALT values 8× ULN (whichever is 
lower)

It is recommended to monitor elevations in AST or ALT approximately every 3 days until 
levels peak and begin to decline. Dosing of study drugs can be resumed where criteria to 
resume treatment are met (Section 7.6.4).
7.6.3.2
Protocol-Specific Recommendation for Management of Hepatic Events 
in HCC Participants
The algorithms recommended for the management of irAEs in this protocol are in Appendix 6. 
Protocol-specific recommendation for the management of hepatic events in HCC participants are 
as follows:

Dose delay criteria for hepatic events are outlined in Section 7.6.3.1. If AST or ALT levels do 
not improve with a dose delay of 3 to 5 days, or if the levels worsen, steroid therapy should be 
initiated at 0.5 mg/kg/day to 2 mg/kg/day methylprednisolone or oral equivalent

For ALT or AST levels > 8× ULN, steroid therapy should be initiated promptly at 1 mg/kg/day 
to 2 mg/kg/day methylprednisolone IV, intramuscularly, or oral equivalent

For all participants receiving steroid treatment for hepatic events, the BMS Medical Monitor 
should be consulted within 24 hours after initiation of steroids. Gastroenterology consult is 
recommended

If AST or ALT levels do not improve within 3 to 5 days after the start of steroid therapy, or 
the levels worsen after the start of steroid therapy, discussion with the BMS Medical Monitor 
regarding the possibility of adding mycophenolate mofetil 1 g twice daily should occur

Tapering of steroids can start once AST or ALT levels have declined by 1 CTCAE grade. 
Steroids should be tapered slowly, over no less than 1 month

As outlined in Section 7.6.4, study therapy may resume when AST or ALT have returned to 
Grade 1 or baseline unless the AE meets the criteria for permanent discontinuation 
(Section 8.2). The BMS Medical Monitor must be consulted prior to resuming study treatment 
for all participants who required steroid intervention.
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7.6.4
Criteria to Resume Treatment
Participants may resume treatment with study drug if they have completed AE management (ie, 
corticosteroid taper) or are on ≤ 10 mg daily prednisone or equivalent and meet the requirements 
per described below.
Prior to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks, the Medical 
Monitor (or designee) must be consulted. Continue tumor assessments per protocol even if dosing 
is delayed. Continue periodic study visits to assess safety and laboratory studies weekly or more 
frequently if clinically indicated during such dosing delays.
When criteria to resume treatment for nivolumab, ipilimumab, and BMS-986253 (or placebo) are 
met, resume all study drugs unless the investigator determines that one of the agents must be 
discontinued due to toxicity attributed to that agent alone.
Subsequent dosing with study therapy may resume once drug-related non-DLT AEs resolve to 
Grade 1 or baseline for the drugs being resumed.
Participants experiencing AEs not meeting criteria for permanent discontinuation for the drugs 
being resumed as outlined in Section 8.1 may resume treatment with study medication under the 
following criteria:

Participants may resume treatment with study treatment when the drug-related AE(s) resolve 
to Grade 1 or baseline value, with the following exceptions:

Participants may resume treatment in the presence of Grade 2 fatigue.

Participants who have not experienced a Grade 3 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity.

Participants with Grade 2 uveitis, episcleritis, iritis, eye pain, or blurred vision not meeting 
DLT criteria (Section 7.6.1) must resolve to baseline prior to resuming study therapy.

For participants with Grade 2 AST, ALT, or total bilirubin elevations, dosing may resume 
when laboratory values return to baseline and management with corticosteroids (if needed) is 
complete.

Participants with combined Grade 2 AST/ALT and total bilirubin values meeting DLT criteria 
(Section 7.6.1) should have treatment permanently discontinued. 

Criteria for HCC Participants:

Participants with baseline Grade 1 AST, ALT, or total bilirubin who require dose delays, 
for reasons other than a drug-related hepatic event, may resume treatment in the presence 
of Grade 2 AST, ALT, or total bilirubin increases.

Participants who require dose delays for drug-related increased AST, ALT, or bilirubin 
may resume treatment when hepatic parameters are at baseline or Grade 1, and after 
discussion with the BMS Medical Monitor

Participants with AST, ALT or bilirubin values meeting permanent discontinuation 
parameters (Section 7.6.1) should have treatment permanently discontinued.
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
Drug-related pulmonary toxicity, diarrhea, or colitis, must have resolved to baseline before 
treatment is resumed. Participants with persistent Grade 1 pneumonitis after completion of a 
steroid taper over at least 1 month, may be eligible for re-treatment if discussed with, and 
approved by, the BMS Medical Monitor.

Participants with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement may resume treatment.

Participants with confirmed SARS-CoV-2 infection may resume treatment after 1) at least 10 
days (20 days for severe/critical illness) have passed since symptoms first appeared, positive 
RT-PCR test result, or positive viral antigen test result, 2) resolution of acute symptoms 
(including at least 24 hours has passed since last fever without fever reducing medications), 3) 
evaluation by the investigator with confirmation that there are no sequelae that would place 
the participant at a higher risk of receiving investigational treatment, and 4) consultation by 
the Medical Monitor. For suspected cases, treatment may also resume if SARS-CoV-2 
infection is ruled-out and other criteria to resume treatment are met.

Prior to re-initiating on-study treatment in a participant with a dosing delay lasting 
≥8 weeks due to SARS-CoV-2 infection, the Medical Monitor/designee must be 
consulted.
7.6.5
Exceptions to Permanent Discontinuation Criteria
Any drug-related AE occurring at any time that meets DLT criteria as outlined in Section 7.6.1
will require permanent discontinuation of all study drugs, unless the investigator determines that 
one of the agents must be discontinued due to toxicity attributed to that agent alone.
Permanent discontinuation is not required for the following:

Grade 3 diarrhea, nausea, vomiting, or abdominal pain that returns to Grade 1 or baseline 
within 3 days with medical intervention.

Grade 3 pruritus or rash that returns to Grade 1 or baseline within 7 days with medical 
intervention.

Isolated Grade 3 or 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 3 days of 
their onset.

Grade 4 neutropenia < 7 days in duration.

Grade 4 lymphopenia or leukopenia.

Grade 3 or 4 increase in amylase or lipase that is not associated with clinical or radiographic 
evidence of pancreatitis.

Grade 3 infusion reaction that return to Grade 1 in < 6 hours.

Grade 3 CRS that returns to Grade 1 in < 6 hours.

Grade 3 fever not associated with hemodynamic compromise (eg, hypotension, clinical, or 
laboratory evidence of impaired end-organ perfusion).

Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to sites of known or 
suspected tumor).
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
Grade 3 fatigue.

Grade 3 or 4 drug-related endocrinopathy AEs, such as adrenal insufficiency, 
adrenocorticotropic hormone, hyper- or hypothyroidism, or glucose intolerance, which resolve 
or adequately controlled with physiologic hormone replacement (corticosteroids, thyroid 
hormones) or glucose-controlling agents, respectively, may not require discontinuation after 
discussion with and approval from the BMS Medical Monitor.
All participants who discontinue IP should comply with protocol specified follow-up procedures 
as outlined in Section 8.1. 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 (eg, imprisonment, involuntarily incarceration 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 case report form (CRF) page.
7.6.6
Management of Drug-related Infusion Reactions
Since BMS-986253, nivolumab, and ipilimumab contain only human Ig protein sequences, they 
are unlikely to induce hypersensitivity reactions. However, infusion reactions due to T-cell 
activation and cytokine release may occur in combination of both agents. If such a reaction were 
to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, arthralgia, 
hypotension, hypertension, bronchospasm, or other allergic-like reactions. All Grade 3 or 4 
infusion reactions should be reported within 24 hours to the BMS Medical Monitor and reported 
as an SAE. Infusion reactions should be graded according to NCI CTCAE v4.03 guidelines.
Treatment recommendations for infusion reactions 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 pre-medications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 mg to 1000 mg at least 30 minutes 
before study treatment administrations.
For Grade 2 symptoms (moderate reaction requiring therapy or infusion interruption but 
responding promptly to symptomatic treatment such as antihistamines, non-steroidal 
anti-inflammatory drugs, narcotics, corticosteroids, bronchodilators, IV fluids, or prophylactic 
medications indicated for ≤24 hours):

Stop the study treatment infusion, begin an IV infusion of 
 sodium chloride and treat the 
participant 
with 
diphenhydramine 
50 mg 
IV 
(or 
equivalent) 
and/or 
acetaminophen/paracetamol 325 mg to 1000 mg; remain at bedside and monitor participant 
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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 BMS-986253 or nivolumab will be administered at 
that visit.

For future infusions, the following prophylactic pre-medications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 mg to 
1000 mg should be administered at least 30 minutes before study treatment infusions. 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 
 sodium 
chloride and treat the participant as follows: recommend bronchodilators, epinephrine 0.2 mg 
to 1 mg of a 1:1,000 solution for subcutaneous administration or 0.1 mg 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 except for a Grade 3 infusion reaction that returns 
to Grade 1 in less than 6 hours. 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).
7.6.7
Management of Cytokine Release Syndrome (CRS)

Cytokine release plays a role in the pathophysiology of drug-related infusion reactions, which 
should be managed as per guidelines in Section 7.6.6. Infusions of immune-stimulating agents 
can also be associated with a cytokine-associated toxicity known as CRS, which has 
unpredictable onset and could occur many days following treatment.62 CRS is a clinical 
syndrome typically associated with infusions of immune-stimulating agents such as chimeric 
antigen receptor T cell (CAR T-cell) and bispecific antibodies.63 Cytokine release syndrome 
is characterized by fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, 
hypoxia, myalgia/arthralgia, and anorexia. Clinical symptoms and severity of CRS are highly 
variable,63 and management can be complicated by concurrent conditions.
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
Fever (≥ 38.5°C or ≥ 101.3°F) is a commonly-observed hallmark of CRS, and many features 
of CRS mimic infection. Hence, infection must be considered in all participants presenting 
with CRS symptoms, and appropriate cultures should be obtained, and empiric antibiotic 
therapy initiated per institution standard of care.

Less common symptoms associated with CRS include cardiac dysfunction, adult respiratory 
distress syndrome, renal and/or hepatic failure, coagulopathies, disseminated intravascular 
coagulation, and capillary leak syndrome. 

Neurologic toxicity has been observed concurrently with CRS.

High baseline levels of other commonly measured inflammatory markers, such as ferritin and 
C-reactive protein (CRP), were also associated with CRS.
The potential for BMS-986253 in combination with nivolumab or nivolumab plus ipilimumab to 
cause CRS is not yet defined, and CRS due to immune checkpoint inhibitors is rare.63 Most 
guidelines for management of CRS are intended for recipients of CAR T-cell therapy, and widely 
adopted algorithms to manage CRS specifically due to immune checkpoint blockade have not been 
established. If CRS is suspected, local guidelines for CRS management with input from BMS 
Medical Monitor or designee should be followed. General principles for CRS management include 
use of acetaminophen, steroids, IV fluids, and vasopressors. Interleukin-6 (IL-6), a pleiotropic 
cytokine with anti-inflammatory and proinflammatory properties, has been identified as a central 
mediator of toxicity in CRS. In more severe cases, use of tocilizumab, an anti–interleukin-6 
receptor monoclonal antibody, may be considered. CRS severity should be documented by 
CTCAE v4.03 criteria which primarily grades CRS based on clinical judgment as to interventions 
needed and subsequent response to these treatments. Management of study treatment should be 
per the table below. 
Table 7.6.7-1:
Management of Cytokine Release Syndrome (CRS)
Grade (CTCAE v4.03)
Intervention
1
No change to study treatment.
2
Study treatment may resume at next scheduled dose but consider prophylactic 
supportive therapy, eg, with acetaminophen 500-1000 mg
3
Permanently discontinue study treatment if does not improve to Grade 1 within 6 hours 
and contact BMS MM or designee.
4
Permanently discontinue BMS-986253 and contact BMS MM or designee.
Abbreviations: BMS, Bristol-Myers Squibb Company; CRS, cytokine release syndrome; CTCAE, Common 
Terminology Criteria for Adverse Events; MM, medical monitor.
7.6.8
Hemophagocytic Lymphohistiocytosis (HLH)
HLH (or macrophage activation syndrome [MAS]) is a rare, potentially fatal immune-mediated 
disease, with a wide range of causes, symptoms, and outcomes, but all lead to a hyperinflammatory 
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response. 
 
 
 
 
 
 
HLH is divided into primary (genetic) and secondary (reactive) forms. Secondary HLH has both 
infectious and non-infectious triggers.64 Amongst the infectious triggers of secondary HLH, viral 
EBV is the most commonly described, but other viruses including SARS-CoV-2 have been 
associated with HLH.64,65,66 Bacterial and fungal infections can also trigger HLH.64 An alternative 
diagnostic term of macrophage activation-like syndrome (MALS) has been proposed for patients 
with sepsis and co-occurrence of signs/symptoms of HLH. However, clinical criteria for the entity 
of MALS have not been widely adopted.67
Malignancy and immune checkpoint inhibitors (ICIs) are potential non-infectious triggers of HLH. 
BMS conducted a review of Pharmetrics and Marketscan US claims databases, which indicated 
that the incidence of HLH was 0.12% and 0.07% in melanoma patients treated with any immune 
checkpoint inhibitor (ICI), respectively, and 0.2% and 0% in melanoma patients treated with any 
combination of tyrosine kinase inhibitors consisting of BRAF plus mitogen-activated protein 
kinase kinase inhibitor, respectively. Among 49,883 ICI-related Adverse Drug Reactions collated 
in VigiBase (the largest pharmacovigilance database in the world) as of 30-Sep-2018, HLH was 
reported in 38 cases, with the highest reported rate of ICI-related HLH occurring in France, and 
melanoma being the most common cancer type.68
In September 2019, an HLH assessment for nivolumab and ipilimumab was requested by the 
European Medicines Agency Pharmacovigilance Risk Assessment Committee.69 Based on the
conclusions originating from that request, HLH was included on the nivolumab and ipilimumab 
United State Prescribing Information/Summary of Product Characteristics as a post-marketing 
adverse drug reaction with unknown frequency.
The presentation of secondary HLH is heterogeneous and can be acute or subacute with non-
specific symptoms appearing over a few days to 4 weeks.70 The diagnosis of HLH in adults may 
be established if either of the 2 criteria below is fulfilled71: 
1) Documentation of a verified HLH-associated gene mutation with clinical findings associated 
with HLH
OR 
2) Five out of the 8 criteria below for MAS/HLH are fulfilled: 
a) High persistent fever (≥ 38.5°C) 
b) Splenomegaly 
c) Cytopenias (affecting 2 of 3 lineages in the peripheral blood)
i)
Hemoglobin < 9.0 g/dl
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ii) Platelets < 100 x 109/L
iii) Neutrophils < 1.0 x 109/L 
d) Triglycerides: ≥ 3.0 mmol/L (ie, 265 mg/dl) or fibrinogen ≤ 1.5 g/L
e) Hemophagocytosis in bone marrow, spleen and/or lymph nodes
f)
Low or absent NK-cell activity (according to local laboratory reference)
g) Ferritin ≥ 500 µg/L 
h) Soluble CD25 (ie, soluble IL-2 receptor) ≥ 2400 U/mL
An alternative diagnostic scoring system (measured with an online tool) that may also be utilized 
considers hepatic function as well as the magnitude of laboratory test result abnormalities to derive 
an “H-score,” which estimates a probability of HLH.72 When potential clinical features of HLH 
are identified (eg, high fever, splenomegaly, coagulopathy, cytopenia, elevated transaminases), 
further laboratory testing to evaluate for additional HLH diagnostic criteria should be considered. 
In particular, hyperferritinemia has been suggested to be a key laboratory feature, with levels 
>10,000 µg/L having high specificity and sensitivity for HLH.64 Serum ferritin is closely related 
to HLH disease activity and may be useful to monitor treatment response.64 Bone marrow is the 
preferred anatomical site for investigation of hemophagocytosis and may be evaluated as clinically 
warranted. If a genetic predisposition is suspected, testing for an HLH-associated gene mutation 
should be considered. 
Detection of any ongoing infection acting as a trigger for HLH is critical. Standard tests should be 
used to screen for infections caused by the most common viruses such as herpes simplex virus, 
cytomegalovirus and Epstein-Barr virus (EBV), and SARS-CoV-2. Other infectious agents (eg, 
mycobacteria, parasites, and fungi, particularly Candida and Mucor) should be ruled out according 
to specific clinical or epidemiological features.71,72
7.6.8.1
HLH Management Approaches
Effective treatment of HLH requires multiple simultaneous approaches:
1) Supportive care: Life-threatening severe manifestations may be present and should be managed 
with appropriate supportive interventions. 
2) Elimination of triggers (particularly infection): Appropriate broad-spectrum antiviral, 
antibacterial, antifungal therapy should be initiated based on clinical suspicion and infectious 
work-up.
3) Suppression 
of 
the 
inflammatory 
response: 
Treatment 
specific 
for 
cancer 
immunotherapy-related HLH is not established, but HLH treatment generally may include: 
glucocorticoids, IL-1 blockade with anakinra, intravenous immunoglobulin (IVIG), cytotoxic 
agents (eg, etoposide), IL-6 blockade (eg, tocilizumab), and/or IFN-γ blockade (eg, 
emapalumab). Specific treatment should be guided by local standards and clinical judgment. 
A potential algorithm adapted from Carter et al64 for treating HLH in adults is provided below:
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a) First-line treatment: IV methylprednisolone 1 g daily for 3 to 5 days (followed by steroid 
taper) plus IVIG 1 g/kg for 2 days (consider repeating at 14 days due to half-life of 14-21 
days).
b) Second-line treatment (consider if there is clinical deterioration despite first-line 
treatment): Anakinra starting at 1-2 mg/kg, increasing to a maximum of 8 mg/kg/day.
c) Third-line/refractory treatment: Discuss with hematologist/other consultants and consider 
cytotoxic therapy or other additional anti-cytokine therapy.
All participants that develop HLH while on study therapy must be permanently discontinued all 
study treatments, regardless of which (if any) study therapies are considered related to the adverse 
event.
7.7
Preparation/Handling/Storage/Accountability
The IP should be stored in a secure area according to local regulations. It is the responsibility of 
the investigator to ensure that IP is only dispensed to study participants. The IP must be dispensed 
only from official study sites by authorized personnel according to local regulations.
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and contact BMS immediately.
Study treatment not supplied by BMS will be stored in accordance with the prescribing 
information.
IP documentation (whether supplied by BMS or not) must be maintained that includes all processes 
required to ensure drug is accurately administered. This includes documentation of drug storage, 
administration and, as applicable, storage temperatures, reconstitution, and use of required 
processes (eg, required diluents, administration sets).
For study drugs not provided by BMS and obtained commercially by the site, storage should in 
accordance with the product label.
Further guidance and information for final disposition of unused study treatment are provided in 
Appendix 2 and the Pharmacy Manual.
7.7.1
Retained Samples for Bioavailability / Bioequivalence
Not applicable.
7.8
Treatment Compliance
Not applicable.
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7.9
Concomitant Therapy
7.9.1
Prohibited and/or Restricted Treatments
The following medications are prohibited during the study (unless utilized to treat a 
drug-related AE):

Immunosuppressive agents.

Immunosuppressive doses of systemic corticosteroids. Participants are permitted the use of 
topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal 
systemic absorption). Adrenal replacement steroid doses > 10 mg daily prednisone are 
permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast 
dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity 
reaction caused by a contact allergen) is permitted.

Any concurrent approved or investigational anti-neoplastic therapy (ie, chemotherapy, 
hormonal therapy, or immunotherapy) for treatment of study disease. 

Any non-palliative radiation therapy. Radiation therapy administered with palliative intent (ie, 
for pain, bleeding, spinal cord compression, brain metastasis, new or impending pathologic 
fracture, superior vena-cava syndrome, or obstruction) is permitted. 

Any complementary medications (eg, herbal supplements or traditional Chinese medicines) 
intended to treat the disease under study. Such medications are permitted if they are used as 
supportive care.

Any live/attenuated vaccine (eg, varicella, zoster, yellow fever, rotavirus, oral polio and 
measles, mumps, rubella [MMR]) during treatment and until 100 days post last dose.

Administration of investigational SARS-CoV-2 vaccines is not allowed during the study. 
Participants may receive authorized or approved SARS-CoV-2 vaccines while continuing on 
study treatment at the discretion of the investigator.

Treatment of active SARS-CoV-2 infections or high-risk exposures, including use of 
investigational therapies, is allowed and should be discussed with the Medical Monitor.
7.9.2
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 or treatment assignment 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.
7.9.2.1
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 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 
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< 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 are excluded from MRI if they 
have tattoos, metallic implants, pacemakers, etc.
The ultimate decision to perform MRI in an individual participant in this study rests with the site 
radiologist, the investigator, and the standards set by the local Ethics Committee (EC).
7.10
Permitted Therapy
Participants are permitted the use of the following treatments:

Topical, ocular, intra-articular, intra-nasal, and inhalational corticosteroids.

