A Phase 1/2 First-in-human Study of BMS-986288 Alone and in Combination With Nivolumab in Advanced Malignant Tumors
Phase: PHASE1
Conditions: Advanced Cancer
Sponsor: Bristol-Myers Squibb

Official Title of Study: A Phase 1/2 First-in-human Study of BMS-986288 Alone and in Combination with 
Nivolumab in Advanced Malignant Tumors 
 
 
NCT Number: NCT03994601 
Document Date (Date in which document was last revised): 24-Mar-2023 
 
 
 

Page:
1
Protocol Number:
CA043001
IND Number:
141,400
EUDRACT Number:
2021-004284-27
Date:
27-Mar-2019
Revised Date:
24-Mar-2023
CLINICAL PROTOCOL CA043001
A Phase 1/2 First-in-human Study of BMS-986288 Alone and in Combination with Nivolumab 
in Advanced Malignant Tumors
Short Title: An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination 
With Nivolumab in Advanced Solid Cancers
Protocol Amendment: 03
Incorporates Administrative Letters 03, 04, and 05
Clinical Trial Physician - Medical Monitor
Clinical Scientist
Bristol-Myers Squibb Company
1000 Sierra Point Parkway
Brisbane, CA 94005
Bristol-Myers Squibb Company
1000 Sierra Point Parkway
Brisbane, CA 94005
Telephone (office): 
Email:
Telephone (office): 
Email: 
24-hr Emergency Telephone Number
USA: 1-866-470-2267
International: +1-248-844-7390
Bristol-Myers Squibb Research and Development
3401 Princeton Pike
Lawrenceville, NJ 08648
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 
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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 
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Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Protocol Amendment No.: 03
Date: 24-Mar-2023
2
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).
© 2023 Bristol-Myers Squibb Company
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Protocol Amendment No.: 03
Date: 24-Mar-2023
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol 
Amendment 03
24-Mar-2023
The key change in this protocol amendment is the addition of a new 
randomized cohort of microsatellite stable colorectal cancer participants for 
dose expansion (Part 2C) and relevant study procedures and requirements. 
This protocol amendment also removes severe acute respiratory syndrome 
coronavirus 2 serology collection requirement, modifies biomarker sample 
collection plan to reduce participant burden, allows selective backfill after 
selected dose levels are demonstrated safe, and updates secondary and 
exploratory endpoints.
Administrative 
Letter 05
17-Jun-2022
Updated contact information for Clinical Trial Physician - Medical 
Monitor.
Administrative 
Letter 04
01-Apr-2022
Updated contact information for Clinical Trial Physician - Medical 
Monitor.
Administrative 
Letter 03
24-Sep-2021
Provided EUDRACT Number for the study.
Protocol 
Amendment 02
22-Jul-2021
Key changes include the addition of new dose levels for dose escalation 
(Part 1) and clinical outcomes assessments and new indications for dose 
expansion (Part 2). Other changes have been made to align dose 
modification criteria and immuno-oncology agent management algorithms 
with the current CTCAE v5, address COVID-19 infection and vaccination, 
clarify expectations for safety assessments, and remove male contraceptive 
requirements. 
This amendment incorporates Administrative Letter 02.
Administrative 
Letter 02
15-Jan-2021
Corrected a misspelling in the inclusion criteria for participants with 
colorectal cancer.
Revised Protocol 
01
11-Jun-2019
 
 incorporated Administrative Letter 01, and ensured that the 
protocol is consistent with internal BMS policies and operating procedures.
Administrative 
Letter 01
15-May-2019
To add clarity to the infusion times associated with a range of doses.
Original Protocol
27-Mar-2019
Not applicable
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 03:
The key change in this protocol amendment is the addition of a new randomized cohort of 
microsatellite stable (MSS) colorectal cancer (CRC) participants for dose expansion (Part 2C) and 
relevant study procedures and requirements. This protocol amendment also removes the severe 
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology collection requirement, 
modifies the biomarker sample collection plan to reduce participant burden, allows selective 
backfill after selected dose levels are demonstrated safe, and updates secondary and exploratory 
endpoints.
Additional revisions, including revisions to the Protocol Summary, have been made to align the
protocol with respect to the changes listed below. Minor formatting and typographical corrections 
have been made throughout and have not been summarized.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Table 2-1: Screening 
Schedule of Activities for 
All Study Parts

Removed 
manual 
enrollment 
option.