Adrenal replacement steroid doses > 10 mg daily prednisone equivalent.

A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) 
or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction 
caused by a contact allergen).
7.10.1
Palliative Local Therapy
Part 1
If clinically indicated, palliative and supportive care for disease-related symptoms may be offered 
to participants in Part 1 of the study, after the DLT evaluation period. Limited radiation treatment 
or surgery to control isolated lesions may be permitted for participants following consultation with 
the BMS Medical Monitor (or designee).
Participants should not receive study treatment during radiation because the potential for 
overlapping toxicities with radiotherapy and study treatment is not known. If palliative 
radiotherapy in short courses and for isolated fields is required to control symptoms not clearly 
related to disease progression, then study treatment administration should be withheld, if possible, 
for at least 1 week before radiation and for at least 1 week after its completion.
Participants should be closely monitored for any potential toxicity during and after receiving 
radiotherapy. Prior to resuming study treatment, radiotherapy-related AEs should resolve to 
Grade 1 or baseline, and participants must meet relevant eligibility criteria as determined by the 
BMS Medical Monitor (or designee) in discussion with the investigator. The BMS Medical 
Monitor (or designee) must be consulted prior to re-initiating study treatment in a participant with 
a dosing delay lasting > 8 weeks from the previous dose.
Details of palliative radiotherapy should be documented in the source records and electronic case 
report form (eCRF). Details in the source records should include dates of treatment, anatomic site, 
dose administered and fractionation schedule, and AEs.
Symptoms requiring palliative radiotherapy should be evaluated for objective evidence of disease 
progression. If a participant is considered to have progressed at the time of palliative therapy, then 
they must meet the treatment beyond progression criteria (Section 8.1.1) prior to re-initiating study 
treatment. Participants receiving palliative radiation of target lesions will have the evaluation of 
objective response rate (ORR) just prior to radiotherapy if ORR was not assessed in 4 weeks prior 
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to start of radiotherapy, these participants will no longer be evaluable for the determination of 
response subsequent to the date palliative radiation occurs.
For participants who need to undergo surgery during the study, it is recommended to hold study 
treatment(s) for at least 4 weeks before (if elective) and 2 weeks after surgery, or until the 
participant recovers from the procedure, whichever is longer. Prior to resuming study treatment, 
surgically related AEs should resolve to Grade 1 or baseline, and participants must meet relevant 
eligibility criteria as determined by the BMS Medical Monitor (or designee) in discussion with the 
investigator. The BMS Medical Monitor (or designee) must be consulted prior to re-initiating study 
treatment in a participant with a dosing delay lasting > 8 weeks from the previous dose.
Part 2
Palliative (limited-field) radiation therapy and palliative surgical resection are permitted if either 
of the following criterion is met:
1) The participant has radiographic disease progression at the time of palliative therapy and meets 
criteria to continue with treatment beyond progression (Section 8.1.1).
2) If the participant has symptoms not clearly related to disease progression, they may receive a 
short course of palliative radiation to an isolated field or limited tumor-directed surgical 
intervention.
Details of palliative therapy should be documented in the source records and eCRF. Details in the 
source records should include dates of treatment, anatomic site, dose administered and 
fractionation schedule, and AEs. Participants who started tumor-directed radiotherapy or tumor-
directed surgery, without a prior reported radiographic progression per RECIST v1.1, will be 
censored at the last evaluable tumor assessment prior to initiation of radiotherapy. Participants 
receiving palliative radiation should undergo a radiographic tumor assessment just prior to 
radiotherapy/tumor-directed surgery if no such assessment has occurred in the 4 weeks prior to 
start of the radiotherapy/surgery. Participants receiving palliative radiation or surgery impacting a 
target lesion will no longer be evaluable for the determination of response subsequent to the date 
the palliative procedure occurs.
Participants should not receive study treatment during radiation because the potential for 
overlapping toxicities with radiotherapy and study treatment is not known. Study treatment 
administration should be withheld, if possible, for at least 1 week before radiation and for at least 
1 week after its completion. Participants should be closely monitored for any potential toxicity 
during and after receiving radiotherapy. Prior to resuming study treatment, radiotherapy-related 
AEs should resolve to Grade 1 or baseline, and participants must meet relevant eligibility 
criteria. 
For participants who need to undergo surgery during the study, it is recommended to hold study 
treatment(s) for at least 4 weeks before (if elective) and 2 weeks after surgery, or until the 
participant recovers from the procedure, whichever is longer. Prior to resuming study treatment, 
surgically related AEs should resolve to Grade 1 or baseline, and participants must meet relevant 
eligibility criteria. 
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7.11
Treatment After the End of the Study
At the conclusion of the study, participants who continue to demonstrate clinical benefit may be 
eligible to receive BMS-supplied study treatment.
Those participants who demonstrate clinical benefit from treatment without unacceptable toxicity 
may continue treatment beyond the 3-year treatment period, up to a maximum of 5 years from the 
first dose of study treatment, at the discretion of the investigator and after discussion with the 
Medical Monitor, until loss of that benefit, unacceptable toxicity, or participant/physician decision 
to withdraw. 
If a participant continues study treatment beyond the 3-year treatment period, procedures during 
the extended treatment duration will be minimized to clinical and laboratory safety monitoring,
AE collections, and tumor assessments every 12 weeks until the final analysis. 
BMS reserves the right to terminate access to BMS-supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986253 is 
terminated for other reasons, including but not limited to lack of efficacy and/or not meeting the 
study objectives; c) the participant can obtain medication from a government-sponsored or private 
health program. In all cases, BMS will follow local regulations.
8
DISCONTINUATION CRITERIA
8.1
Discontinuation from Study Treatment
Participants MUST discontinue IP for any of the following reasons:

Documented disease progression as defined by RECIST v1.1 (Appendix 8) unless participants 
meet criteria for treatment beyond progression (Section 8.1.1).

Clinical deterioration while receiving active study therapy that, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant.

Any drug-related AE occurring at any time that meets DLT criteria as outlined in Section 7.6.1
will require permanent discontinuation of the implicated study drug. Exceptions to permanent 
discontinuation are listed in Section 7.6.5.

Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information.

Any clinical AE, laboratory abnormality or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant.

Termination of the study by BMS for reasons stated in Section 8.2.1.

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
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has been imprisoned may be permitted to continue as a participant. Strict conditions apply and 
BMS approval is required.)

Inability to comply with protocol.

Discretion of the investigator.

Pregnancy.

Individual participants with confirmed complete response (CR), and all participants after final 
analysis results are available, will be given the option to discontinue any or all of the study 
therapies on a case by case basis after specific consultation and agreement between the 
investigator and BMS Medical Monitor in settings where benefit/risk justifies discontinuation.

Any event that leads to delay in dosing, lasting > 8 weeks from the previous dose, requires 
discontinuation, with the exception of the following:

Dosing delays for prolonged steroid tapers to manage drug-related AEs are allowed. Prior 
to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks from the 
previous dose, the BMS Medical Monitor 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 per protocol, or more frequently if clinically 
indicated, during such dosing delays.

Dosing delays lasting > 8 weeks from the previous dose that occur for non-drug-related 
reasons may not require discontinuation, if approved by the BMS Medical Monitor. Prior 
to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks, the BMS 
Medical Monitor must be consulted.

Any AE, laboratory abnormality, or concurrent illness, which, in the judgment of the 
investigator, presents a substantial clinical risk to the participant with continued study 
treatment dosing.
Refer to the Schedule of Activities for data to be collected at the time of treatment discontinuation 
and follow-up and for any further evaluations that can be completed.
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 Pregnancy.
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.
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The assessment for discontinuation of BMS-986253 (or placebo), nivolumab, and ipilimumab 
should be made separately. For example, if the AEs are assessed to be related to ipilimumab only 
and meet the discontinuation criteria, BMS-986253 (or placebo) and/or nivolumab may resume.
If a participant in any of the combination cohorts meets criteria for discontinuation and the 
investigator is unable to determine whether AE is attributable to individual or combination study 
drugs, the participant should discontinue all study drugs.
8.1.1
Treatment Beyond Progression
As described in Section 5.4.6, accumulating evidence indicates that a minority of participants with 
tumors treated with immunotherapy may derive clinical benefit despite initial evidence of disease 
progression. 
Participants 
will 
be 
permitted 
to 
continue 
treatment 
beyond 
initial 
RECIST v1.1-defined disease progression, as assessed by the investigator (see Appendix 8), as 
long as they meet the following criteria:

Investigator-assessed clinical benefit, and no rapid disease progression.

Continue to meet all other study protocol eligibility criteria.

Tolerance of study treatment.

Stable performance status.

Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, CNS metastases).

Participant provides written informed consent prior to receiving any additional nivolumab, 
ipilimumab, and BMS-986253 treatment, using an ICF describing any reasonably foreseeable 
risks or discomforts, or other alternative treatment options.
The assessment of clinical benefit should take into account whether the participant is clinically 
deteriorating and unlikely to receive further benefit from continued treatment. If the investigator 
feels that the participant continues to achieve clinical benefit by continuing treatment with the 
study treatments, the participant should remain on the trial and continue to receive monitoring 
according to the Schedule of Activities (see Section 2). All decisions to continue treatment beyond 
initial progression must be discussed with the BMS Medical Monitor, and an assessment of the 
risk/benefit of continuing with study therapy must be documented in the study records (see 
Appendix 2).
Participants must be re-consented with an ICF addendum or similar document to continue 
treatment beyond progression. Treatment beyond progression will require continued tumor 
assessments and scans should continue to be submitted to the imaging core laboratory.
Participants who continue study therapy beyond progression will continue to receive monitoring 
according to the on-treatment assessments in Section 2, and radiographic assessment per 
Section 9.4.1 and Section 2 to determine whether there has been continued disease progression or 
not.
Further progression is defined as an additional 10% increase in tumor burden with a minimum 
5 mm absolute increase from time of initial progression of disease. This includes an increase in 
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the sum of diameters of all target lesions and/ or the diameters of new measurable lesions compared 
to the time of initial progression of disease. It is recommended that study treatment should be 
discontinued permanently upon documentation of further progression.
New lesions are considered measurable at the time of initial progression if the longest diameter is 
at least 10 mm (except for pathological lymph nodes, which must have a short axis of at least 
15 mm). Any new lesion considered non-measurable at the time of initial progression may become 
measurable and therefore included in the tumor burden if the longest diameter increases to at least 
10 mm (except for pathological lymph nodes, which must have a short axis of at least 15 mm). In 
situations where the relative increase in total tumor burden by 10% is solely due to inclusion of 
new lesions that become measurable, these new lesions must demonstrate an absolute increase of 
at least 5 mm.
8.1.2
Post Treatment Follow-up
Post treatment follow-up is of critical importance and is essential to preserving participant safety 
and the integrity of the study. Participants who discontinue study treatment must continue to be 
followed for safety follow-up as required and in line with Section 5.1.5.
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, 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.
8.2.1
Study Termination
BMS reserves the right to terminate the study at any time for reasons including but not limited to 
the following: safety concerns, termination of drug development, lack of efficacy, and lack of 
meeting study objectives/endpoints.
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.
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
Lost to follow-up is defined by the inability to reach the participant after a minimum of three
documented phone calls, faxes, or emails as well as lack of response by participant to one 
registered mail letter. All attempts should be documented in the participant’s medical records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If investigator’s use of 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 (See Section 2).

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 injury [DILI] enzyme evaluations) will be monitored during the follow-up phase via 
on site/local labs until all study treatment related toxicities resolve, return to baseline, or are 
deemed irreversible.
If a participant shows pulmonary-related signs (hypoxia, fever) or symptoms (eg, dyspnea and 
cough) consistent with possible pulmonary AEs, the participant should be immediately evaluated 
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to rule out pulmonary toxicity, according to the suspected pulmonary toxicity management 
algorithm in the BMS-936558 (nivolumab) IB.
Some of the assessments referred to in this section may not be captured as data in the eCRF. They 
are intended to be used as safety monitoring by the treating physician.
Additional testing or assessments may be performed as clinically necessary or where required by 
institutional or local regulations.
9.1
Safety Assessment
Safety assessments will be based on reported AE and the measurement results of vital signs 
including oxygen saturation, ECGs, physical examinations, and clinical laboratory tests. AEs will 
be coded using the most current version of Medical Dictionary for Regulatory Activities and the 
incidence of observed AEs will be tabulated and reviewed for potential significance and clinical 
importance. AEs will be assessed continuously during the study and for a minimum of 100 days 
after the last dose of study treatment. A local laboratory will perform the clinical laboratory tests 
and will provide reference ranges for these tests. Both AEs and laboratory tests will be graded 
using the NCI CTCAE v4.03.
Planned timepoints for all safety assessments are listed in the Schedule of Activities in Section 2.
9.1.1
Physical Examinations
A full physical exam will be obtained during select times during study participation. Refer to the 
Schedule of Activities for timing of assessments in Section 2.
9.1.2
Vital signs
Pre and post dose vital signs will be obtained during the dosing visits. Vital signs including oxygen 
saturation will be obtained during select times during study participation. Refer to the Schedule of 
Activities for timing of assessments in Section 2.
9.1.3
Electrocardiograms
Refer to the Schedule of Activities for timing of ECG assessments for safety in Section 2. The 
investigators will review the 12-lead ECGs using their site’s standard ECG machines throughout 
the study. 
Refer to the Schedule of ECG collection for effect of BMS-986253 in combination with nivolumab 
 Electrocardiogram recording 
should be obtained prior to PK samples at each time point as indicated 
 The ECGs will be assessed by an independent core laboratory until final 
analysis. A separate manual will include additional details and instructions. All ECG tests will be 
performed in triplicate for Cycles 1 and 4 in Part 1A and 1B, and for Cycles 1, 2, and 3 in Part 1C 
(ie, 1 ECG test equals 3 consecutive individual 12-lead ECGs performed at least 5 minutes apart). 
Special Restrictions: Subjects should refrain from strenuous physical activity and use of (methyl) 
xanthines (eg, coffee, tea, cola, chocolate) or alcohol on the days when ECG measurements will 
be obtained.
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9.1.4
Clinical Safety Laboratory Assessments

Investigators must document their review of each laboratory safety report.

A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests must be available prior to dosing. Laboratory samples may 
be obtained up to 48 hours prior to dosing. 

The laboratory tests that will be performed for study participants are shown in Table 9.1.4-1.

Results of all laboratory tests required by this protocol must be provided to the Sponsor, 
recorded either on the laboratory pages of the CRF or by another mechanism as agreed upon 
between the investigator and BMS (eg, provided electronically). If the units of a test result 
differ from those printed on the CRF, the recorded laboratory values must specify the correct 
units.
Any abnormal laboratory test result considered clinically significant by the investigator must be 
recorded on the appropriate AE page of the CRF.
Table 9.1.4-1:
Laboratory Tests
Hematology
Hemoglobin and hematocrit
Total leukocyte count, including differential
Platelet count
Prothrombin time, activated partial thromboplastin time, and international normalized ratio (screening only)
Chemistry
Alanine aminotransferase 
Aspartate aminotransferase
Total bilirubin
Direct bilirubin (only if total bilirubin is abnormal)
Alkaline phosphatase
Lactate dehydrogenase
Creatinine
Blood Urea Nitrogen
Uric acid 
Glucose
Lipase (screening only for Part 2)
Amylase (screening only for Part 2)
Thyroid stimulating hormone
T3 and free T4 (screening and only if TSH is abnormal 
when checked every third cycle ) 
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase
Creatinine clearance - screening only
Troponin (screening and at each cycle for Part 1 
and screening only for Part 2)
Urinalysis
Protein
Glucose
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Blood
Leukocyte esterase
Specific gravity
pH
Serology
Serum for hepatitis B surface antigen, hepatitis C antibody (screening only)
For HCC participants: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, 
hepatitis B DNA PCR, hepatitis C antibody and hepatitis C RNA PCR, and hepatitis D antibody testing for those 
with concurrent hepatitis B infection
Other Analyses:
Pregnancy test (WOCBP only: screening, predose at each cycle, EOT).
Follicle stimulating hormone (screening only for post-menopausal women < 55 years old) 
AFP only for HCC participants in Part 1C
Abbreviations: AFP, alpha fetoprotein; CRC, colorectal cancer; DNA, deoxyribonucleic acid; EOT, end of treatment; 
HCC, hepatocellular carcinoma; PCR, polymerase chain reaction; RNA, ribonucleic acid; T3, triiodothyronine; 
T4, thyroxine; TSH, thyroid-stimulating hormone; WOCBP, women of childbearing potential.
9.2
Adverse Events Assessments
The definitions of an AE or SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study. All SAEs and AEs will be assessed using NCI 
CTCAE v4.03.
Contacts for SAE reporting specified in Appendix 3.
9.2.1
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
All nonserious adverse events (not only those deemed to be treatment related) must be collected 
starting with the first dose of study drug and for a minimum of 100 days after discontinuing study 
treatment.
All SAEs must be collected from the time of signing the ICF and for a minimum of 100 days after 
discontinuing study treatment. Death due to disease progression within 100 days of discontinuation 
of dosing must be reported as an SAE. Time points are specified in the Schedule of Activities 
(Section 2).
Sections 5.6.1 and 5.6.2 in the BMS-986253, nivolumab, and ipilimumab IBs represent the 
Reference Safety Information to determine expectedness of SAEs for expedited reporting.
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After the participant signs the Pre-Screen ICF for serum IL-8 collection, all SAEs related to the 
blood draw must be collected and followed until resolution or stabilization. 
After the participant signs the main ICF to participate in the study, all SAEs whether related or not 
related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures.
After the Pre-Screen ICF is signed:

Only SAEs related to the blood draw for IL-8 serum will be collected and followed until 
resolution or stabilization.
All related SAEs will be recorded and reported to Sponsor or designee within 24 hours, as 
indicated in Appendix 3.

The investigator will submit any updated SAE data to the Sponsor within 24 hours of this being 
available.

All SAEs related to the blood draw for IL-8 serum in Pre-Screening will be followed until 
resolution or stabilization.
After the Main ICF is signed:

All SAEs must be collected that occur during the participant’s written consent and for a 
minimum of 100 days after discontinuing study treatment, or if the last scheduled visit occurs 
at a later time. 

The investigator must report any SAE that occurs after these time periods and that is believed 
to be related to study treatment or protocol-specified procedure.

Medical occurrences that begin before the start of study treatment but after signing the main 
informed consent will be recorded on the appropriate section of the eCRF section.

All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. Death due to disease progression within 100 days of discontinuation of dosing 
must be reported as an SAE regardless of assessed relatedness to the study drug.

The investigator will submit any updated SAE data to the Sponsor within 24 hours of this being 
available.
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the investigator must promptly notify the Sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3.
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9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgment in the context of known 
AEs, when appropriate for the program or protocol.
9.2.3
Follow-up of Adverse Events and Serious Adverse Events
Nonserious AEs should be followed to resolution or stabilization, or reported as an SAEs if they 
become serious (see Section 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. 
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 IB and will notify the Institutional Review Board/Independent Ethics Committee, if 
appropriate according to local requirements.
Sponsor or designee will be reporting AEs to regulatory authorities and ECs according to local 
applicable laws including European Regulation 536/2014 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.
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In most cases, the study treatment will be permanently discontinued in an appropriate manner (eg, 
dose tapering if necessary for participant safety). Please call the BMS Medical Monitor within 
24 hours of awareness of the pregnancy.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
participant.
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 ICF for disclosure of this 
information. Information on this 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
Immune-mediated Adverse Events
Immune-mediated AEs are AEs consistent with an immune-mediated mechanism or 
immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor 
progression) have been ruled out. Immune-mediated AEs can include events with an alternate 
etiology which were exacerbated by the induction of autoimmunity. Information supporting the 
assessment will be collected on the participant’s CRF.
9.2.8
Potential Drug-induced Liver Injury
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a p-DILI event. All occurrences of p-DILIs, meeting the defined 
criteria, must be reported as an SAEs (see Section 9.2 and Appendix 3 for reporting details).
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Potential DILI is defined as: 
1) ALT or AST elevation > 3× ULN
AND
2) Total bilirubin > 2× ULN, without initial findings of cholestasis (elevated serum ALP),
AND
3) No other immediately apparent possible causes of ALT 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.
Specifically for HCC: p-DILI is defined as:

Concurrent ALT > 10× ULN AND total bilirubin > 2× ULN or baseline value (if elevated 
bilirubin at study entry), AND

No other immediately apparent possible causes of ALT elevation and hyperbilirubinemia, 
including, but not limited to, tumor progression, acute viral hepatitis, cholestasis, preexisting 
hepatic disease or the administration of other drug(s), herbal medications and substances 
known to be hepatotoxic. 
This is the standard DILI definition across the BMS HCC program.
The key responsibilities for investigators during p-DILI assessment include: (i) early detection, 
medical evaluation (including the exclusion of other potential causes), and rapid laboratory 
confirmation of liver-related abnormalities and (ii) BMS notification of p-DILI cases via SAE 
forms. Following the gathering and assessment of relevant clinical information, BMS is 
responsible for: (iii) timely evaluation and triaging of p-DILI cases, (iv) expedited reporting of 
p-DILI cases and (v) expanded review of p-DILI cases including a detailed assessment of all 
available clinical information, investigations, and biochemical data.
Investigators are expected to monitor ongoing routine and ad hoc hepatic laboratory test results to 
rapidly determine whether a participant meets p-DILI criteria. They are expected to promptly 
notify BMS of all p-DILI cases. p-DILI cases may be identified by abnormal liver biochemistry 
values, whether or not they are accompanied by liver-related signs and/or symptoms. In both cases, 
expedited confirmation with repeat laboratory testing should occur within 3 business days using a 
Hepatic Laboratory Panel (ALT, AST, total bilirubin, ALP). Any participant with an abnormal 
Hepatic Laboratory Panel that meets p-DILI criteria is a candidate for study treatment 
discontinuation. Any confirmed p-DILI events must be reported (along with a description of the 
clinical findings) to BMS as an SAE within 24 hours of confirmation.
An extensive clinical history, examination and appropriate investigations should be obtained to 
exclude cholestatic and other apparent causes that may explain the observed abnormalities in liver 
function and/or hepatic signs and symptoms. Other apparent causes include, non-exhaustively and 
by way of example only: infectious diseases (such as active hepatitis A, B, and C), congenital 
diseases (such as Gilbert’s syndrome), neoplastic diseases, autoimmune diseases (such as primary 
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biliary cirrhosis), and the use of concomitant hepatotoxic medications (such as antibiotics, the oral 
contraceptive pill and herbal medicines). All investigations to exclude potential causes of liver 
function abnormalities or hepatic signs and/or symptoms should be guided by relevant factors such 
as the participant’s age, gender, clinical history, and signs and symptoms.
9.2.9
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, x-ray 
filming, any other potential safety assessment required or not required by protocol should also be 
recorded as a non-serious or serious AE, as appropriate, and reported accordingly.
9.3
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 9.2).
For this study, any dose of BMS-986253, nivolumab, and/or ipilimumab greater than the assigned 
dose and considered excessive and medically important by the investigator will be considered an 
overdose.
In the event of an overdose the [investigator/treating physician] should:
1) Contact the Medical Monitor immediately
2) Closely monitor the participant for AEs/SAEs and laboratory abnormalities until 
BMS-986253, nivolumab, and/or ipilimumab can no longer be detected systemically
3) Obtain a plasma sample for PK if requested by the Medical Monitor (determined on a 
case-by-case basis)
4) Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
Decisions regarding dose interruptions or modifications secondary to an overdose will be made by 
the investigator in consultation with the Medical Monitor based on the clinical evaluation of the 
participant.
9.4
Efficacy Assessments
Following the database lock for the final analysis, efficacy will no longer be assessed. Imaging
should be performed per standard of care at the discretion of the treating physician. 
Efficacy assessments for the anti-tumor activity of BMS-986253, in combination with nivolumab
or in combination with nivolumab and ipilimumab, will use investigator assessed tumor 
measurements, per RECIST v1.1 (Appendix 8).
Assessments of partial response (PR) and CR must be confirmed at least 4weeks after initial 
response. Changes in tumor measurements and tumor responses will be assessed by the 
investigator per study design using RECIST v1.1 criteria (Appendix 8). Investigators will also 
report the number and size of new lesions that appear while on study. The timepoint of tumor 
assessments will be reported on the eCRF based on the investigator’s assessment.
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A BICR will be utilized in this study for determination of BICR-assessed endpoints. The BICR 
will review all available tumor assessment scans for all treated participants until the final analysis 
is completed. Details of BICR responsibilities and procedures will be specified in the BICR 
charter.
A Best Overall Response of SD requires a minimum of 49 days on study from the date of first dose 
to the date of the first imaging assessment.
 
9.4.1
Imaging Assessment for the Study
Following the final analysis, images will no longer be submitted for BICR evaluation. Imaging
should be performed per institutional standard of care.
Until final analysis, images will be submitted to an imaging core laboratory and may be reviewed 
by BICR at any time during the study. Sites should be qualified prior to scanning the first 
participant and understand the image acquisition guidelines and submission process as outlined in 
the CA027002 Imaging Manual provided by the core laboratory.
Baseline images should be acquired as outlined in Table 2-2. On-study images should be acquired 
as outlined in Table 2-3, Table 2-4, and Table 2-5 from the date of first dose. Tumor assessments 
at other timepoints may be performed if clinically indicated and should be submitted to the central 
imaging vendor as soon as possible. Unscheduled CT/MRI should be submitted to the central 
imaging vendor. X-rays and bone scans that clearly demonstrate interval progression of disease, 
for example most commonly as unequivocal lesions that are unmistakably new since the prior 
CT/MRI, should be submitted to the central imaging vendor. Otherwise, they do not need to be 
submitted centrally. 
Images will be acquired within 28 days prior to the first treatment dose. Images acquired as part 
of care prior to signing the ICF, but within the 28-day limit, will be acceptable if there is no 
intervening treatment, and all required scanning acquisition parameters are met (if feasible per 
local regulations).
For Part 1: On-treatment images will be acquired every 8 weeks (± 7 days) up until Week 48 and 
then every 12 weeks (± 7 days) until withdrawal of consent, death, or initiation of another anti-
cancer treatment, whichever occurs first. For Part 2: On-treatment images will be acquired every 
8 weeks (± 7 days) up until Week 48 and then every 12 weeks (± 7 days) until BICR-confirmed 
disease progression, or treatment discontinuation (including treatment beyond progression), 
whichever occurs later. 
For Part 1: At the time of study treatment discontinuation, participants should continue to have 
radiologic and clinical tumor assessment on the same schedule, every 8 weeks (± 7 days), starting 
from first dose for the first 48 weeks, then every 12 weeks (± 7 days), until withdrawal of consent, 
death, or initiation of another anti-cancer treatment or for up to a maximum of 2 years, whichever 
occurs first. For Part 2: At the time of study treatment discontinuation, participants in Part 2 will 
continue to have radiologic and clinical tumor assessments on the same schedule, every 8 weeks 
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(± 7 days), starting from first dose for the first 48 weeks, then every 12 weeks (± 7 days), until 
BICR-confirmed disease progression, or treatment discontinuation (including treatment beyond 
progression), whichever occurs later. 
Tumor assessment with contrast-enhanced CT scans acquired on dedicated CT equipment is 
preferred for this study. Contrast-enhanced CT of the chest, abdomen, pelvis, and all other 
known/suspected sites of disease should be performed for tumor assessments. 
For participants with SCCHN, a CT or MRI the neck is required for all tumor assessments.
For participants with HCC, imaging of the abdomen should include multi-phasic (at least three of 
the following four phases: precontrast, arterial, venous, delayed) CT or MRI of the liver. 
Images should be acquired with slice thickness of 5 mm or less with no intervening gap 
(contiguous). Every attempt should be made to image each participant using an identical 
acquisition protocol on the same scanner for all imaging timepoints. Tumor measurements should 
be made by the same investigator or radiologist for each assessment whenever possible. Change 
in tumor measurements and tumor response to guide ongoing study treatment decisions will be 
assessed by the investigator using the RECIST 1.1 criteria (Appendix 8).
Should a participant have contraindication for a CT IV contrast, a non-contrast CT of the chest and 
a contrast-enhanced MRI of the abdomen, pelvis, and all other known/suspected sites of disease 
should be obtained. If the primary tumor is not of lung origin, a contrast-enhanced MRI of the 
chest may be obtained instead of a non-contrast CT of the chest.
Should a participant have contraindication for both MR and CT IV contrasts, a non-contrast CT of 
the chest and a non-contrast MRI of the abdomen, pelvis, and all other known/suspected sites of 
disease should be obtained. If the primary tumor is not of lung origin, a non-contrast MRI of the 
chest, abdomen, pelvis, and other known/suspected sites of disease is also acceptable.
Should a participant have contraindication for MRI (eg, incompatible pacemaker) in addition to 
contraindication to CT IV contrast, a non-contrast CT of the chest, abdomen, pelvis, and all other 
known/suspected sites of disease is acceptable.
Use of CT component of a PET-CT scanner: Combined modality scanning such as with PET-CT 
is increasingly used in clinical care, and is a modality/technology that is in rapid evolution; 
therefore, the recommendations outlined here may change rather quickly with time. At present, 
low dose or attenuation correction CT portions of a combined PET-CT are of limited use in 
anatomically-based efficacy assessments and it is therefore suggested that they should not be 
substituted for dedicated diagnostic contrast enhanced CT scans for anatomically-based RECIST
measurements. However, if a site can document that the CT performed as part of a PET-CT is of 
identical diagnostic quality to a diagnostic CT (with IV and oral contrast) then the CT portion of 
the PET-CT can be used for RECIST 1.1 measurements. Note, however, that the PET portion of 
the CT introduces additional data which may bias an investigator if it is not routinely or serially 
performed.
Bone scan or PET scan is not adequate for assessment of RECIST 1.1 response in target lesions. 
In selected circumstances where such modalities are the sole modality used to assess certain 
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non-target organs, those non-target organs may be evaluated less frequently. For example, bone 
scans may need to be repeated only when CR is identified in target disease or when progression in 
bone is suspected.
Bone scans may be collected per local standards, as clinically indicated.
MRI of brain (without and with contrast) should be acquired as outlined in Section 2 (Schedule of 
Activities). CT of the brain (without and with contrast) can be performed if MRI is contraindicated.
9.4.2
BICR Confirmation of Progression (Part 2)
Following the final analysis, images will no longer be submitted to BICR for evaluation. Imaging
should be performed per institutional standard of care.
Until final analysis, sites should submit all scans to the central imaging vendor on a rolling basis, 
throughout the duration of the study. BICR of scans will occur on a rolling basis, blinded to 
treatment arm, clinical data, and investigator assessment of submitted scans. For Part 2, when 
progression per RECIST 1.1 criteria is assessed by the investigator, the site will inform the central 
imaging vendor, in order for BICR assessment of progression to be performed. The BICR will be 
completed and the results provided to the site as specified in the imaging vendor documents, 
provided there are no pending imaging queries to the site. All details on the timelines and 
associated process requirements will be outlined in the Imaging Manual. 
Participants whose progression is not confirmed by the BICR will be required to continue tumor 
assessments (if clinically feasible) according to the protocol-specified schedule, or sooner if 
clinically indicated. Also, if participants discontinue treatment without radiographic progression, 
tumor assessments will continue according to the protocol-specified schedule, as noted in 
Section 2 (Schedule of Activities) until progression has been confirmed by BICR.
All study treatment decisions will be based on the investigator’s assessment of tumor images and 
not on the BICR assessment. 
9.5
Pharmacokinetics and Immunogenicity Assessments
Following the final analysis, PK and IMG samples will no longer be collected. 
Pharmacokinetic (PK) and immunogenicity (IMG) assessment data for BMS-986253, nivolumab, 
and ipilimumab will be collected from study participants assigned to the study at the time points 
indicated 
 All time points are relative to the start of the first drug 
administration on that day. All on-treatment time points are intended to align with days on which 
study drug is administered; if dosing occurs on a different day, the PK and IMG sampling should 
be adjusted accordingly. 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. All pre-
dose samples should be taken within 30 minutes before the start of any dose infusion. End of 
infusion (EOI) samples should be taken immediately prior to completion of the infusion, preferably 
within 2 minutes. Blood samples should be drawn from a site other than the infusion site (ie, 
contralateral arm) on days of infusion.
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Pharmacokinetics of BMS-986253 will be derived, if feasible, from serum concentration versus 
time data following administration of BMS-986253. PK parameters that will be assessed are shown 
below:
Table 9.5-1:
Pharmacokinetic Parameters
Cmax
Maximum observed serum concentration
Tmax
Time of maximum observed serum concentration
AUC(0-T)
Area under the serum concentration-time curve from time zero to time of last quantifiable 
concentration; may be calculated if concentrations are not quantifiable up to TAU across a
treatment group
AUC(TAU)
Area under the serum concentration-time curve in 1 dosing interval
Ctau
Observed serum concentration at the end of a dosing interval
Ctrough
Trough observed serum concentrations (this includes pre-dose concentrations [C0] and Ctau)
Table 9.5-2:
Pharmacokinetic Parameters that May be Assessed Following the 
Administration of BMS-986253
CLT
Total body clearance
Css-avg
Average serum concentration over a dosing interval (AUC[TAU]/tau) at steady state
AI
Ratio of an exposure measure at steady state to that after the first dose (exposure measure
includes AUC[TAU] and Cmax)
Abbreviations: AUC(TAU), area under the serum concentration-time curve in 1 dosing interval; Cmax, maximum 
observed plasma concentration; tau, dosing interval.
Individual participant PK parameter values will be derived by non-compartmental methods using 
a validated PK analysis program (Part 1 only). Actual times will be used for all formal analyses.
Sparse nivolumab and ipilimumab concentration-time data will be collected and may be used
in an integrated population pharmacokinetics (PPK) or exposure response analysis along
with data from other studies, which will be the subject of a separate report. Separate samples
will be collected for PK and IMG assessments.
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Immunogenicity samples will be analyzed for anti-nivolumab/anti-ipilimumab/anti-BMS-986253 
antibodies by validated bioanalytical method(s). Immunogenicity samples positive for any anti-
nivolumab, anti-ipilimumab, or anti-BMS-986253 antibodies may be analyzed for neutralizing 
antibodies by validated bioanalytical method(s). Exploratory results will not be reported. 
Bioanalytical samples designated for assessments (eg, immunogenicity, PK, or biomarker) from 
the same collection time point may be used interchangeably for analyses, if required (including 
but not limited to insufficient volume for complement assessment, to follow-up on suspected 
immunogenicity related AE, etc). For all PK and immunogenicity plasma/serum samples, the date 
and actual time collected must be recorded. For participants whose only peripheral access is via a 
venous access device or peripherally inserted central catheter, refer to the Laboratory Manual for 
the proper technique to ensure undiluted whole blood for PK assessments.
Further details of sample collection, processing, and shipment will be provided in the laboratory 
procedures manual.
9.6
Pharmacodynamics
Details on pharmacodynamic biomarker assessments are in Section 9.8.2.1.
9.7
Pharmacogenomics
Not applicable.
9.7.1
Absorption, Distribution, Metabolism, and Excretion Sampling
Not applicable.
9.8
Biomarkers
Following the final analysis, biomarker samples will no longer be collected. 
 
 
 
 
 
If biomarker samples are drawn but study treatment(s) is not administered, samples will be 
retained. A detailed description of each biomarker sample analysis and assessment is described 
below, and a schedule of biomarker sample collections is provided 
 Further details of blood, serum, and tumor tissue collection and processing will be provided to 
the site in the procedure manual.
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9.8.1
Serum IL-8 Levels for Participant Selection
Previous studies have demonstrated that changes in serum IL-8 levels are associated with response 
to nivolumab or pembrolizumab in patients with metastatic melanoma and NSCLC. In addition, it 
has been shown that early changes in serum IL-8 levels post-treatment can predict response and 
OS.20 It has also been demonstrated that expression of CXCR2, one of two IL-8 receptors, is 
upregulated in metastatic melanoma lesions that progressed following treatment with nivolumab 
compared to lesions from the same patient that regressed during nivolumab treatment.19 Finally, a 
relatively high median level of serum IL-8 at baseline has been shown to correlate with OS in 
melanoma, NSCLC, and RCC patients in response to ipilimumab.3 In light of these findings and 
of the concept that BMS-986253 can compromise IL-8-mediated immunosuppression, serum IL-8 
levels at baseline could conceivably be used as a biomarker to select participants more likely to 
benefit from nivolumab when combined with BMS-986253.
To participate in Parts 1A and 1B, participants must have a screening 
To 
participate in Parts 1C and 2, participants will have screening IL-8 measured, but may enroll 
regardless of the serum IL-8 level. 
 
 
 Rationale for selection based on serum 
IL-8 is provided in Section 5.4.3. Any further segregation will be based upon post-hoc allocation 
of participants into intermediate or low- versus high-expression categories based upon IL-8 level 
cut-offs determined from the aforementioned analyses but inclusion will be based solely upon the 
Clinical Laboratory Improvement Amendments-certified analytical cut-off.
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9.8.4
Additional Research Collection
This protocol will include residual sample storage for additional research.
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For All US sites:
Additional research participation is required for all investigational sites in the US.
For non-US Sites
Additional research is required for all study participants, except where retention and/or collection 
is prohibited by local laws or regulations, ECs, or institutional requirements. 
This collection for additional research is intended to expand the translational Research and 
Development capability at BMS, and will support as yet undefined research aims that will advance 
our understanding of disease and options for treatment. It may also be used to support health 
authority requests for analysis, and advancement of pharmacodiagnostic development to better 
target drugs to the right participants. This may also include genetic/genomic exploration aimed at 
exploring disease pathways, progression, and response to treatment etc.
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study sponsor’s senior leaders in Research and Development (or designee) to 
ensure the research supports appropriate and well-defined scientific research activities.

Residual samples (see Table 9.8.4-1) will be retained for additional research purposes
Samples kept for future research will be stored at the BMS Biorepository in 
 or 
an independent, BMS approved storage vendor.
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than fifteen (15) 
years after the end of the study or the maximum allowed by applicable law.
Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
Table 9.8.4-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Timepoints for which residual samples will be retained
Serum/Plasma 
(including PK/IMG 
samples)
All
Peripheral Blood
All
All
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Abbreviations: IMG, immunogenicity; PK, pharmacokinetics.
9.8.5
Methods to Detect HPV Status of SCCHN Originating in the Oropharynx
HPV status for oropharyngeal cancer must be determined locally 
 as 
described below. If HPV status was previously determined using an acceptable method listed 
below, re-testing is not necessary.
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9.9
Health Economics OR Medical Resource Utilization and Health 
Economics

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
10.1
Sample Size Determination
10.1.1
Parts 1A and 1B
Participants will be dosed in Cohorts 1B1, 1B2, and 1B3, and may be dosed in up to 4 other 
treatment regimens based on PK, pharmacodynamic, and/or safety analyses (Cohorts 1B4, 1B5, 
1B6, 
. Approximately
participants will be initially dosed in the treatment arm(s) of interest 
in Part 1.
Approximately 4 participants were treated initially with BMS-986253 2400 mg in combination 
with 480 mg nivolumab Q4W in Part 1A. With no safety concern identified, participants will be 
randomly assigned in an approximately 1:1:1 allocation ratio into 3 dose combinations, 
BMS-986253 2400 mg, 1200 mg, and 600 mg Q4W in combination with 480 mg nivolumab Q4W. 
See Section 7.4 for details regarding randomization. 
There will be continuous analysis 
. If these analyses indicate 
that further assessment of a treatment regimen is not warranted and/or a need for assessing 
additional treatment regimens is indicated, then the randomization will be stopped, and subsequent 
participants will be assigned sequentially to either existing treatment regimens, or treatment 
regimens with alternative dosing schedules. The highest dosing regimen used will be 3600 mg 
BMS-986253 Q2W in combination with 480 mg nivolumab. If any dosing regimen evaluates a 
higher dose of BMS-986253 than previously explored, an initial 4-participant safety lead-in with 
a 28-day DLT period will be required.
 
 
 
 
 
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10.1.2
Part 1C
The purpose of Part 1C is to generate safety data on the triplet combination of BMS-986253, 
nivolumab, and ipilimumab. Although the number of participants is not based on statistical power 
considerations, 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A maximum of approximately 
 participants will be dosed in Part 1 as a whole.
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10.1.3
Part 2
The purpose of Part 2 is to evaluate efficacy and gather additional safety, tolerability, PK, and 
pharmacodynamic information between BMS-986253 RP2D in combination with nivolumab and 
ipilimumab versus placebo in combination with nivolumab and ipilimumab. Participants with 
anti-PD-(L)1-refractory unresectable or metastatic melanoma (non-ocular) who have not been 
treated with prior anti-CTLA-4 therapy will be randomly assigned in a 1:1 ratio to 1 of 2 treatment 
arms.
 