To align with current enrollment process.

Added 
instruction to 
specify 
systemic and 
local therapy.

Added to ensure relevant data are collected for 
future analysis.
Table 2-1: Screening 
Schedule of Activities for 
All Study Parts
Table 2-2: On-Treatment -
Schedule of Activities for 
All Study Parts
Table 2-3: Follow-up 
Procedural Outline for All 
Study Parts
Section 3.3: Benefit-Risk 
Assessment
Table 4-1: Objectives and 
Endpoints
Section 5.1: Overall Design
Figure 5.1-1: Study Design 
Schematic
Figure 5.1-2: Study Design 
Schematic for Expansion 
Part 2C
Added Part 2C 
Cohort 
(BMS-986288 in 
combination with 
nivolumab [Arm C] 
or regorafenib 
[Arm D]) for MSS 
CRC participants.
If more than 1 dose 
level is evaluated, 
additional 
participants may be 
enrolled in a 
separate arm (Arm 
E) in Part 2C.
Participants on 
Arm D will have 
the option to 
transition to 
BMS-986288 in 
combination with 
To explore the safety and efficacy of BMS-986288 
in combination with nivolumab in MSS CRC 
participants based on emerging data.
Protocol Amendment No.: 03
Date: 24-Mar-2023
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Section 5.1.2: Treatment 
Period
Section 5.1.2.3: The 
Expansion Phase of 
BMS-986288 
 
(Part 2A) 
 
 Nivolumab (Part 2B
and Part 2C Arm C, Arm 
E, and Arm Z)
Section 5.2: Number of 
Participants
Section 5.4.3: Rationale for 
Tumor Selection in Part 2C
Section 5.4.4: Rationale for 
Randomization in Part 2C
Section 5.4.6: Rationale for 
Two Years Fixed Duration 
with Checkpoint Blockade
Section 5.4.7: Rationale for 
Quality of Life Evaluation
Section 5.4.8: Rationale for 
Using a 
 
Arm
Section 5.5.3: Rationale for 
BMS-986288 Dose 
Selection in Part 2C
Section 5.5.4.5: Rationale 
for 
Section 5.5.4.6: Rationale 
for Choice of Standard of 
Care Treatment in Part 2C
Section 5.5.4.7: Rationale 
for KRAS Testing
Section 5.5.4.8: Rationale 
for 
 Testing
Section 5.5.4.9: Rationale 
for Dose Selection of 
Regorafenib and Line of 
Therapy (in 3rd/4th Line 
MSS CRC)
Section 6.1: Inclusion 
Criteria
nivolumab upon 
progression (Arm 
Z).
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Date: 24-Mar-2023
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Section 6.2: Exclusion 
Criteria
Section 7: Treatments 
Administered
Table 7-1: Investigational 
Product Description for 
CA043001
Table 7.1-1: Selection and 
Timing of Dose
Section 7.1: Schedule of 
Dose for Each 
Investigational Product
Section 7.2: Method of 
Treatment Assignment
Section 7.4: Dosage 
Modification
Section 7.4.6: Dose 
Modification for 
Regorafenib
Section 7.7.2: Permitted 
Therapy
Section 8.1: 
Discontinuation from 
Study Treatment
Section 9.1: Efficacy 
Assessments
Section 9.1.1: Imaging 
Assessment for the Study
Section 9.1.2.2: EQ-5D-5L
Section 9.2: Adverse 
Events
Section 9.2.5: Pregnancy
Section 9.3: Overdose
Table 9.4.5-1: Clinical 
Laboratory Assessments
Table 9.5-4: PK and ADA 
Sampling Schedule for 
BMS-986288 
 in 
Combination with 
Nivolumab 
 