 
 
 
 
 
 
10.2
Populations for Analyses
Population
Description
Enrolled/Randomized
All participants who have signed informed consent and are registered into 
the IRT
Treated
All participants who received at least 1 dose of study treatment
Efficacy
All participants who take at least 1 dose of their planned full combination 
treatment.
Response-evaluable
All treated participants with measurable disease at baseline and one of the 
following: (1) at least 1 post-baseline tumor assessment, (2) clinical 
progression, or (3) death
Pharmacokinetic
All treated participants who have evaluable concentration-time data
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Population
Description
Immunogenicity
All treated participants who have baseline and at least one post baseline 
immunogenicity assessment
Biomarker
All treated participants with available biomarker data
Abbreviation: IRT, Interactive Response Technologies.
10.3
Statistical Analyses
The statistical analysis plan will be developed and finalized before database lock and will describe 
the selection of participants to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. Below is a summary of planned statistical analyses of the 
primary and secondary endpoints.
A description of the participant population will be included in a statistical output report, including 
subgroups of age, gender, and race.
10.3.1
Efficacy Analyses
The main efficacy analyses will be performed on the efficacy population for the final analysis. 
Efficacy analyses based on the response-evaluable population may be performed for interim 
analyses (as per Section 10.3.8). Efficacy analyses may be performed on selected subgroups, 
including biomarker-selected subgroups. Efficacy analyses will be performed using the RECIST 
v1.1 criteria. Additional details on efficacy analyses are provided in Table 10.3.1-1.
Table 10.3.1-1:
Part 1 Efficacy Analysis
Endpoint
Statistical Analysis Methods
ORR is defined as the proportion of participants whose BOR is either CR 
or PR in the population of interest.
BOR for a participant will be assessed per RECIST v1.1 by investigator, 
otherwise specified
Estimate of ORR and corresponding 
two-sided exact 95% CI using the 
 by 
treatment for each tumor type 
DOR
DOR for a participant with a BOR of CR or PR, is defined as the time 
between the date of first response and the date of the first objectively 
documented tumor progression per RECIST v1.1 or death, whichever 
occurs first.
Median duration of response using 
 and 
corresponding two-sided 95% CI 
using Brookmeyer and Crowley 
methodology (using log-log 
transformation) by treatment for 
each tumor type
Abbreviations: BOR, best overall response; CI, confidence interval; CR, complete response; DOR, duration of 
response; ORR, objective response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.
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Table 10.3.1-2:
Part 2 Efficacy Analysis
Endpoint
Statistical Analysis Methods
BICR-assessed ORR
ORR is defined as the proportion of participants whose BOR 
is either CR or PR in the population of interest.
BOR for a participant will be assessed per RECIST v1.1. BOR 
per RECIST v1.1 is defined as the best response designation 
recorded between the date of the first dose and the date of first 
objectively documented progression per RECIST v1.1 or the 
date of subsequent therapy, whichever occurs first. For 
participants who continue treatment beyond progression per 
RECIST v1.1 or begin subsequent therapy, the BOR should 
be determined based on response designations recorded up to 
the time of the initial progression or subsequent therapy, 
whichever occurs first. For participants without documented 
progression or subsequent therapy, all available response 
designations should contribute to the BOR assessment.
 
 will be used to 
compare ORR between 2 treatment groups. The 
associated odds ratio and CI will also be 
calculated.
DOR
DOR for a participant with a BOR of CR or PR is defined as 
the time between the date of first response and the date of the 
first 
objectively 
documented 
tumor 
progression 
per 
RECIST v1.1 or death, whichever occurs first. Participants 
who die without a reported progression will be considered to 
have progressed on the date of their death. Participants who 
did not progress or die will be censored on the date of their 
last evaluable tumor assessment. Participants who did not 
have any on-study tumor assessments and did not die will be 
censored on the date of first dose. Participants who started any 
subsequent anticancer therapy, including tumor-directed 
radiotherapy and tumor-directed surgery, without a prior 
reported progression will be censored at the last evaluable 
tumor assessment prior to initiation of the subsequent 
anticancer therapy.
The approach to handling events such as subsequent cancer 
therapy will be consistent between ORR and DOR. 
Median duration of response using 
method 
and corresponding two-sided 95% CI 
 
 
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Table 10.3.1-2:
Part 2 Efficacy Analysis
BICR-assessed PFS
PFS is defined as the time from first dose to the date of first 
objectively documented progression, per RECIST v1.1, or 
death due to any cause, whichever occurs first. Clinical 
deterioration in the absence of objectively documented 
progression per RECIST v1.1 is not considered progression 
for the purpose of determining PFS. Participants who die 
without a reported progression will be considered to have 
progressed on the date of their death. Participants who did 
not progress or die will be censored on the date of their last 
evaluable tumor assessment. Participants who did not have 
any on study tumor assessments and did not die will be 
censored on the date of first dose. Participants who started 
any subsequent anticancer therapy, including tumor-directed 
radiotherapy and tumor-directed surgery, without a prior 
reported progression will be censored at the last evaluable 
tumor assessment prior to initiation of the subsequent 
anticancer therapy. The PFSR at time T is defined as the 
probability that a participant has not progressed and is alive 
at time T following first dose.
The estimate of the PFS hazard ratio between 
treatment groups will be calculated using a 
stratified 
 with 
treatment and stratification factors as covariates. 
A two-sided 95% CI for the hazard ratio will also 
be presented.
The PFS curves for each treatment group will be 
estimated using 
 product limit method and 
will be displayed graphically. Median PFS with 
corresponding two-sided 95% CI in each 
treatment group will be computed via the log-log 
transformation method. 
PFS rates at fixed time points (eg, 3, 6, 9 months, 
depending on the minimum follow-up) will be 
presented along with their associated 95% CIs. 
These estimates will be derived from 
 
estimate and corresponding CIs will be derived 
based on 
 for variance 
derivation and on log-log transformation applied 
to the survivor function.
OS
OS is defined as the time between the date of first dose and 
the date of death due to any cause. For participants that are 
alive, their survival time will be censored at the date of last 
contact date (or “last known alive date”). OS will be 
censored at the date of first dose for participants who were 
dosed but had no follow-up.
A 2-sided 95% CI for median OS in each 
treatment group will be computed via the log-log 
transformation method. OS rates at fixed time 
points (eg, 12 months, depending on the 
minimum follow-up) will be presented along with 
their associated 95% CIs. These estimates will be 
derived from 
 estimate and corresponding 
CIs will be derived based on 
 
for variance derivation and on log-log 
transformation applied to the survivor function.
Abbreviations: BICR, blinded independent central review; BOR, best overall response; CI, confidence interval; 
 
CR, complete response; DOR, duration of response; 
 ORR, objective
response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RECIST, Response 
Evaluation Criteria in Solid Tumors.
10.3.2
Safety Analyses
All safety analyses for will be performed on the treated population.
Endpoint
Statistical Analysis Methods
Incidence of AEs, SAEs, AEs meeting protocol-
defined DLT criteria, AEs leading to 
discontinuation, deaths
AEs will be graded according to CTCAE v4.03.
DLT rate by dose level; Frequency distribution of treated 
participants with AE using the worst CTC grade. Participants 
will only be counted (1) once at the PT level, (2) once at the 
SOC level, and (3) once in the ‘Total participants’ row at 
their worst CTC grade, regardless of SOC or PT.
Laboratory abnormalities
Laboratory values will be graded according to 
CTCAE v4.03.
Laboratory shift table using the worst CTC grade on 
treatment per participant
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Abbreviations: AE, adverse event; CTC, Common Terminology Criteria; CTCAE, Common Terminology Criteria for 
Adverse Events; DLT, dose-limiting toxicity; PT, Preferred Term; SAE, serious adverse event; SOC, System Organ 
Class.
10.3.3
Pharmacokinetic Analyses
Endpoint
Statistical Analysis Methods
Cmax, AUC(0-T), AUC(TAU), Ctau, CLT, Css-avg, AI_AUC, 
AI_Cmax, AI_Ctau, T-HALF
Summary statistics: geometric means and 
coefficients of variation
Tmax
Summary statistics: medians and ranges
Ctrough
Summary statistics to assess attainment of 
steady state: geometric means and coefficients 
of variation; plots vs time by dose
Abbreviations: AI_AUC, AUC Accumulation Index; AI_Cmax, Cmax Accumulation Index; AI_Ctau, Ctau 
Accumulation Index; AUC(0-T), area under the plasma serum concentration-time curve from time zero to time of last
quantifiable concentration; AUC(TAU), area under the serum concentration-time curve in 1 dosing interval; CLT, total
body clearance; Css-avg, average serum concentration over a dosing interval (AUC[TAU]/tau) at steady state; Ctau, 
observed serum concentration at the end of a dosing interval; Tmax, Time of maximum observed plasma serum
concentration; Ctrough, trough observed serum concentrations (this includes pre-dose concentrations [C0] and Ctau).
Note: PK time-concentration data may be pooled with data from other studies for PPK analysis, which will be 
presented in a separate report.
10.3.4
Immunogenicity Analyses
Endpoint
Statistical Analysis Methods
Incidence of ADA to BMS-986253, nivolumab, or ipilimumab 
administrated in combination
Baseline ADA-positive participant is defined as a participant
who has an ADA detected sample at baseline. ADA-positive 
participant is a participant with at least 1 ADA-positive sample 
relative to baseline after initiation of the treatment
Frequency distribution of baseline ADA-
positive participants and ADA-positive 
participants after initiation of the treatment; 
summary of ADA peak titer, ADA onset and 
duration, summary of select AEs by ADA 
status, summary of BOR by ADA status
Abbreviation: ADA, anti-drug antibody; AE, adverse event; BOR, best overall response.
10.3.5
Biomarker Analyses
Endpoint
Statistical Analysis Methods
Summary measures of absolute values of serum IL-8, and 
change (or percent change) from baseline in serum IL-8
Summary statistics by planned study day and 
cohort; Plots of the time course of biomarkers, 
geometric mean of the ratio of post-baseline 
IL-8 and corresponding CI.
Abbreviations: CI, confidence interval; IL-8, interleukin-8.
10.3.6
ECG Analyses
All ECG data analyses including summaries of each ECG parameter, frequency distribution of 
participants’ maximum values/changes, and scatter plots will be performed following the current 
practice of ECG data analysis. Concentration-response analysis may be performed using the mixed 
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effect model, if appropriate and applicable. The details of ECG data analysis will be provided in 
the Statistical Analysis Plan (SAP).
10.3.7
Other Analyses
 
 
 
 PFS for a participant is defined as the time 
from the first dosing date to the date of first objectively documented disease progression or death 
due to any cause, whichever occurs first. 
 
 
 OS is defined as the time between the date of first dose and the date of death due 
to any cause. For participants who are alive, their survival time will be censored at the date of last 
contact date (or “last known alive date”). OSR at 1 year and 2 years will be analyzed similarly to 
PFSR. The PPK and pharmacodynamic analyses may be presented separately from the main 
clinical study report.
10.3.8
Interim Analyses
10.3.8.1
Part 1
Interim analyses will be performed for administrative purposes or publication. No formal 
inferences requiring any adjustment to statistical significance level will be performed.
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35 Highfill SL, Cui Y, Giles AJ, et al. Disruption of CXCR2-mediated MDSC tumor trafficking 
enhances anti-PD1 efficacy. Sci Transl Med. 2014 May 21;6(237):237ra67.
36 Steele CW, Karim SA, Leach JDG, et al. CXCR2 Inhibition Profoundly Suppresses Metastases 
and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 2016 Jun 
13;29(6):832-845.
37 Curran MA, Montalvo W, Yagita H, et al. PD-1 and CTLA-4 combination blockade expands 
infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. 
Proc Natl Acad Sci USA 2010;107:4275-80.
38 Benoy IH, Salgado R, Van Dam P, et al. Increased serum interleukin-8 in patients with early 
and metastatic breast cancer correlates with early dissemination and survival. Clin Cancer Res 
2004;10:7157-62.
39 Xiao YC, Yang ZB, Cheng XS, et al. CXCL8, overexpressed in colorectal cancer, enhances 
the resistance of colorectal cancer cells to anoikis. Cancer Lett 2015;361:22–32.
40 Fang Y, Saiyin H, Zhao X, et al. IL-8-positive tumor-infiltrating inflammatory cells are a novel 
prognostic marker in pancreatic ductal adenocarcinoma patients. Pancreas 2016;45(5):671-8.
41 Li XP, Yang XY, Biskup E, et al. Co-expression of CXCL8 and HIF-1α is associated with 
metastasis and poor prognosis in hepatocellular carcinoma. Oncotarget 2015;6(26):22880-9.
42 Akiba J, Yano H, Ogasawara S, et al. Expression and function of interleukin-8 in human 
hepatocellular carcinoma. Int J Oncol 2001;18(2):257-64.
43 Welling TH, Fu S, Wan S et al. Elevated serum IL-8 is associated with the presence of 
hepatocellular carcinoma and independently predicts survival. Cancer Invest 2012;30(10):689-
97.
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44 Fu X, Dai Z, Song K, et al. Macrophage-secreted IL-8 induces epithelial-mesenchymal 
transition in hepatocellular carcinoma cells by activating the JAK2/STAT3/Snail pathway. Int 
J Oncol 2015;46:587-96.
45 Diaz-Montero CM, Salem ML, Nishimura MI, et al. Increased circulating myeloid-derived 
suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-
cyclophosphamide chemotherapy. Cancer Immunol Immunother 2009;58(1):49-59.
46 Gentzler R, Hall R, Kunk PR, et al. Beyond melanoma: inhibiting the PD-1/PD-L1 pathway in 
solid tumors. Immunotherapy 2016;8(5):583-600.
47 Olson DJ, Eroglu Z, Brockstein B, et al. Pembrolizumab plus ipilimumab following anti-PD-
1/L1 failure in melanoma. J Clin Oncol 2021;39:2647-55.
48 Pires da Silva I, Ahmed T, Reijers ILM, et al. Ipilimumab alone or ipilimumab plus anti-PD-1 
therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a 
multicentre, retrospective, cohort study. Lancet Oncol 2021;22:836-47.
49 National Comprehensive Cancer Network. Melanoma: Cutaneous Version 2.2021. Available 
from: URL: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf
50 Michielin O, van Akkooi ACJ, Ascierto PA, et al.; ESMO Guidelines Committee. Electronic 
address: clinicalguidelines@esmo.org. Cutaneous melanoma: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2019;30:1884-1901.
51 Patrinely, JR, Baker, LX, Davis, EJ, et al. Oucomes after progression of disease with anti-PD-
1/PD-L1 therapy for patients with advanced melanoma. Cancer 2020;126:3448-55.
52 Diem S, Kasenda B, Spain L, et al. Serum lactate dehydrogenase as an early marker for 
outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br J Cancer 
2016;114(3); 256-61.
53 Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab 
and ipilimumab in advanced melanoma. N Engl J Med 2019;381:1535-46.
54 Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and 
survival among patients with advanced melanoma. JAMA 2016;315(15):1600-9.
55 Spigel DR, McLeod M, Hussein MA. Randomized results of fixed-duration (1-yr) vs 
continuous nivolumab in patients (pts) with advanced non-small cell lung cancer (NSCLC) 
(Abstract 1297O) 2017, Ann Oncol 2017;28(Suppl 5):461.
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60 Wang DD, Zhang S, Zhao H, et al. Fixed dosing versus body size-based dosing of monoclonal 
antibodies in adult clinical trials. J Clin Pharmacol 2009;49(9):1012-24.
61 Bai S, Jorga K, Xin Y, et al. A guide to rational dosing of monoclonal antibodies. Clin 
Pharmacokinet 2012;51(2):119-35.
62 Hay KA, Hanafi LA, Li D, et al. Kinetics and biomarkers of severe cytokine release syndrome 
after CD19 chimeric antigen receptor-modified T-cell therapy. Blood 2017;130:2295-306.
63 Ceschi A, Noseda R, Palin K, et al. Immune checkpoint inhibitor-related cytokine release 
syndrome: analysis of WHO global pharmacovigilance database. Front Pharmacol 
2020;11:557.
64 Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent 
advances in pathophysiology, diagnosis and treatment. Rheumatology 2019;58:5-17. doi: 
10.1093/rheumatology/key006. PMID: 29481673.
65 Retamozo S, Brito-Zerón P, Sisó-Almirall A, et al. Haemophagocytic syndrome and COVID-
19. Clin Rheumatol 2021;40:1233-44. doi: 10.1007/s10067-020-05569-4. PMID: 33389315; 
PMCID: PMC7778844. 
66 Mohamed Jiffry MZ, Ahmed-Khan M, Vargas J, et al. Hemophagocytic Lymphohistiocytosis 
in a Patient With Post-acute COVID-19 Infection. Cureus 2022;14:e31451. doi: 
10.7759/cureus.31451. PMID: 36523678; PMCID: PMC9747112. 
67 Karakike E, Giamarellos-Bourboulis EJ. Macrophage Activation-Like Syndrome: A Distinct 
Entity Leading to Early Death in Sepsis. Front Immunol 2019;31:10-55. doi: 
10.3389/fimmu.2019.00055. PMID: 30766533; PMCID: PMC6365431. 
68 Noseda R, Bertoli R, Müller L, et al. Haemophagocytic lymphohistiocytosis in patients treated 
with immune checkpoint inhibitors: Analysis of WHO global database of individual case safety 
reports. J ImmunoTher Cancer 2019;7:117.
69 Nivolumab (BMS-936558). Response to the Pharmacovigilance Risk Assessment Committee 
(PRAC) signal assessment report on haemophagocytic lymphohistiocytosis (HLH) with 
Nivolumab (OPDIVO); dated 03-Oct-2019. Bristol-Myers Squibb. Response document dated 
26-Nov-2019. Document Control No. 930146897.
70 Ramos-Casals M, Brito-Zerón P, López-Guillermo A, et al. Adult haemophagocytic syndrome. 
Lancet 2014; 26;383:1503-16. doi: 10.1016/S0140-6736(13)61048-X. Epub 2013 Nov 27. 
Erratum in: Lancet. 2014 Apr 26;383(9927):1464. PMID: 24290661.
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71 Lehmberg K, Nichols KE, Henter JI, Girschikofsky M, Greenwood T, Jordan M, Kumar A, 
Minkov M, La Rosée P, Weitzman S; Study Group on Hemophagocytic Lymphohistiocytosis 
Subtypes of the Histiocyte Society. Consensus recommendations for the diagnosis and 
management of hemophagocytic lymphohistiocytosis associated with malignancies. 
Haematologica. 2015 Aug;100(8):997-1004. doi: 10.3324/haematol.2015.123562. PMID: 
26314082; PMCID: PMC5004414. 
72 Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, Coppo P, Hejblum G. 
Development and validation of the HScore, a score for the diagnosis of reactive 
hemophagocytic 
syndrome. 
Arthritis 
Rheumatol. 
2014 
Sep;66(9):2613-20. 
doi: 
10.1002/art.38690. PMID: 24782338. (available from http://saintantoine.aphp.fr/score/)
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12
APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
ADA
anti-drug antibody
AE
adverse event
AFP
alpha fetoprotein
AI
accumulation index
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after 
the first dose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALK
anaplastic lymphoma kinase
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the serum concentration-time curve
AUC(0-T)
area under the concentration-time curve from time zero to the time of last 
quantifiable concentration
AUC(TAU)
area under the serum concentration-time curve in 1 dosing interval
BICR
blinded independent central review
BMS
Bristol Myers Squibb
BOR
best overall response
BP
blood pressure
BRAF
proto-oncogene B-Raf
C
Cycle
Cavgss
average steady-state concentration
CBC
complete blood count
CD8
cluster of differentiation 8
CFR
Code of Federal Regulations 
CI
confidence interval
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Term
Definition
CLT
total body clearance
Cmax
maximum observed plasma concentration
CNS
central nervous system
CONSORT
Consolidated Standards of Reporting Trials
CR
complete response
CRC
colorectal cancer
CrCl
creatinine clearance
CRF
case report form, paper or electronic
CSC
cancer stem cell
Css-avg
average serum concentration over a dosing interval (AUC[TAU]/tau) at
steady state
CT
computed tomography
Ctau
observed serum concentration at the end of a dosing interval
CTC
common terminology criteria
CTCAE
Common Terminology Criteria for Adverse Events
CTLA-4
cytotoxic T-lymphocyte-associated protein 4
Ctrough
trough observed serum concentrations 
CXCR1/2
C-X-C chemokine receptor type 1/2
CxDx
Cycle x Day x
d
days
D
Day
DILI
drug-induced liver injury
dL
deciliter
DLT
dose-limiting toxicity
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
DOR
duration of response
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Term
Definition
EBV
Epstein-Barr virus
EC
Ethics Committee
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
Electronic Data Capture
eg
exempli gratia
EGFR
epidermal growth factor receptor
EMT
epithelial mesenchymal transition
EOI
end of infusion
EOT
end of treatment
FDA
Food and Drug Administration
FPFV
first patient first visit
FSH
follicle-stimulating hormone
FU
follow-up
g
gram
GPVE
Global Pharmacovigilance and Epidemiology
HCC
hepatocellular carcinoma
HER2
human epidermal growth factor receptor 2
hCG
human chorionic gonadotropin
HCV
hepatitis C virus
HIPAA
Health Insurance Portability and Accountability Act
HIV
human immunodeficiency virus
HLH
hemophagocytic lymphohistiocytosis
HPV
human papillomavirus
Hr, hr
hour
HR
hazard ratio
IB
Investigator’s Brochure
ICF
informed consent form
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Term
Definition
ICI
immune checkpoint inhibitor
IFN-γ
interferon gamma
Ig
immunoglobulin
IgG1κ
immunoglobulin G1 kappa
IHC
immunohistochemistry
IL-8
interleukin-8
IMAR
immune-mediated adverse reaction
IMG
immunogenicity
IMP
Investigational Medicinal Product
I-O
immuno-oncology
IP
Investigational Product
irAE
immune-related adverse event
IRT
Interactive Response Technology
iu
international unit
ius
intrauterine hormone releasing system
IV
intravenous
IVIG
intravenous immunoglobulin
kg
kilogram
L
liter
LAM
lactational amenorrhea method
LDH
lactate dehydrogenase
LPLV
last patient last visit
mAb
monoclonal antibody
MALS
macrophage activation-like syndrome
MAS
macrophage activation syndrome
MDSC
myeloid-derived suppressor cells
mg
milligram
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Term
Definition
min
minute
mL
milliliter
MLH1
MutL homolog 1
MM
medical monitor
MMR
measles, mumps, rubella
MR
medical research
mRECIST
modified Response Evaluation Criteria in Solid Tumors
MRI
magnetic resonance imaging
msec
millisecond
MSH2
MutS Homolog 2
MSH6
MutS Homolog 6
MSI
microsatellite instability status
MSI-H
microsatellite instability-high
MSS
microsatellite stable
MTD
maximum tolerated dose
g
microgram
N
number of participants or observations
NCI
National Cancer Institute
Nivo
nivolumab
NK
natural killer
NLR
neutrophil-to-leukocyte ratio
Non-IMP
noninvestigational Medicinal Product
NSCLC
non-small cell lung cancer
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
progressive disease
PD-1
programmed cell death 1
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Term
Definition
p-DILI
potential drug-induced liver injury
PD-L1
programmed death ligand-1
PD-L2
programmed death ligand-2
PE
physical examination
PET
positron emission tomography
PFS
progression-free survival
PFSR
progression-free survival rate
PID
patient identifier number
PK
pharmacokinetic(s)
pMMR
mismatch repair proficient
PMS2
protein homolog 2, mismatch repair system component
PPK
population pharmacokinetics
PR
partial response
PT
Preferred Term
Q
quartile
Q12W
every 12 weeks
Q2W
every 2 weeks
Q3W
every 3 weeks
Q4W
every 4 weeks
Q8W
every 8 weeks
QXW
every X weeks
R
randomized
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
ROS1
c-ros oncogene 1
RP2D
recommended Phase 2 dose
RSI
Reference Safety Information
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Term
Definition
RT
reverse transcriptase
S
sequential assignment
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
SD
standard deviation
sIL-8
serum interleukin 8
SMT
Safety Management Team
SOC
System Organ Class
SpO2
percentage of blood saturation
SUSAR
Suspected, Unexpected Serious Adverse Reaction
T3
triiodothyronine
T4
thyroxine
TAU
dosing interval
Tmax
time of maximum observed plasma serum concentration
TMB
tumor mutational burden
 
TNBC
triple-negative breast cancer
TRAE
treatment-related adverse event
TSH
thyroid-stimulating hormone
UCC
urothelial cancer
ULN
upper limit of normal
US
United States [of America]
WOCBP
women of childbearing potential
WNOCBP
women not of childbearing potential
WS
World-wide Patient Safety
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The terms “participant” and “subject” refer to a person who has consented to participate in the 
clinical research study. Typically, the term “participant” is used in the protocol and the term 
“subject” is used in the Case Report Form (CRF).
REGULATORY AND ETHICAL CONSIDERATIONS
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 

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP)
Guidelines

Applicable laws, regulations, and requirements
The study will be conducted in compliance with the protocol. The protocol,
any 
revisions/amendments,
and the participant
informed consent
form (ICF)
will receive 
approval/favorable 
opinion 
by 
Institutional 
Review 
Board/Independent 
Ethics 
Committee (IRB/IEC), and regulatory authorities according to applicable 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) that is likely to affect, 
to a significant degree, one or more of the following: (1) the rights, physical safety or mental 
integrity of one or more participants; (2) the scientific value of the clinical 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, Investigator’s Brochure, product labeling information, ICF, 
participant recruitment materials (eg, advertisements), and any other written information to be 
provided to participants.
The investigator, Sponsor, or designee should provide the IRB/IEC with reports, updates, and other 
information (eg, expedited safety reports, amendments, administrative letters) annually, or more 
frequently, in accordance with regulatory requirements or institution procedures.
The investigator is responsible for providing oversight of the conduct of the study at the site and 
adherence to requirements of the following where applicable:
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
ICH guidelines,

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50),

European Regulation 536/2014 for clinical studies, 

European Medical Device Regulation 2017/745 for clinical device research,

the IRB/IEC,

and all other applicable local regulations.
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 the local Health Authority), except where necessary to eliminate an immediate 
hazard(s) to study 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 the local Health Authority must be sent to Bristol-Myers 
Squibb (BMS).
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the ICF 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 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 participants prior to enrollment.
FINANCIAL DISCLOSURE
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information, in accordance with 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 participants are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which they volunteer to 
participate. 
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The Sponsor or designee will provide the investigator with an appropriate sample ICF, which will 
include all elements required by the ICH GCP, and applicable regulatory requirements. The sample 
ICF will adhere to the ethical principles that have their origin in the Declaration of Helsinki.
The investigator or his/her representative must:

Obtain IRB/IEC written approval/favorable opinion of the written ICF and any other 
information to be provided to the participant prior to the beginning of the study and after any 
revisions are completed for new information.

Provide a copy of the ICF and written information about the study in the language in which 
the participant is proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 

Explain the nature of the study to the participant or his/her legally acceptable representative
and answer all questions regarding the study.

Inform participant that his/her participation is voluntary. Participant or his/her legally 
acceptable representative (defined as an individual or juridical or other body authorized under 
applicable law to represent the interests of an individual, including providing consent on behalf 
of a prospective subject to the subject's participation in the clinical trial) will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.

Allow time necessary for participant or his/her legally acceptable representative to inquire 
about the details of the study.
Obtain an ICF signed and personally dated by participant or his/her legally acceptable 
representative and by the person who conducted the informed consent discussion. 

Include a statement in participant’s medical record that written informed consent was obtained 
before participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.

Re-consent participant to the most current version of the ICF(s) during his/her participation in 
the study, as applicable.
Revise the ICF 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 his/her legally acceptable representative 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 participants must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the participant’s signed 
ICF, and, in the US, the participant’s signed HIPAA Authorization.
The ICF must also include a statement that BMS and local and foreign regulatory authorities have 
direct access to participant records. 
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In situations where consent cannot be given by participants, their legally acceptable representatives 
(as per country regulations) are clearly and fully informed about the purpose, potential risks, and 
other critical issues regarding clinical studies in which the participant volunteers to participate. 
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.
The rights, safety, and well-being of the study participants are the most important considerations 
and should prevail over interests of science and society.
BMS COMMITMENT TO DIVERSITY IN CLINICAL TRIALS
The mission of BMS is to transform patients’ lives through science by discovering, developing, 
and delivering innovative medicines that help them prevail over serious diseases. 
BMS is committed to doing its part to ensure that patients have a fair and just opportunity to 
achieve optimal health outcomes.
BMS is working to improve the recruitment of a diverse participant population with the goal that 
the clinical trial becomes more reflective of the real-world population and the people impacted by 
the diseases studied.
DATA PROTECTION, DATA PRIVACY, AND DATA SECURITY
BMS collects and processes personal data of study participants, patients, health care providers, 
and researchers for biopharmaceutical research and development to advance innovative, high-
quality medicines that address the medical needs of patients. BMS ensures the privacy, protection, 
and confidentiality of such personal data to comply with applicable laws. To achieve these goals, 
BMS has internal policies that indicate measures and controls for processing personal data. BMS 
adheres to these standards to ensure that collection and processing of personal data are limited and 
proportionate to the purpose for which BMS collects such personal data. This purpose is clearly 
and unambiguously notified to the individual at the time of collection of personal data. In the true 
spirit of science, BMS is dedicated to sharing clinical trial information and data with participants, 
medical/research communities, the media, policy makers, and the general public. This is done in a 
manner that safeguards participant privacy and informed consent while respecting the integrity of 
national regulatory systems. Clinical trial data, health-related research, and pharmacovigilance 
activities on key-coded health data transferred by BMS across national borders is done in 
compliance with the relevant data protection laws in the country and GCP requirements.
BMS protects Personal Information with adequate and appropriate security controls as indicated 
under the data protection laws. To align with the recommended security standards, BMS has 
adopted internal security standards and policies to protect personal data at every stage of 
its processing.
To supplement these standards, BMS enters into Clinical Trial Agreements (CTAgs) with 
confidentiality obligations to ensure proper handling and protection of personal data by third 
parties accessing and handling personal data.
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BMS takes unauthorized access and disclosure of Personal Information very seriously. BMS has 
adopted the security standards that include National Institute of Standards and Technology 
Cybersecurity Framework for studies in the US. BMS aligns with these standards to continuously 
assess and improve its ability to protect, detect, and respond to cyber attacks and other 
unauthorized attempts to access personal data. These standards also aid in mitigating possible 
adverse effects. Furthermore, BMS Information Technology has defined 6 principles to protect our 
digital resources and information: 
1)
Responsibilities of IT Personnel
2) Securing the BMS Digital Infrastructure
3) Identity and Access Management
4) External Partner Connections
5) Cyber Threat Detection and Response
6) Internal Cyber Incident Investigation
SOURCE DOCUMENTS
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be explained. 

The investigator may need to request previous medical records or transfer records, depending 
on the study. Also, current medical records must be available.

Definitions of what constitutes source data can be found in ICH E6 GCP.
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are handwritten on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical records/electronic health 
records, adverse event (AE) tracking/reporting, protocol-required assessments, and/or drug 
accountability records.
When paper records from such systems are used in place of an 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. 
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STUDY TREATMENT RECORDS
Records for study intervention (whether supplied by BMS, its vendors, or the site) must 
substantiate study intervention 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 site’s stock or 
commercial supply or a specialty 
pharmacy)
The investigator or designee accepts responsibility 
for documenting traceability and study treatment
integrity in accordance with requirements applicable 
under
law 
and 
the 
standard 
operating 
procedures/standards of the sourcing pharmacy
BMS or its 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 
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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 (EDC) tool, eCRFs 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 the 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
the Sponsor or designee. 
The confidentiality of records that could identify 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 and SAE/pregnancy CRFs must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a sub-investigator and who is delegated this task on 
the Delegation of Authority Form. Sub-investigators in Japan may not be delegated the CRF 
approval task. For eCRFs, review and approval/signature is completed electronically through the 
BMS EDC tool. The investigator must retain a copy of the CRFs including records of the changes 
and corrections.
Each individual electronically signing eCRFs must meet Sponsor or designee training 
requirements and must only access the BMS EDC tool using the unique user account provided by 
the Sponsor or designee. User accounts are not to be shared or reassigned to other individuals
MONITORING
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site, they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable.
In addition, the study may be evaluated by the 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 the Sponsor or designee.
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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 its 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 its 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 its designee. 
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS or 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 interventions 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).
Partially used study interventions and/or 
empty containers may be destroyed after 
proper reconciliation and documentation. But 
unused IMP must be reconciled by site 
monitor/Clinical Research Associate prior to 
destruction.
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; eg, study treatments 
sourced from the site’s stock or commercial 
supply or a specialty pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
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It is the investigator’s or designee’s responsibility to arrange for disposal of study interventions, 
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 standard operating procedures 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 (eg, 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 Study 
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.
It is, however, the investigator’s or designee’s responsibility to arrange for disposal of all empty 
study treatment containers, 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 return of full or partially used study 
treatments supplied by BMS or its vendors will be arranged by the responsible Study Monitor.
STUDY AND SITE START AND CLOSURE
The Sponsor/designee reserves the right to close the study site or to terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or investigator may include, but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local Health Authorities, the Sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator
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
Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
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.
In the European Union (EU), the summary of results and summary for laypersons will be submitted 
within 1 year of the end of trial in EU/European Economic Area and third countries.
CLINICAL STUDY REPORT 
A Signatory Investigator must be selected to sign the Clinical Study Report (CSR). 
For each CSR related to this protocol, the following criteria will be used to select the Signatory 
Investigator:

Participant recruitment

Involvement in trial design

Other criteria (as determined by the study team)
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to the 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 the 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.  
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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 participants 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.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW UP, AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in a clinical investigation participant administered study 
treatment that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, electrocardiogram, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis.

Exacerbation of a chronic or intermittent pre-existing condition, including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration, even though 
it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/serious adverse event (SAE) unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae and should specify “intentional overdose” as the verbatim 
term.
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy); the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE, even if serious conditions 
are met.
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SERIOUS ADVERSE EVENTS
A 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 Bristol-Myers Squibb (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 (eg, 
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 (eg, 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 [eg, 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 and 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.) 
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Pregnancy and DILI must follow the same transmission timing and processes to BMS as used for 
SAEs. (See Section 9.2.5 for reporting pregnancies.)
Any component of a study endpoint that is considered related to study therapy should be reported 
as an SAE (eg, death is an endpoint; if death occurred due to anaphylaxis, anaphylaxis must be 
reported).
EVALUATING AES AND SAES
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated.

The investigator will also consult the Investigator’s Brochure 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 the 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 the Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.

Assessment of Intensity
All SAEs and AEs will be assessed using National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03.
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.) 
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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.
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 electronic case report 
form (eCRF).

The paper SAE Report Form is intended only as a back-up option when the electronic 
data capture system is unavailable/not functioning for transmission of the eCRF to BMS 
(or designee).
In this case, the paper form is transmitted via email or confirmed facsimile 
transmission.
When paper forms are used, the original paper forms are to remain on site.

Pregnancies must be recorded on paper Pregnancy Surveillance Forms and transmitted via 
email or confirmed facsimile transmission 
SAE Email Address: 
SAE Facsimile Number: Will be provided by local site monitor.
SAE Telephone Contact (required for SAE and pregnancy reporting): Will be provided by local 
site monitor.
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
Appendix 4 provides general information and definitions related to Woman of Childbearing 
Potential and methods of contraception that can be applied to most clinical trials. For information 
specific to this study regarding acceptable contraception requirements for female and male 
participants, refer to Section 6.1 of the protocol. Only the contraception methods as described in 
Section 6.1 are acceptable for this study.
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.
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. Suggested 
guidelines for the duration of the washout periods for HRT types are presented below. Investigators 
should use their judgement in checking serum FSH levels. 

1-week minimum for vaginal hormonal products (rings, creams, gels)

4-week minimum for transdermal products

8-week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
End of Relevant Systemic Exposure
End of relevant systemic exposure is the timepoint where the Investigational Medicinal Product 
(IMP) or any active major metabolites have decreased to a concentration that is no longer 
considered to be relevant for human teratogenicity or fetotoxicity. This should be evaluated in 
context of safety margins from the no-observed-adverse-effect level or the time required for 5 half-
lives of the IMP to pass.
METHODS OF CONTRACEPTION 
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of < 1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation. (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol.)b

Oral (birth control pills)

Intravaginal (rings)

Transdermal

Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy.

Progestogen-only hormonal contraception associated with inhibition of ovulation. (This
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol.)b

Oral

Injectable

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy.
Highly Effective Methods That Are User Independent

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation. (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol.)b

Intrauterine device.

Intrauterine hormone-releasing system (IUS). (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol.)b,c

Bilateral tubal occlusion.
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
Vasectomized partner 
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 

Sexual abstinence.
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant.

Continuous abstinence must begin at least 30 days prior to initiation of study therapy.

It is not necessary to use any other method of contraception when complete abstinence is 
elected.

WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2.

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participant chooses to forego complete abstinence.

Periodic abstinence (including, but not limited to, calendar, symptothermal, postovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES: 
a Typical use failure rates may differ from failure rates when contraceptive methods are used consistently and 
correctly. Use should be consistent with local regulations regarding the use of contraceptive methods for 
participants in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous. In this case, alternative 
methods of contraception should be utilized. For information specific to this study regarding permissibility of 
hormonal contraception, refer to Sections 6.1 INCLUSION CRITERIA and 7.9.1 PROHIBITED AND/OR 
RESTRICTED TREATMENTS of the protocol.
c IUSs are acceptable methods of contraception in the absence of definitive drug interaction studies when hormone 
exposures from intrauterine devices do not alter contraception effectiveness. For information specific to this 
study regarding permissibility of hormonal contraception, refer to Sections 6.1 INCLUSION CRITERIA and 
7.9.1 PROHIBITED AND/OR RESTRICTED TREATMENTS of the protocol.
Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of > 1% per year when used consistently and correctly.

Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously.

Diaphragm with spermicide.

Cervical cap with spermicide.

Vaginal sponge with spermicide.
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
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action. (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited.)
Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, postovulation methods).

Withdrawal (coitus interruptus).

Spermicide only.

LAM.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of pregnancy information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and Appendix 3.
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APPENDIX 5
ECOG PERFORMANCE STATUS
These scales and criteria are used by doctors and researchers to assess how a patient's disease is 
progressing, assess how the disease affects the daily living abilities of the patient, and determine 
appropriate treatment and prognosis. They are included here for health care professionals to access.
ECOG PERFORMANCE STATUS*
Grade
ECOG
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, 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
* As published in Am. J. Clin. Oncol.:
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.
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APPENDIX 6
MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 4.0
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.
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APPENDIX 8
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS
1
EVALUATION OF LESIONS
Solid tumors will be evaluated using Response Evaluation Criteria In Solid Tumors version 1.1 
(RECIST 1.1) guideline with BMS modifications.1
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows:
2
MEASURABLE
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of:
10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ൒2x slice thickness if 
greater than 5mm.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be ≥15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm).
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
3
NON-MEASURABLE
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10mm or pathological lymph nodes with ≥10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
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3.1
Special considerations regarding lesion measurability
3.1.1 Bone lesions

Bone scan, PET scan and plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 

Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.

Blastic bone lesions are non-measurable.
4
BASELINE DOCUMENTATION OF ‘TARGET’ AND ‘NON-TARGET’ LESIONS
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline (this means in 
instances where patients have only one or two organ sites involved a maximum of two and four 
lesions respectively will be recorded).
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum of 
two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’).
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5
RESPONSE CRITERIA
5.1
Evaluation of Target Lesions

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.

Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed 
as either fully resolved or too small to measure (due to missing or poor quality images), and 
the sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above. 
5.1.1 Special Notes on the Assessment of Target Lesions
5.1.1.1 Lymph nodes
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target lesions, 
the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a normal 
lymph node is defined as having a short axis of < 10 mm. Case report forms or other data collection 
methods may therefore be designed to have target nodal lesions recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions.
5.1.1.2 Target lesions that become ‘too small to measure’
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
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small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 
default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm.
5.1.1.3 Lesions that split or coalesce on treatment
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’.
5.2
Evaluation of Non-Target Lesions
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need 
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol.

Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10mm short axis). 