Cohort Expansion (Part 2C 
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Arm C, Arm E, and Arm 
Z)
 
Table 9.8.3-1: Biomarker 
Sampling Schedule for 
 Dosing Schedule for 
Part 1, Part 2A, Part 2B, 
and Part 2C Arm C, Arm 
E, and Arm Z
Table 9.8.3-2: Biomarker 
Sampling Schedule for 
 Dosing Schedule for 
Part 2C Arm D
Section 10.1.6: The 
BMS-986288 in 
Combination with 
Nivolumab Cohort 
Expansion in MSS CRC 
Participants (Part 2C)
Table 10.3.1-1: Efficacy -
Statistical Analyses
Table 10.3.8.1-1: 
Monitoring Boundaries for 
Treatment-related 
Toxicities Meeting DLT 
Criteria in Part 2
Table 2-1: Screening 
Schedule of Activities for 
All Study Parts
Table 2-2: On-Treatment -
Schedule of Activities for 
All Study Parts
Table 2-3: Follow-up 
Procedural Outline for All 
Study Parts
Section 9.1.1: Imaging 
Assessment for the Study
Updated imaging 
language.
To clarify imaging modalities to be used at 
screening, on-treatment, and follow-up phase of the 
study. Clarification from which date (date of first 
dose) the brain imaging interval is to be calculated.
Table 2-1: Screening 
Schedule of Activities for 
All Study Parts
Removed 
screening, 
on-treatment, and 
follow-up
SARS-CoV-2 
To remove serology as the impact of SARS-
CoV-2 serology status on study is no longer in 
the scope, due to the population having already
had SARS-CoV-2 infections.
Protocol Amendment No.: 03
Date: 24-Mar-2023
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BMS-986288
anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Table 2-2: On-Treatment -
Schedule of Activities for 
All Study Parts
Table 2-3: Follow-up 
Procedural Outline for All 
Study Parts
Section 3.3: Benefit-Risk 
Assessment
Table 4-1: Objectives and 
Endpoints
Table 9.8.3-1: Biomarker 
Sampling Schedule for 
 Dosing Schedule for 
Part 1, Part 2A, Part 2B, 
and Part 2C Arm C, Arm 
E, and Arm Z
Section 9.8.4.1: 
Exploratory Serum and 
Plasma Biomarkers
Appendix 8: Schedule of 
Activities, 
Pharmacokinetics 
Sampling Schedule, and 
Biomarker Sampling 
Schedule for Potential 
Alternative Dose Schedules 
in CA043001
serology
assessments.
Section 9.8.4.1: 
Exploratory Serum 
and Plasma 
Biomarkers was 
removed.
Table 2-2: On-Treatment -
Schedule of Activities for 
All Study Parts
Section 9.8: Biomarkers
Section 9.8.3: Gut 
Microbiome Analysis
Table 9.8.3-1: Biomarker 
Sampling Schedule for 
 Dosing Schedule for 
Part 1, Part 2A, Part 2B, 
and Part 2C Arm C, Arm 
E, and Arm Z
Appendix 8: Schedule of 
Activities, 
Pharmacokinetics 
Sampling Schedule, and 
Removed stool 
sample collection.
Section 9.8.3: Gut 
Microbiome 
Analysis was 
removed.
To reduce study burden on participants.
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Date: 24-Mar-2023
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Biomarker Sampling 
Schedule for Potential 
Alternative Dose Schedules 
in CA043001
Table 4-1: Objectives and 
Endpoints

Removed 
incidence 
of 
anti-drug 
antibody 
(ADA) 
from 
secondary 
endpoint.

To remove redundancy with exploratory endpoint 
of 
ADA 
incidence 
of 
nivolumab 
and 
BMS-986288, 
as 
immunogenicity 
characterization is an exploratory objective. 