Non-CR/Non-PD: Persistence of one or more non-target lesion(s)

Progressive Disease (PD): Unequivocal progression of existing non-target lesions.
5.2.1 Special Notes on Assessment of Progression of Non-Target Disease
The concept of progression of non-target disease requires additional explanation as follows:
5.2.1.1 When the patient also has measurable disease
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy A modest ‘increase’ in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. Pleural effusions, pericardial 
effusions and ascites will not be followed as target or non-target lesions and will not contribute to 
response or progression. The designation of overall progression solely on the basis of change in 
non-target disease in the face of SD or PR of target disease will therefore be extremely rare.
5.2.1.2 When the patient has only non-measurable disease
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
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disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 
if all lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the change 
in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in lymphangitic disease from localized to widespread, or may be 
described as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the 
patient should be considered to have had overall PD at that point. While it would be ideal to have 
objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore the increase must be substantial.
5.2.2 New Lesions
The appearance of new malignant lesions denotes disease progression; therefore, some comments 
on detection of new lesions are important. There are no specific criteria for the identification of 
new radiographic lesions; however, the finding of a new lesion should be unequivocal: ie, not 
attributable to differences in scanning technique, change in imaging modality or findings thought 
to represent something other than tumor (for example, some ‘new’ bone lesions may be simply 
healing or flare of pre-existing lesions). This is particularly important when the patient’s baseline 
lesions show partial or complete response. For example, necrosis of a liver lesion may be reported 
on a CT scan report as a ‘new’ cystic lesion, which it is not.
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new fluid 
collection is seen on a post-baseline imaging exam, a comment may be made, but the appearance 
of a new fluid collection alone should not result in an assessment of Progressive Disease (PD). A 
lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD).
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. While FDG-PET 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
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possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according 
to the following algorithm:
1. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion.
2. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 
CT scans are needed to determine if there is truly progression occurring at that site (if so, the 
date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET 
at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD.
5.3
Response Assessment
5.3.1 Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
disease progression or the last response recorded, taking into account any requirement for 
confirmation and censoring rules regarding subsequent therapy. The patient’s best overall response 
assignment will depend on the findings of both target and non-target disease and will also take into 
consideration the appearance of new lesions. Furthermore, depending on the nature of the study 
and the protocol requirements, it may also require confirmatory measurement.
5.3.2 Time Point Response
At each protocol specified time point, a response assessment occurs. Table 5.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) disease 
only, Table 5.3.2-2 is to be used. 
Table 5.3.2-1:
Time Point Response: Patients With Target (± Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all 
evaluated
No
PR
SD
Non-PD or not all 
evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
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Table 5.3.2-1:
Time Point Response: Patients With Target (± Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable
Table 5.3.2-2:
Time Point Response: Patients with Non-target Disease Only
Non-Target Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR = complete response, PD = progressive disease and NE = inevaluable
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.
5.3.3 Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point of 
4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as in 
Table 5.3.3-1. When SD is believed to be best response, it must meet the protocol specified 
minimum time from the date of first treatment or randomization date.
For example, if the first scheduled follow-up imaging visit is Week 6 (± 7 days) for a particular 
protocol, a Best Response of SD can only be made after the subject is on-study for a minimum of 
6 weeks (42 days) minus 7 days, for an absolute minimum time on-study of 35 days from the 
reference start date (reference date is considered Day 1 on study).  If the subject is not on-study 
for at least this amount of time, any tumor assessment indicating stable disease before this time 
period will have a Best Response of NE unless PD is identified.
Special note on response assessment: When nodal disease is included in the sum of target lesions 
and the nodes decrease to ‘normal’ size (< 10 mm), they may still have a measurement reported 
on scans. This measurement should be recorded even though the nodes are normal in order not to 
overstate progression should it be based on increase in size of the nodes. As noted earlier, this 
means that patients with CR may not have a total sum of ‘zero’ on the case report form (CRF).
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Table 5.3.3-1:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
CR
CR
CR
PR
SD, PD OR PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
PR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and 
NE = inevaluable
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR.
5.3.4 Confirmation Scans
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation.
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease.
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REFERENCES
1 Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47
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APPENDIX 9
CHILD-PUGH SCORE
Score
Points
Child-Pugh A
5 - 6
Child-Pugh B
7 - 9
Child-Pugh C
> 9
Scoring
Score
Measure
1 Point
2 Points
3 Points
Ascites
Absent
Slight
Moderate
Serum bilirubin (mg/dl)
< 2.0
2.0 - 3.0
> 3.0
Serum albumin (g/dl)
> 3.5
2.8 - 3.5
< 2.8
PT prolongation or INR
< 4 sec
< 1.7
4 - 6 sec
1.7 - 2.3
> 6 sec
> 2.3
Encephalopathy grade
None
1 - 2
3 - 4
Abbreviations: INR = International normalized ratio; PT = prothrombin time.
Encephalopathy Grading
Encephalopathy Grade
Clinical Definition
Grade 0
Normal consciousness, personality, and neurological examination
Grade 1
Restless, sleep disturbed, irritable/agitated, tremor, and impaired handwriting
Grade 2
Lethargic, time-disoriented, inappropriate, asterixis, and ataxia
Grade 3
Somnolent, stuporous, place-disoriented, hyperactive reflexes, and rigidity
Grade 4
Unarousable coma, no personality/behavior, decerebrate
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APPENDIX 10
NEW YORK HEART ASSOCIATION FUNCTIONAL 
CLASSIFICATION
NYHA Class
Patients with Cardiac Disease (Description of Heart Failure 
Related Symptoms)
Class I (Mild)
Patients with cardiac disease but without resulting in limitation of 
physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation (rapid or pounding heart beat), dyspnea (shortness 
of breath), or anginal pain (chest pain).
Class II (Mild)
Patients with cardiac disease resulting in slight limitation of physical 
activity. They are comfortable at rest. Ordinary physical activity results 
in fatigue, palpitation, dyspnea, or anginal pain
Class III (Moderate)
Patients with cardiac disease resulting in marked limitation of physical 
activity. They are comfortable at rest. Less than ordinary activity causes 
fatigue, palpitation, dyspnea, or anginal pain.
Class IV (Severe)
Patients with cardiac disease resulting in the inability to carry on any 
physical activity without discomfort. Symptoms of heart failure or the 
anginal syndrome may be present even at rest. If any physical activity 
is undertaken, discomfort is increased.
Reference: The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of 
Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.
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APPENDIX 11
COUNTRY SPECIFIC AMENDMENTS
Germany and Any Other Countries Where Exclusion of HIV Positive Participants Is Locally 
Mandated
Country-specific language
Section 6.2 Exclusion
Criteria, Exclusion criterion 3) e)
“Known history of testing positive for human
immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS)”to be replaced with
“Positive test for HIV”.
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APPENDIX 13
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for Protocol Amendment 06, 17-May-2023
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 06
Section Number & Title
Description of Change
Brief Rationale
Table 2-2: Screening 
Procedural Outline (All 
Study Phases)
Table 2-5: On-treatment 
Procedural Outline 
 
 
Table 2-6: On-treatment 
Procedural Outline (Part 1C 
and Part 2 - BMS-986253 
Q2W and Nivolumab and 
Ipilimumab Q3W)
Table 2-7: Safety Follow-up 
Procedural Outline
Section 3.3.1: Safety 
Monitoring on Study 
Treatment
Table 4-2: Objectives and 
Endpoints - Part 2
Section 9.2.3: Follow-up of 
Adverse Events and Serious 
Adverse Events
Removed severe acute respiratory syndrome 
coronavirus 2 serology testing.
To align with revised Bristol-
Myers Squibb Company (BMS) 
guidelines. 
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 06
Section Number & Title
Description of Change
Brief Rationale
Section 9.8: Biomarkers
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 2-2: Screening 
Procedural Outline (All 
Study Phases)
Removed fasting requirement.
Fasting is no longer a 
requirement as it is not 
clinically necessary.
Table 2-2: Screening 
Procedural Outline (All 
Study Phases)
Table 2-3: On-treatment 
Procedural Outline (Part 1A 
and Cohorts 1B1 through 
1B3 - BMS-986253 Q4W 
and Nivolumab Q4W)
Table 2-4: On-treatment 
Procedural Outline (Cohorts 
1B4 through 1B6 - BMS-
986253 Q2W and Nivolumab 
Q4W)
Table 2-5: On-treatment 
Procedural Outline 
 
 
Table 2-6: On-treatment 
Procedural Outline (Part 1C 
and Part 2 - BMS-986253 
Q2W and Nivolumab and 
Ipilimumab Q3W)
Table 2-7: Safety Follow-up 
Procedural Outline
Added serious adverse event reporting 
requirements.
Clarified adverse event reporting.
Clarification and alignment 
throughout the protocol.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 06
Section Number & Title
Description of Change
Brief Rationale
Section 9.2.1:
Time 
Period and Frequency for 
Collecting Adverse Event 
and Serious Adverse Event
Information
Table 2-2: Screening 
Procedural Outline (All 
Study Phases)
Section 5.1.2: Screening 
Period
Section 6.1: Inclusion 
Criteria 
 
 
Clarified biopsy language.
Revised inclusion criteria for pre-treatment 
biopsy for participants enrolled in Part 2. 
To ensure data quality.
To improve study accessibility 
for participants in Part 2.
Table 2-2: Screening 
Procedural Outline (All 
Study Phases)
Specified timing of image acquisition.
Clarification.
Table 2-3: On-treatment 
Procedural Outline (Part 1A 
and Cohorts 1B1 through 
1B3 - BMS-986253 Q4W 
and Nivolumab Q4W)
Table 2-4: On-treatment 
Procedural Outline (Cohorts 
1B4 through 1B6- BMS-
986253 Q2W and Nivolumab 
Q4W)
Table 2-5: On-treatment 
Procedural Outline 
 
 
Table 2-6: On-treatment 
Procedural Outline (Part 1C 
and Part 2 - BMS-986253 
Q2W and Nivolumab and 
Ipilimumab Q3W)
Section 5.1.1: Follow-up
Section 5.1.5.1: Safety 
Follow-up Period
Specified end of treatment (EOT) definition. 
For participants who do not complete all 
scheduled cycles of therapy, the EOT visit 
will be the next visit following the last study 
dose. If the EOT visit occurs 30 days or more 
after receipt of the last dose, then the EOT 
visit and Follow-up 1 visit can be completed 
at the same time.
Clarification.
Table 2-7: Safety Follow-up 
Procedural Outline
Section 5.1.5.3: Survival 
Follow-up Period
Clarified language for survival follow-up and 
safety follow-up.
To maintain alignment 
throughout the protocol.
Section 5.1: Overall Design
Section 10.1.2: Part 1C
Added information about Cohort 1C1 and the 
impact of that data on Cohort 1C2.
To confirm the safety and
evaluate the efficacy of the 
triplet regimen in participants 
with MSS and/or pMMR CRC.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 06
Section Number & Title
Description of Change
Brief Rationale
Added justification to open Part 1C2 for 
enrollment of approximately up to 10 
participants with CRC.
Section 5.1: Overall Design
Figure 5.1-2: Study Design 
Part 1
Figure 5.1-3: Study Design 
Part 2
Section 5.5.2: Rationale for 
Part 1B Dosing Schedules 
and Maximum Administered 
Dose
Section 5.5.4: Rationale for 
Nivolumab Dose Selection
Section 5.5.5: Rationale for 
Ipilimumab Dose Selection
Section 5.5.6: Rationale for 
Part 2 Dosing Schedules and 
Maximum Administered 
Dose/RP2D
Section 7.4: Method of 
Treatment Assignment and 
Stratification
Table 7.3-1: Dose, 
Frequency, Infusion Time, 
and Sequence of IPs
 

Updated study designs with the number of 
participants enrolled as of publication of 
Protocol Amendment 06.

Identified the MTD/MAD of
BMS-
986253 as 3600 mg every 2 weeks (Q2W)

 
 
 

Updated Study Design Part 2 to reflect the
RP2D.

Added a new section.
To justify the selection of the 
RP2D for Part 2.
Section 5.1: Overall Design
Figure 5.1-2: Study Design: 
Part 1
Updated the number of participants for Part A 
Cohort 1B1 
Part A Cohort 1B1 enrolled a 
total of 
 participants.
Section 5.1.2: Screening 
Period
Added “Repeat serum IL-8 testing will not be 
required if the previous sample was obtained 
within 42 days of study treatment initiation.”
Clarification
Section 6.1: Inclusion 
Criteria
Clarified inclusion criterion 2) a) that 
participants must have radiographically 
measurable disease.
Added criterion 2) c) xii) (4) (a) with 
palliative radiation considerations.
Updated criterion 2 a) for screening 
 
 requirements.
Updated criterion 2) c) vi) (2) with 
microsatellite instability status or mismatch 
repair information.
To clarify the inclusion criteria 
and improve readability.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 06
Section Number & Title
Description of Change
Brief Rationale
Section 6.2: Exclusion 
Criteria
Section 7.6.8: 
Hemophagocytic 
Lymphohistiocytosis (HLH)
Section 7.6.8.1: HLH 
Management Approaches
Added exclusion criterion 3) i): History of 
HLH/macrophage activation syndrome 
(MAS).
Added exclusion criterion 3) j): diseases 
related to chronic Epstein-Barr virus 
infections.
Added HLH as a dose-limiting toxicity that 
requires treatment discontinuation
Added new sections with background 
information about HLH and management of 
HLH.
 
 
Table 7.3-1: Dose, 
Frequency, Infusion Time, 
and Sequence of IPs
Added footnote h to specify the infusion time.
Clarification and to maintain 
alignment throughout the 
protocol.
Section 7.4: Method of 
Treatment Assignment and 
Stratification
Corrected an error in the description of 
assigning the participant identifier number.
Removed description of replacing 
participants.
Correction.
Participants will not be replaced 
in this way.
Section 10.3.4: 
Immunogenicity Analyses
Added “summary of anti-drug antibody 
(ADA) peak titer, ADA onset and duration, 
summary of select adverse events, by ADA 
status, summary of best overall response by 
ADA status.”
To align with the updated 
immunogenicity statistical 
analysis plan.
Appendix 2: Study 
Governance Considerations
Added sections:

BMS Commitment to Diversity in Clinical 
Trials

Data Protection, Data Privacy, and Data 
Security
To align with BMS 
commitment to diversity in 
clinical trials.
To comply with the European 
Union Clinical Trials 
Regulation requirement.
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Overall Rationale For Protocol Amendment 05, 17-Feb-2022
Protocol Amendment 05 
 
 Although there have been no such events to date, 
management guidelines for potential cytokine release syndrome (CRS) and myocarditis are added 
Criteria regarding prior use of targeted therapy in participants with 
 
melanoma is also updated to accommodate prioritization of combination immunotherapy when 
appropriate, with added justification provided for the use of combination ipilimumab and 
nivolumab in Part 2 based on newly published data. 
Several other changes are made to improve clarity and readability and to update guidance regarding 
coronavirus disease 2019 (COVID-19) and COVID-19 vaccines. 
Updates were made to align with the 2021 editions of the nivolumab Investigator Brochure 
(Version 20, Document Control No. 930128344), the ipilimumab Investigator Brochure (Version 
24, Document Control No. 930017531), and the BMS-986253 Investigator Brochure (Version 6, 
Document Control No. 930106282).
This amendment incorporates the changes from the approved Administrative Letter 05, which are 
detailed in the Document History but not listed in the Summary of Key Changes below.
Changes made to align the Summary (formerly Synopsis) with updates made to the Body.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
Title Page
Updated name and title of study personnel. 
Corrected contact information and added 
European BMS address.
To reflect the updates in study 
team personnel and contact 
information.
Section 2: Schedule of 
Activities
Removed Table 2-6: On-treatment Procedural 
Outline Part 2 for BMS-986253 Q3W 
Schedule: BMS-986253 or Placebo Q3W, 
Nivolumab Q3W, and Ipilimumab Q3W (x 4 
doses). Subsequent tables are renumbered to 
account for this deletion.
BMS-986253 will be 
administered every 2 weeks 
(Q2W) in Part 2, therefore this 
table is not needed.
Section 5.1: Overall Design
Clarified the current status of the study 
(ongoing vs already enrolled cohorts). 
 
 
 
To clarify the study design.
Figure 5.1-2:
Study Design: Part 1
Updated figure to reflect Part 1 study design.
To reflect changes to the study 
design.
Table 2-2: Screening 
Procedural Outline (All 
Study Phases)
Section 5.1.1 Pre-Screening 
Period (Applicable for Part 1 
Only)
Clarified timepoint from IL-8 results by 
central laboratory and signature of the main 
informed consent.
To clarify the enrollment 
process.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
Section 5.1.5.2: Response 
Follow-up Period
Clarified imaging collection during the 
follow-up period in Part 2 of the study.
To clarify when imaging 
procedures are required during 
the follow-up period.
Section 5.4.8: Rationale for 
Treatment of Post-PD-(L)1 
Melanoma in Part 2
Updated to include new references and 
current treatment guidelines.  
To provide additional rationale 
for nivolumab and ipilimumab 
combination as control arm for 
Part 2.
Section 5.5.2: Rationale for 
Part 1B Dosing Schedules 
and Maximum Administered 
Dose
Section 6.1: Inclusion 
Criteria
Inclusion criteria were added or updated for:
2) c) i): Non-small cell lung carcinoma is no 
longer enrolling per Protocol Amendment 04.
2) c) ii) 2): Reintroduced the following criteria 
for RCC participants with a clear cell 
component: 
Must 
have 
received 
and 
progressed/been intolerant of (or not be a 
candidate for) an anti-angiogenic therapy (eg, 
including but limited to bevacizumab, axitinib, 
cabozantinib, pazopanib, sorafenib, sunitinib 
and tivozanib).  
2) c) iii) 4) a: BRAF-mutated participants 
must have received (or not be a candidate for) 
BRAF inhibitor treatment, or declined 
targeted therapy after having been provided 
adequate information to make an informed 
decision.
2) c) vi) 4) Microsatellite Stable Colorectal 
cancer participants with epidermal growth 
factor receptor (EGFR)-expressing RAS 
wildtype tumors must have received (or not 
be a candidate for) EGFR directed therapy 
(eg, cetuximab).
2) c) xii) 3) a: If participant has a 
 
 they must have received (or 
not be a candidate for) BRAF inhibitor 
treatment, or declined targeted therapy after 
having been provided adequate information to 
make an informed decision.
Removed wording for the non-applicable 
inclusion criteria. 
 
to update language regarding 
prior use of targeted therapy in 
participants with 
 
melanoma to 
accommodate prioritization of 
immunotherapy when 
appropriate.
Table 7.3-1: Dose, 
Frequency, Infusion Time 
and Sequence of IPs
Updated table. 
To reflect the current study 
design and dose schedule for 
Part 2 (Q2W).
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
 
Section 7.6.5: Exceptions to 
Permanent Discontinuation 
Criteria
Updated list of exceptions, including Grade 3 
CRS that returns to Grade 1 in < 6 hours. 
Removed information not applicable in this 
section which belongs in Section 8.1: 
Discontinuation from Study Treatment
To align with the Bristol-Myers 
Squibb (BMS) Protocol Model 
Document.
Section 7.6.7: Management 
of Cytokine Release 
Syndrome (CRS)
Added a new section regarding management 
of CRS.
Section 7.10.1: Palliative 
Local Therapy
Updated wording for Part 2 palliative 
radiation.
To clarify when participants in 
part 2 may receive palliative 
radiation.
Section 7.11 Treatment After 
the End of the Study
Updated wording regarding treatment after 
the end of study for participants receiving 
clinical benefit
To clarify that participants 
receiving clinical benefit could 
be treated beyond 3 years after 
consultation with the Medical 
Monitor.
Table 9.1.4-1: Laboratory 
Tests
Removed occult blood stool testing 
(colorectal cancer [CRC] participants at 
screening only) and gamma-glutamyl 
transferase test for all participants. In 
addition, some laboratory tests are only 
needed at screening for Part 2.
To remove participant 
assessments that do not add 
clinical value.
Section 9.4.1: Imaging 
Assessment for the Study
Clarified imaging collection during the 
follow-up period in Part 2 of the study.
To clarify when imaging 
procedures are required during 
the follow-up period.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
Section 10.1.3: Part 2
Updated Part 2 statistical section.
To provide additional details 
regarding primary objective in 
Part 2.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 05
Section Number & Title
Description of Change
Brief Rationale
Appendices 1-4
Updated Appendix 1, Appendix 2, Appendix 
3, and Appendix 4. 
To align with BMS global 
standards.
Appendix 6: Management 
Algorithms for Studies Under 
CTCAE Version 4.0
Appendix 6 was updated.
To align with IB Version 19, 
Addendum 01, for nivolumab.
Entire document 
Additional corrections and editorial or 
formatting changes, where appropriate.
To provide clarity.
Protocol Amendment No.: 07
Date: 17-May-2024
264
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Overall Rationale for Protocol Amendment 04: 23-Nov-2020
Based on interim analysis of Part 1 (as described in BMS-986253 IB version 05, March 2020) the 
following key revisions to the protocol were made: 
The maximum administered dose of BMS-986253 was increased to 3600 mg Q2W (in 
combination with nivolumab 480 mg Q4W in Cohort 1B6). Based on safety data from Cohorts 
1A, and 1B1-1B5, BMS-986253 plus nivolumab was well tolerated at BMS-986253 2400 mg 
Q2W + nivolumab 480 mg Q4W (Cohort 1B4), and dose-dependent AEs were not identified based 
on available data.  Furthermore, dose and frequency-dependent-free serum IL-8 suppression was 
observed, with robust suppression at 2400 mg Q2W + nivolumab 480 mg Q4W. Additionally, 
based on PK/PD modeling, higher doses of BMS-986253 may improve serum IL-8 suppression.  
For the aforementioned reasons, the maximum administered dose of BMS-986253 in Part 1B will 
be 3600 mg Q2W (in combination with nivolumab 480 mg Q4W in Cohort 1B6); Cohort 1B6 will 
include a safety lead-in with 4 participants. 
 
 
 
Evaluation of the triplet combination of BMS-986253 plus nivolumab plus ipilimumab was added 
to the protocol. Combining immunotherapeutic agents with different mechanisms of action offers 
the possibility of synergistic response. The combination of nivolumab and ipilimumab is approved 
in several cancers, including RCC, melanoma, NSCLC, and MSI-high CRC. Baseline serum IL-8 
levels correlate with prognosis in patients treated with anti-PD-1 therapy, including melanoma 
patients, treated with a combination of nivolumab and ipilimumab on CA224067. Adding BMS-
986253, a fully human mAb against IL-8, to nivolumab plus ipilimumab could improve clinical 
outcomes.   
Change Part 2 from a dose expansion phase to a double-blind, randomized investigation of BMS-
986253 plus nivolumab plus ipilimumab versus nivolumab plus ipilimumab in advanced 
melanoma study.  
 
 
 
 
  There are currently no approved agents for 
patients with melanoma who have progressed on prior anti-PD-(L)1 therapy.  However, based on 
retrospective analyses and prospective Phase II data on pembrolizumab and ipilimumab in patients 
who have progressed on anti-PD-1 therapy (NCT02743819), the combination of nivolumab plus 
ipilimumab (plus placebo) was chosen for the control arm. 
In addition, treatment duration was increased from 2 years to 3 years, and some sections were 
added or updated to align the protocol wording with the most recent Protocol Model Document.
Protocol Amendment No.: 07
Date: 17-May-2024
265
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8.0
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1.0
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Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 1 
Synopsis
Updated to incorporate changes from 
revision 4
Section 2 
Schedule of Activities
Table 2-1 Modified Prescreening 
requirements for Part 1 and removed 
Prescreening requirements for Part 2.  
Part 1: Prescreening is required as serum IL-
8 levels impact cohort eligibility. Parts 1A 
and 1B require participants to have a 
 
to guide PD evaluation and 
dose selection.  Part 1C allows participants 
with any serum IL-8 level to enroll, since the 
main goal is to generate safety data for BMS-
986253 plus nivolumab plus ipilimumab. 
Part 2: Prescreening is not required.  
Participants with any serum IL-8 level may 
participate to allow for generation of data to 
support a future patient selection strategy.  
Table 2-2 Added serology for SARS-
CoV-2 to required assessments during 
the screening period 
Added MRI of the brain for all 
participants in Part 2
To align with revised objectives and 
endpoints
To rule out evidence of progression for brain 
metastases 
 
 
 
Table added to align with the current 
protocol design
Added Table 2-6 including the required 
assessments during the treatment period 
for Part 2 if BMS-986253 Q3W is used.
Table added to align with the current 
protocol design
Added Table 2-7 including the required 
assessments during the treatment period 
for Part 2 if BMS-986253 Q2W is used.
Table added to align with the current 
protocol design
Table 2-8.  Added serology for SARS-
CoV-2 to required assessments during 
the follow-up period 
To align with revised objectives and 
endpoints
Section 3 
Introduction
Updated introduction to the study 
To reflect current study design
Section 3.1 
Study Rationale
Section 3.2.1 
BMS-986253
Added combination of nivolumab and 
ipilimumab
To reflect current study design 
Section 3.2.2 
Nivolumab
Updated nivolumab background
Updated to reflect updated latest version of 
the nivolumab IB.
Section 3.2.3 
Ipilimumab
Added section
To provide information of new 
investigational product added to this study
Section 3.2.4 
Nivolumab plus 
Ipilimumab
Added section
To provide safety information regarding 
nivolumab plus ipilimumab treatment
Protocol Amendment No.: 07
Date: 17-May-2024
266
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8.0
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Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 3.3 
Benefit /Risk 
Assessment
Updated information for combination 
BMS-986253 + nivolumab. Added 
benefit /risk assessment for the 
combination of BMS-986253 + 
nivolumab + ipilimumab, and safety 
profile of ipilimumab monotherapy and 
modified safety of BMS-986253 
To reflect updated study design and safety 
data presented in latest versions of the BMS-
986253, nivolumab and ipilimumab IBs.
Section 4 
Table 4-1 Objectives 
and Endpoints-Part 1
Added the triplet combination to 
objectives and endpoints and added 
specific objectives for ipilimumab 
To incorporate changes related to the 
evaluation of the triplet combination of 
BMS-986253 plus nivolumab plus 
ipilimumab in Part 1. 
Section 4 
Table 4-2 Objectives 
and Endpoints-Part 2
Added and modified objectives and 
endpoints for double-blinded 
melanoma participants
To reflect change in Part 2 study design, and 
add objectives related to SARS-CoV-2.
Section 5.1 
Overall Design
Added Cohort 1B6: 3600 mg BMS-
986253 Q2W + nivolumab Q4W
 
Modified tumor types to be included in 
Part 1B.  
 
Added Part 1C (Cohorts 1C1 
 
safety evaluation of BMS-986253 plus 
nivolumab plus ipilimumab 
Added tumor types allowed to be 
enrolled in Part 1C
Changed Part 2 from a single-arm 
expansion in multiple tumor types to a 
double-blind, randomized study in 
advanced melanoma in participants 
who have progressed on anti-PD-(L)1 
therapy. 
Safety was confirmed for 2400 mg 
 
Q2W + nivo Q4W, and MTD has not been 
reached.  A higher dose of BMS-986253 may 
offer better serum IL-8 suppression.
To allow for ease in scheduling for the triplet 
combination with ipilimumab and 
nivolumab, which are given at a Q3W 
schedule for the first 12 weeks of treatment.
Based on preliminary clinical activity from 
interim analysis of Part 1 data
A new triplet combination BMS-986253 plus 
nivolumab plus ipilimumab will be explored 
to evaluate the safety and to determine the 
RP2D for Part 2.
To reflect current study design
Based on interim analysis of Part 1, there 
was evidence of early clinical activity in 
melanoma
Protocol Amendment No.: 07
Date: 17-May-2024
267
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8.0
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1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
Figure 5.1-2 
Study Design: Part 1
Updated figure to reflect Part 1 study 
design
To reflect changes to the study design.
Figure 5.1-3 
Study Design: Part 2
Added figure for Part 2
To reflect changes to the study design.
Section 5.1.1 
Prescreening Period 
(applicable for Part 1A 
only)
Modified Prescreening requirements 
for Part 1 and removed Prescreening 
requirements for Part 2.  
See Rationale for Table 2-1.
Section 5.1.2 
Screening Period
Updated assignment to a Study Part 
during the screening period
To align with the current study design, as 
Part 2 is double-blind, randomized study
Section 5.1.3 
Treatment Period
Added schedules for study procedures 
in Cohort 
, Part 1C, and Part 2.
Increased treatment duration from 2 to 
3 years. 
To align study with updated study design.
To allow participants who continue to derive 
clinical benefit after 2 years of treatment 
(CR, PR, SD), to continue treatment for an 
extra 1 year on study, since BMS-986253 is 
blocking a cytokine produced by the tumor.
Section 5.1.6 
Data Monitoring 
Committee and Other 
External Committees
Added independent Data Monitoring 
Committee in Part 2
Part 2 is double-blinded and an independent 
Data Monitoring Committee will help to 
monitor the patient safety while the study 
team is blinded
Section 5.4.4 
Rationale for 
Combination of BMS-
986253, Ipilimumab, 
and Nivolumab
New section added
To provide the rationale for triplet 
combination of BMS-986253, nivolumab, 
and ipilimumab 
Section 5.4.5
Rationale for Testing 
Different Doses in 
Parallel in Part 1
Modified section to include Part 1C
To reflect the current study design.
Section 5.4.8
Rationale for 
Treatment of Post-PD-
(L)1 Melanoma in Part 
2
Added section
To reflect the current study design
Section 5.4.9
Rationale for 
Stratification in Part 2
Added section
To reflect the current study design
Protocol Amendment No.: 07
Date: 17-May-2024
268
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8.0
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Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 5.5.2
Rationale for Part 1B 
Dosing Schedules and 
Maximum 
Administered Dose
Updated and renamed section 
“Rationale for assessing Q2W dosing” 
To align with the current study design and 
provide rationale for BMS-986253 MAD and 
schedules.
Section 5.5.4
Rationale for 
Nivolumab Dose 
Selection
Updated and renamed section from 
“Rationale for Nivolumab 30-minute 
infusion”
To align with the current study design and 
provide rationale for nivolumab dose 
selection.
Nivolumab is approved to be administered 
for 30 min, for all doses used on study. 
Section 5.5.5
Rationale for 
Ipilimumab Dose 
Selection
Added section
To reflect the current study design
Section 6.1
Inclusion Criteria
Modified inclusion criterion to remove 
tumor types in Part 2 (to include 
melanoma only) and add tumor types 
(HCC and CRC) to Part 1C. 
2c i) Modified criteria so that NSCLC 
cannot be enrolled in Cohorts 1B6 and 
2c v) Removed criteria for triple 
negative breast cancer
2c vi) Modified criteria for CRC, which 
will be included in Part 1C (originally 
in Part 2)
2c vii) Removed criteria for pancreatic 
ductal adenocarcinoma
2c viii) Modified criteria for HCC, 
which will be included in Part 1C 
(originally in Part 2)
2c xii) Added information for 
Melanoma Part 2 inclusion criteria
To align the type of participant and target 
disease characteristics with the current study 
design
3a. Modified criteria to so that only 
participants in Parts 1A and 1B are 
required to have baseline 
 
To reflect study design changes -- see above 
(Prescreening changes)
Section 6.2
Exclusion Criteria
1b. Added that participants with 
leptomeningeal metastases will be 
excluded.
3g and 3h. Added SARS-CoV-2 
language regarding receipt of a SARS-
CoV-2 vaccine within 14 days of C1D1 
and participants with SARS-CoV-2 
infection at baseline.
To clarify exclusion criteria around CNS 
metastases
To exclude participants who have previously 
received a SARS-CoV-2 vaccine within 14 
days of C1D1 and participants with prior 
SARS-CoV-2 infection, symptoms must 
have completely resolved and based on 
investigator assessment in consultation with 
the clinical trial physician, there are no 
Protocol Amendment No.: 07
Date: 17-May-2024
269
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8.0
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1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
3e. Clarified wording for participants 
requiring adrenal replacement steroid 
treatment 
3e v) 3) Modified exclusion criteria for 
HCC
sequelae that would place the participant at a 
higher risk of receiving investigational 
treatment.
To allow participants using adrenal 
replacement steroid doses > 10 mg daily 
prednisone equivalent in the absence of 
active autoimmune disease
To align the type of participant and target 
disease characteristics with the current study 
design
Section 6.4.1
Restesting During 
Screening or Lead-In 
Period
Added language for SARS-CoV-2 
infection
To allow for participants to be rescreened if 
they develop suspected or confirmed 
symptomatic SARS-CoV-2 infection
Section 7.1
Treatments 
Administered
Added ipilimumab and placebo 
 
sodium chloride for injection or 
 
dextrose for injection) to treatments 
and updated BMS-986253 and 
nivolumab product descriptions
To reflect the current study design 
Section 7.2
Handling and 
Dispensing
Added information on how to 
handle/dispense/infuse placebo
To reflect the current study design
Section 7.3
Schedule of Dose for 
Each Investigational 
Product
Added treatment sequence and 
administration time for each study part.
Updated Table 7.3-1 Dose, Frequency, 
Infusion, Time and Sequence of IPs
To reflect the current study design
Section 7.4 
Method of Treatment 
Assignment
Added information for Part 1C and Part 
2
 
To reflect the current study design
To facilitate the parallel enrolment in Part 1
Section 7.5 
Blinding
Added Part 2 blinding information
To reflect the current study design
Section 7.6. 
Dose Modification
Added ipilimumab
To reflect the current study design
Section 7.6.1 
Dose-limiting 
Toxicities
Clarified discontinuation due to dose-
limiting toxicities
To reflect the current study design
Section 7.6.3 
Dose Delays Due to 
Toxicities
Added information regarding toxicity 
reevaluation and tumor assessment 
during delays due to toxicities
To clarify assessments and reevaluation of 
toxicity during dose delays due to toxicities
Section 7.6.4 
Criteria to Resume 
Treatment
Added information regarding criteria 
for resuming treatment
Added guidance for resuming treatment 
after COVID-19 infection 
To clarify the criteria for resuming treatment
Addition of standard language for BMS 
protocol due to COVID-19
Protocol Amendment No.: 07
Date: 17-May-2024
270
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 7.6.6 
Management of Drug-
related Infusion 
Reactions
Added ipilimumab. 
To reflect the current study design
Section 8.1 
Discontinuation from 
Study Treatment
Updated required language and added 
specific information related to the study 
This section was updated to align with the 
most recent Protocol Model Document and 
to reflect the current study design
Section 8.2 
Discontinuation from 
the Study
Updated section
This section was updated to align with the 
most recent Protocol Model Document
Section 9.2.2
Method of Detecting 
AEs and SAEs
Deleted sentence "In order to prevent 
reporting bias, participants should not 
be questioned regarding the specific 
occurrence of one or more AEs"
This section was updated to align with the 
most recent Protocol Model Document
Section 9.3
Overdose
Added ipilimumab
To reflect current study design
Section 9.4
Efficacy Assessments
Added combination nivolumab and 
ipilimumab
To reflect current study design
Section 9.4.1
Imaging Assessment 
for the Study
Specified how to handle unscheduled 
CT/MRI images
To aid in assessment of efficacy
Section 9.4.2
BICR Confirmation of 
Progression (Part 2)
Added section
To aid in assessment of efficacy in Part 2
Section 9.5
Pharmacokinetics and 
Immunogenicity 
Assessments
 
 
To reflect the current study design for PK 
and immunogenicity assessments
Section 9.8.1
Serum IL-8 Levels for 
Participant Selection
Updated serum IL-8 requirements for 
Parts 1 and 2
 
      
To reflect the current study design for 
biomarker samples.  Minimize procedures 
for participants
Protocol Amendment No.: 07
Date: 17-May-2024
271
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8.0
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Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Protocol Amendment 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 10.1
Sample Size 
Determination
Divided into Subsection 10.1.1, for 
Parts 1A and 1B, Subsection 10.1.2, for 
Part 1C, and Subsection 10.1.3, for Part 
2 
Added sample size justification for Part 
1C, and changed sample size 
justification for Part 2
To reflect the current study design
Section 10.3.1
Efficacy Analyses
Added Table 10.3.1-2: Part 2 Efficacy 
Analysis
To align primary endpoint efficacy analysis 
with the current study design
Protocol Amendment No.: 07
Date: 17-May-2024
272
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Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Overall Rationale for Revised Protocol 03: 10-Jul-2019
The purpose of this revised protocol is to expand enrollment in Part 1 to allow further assessment 
of pharmacodynamic changes in the tumor microenvironment at a specific dosing regimen, if 
warranted. The maximum number of treated participants in Part 1 was increased from 
approximately 
 The presentation of the objectives and endpoints have been changed 
 
 Lastly, inclusion criteria for participants within 
Part 1 have been modified. The tumor types in Part 1 have not changed; however, modifications 
of the inclusion criteria define a more homogeneous population within those tumor types 
(restricted to participants who progressed on or within 3 months of anti-PD[L]1-based therapy) to 
aid in additional pharmacodynamic analysis. The synopsis has been updated to reflect the changes 
below and minor typographical and formatting errors have been corrected.
Summary of Key Changes for Revised Protocol 03
Section Number 
& Title
Description of Change
Brief Rationale
Section 2 Schedule 
of Activities
Table 2-2: 
Updated instructions for HPV testing; 
Added stool collection to schedule of assessments.
To clarify acceptable methods 
for establishing HPV status in 
participants with oropharyngeal 
squamous cell carcinoma of the 
head and neck (SCCHN)
To clarify screening schedule 
for stool sample collection
Section 2 Schedule 
of Activities
Table 2-3: 
Notes on ECG testing now refer to C1D1 and C4D1.
Added EOT pregnancy test to schedule of assessments
To clarify instructions for PK 
time-matched ECGs
To add EOT pregnancy testing
Section 2 Schedule 
of Activities
Table 2-4: 
Notes on ECG testing now refer to C1D1 and C4D1. 
To clarify instructions for PK 
time-matched ECGs.
Section 3-3 
Benefit/Risk 
Assessment
The following text added:
Based on preliminary safety data from this study 
presented in the BMS-986253 IB, an increase in 
immune mediated adverse reactions with the 
combination of BMS-986253 and nivolumab compared 
with nivolumab monotherapy is not expected.
To reflect updated safety data 
presented in latest version of the 
IB.
Section 4 
Objectives and 
Endpoints
Objectives and endpoints for Part 1 and Part 2 are 
presented in separate tables.
 
  
OBJECTIVES HAVE NOT 
BEEN CHANGED; only the 
presentation is altered. 
Protocol Amendment No.: 07
Date: 17-May-2024
273
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Approved
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8.0
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Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Revised Protocol 03
Section Number 
& Title
Description of Change
Brief Rationale
Section 5.1 Overall 
Design
Added dose levels of BMS-986253 for Cohorts B4 and 
B5;
Added the following text:
Additional exploration of a specific dosing regimen 
may be warranted, in which case a maximum of 
approximately 
 additional participants will be 
assigned to a dosing regimen of interest in Part 1B. A 
maximum of approximately 
 participants will be 
dosed in Part 1.
Updated study design figure to include Cohorts B4, B5, 
and B6. Updated figure caption to include potential 
pharmacodynamic dosing group and safety lead-in for 
2400 mg BMS-986253 Q2W + Nivo 480 mg Q4W 
dosing regimen. 
Dose levels for Cohorts B4 and 
B5 have been identified and so 
were added to the protocol.
Other changes made to reflect 
changes to the study design.
Section 5.2 
Number of 
Participants
Number of participants updated
To reflect addition of patients 
for pharmacodynamic 
assessment 
Section 5.4.5 
Rationale for 
Assessing Q2W 
Dosing
New section added.
To provide a rationale for Q24 
dosing 
 
 
Section 6.1 
Inclusion Criteria
Criterion 2.a i has been added
To clarify criteria for selecting 
target lesions for inclusion 
Section 6.1 
Inclusion Criteria
Changes to IC criteria for NSCLC participants:
IC 2 c i (6) and IC 2 c i (8) removed
IC 2 c i (9) added. 
To further refine eligibility 
criteria based on baseline 
disease characteristics and 
previous treatment with anti-
cancer therapies.
Section 6.1 
Inclusion Criteria
Changes to IC criteria for renal cell carcinoma 
participants:
IC 2 c ii (2) and IC 2 c ii (4) removed
IC 2 c ii (5) added.
To further refine eligibility 
criteria based on baseline 
disease characteristics and 
previous treatment with anti-
cancer therapies.
Section 6.1 
Inclusion Criteria
Changes to IC criteria melanoma participants:
IC 2 c iii (1) a added
IC 2 c iii (3) removed
IC 2 c iii (5) added. 
To further refine eligibility 
criteria based on baseline 
disease characteristics and 
previous treatment with anti-
cancer therapies.
Section 6.1 
Inclusion Criteria
Changes to IC criteria for urothelial carcinoma 
participants:
IC 2 c x (5) removed
IC 2 c x (6) added.
To further refine eligibility 
criteria based on baseline 
disease characteristics and 
previous treatment with anti-
cancer therapies.
Protocol Amendment No.: 07
Date: 17-May-2024
274
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Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Revised Protocol 03
Section Number 
& Title
Description of Change
Brief Rationale
Section 6.1 
Inclusion Criteria
Changes to IC criteria SCCHN participants:
IC 2 c xi (5) modified
IC 2 c xi (6) removed
IC 2 c xi (7) added.
To further refine eligibility 
criteria based on baseline 
disease characteristics and 
previous treatment with anti-
cancer therapies.
Section 6.1 
Inclusion Criteria
IC 4 f: The following text added: 
In addition, male participants must be willing to refrain 
from sperm donation during this time
 
Section 6.1 
Inclusion Criteria
IC 4 g removed
Duplicate text
Section 6.2 
Exclusion Criteria
EC 5 a: The following text (bolded) added:
Note: under certain specific circumstances and only in 
countries where local regulation permit a person who 
has been imprisoned may be included or permitted to 
continue as a participant.
To align with BMS global 
standards
Section 7.3 
Schedule of Dose 
for Each 
Investigational 
Product
The following text added:
For both nivolumab and BMS-986253, participants may 
be dosed within a ±2 day window. Premedications are 
not recommended.
To clarify minimum dosing 
interval for nivolumab and 
BMS-986253
Section 7.4 Method 
of Treatment 
Assignment
Number of subjects updated and rationale for additional 
participants for pharmacodynamic assessment added
To align with changes in study 
design
Section 9.1.3
The following text added (bold): All ECG tests will be
performed in triplicate for Cycles 1 and 4 (ie, 1 ECG 
test equals 3 consecutive individual 12 lead ECGs 
performed at least 5 minutes apart).
To clarify ECG collection on 
Cycles 1 and 4
Section 8.2.1 Study 
Termination
The following text added:
BMS reserves the right to terminate the study at any 
time for reasons including but not limited to the 
following: safety concerns, termination of drug 
development, lack of efficacy, and lack of meeting 
study objectives/endpoints
 
Section 9.5
Pharmacokinetics 
and 
Immunogenicity 
Assessments
Footnotes 
updated
To clarify instructions for end-
of-infusion sample collection
Section 9.8 
Biomarkers
Table 9.8-1 updated
To clarify pretreatment sample 
collection
Protocol Amendment No.: 07
Date: 17-May-2024
275
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930120018
8.0
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Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of Key Changes for Revised Protocol 03
Section Number 
& Title
Description of Change
Brief Rationale
Section 9.8.5 
Methods to detect 
HPV status of 
SCCHN 
originating in the 
Oropharynx
New section added
To clarify acceptable methods 
for establishing HPV status in 
participants with oropharyngeal 
squamous cell carcinoma of the 
head and neck (SCCHN)
Section 10.1 
Sample Size 
Determination
Sample size updated; rationale for sample size of 
pharmacodynamic assessment group added.
To support potential additional 
participants for 
pharmacodynamic assessment
Appendix 2
Updated definition of serious breach
To align with BMS global 
standards
Protocol Amendment No.: 07
Date: 17-May-2024
276
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8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Overall Rationale for Revised Protocol 02: 02-Nov-2018
There are several reasons for this protocol revision. The study design is being modified for 
participants enrolling in Part 1B to provide flexibility to explore additional dosing regimens. In 
addition, we would like to clarify and amend procedures related to collection of SAEs during the 
Pre-Screen Period. All participants will be entered into IRT and receive a unique subject ID after 
signing the Pre-Screen ICF. SAEs related to the pre-screen blood draw will be collected and 
followed until resolution or stabilization. The inclusion criteria are also being modified to allow 
certain PD-(L)1 naive participants with NSCLC, RCC, SCCHN, and UCC into the study. Lastly, 
we would like to include guidance on palliative treatments that occur during the study period. 
Summary of key changes for Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Synopsis

Text in Synopsis updated
Synopsis was updated to reflect 
the changes made in the 
protocol 
Section 2 Schedule of 
Activities; 
Section 5 Study Design;

New “Table 2-1 - Prescreening 
Procedural Outline (All Study Phases)” 
and “Section 5.1.1 Pre-Screening Period” 
have been added for Pre-screening visits. 