Moved 
“To 
measure 
 
 
 
and assess 
 
change 
over 
time 
and 
in 
association 
with response” 
objective 
and 
endpoint from 
secondary 
to 
exploratory.

Measurement of 
 has been changed from a 
secondary to an exploratory endpoint due a lack 
of clear association of 
 with clinical 
response. There is no impact to study participants, 
as treatment decisions are not guided by the use 
of biomarkers.
Table 4-1: Objectives and 
Endpoints
Section 9.8: Biomarkers
 
Removed 
 
expression and 
 specific 
genes.
To clarify that tumor specific expression is no longer 
in the biomarker analysis scope and has not been
associated with response.
Figure 5.1-1: Study Design 
Schematic
Updated study 
design schematic.
To clarify study design and reflect Part 1B 
intermediate dose level and Part 2B selected dose 
level, and addition of the new cohort.
Section 5.1.2.1: Dose-
Escalation Decisions for 
the BMS-986288 
Monotherapy Escalation 
(Part 1A) and the Safety 
Evaluation of BMS-986288 
in Combination with 
Nivolumab (Part 1B)
Added that Sponsor 
may choose to 
enroll only certain 
cancer types from 
dose escalation 
during the backfill, 
based on emerging 
data.
To allow the option to focus on indications of 
interest to gather more 
pharmacokinetic/pharmacodynamic/safety/efficacy 
data after the dose levels are demonstrated as 
tolerable.
Section 5.4.9: Rationale for 
Not Blinding
Added section.
To clarify that the study will be open label in order 
to facilitate safety monitoring by the Sponsor and to 
ensure adequate ability of the clinical trial physician 
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BMS-986288
anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
to monitor and discuss the management of the 
participants with the investigators. 
Table 7-1: Investigational 
Product Description for 
CA043001
Updated vial 
information for 
nivolumab.
To clarify for operational efficiency that only
100-mg vials of nivolumab will be provided for this 
study. There is no use for the 40-mg vials moving 
forward.
Section 9.1.1.1: Methods of 
Measurement
Added clarification 
that use of other 
imaging modalities 
in case of contrast 
contraindication is a
guideline and is not 
mandatory.
To clarify that this section is to be used as guidance 
and not be considered a protocol deviation in case of 
the selection of a different modality based on 
participant-specific factors or local guidelines when 
a participant has an imaging contraindication.
Section 9.8.1.3: 
 
 Analysis
Added “or RNA.”
To add flexibility and clarify that
 receptor 
sequence analysis can be performed from extracted 
deoxyribonucleic acid or RNA material.
Section 9.8.2.2: 
Characterization of 
 
Updated language 
regarding 
 
 
may be performed 
on pre- and 
post-treatment 
 and/or 
samples.
To represent that 
technology can utilize both 
 material.
Table 9.8.3-1: Biomarker 
Sampling Schedule for 
 Dosing Schedule for 
Part 1, Part 2A, Part 2B, 
and Part 2C Arm C, Arm 
E, and Arm Z
Updated biomarker 
sampling schedule.
To reduce study burden on participants.
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & Title
Description of 
Change
Brief Rationale
Section 10.3.8: Interim 
Analyses
Added details of 
the planned interim 
analyses.
To describe the planned interim analyses.
Appendix 2: Study 
Governance Considerations
Added new 
sections on Bristol 
Myers Squibb
commitment to 
diversity in clinical 
trials and data 
protection, data 
privacy, and data 
security.
To align with BMS practice and comply with 
European Union Clinical Trials Regulation
requirement.
Appendix 11: 
Country-specific 
Requirements/Differences
Added new 
appendix.
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 03: ............................ 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 ................ 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 SYNOPSIS ................................................................................................................. 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.2.1 BMS-986288 ............................................................................................ 
 