All the preceding tables in Section 2 have 
new numbering due to addition of this 
Table 2-1. 

Table 2-2 - Screening Procedural Outline:

Procedures (Informed Consent, IRT 
) 
have been re-arranged in the table.

IL-8 serum procedure has been 
removed from the Screening table as 
it is now listed under Table 2-1 
Prescreening Procedural.

Notes section under human 
papillomavirus status of tumor for 
SCCHN of the oropharynx has been 
updated.

All the preceding sections in Section 5 
have new numbering due to addition of 
this new Section 5.1.1.
To clarify and update 
Pre-Screening Procedures. 
Section 2, Schedule of 
Activities

On-treatment Procedural Outline table is 
now presented in two separate tables as 
listed below: 

Table 2-3 On-treatment Procedural 
Outline (BMS-986253 Q4W and 
Nivolumab Q4W) 

Table 2-4 On-treatment Procedural 
Outline (BMS-986253 Q2W and 
Nivolumab Q4W)
Based on safety, PD, and PK 
data evaluation, we may explore 
additional dosing regimens for 
BMS-986253. Time points were 
changed to accommodate 
exploration of Q2W dosing of 
BMS-986253.
Protocol Amendment No.: 07
Date: 17-May-2024
277
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930120018
8.0
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Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes for Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Section 2, Schedule of 
Activities;
Table 2-5 Safety Follow-Up 
Procedural Outline

Pharmacokinetic Assessments has been 
added under Procedure.
To clarify procedures
Section 3.1 Study Rationale;
Section 5.1.4 Window Visits;
Section 7.4 Method of 
Treatment Assignment;
Section 9.1.4 Clinical Safety 
Laboratory Assessments;
Section 10.3.5 Biomarker 
Analyses

Clarifying details have been added in 
these sections and text has been updated
Clarification of text
Section 5.1, Overall Design;
Section 10.1, Sample Size 
Determination

Clarifying details have been added and 
text has been updated under overall 
design for participants enrolling in Part 
1B. The study design schema has been 
updated to reflect the change.
Based on review of safety, PD, 
and PK data we may close 
current treatment arms and/or 
explore additional dosing 
regimens for BMS-986253

Section 5.1.3 Treatment 
Period;

Table 2-3 On-treatment 
Procedural Outline 
(BMS-986253 Q4W and 
Nivolumab Q4W);

Table 2-4 On-treatment 
Procedural Outline 
(BMS-986253 Q2W and 
Nivolumab Q4W);

Section 9.8.2.1.3 Tumor-
Based Biomarkers

Sections and tables have been updated to 
modify 
 
 to be collected at 5 weeks 
(3 days) at Cycle 2 Day 8 (3 days) 
after first dose. 
Based on safety, PD, and PK 
data evaluation, we may explore 
additional dosing regimens for 
BMS-986253. Time points were 
changed to accommodate 
exploration of Q2W dosing of 
BMS-986253
Section 5.2 Number of 
Participants; 
Section 10.1 Sample Size 
Determination

Total number of participants have been 
updated 
 as the number 
of participants for Part 1 (dose-finding 
phase) are now 
Based on review of safety, PD, 
and PK data we may close 
current treatment arms and/or 
explore additional dosing 
regimens for BMS-986253
Section 5.5.2, Rationale for 
Dose Selection and Dosing 
Schedule

Text for Part 1B table-note has been 
updated.
Based on review of safety, PD, 
and PK data we may close 
current treatment arms and/or 
explore additional dosing 
regimens for BMS-986253
Protocol Amendment No.: 07
Date: 17-May-2024
278
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes for Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Section 6.1 Inclusion Criteria

Criteria 2) c) i) (2), 2) c) i) (4), 
2) c) ii) (1), 2) c) iv), 2) c) x) (2), and 2) 
c) xi) (2) are not applicable after 
implementation of this revised protocol 
02 and “Not applicable as per revised 
protocol 02” has been added in the 
beginning of each listed criteria. 
Inclusion criteria are expanding 
to include specific IO naive 
populations

Criteria 2) c) has been modified as below: 

“The following tumor histologies will be 
permitted except for participants with 
CNS metastases as the only site of 
active disease. All participants must 
have received, and then progressed, 
relapsed, or been intolerant to at least 
1 standard treatment regimen in the 
advanced or metastatic setting 
according to tumor type. Part 1 will 
include patients with NSCLC, RCC, 
melanoma, HNSCC, and UCC. Part 2 
will include patients with NSCLC, 
RCC, melanoma, TNBC, colorectal 
cancer, HCC, and PDAC”. 
The phrase in the bold was 
added as a clarification of text

Criteria 2) c) i) (5) has been modified as 
below: 
1)
“Epidermal growth factor receptor 
(EGFR), anaplastic lymphoma kinase 
(ALK), and ROS1 mutational status 
must be known for patients with lung 
adenocarcinoma.”

New eligibility criteria under NSCLC, 
RCC, UCC, and SCCHN have been 
added as listed below: 

NSCLC: Criteria 2) c) i) (6), 2) c) i) (7), 
2) c) i) (8), 

RCC: Criteria 2) c) ii) (3), 2) c) ii) (4), 

UCC: Criteria 2) c) x) (5), 

SCCHN: Criteria 2) c) xi) (6) 
Inclusion criteria are expanding 
to include specific IO naive 
populations

Criteria 2) c) iii) (3) has been modified as 
below: 
2)
“Must have had radiologically 
documented progressive or recurrent 
disease either during or after completion 
of anti-PD-(L)1 therapy (administered 
as monotherapy or as part of a 
combination). No more than one 
The phrase in the bold was 
added as a clarification of text
Protocol Amendment No.: 07
Date: 17-May-2024
279
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes for Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
intervening systemic therapy is permitted 
between anti-PD-(L)1 treatment and 
enrollment on this trial.”

Criteria 2) c) vii) (2) has been modified 
as below: 
3)
“Participants must have received and 
progressed on or been intolerant to (not 
candidates for) at least 1 line of standard 
of care treatment.”

Criteria 2) c) viii) (1) has been modified 
as below: 
4)
“Participants cannot be eligible for 
liver transplant at the time of inclusion. 
For participants who progressed after 
locoregional therapy, locoregional 
therapy for HCC must be completed at 
least 4 weeks prior to the baseline scan. 
All acute toxic effects of any prior local 
treatment must have resolved to National 
Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events 
(CTCAE) v4.03 Grade > 1 or been 
deemed irreversible.” 

Criteria 2) c) viii) (2) has been modified 
as below: 
5)
“Participants may either have 
histologically or radiologically 
confirmed HCC. Participants with a 
radiological diagnosis may be enrolled 
for screening in the study but histological 
confirmation is mandatory prior to 
initiation of study therapy.”

Criteria 4) g) has been modified to 
remove “Azoospermic males are exempt 
from contraceptive requirements”. 
This modification was made 
since sperm counts are not 
performed on this study. 
Section 6.2 Exclusion 
Criteria;
Section 7.9.1 Prohibited 
and/or Restricted Treatments

Criteria 3) e) ix) has been modified as 
below: 
6)
“Receipt of a live/attenuated vaccine 
within 30 days of first treatment.”
7)
Additional bullet 4 has been added. 
The modification was made to 
comply with the current BMS 
standards for studies using 
nivolumab. This restriction is 
based on theoretical risk of 
adverse effects for nivolumab 
and not on clinical or safety 
data. The administration of live 
vaccines is contraindicated in 
patients receiving BMS-986253 
treatment.
Protocol Amendment No.: 07
Date: 17-May-2024
280
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes for Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Section 7.1 Treatment 
Administered

Table 7.1-1 has been updated for 
additional potency for BMS-986253 
100 mg/mL.
This has been modified due to a 
change in drug supply.
Section 7.3 Schedule of Dose 
for Each Investigational 
Product

Clarifying details about infusion of 
BMS-986253 administered at Q2W have 
been added and Table 7.3-1 has been 
updated with these details. 

Additional table-note has been added 
explaining infusion time for 2,400 mg 
BMS-986253.
 
 we may explore 
additional dosing regimens for 
BMS-986253.
Section 7.5 Blinding
Text in this section has been revised and 
clarification about access to IRT treatment 
codes has been added. 
To meet new BMS standards on 
randomization and blinding
Section 7.10.1 Palliative 
Local Therapy
New section added
To add guidelines for palliative 
therapy during the study
Section 9.2.1 Time Period 
and Frequency for Collecting 
Adverse Event and Serious 
Adverse Event Information
Text under this section has been modified and 
clarifying details about collecting serious 
adverse events after the participant sign the 
pre-screen ICF and the main ICF has been 
updated.
We are now going to collect 
related SAEs from Pre-
Screening, and follow them 
until resolution. These related 
SAEs will now be collected 
electronically per new 
guidelines.
Section 9.4.1 Imaging 
Assessment for the Study;
Table 2-2 Screening 
Procedural Outline;

Table 2-3 On-treatment 
Procedural Outline 
(BMS-986253 Q4W and 
Nivolumab Q4W);

Table 2-4 On-treatment 
Procedural Outline 
(BMS-986253 Q2W and 
Nivolumab Q4W);
Table 2-5 Safety Follow-Up 
Procedural Outline

Text has been modified to update the 
period for acquiring images to 28 days. 

Text under Section 9.4.1 and within 
Tables 2-2 through 2-5 have been revised 
to align across these sections.
Update in section 9.4 was to 
correct an error in the text. All 
other changes were made to 
reflect changes in study design. 
Protocol Amendment No.: 07
Date: 17-May-2024
281
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes for Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Section 9.5 Pharmacokinetics 
and Immunogenicity 
Assessments

The text in this section has been modified 
by adding clarifying details for collection 
of pharmacokinetics and immunogenicity 
assessment data from participants 
enrolled in the study. Additional time 
points have been added to 
 
 

Title for subsection 9.5.1 was removed as 
Section 9.5 title already contains 
“Immunogenicity”.
Updates were made to reflect 
change of collection from C3 to 
C4 to better characterize 
BMS-986253 exposure at 
steady state. 
Section 9.8 Biomarkers
Updates were made to reflect 
changes in study design, and so 
biomarker collection correlates 
with imaging
Section 9.8.2.1.2 Whole 
blood Gene Expression

New section has been added
We may use gene expression 
data to assess changes in 
immune cells in the blood.
Section 10.3 Statistical 
Analysis;
Appendix 3: Adverse Events 
and Serious Adverse Events: 
Definitions and Procedures 
for Recording, Evaluating, 
Follow Up and Reporting; 
Appendix 6 Management 
Algorithms

Text under section 10.3 and appendices 
have been updated
Updates were made to align 
with the recent BMS protocol 
model document
Appendix 4 Women of 
Childbearing Potential 
Definitions and Methods of 
Contraception
Text under “Contraception Guidance for 
Female Participants of Child Bearing 
Potential” for relevant systemic exposure for 
female participants has been corrected to 
5 months.
The update was made to correct 
a typographical error regarding 
number of months in the 
previous protocol version.
Appendix 11 Country 
Specific Amendment
New appendix added
Appendix was added to specify 
HIV country-specific 
requirements for Germany. 
All
Minor formatting and typographical 
corrections
Minor, therefore have not been 
summarized
Protocol Amendment No.: 07
Date: 17-May-2024
282
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Overall Rationale for the Revised Protocol 01, 13-Mar-2018
The primary reasons for these changes are to expand enrollment in Part 1 to include advanced 
Squamous cell carcinoma of the head and Neck (SCCHN) and Urothelial cancer (UCC) 
participants, modify eligibility criteria for participants with NSCLC, RCC, TNBC, HCC, CRC, 
and modify the sampling schedule for pharmacodynamic assessment. Additional revisions have 
been made to align the protocol with respect to these changes. . Additionally, the revised protocol 
incorporates Administrative Letters 01 and 02 which correct typographical errors in the numbering 
of inclusion and exclusion criteria.
Summary of key changes of Revised Protocol 01
Section Number & 
Title
Description of Change
Brief Rationale
Synopsis
Synopsis was updated
Synopsis was updated to reflect the changes 
made in the protocol 
Section 2, Table 2-1 
Screening 
Procedural Outline
Body imaging added to Tumor Type 
Assessment along with details in notes 
section for participant with SCCHN, HCC 
and TNBC.
Alignment with standard Imaging protocol 
language.  Indication specific imaging 
added for SCCHN, HCC, and TNBC
Notes section was updated for IL-8 Serum
Clarification to the requirement of a 
prescreening test for serum IL-8 to 
determine eligibility
Laboratory test for human papillomavirus 
status of tumor for SCCHN of the 
oropharynx was added
Inclusion of SCCHN and requirement to 
determine HPV status for stratification 
purpose.
Section 2, Table 2-2 
On-treatment 
Procedural Outline
Eastern Cooperative Oncology Group 
(ECOG) Performance Status was added on 
Day 1 of each cycle
The test was unintentionally omitted from 
the On-treatment study table. ECOG is used 
to monitor a participant’s daily living 
abilities and is important to assess while on 
treatment.
Revised the ECG notes column to indicate 
when time matched ECGs are to be taken 
in Part 1 and Part 2 of the study
The notes column was updated to clarify 
during which cycles time matched ECGs are 
taken in Part 1 of the study and to clarify 
ECGs are taken only pre-dose in Part 2 of 
the study
Weight collection was added
Required but accidentally omitted in the 
previous version.
Protocol Amendment No.: 07
Date: 17-May-2024
283
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes of Revised Protocol 01
Section Number & 
Title
Description of Change
Brief Rationale
A clarifying note was added to the notes 
column for Vital Signs and Oxygen 
Saturations
The notes column was updated to clarify 
that post-dose vital signs are required after 
BMS 986253 dosing AND after Nivolumab 
dosing
Tumor Imaging changed to Body Imaging 
and additional details on CT/MRI scan 
locations.  Additional details for 
participant with SCCHN, HCC and TNBC 
were added
Alignment with standard Imaging protocol 
language.  Indication specific imaging 
added for SCCHN, HCC, and TNBC
Section 2, Table 2-3 
Safety Follow-up 
Procedural Outline
Tumor Imaging changed to Body Imaging. 
Additional details for participants with 
SCCHN, HCC and TNBC were added
Alignment with standard Imaging protocol 
language.  Indication specific imaging 
added for SCCHN, HCC, and TNBC
Section 2, Table 2-3 
Safety Follow-up 
Procedural Outline 
and Section 5.1 
Overall Design
Clarifying note was added to Assessment 
of Participant Survival Status regarding 
time frame and length of follow up.
The notes column was updated to include a 
specific time frame of every 12 weeks for 2 
years for participant survival status.
Section 4, Table 4-1 
Objectives and 
Endpoints
 
 
 
ORR, mDOR, and PFSR 
 by 
BICR was added as an endpoint
Section 5.1 Overall 
Design 
 
Limit of quantitation (LLOQ) of IL-8 
defined 
Precision to the definition of Serum IL-8
level for the eligibility in the study.
Section 5.1.2 
Treatment period
Section 5.1.2 
Treatment period 
and Section 9.8, 
Table 9.8.1-1
Added collection of stool sample during 
screening, on treatment and at progression
To explore the potential effect of the gut 
microbiome to the therapy.
Section 6.1 
Inclusion Criteria
Clarifying detail added for prior therapy to 
include standard of care chemotherapy for 
non-small cell lung carcinoma, renal cell 
carcinoma, triple negative breast cancer, 
colorectal cancer and pancreatic ductal 
adenocarcinoma. 
To resolve discrepancies of inclusion 
criteria with the current standard therapies.
Protocol Amendment No.: 07
Date: 17-May-2024
284
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes of Revised Protocol 01
Section Number & 
Title
Description of Change
Brief Rationale
For patients with melanoma criteria change 
to include no more than one intervening 
systemic therapy is permitted between 
anti-PD-(L)1 treatment and enrollment on 
this trial.
To resolve discrepancies of inclusion 
criteria with the current standard therapies.
Applicable in 
section 6.1 Inclusion 
criteria and 
throughout
Permitted tumor histologies was updated to 
include urothelial carcinoma and 
squamous cell carcinoma head and neck
Adding tumor type to explore the role of IL-
8 in post-PD1 resistance
Section 7.9.2 7.9.2 
Other Restrictions 
and Precautions
Corrected the allowed dose of inhaled, 
topical and adrenal replacement steroids 
from > 10 mg to 10 mg
To correct a typographical error regarding 
the allowed steroid dose
Section 8.1.1 
Treatment Beyond 
Progression
Additional information regarding required 
re-consent with an ICF to continue 
treatment beyond progression was added
Alignment with standard protocol template
language
Section 8.1.1.1 
Discontinuation Due 
to Further 
Progression
This section was removed and the 
information added to section 8.1.1
To reduce repetition
Section 9.1.4, Table 
9.1.4-1 Laboratory 
Tests
Added alanine aminotransferase (ALT) to 
the list of laboratory tests
ALT was mistakenly omitted from the 
original protocol and should be included
Section 9.4 Efficacy 
Assessments
Additional detail provided about change in 
tumor response and measurement will be 
assessed using RECIST v1.1 criteria. 
 
 
To clarify that RECIST v1.1 is to be 
performed by the Investigator 
 
Section 9.4.1 
Imaging Assessment 
for the Study
Clarifying information added for time 
frame to acquire images
To ensure accuracy
Section 9.8 
Biomarkers
Clarifying details added to biomarkers 
description
To ensure accuracy with the clinical plan
Appendix # 4
Relevant systemic exposure for male 
participants updated to 7 months
To correct a typographical error regarding 
number of months
Protocol Amendment No.: 07
Date: 17-May-2024
285
9.0
Approved
930120018
8.0
v
Approved
1.0
v

Clinical Protocol
CA027002
BMS-986253
Anti-IL-8
Summary of key changes of Revised Protocol 01
Section Number & 
Title
Description of Change
Brief Rationale
Appendix # 7
Appendix 07 was updated.
Fixed incorrect dose that was presented in 
the graph. Corrected graph and 
corresponding table were presented.
Appendix # 8
Appendix 8 was updated
Appendix was updated to include RECIST 
criteria with BMS modifications
All
Minor formatting and typographical 
corrections
Minor, therefore have not been summarized
Protocol Amendment No.: 07
Date: 17-May-2024
286
9.0
Approved
930120018
8.0
v
Approved
1.0
v