3.2.1.1 Generation of an Anti-human-CTLA-4 NF Probody mAb .............. 
 
3.2.1.2 BMS-986288 Nonclinical Pharmacology ....................................... 
 
3.2.1.3 BMS-986288 Nonclinical Pharmacokinetics .................................. 
 
3.2.1.4 BMS-986288 Nonclinical Toxicology ............................................. 
 
3.2.2 Nivolumab ................................................................................................ 
 
3.2.3 Ipilimumab ............................................................................................... 
 
3.2.4 Nivolumab Combined with Ipilimumab ................................................... 
 
3.3 Benefit-Risk Assessment .................................................................................. 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Screening Period ...................................................................................... 
 
5.1.2 Treatment Period ..................................................................................... 
 
5.1.2.1 Dose-Escalation Decisions for the BMS-986288 Monotherapy 
Escalation (Part 1A) and the Safety Evaluation of BMS-986288 in 
Combination with Nivolumab (Part 1B) ............................................... 
 
5.1.2.2 
 Evaluation of BMS-986288 as a Monotherapy and in 
Combination with Nivolumab 
 ............................................. 
 
5.1.2.3 The Expansion Phase of BMS-986288 
 (Part 2A) 
 
 Nivolumab (Part 2B and Part 2C 
Arm C, Arm E, and Arm Z) ................................................................... 
 
5.1.2.4 Visit Windows.................................................................................. 
 
5.1.3 Follow-up ................................................................................................. 
 
5.1.3.1 Safety Follow-up Period ................................................................. 
 
5.1.3.2 Imaging Follow-up Period .............................................................. 
 
5.1.3.3 Survival Follow-up Period .............................................................. 
 
5.1.4 Treatment Beyond Progression ................................................................ 
 
5.1.4.1 Discontinuation Due to Further Progression (Confirmed 
Progression) .......................................................................................... 
 
5.1.5 Criteria for Transition From Regorafenib (Part 2C Arm D) to BMS-
986288 in Combination with Nivolumab .................................................... 
 
5.1.6 Data Monitoring Committee and Other External Committees ................ 
 
5.2 Number of Participants ..................................................................................... 
 
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5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.4.1 Rationale for BMS-986288 Monotherapy Dose Escalation (Part 1A) and 
the Safety Evaluation of BMS-986288 in Combination with Nivolumab 
(Part 1B) ..................................................................................................... 
 
5.4.2 Rationale for Tumor Selection in Part 1 .................................................. 
 
5.4.3 Rationale for Tumor Selection in Part 2C ............................................... 
 
5.4.4 Rationale for Randomization in Part 2C ................................................. 
 
5.4.5 Rationale for BMS-986288 in Participants Previously Treated with 
 Immunotherapy ...................................................................... 
 
5.4.6 Rationale for Two Years Fixed Duration with Checkpoint Blockade ...... 
 
5.4.7 Rationale for Quality of Life Evaluation ................................................. 
 
5.4.8 Rationale for Using a 
 Arm ............................................. 
 
5.4.9 Rationale for Not Blinding ....................................................................... 
 
5.5 Justification for Dose ........................................................................................ 
 
5.5.1 Rationale for BMS-986288 Starting Dose in Humans ............................. 
 
5.5.2 Rationale for BMS-986288 Maximum Dose ............................................ 
 
5.5.3 Rationale for BMS-986288 Dose Selection in Part 2C ........................... 
 
5.5.4 Rationale for 
 Selection and Dosing Schedule ......................... 
 
5.5.4.1 BMS-986288 ................................................................................... 
 
5.5.4.2 Rationale for 
 Administration of BMS-986288 with or 
without Nivolumab 
 ............................................................. 
 
5.5.4.3 Rationale for Nivolumab 30-minute Infusions ................................ 
 
5.5.4.4 Rationale for 
 of Nivolumab ........................................ 
 
5.5.4.5 Rationale for 
 ..................................................... 
 
5.5.4.6 Rationale for Choice of Standard of Care Treatment in Part 2C ... 
 
5.5.4.7 Rationale for KRAS Testing ............................................................ 
 
5.5.4.8 Rationale for 
 Testing .................................................. 
 
5.5.4.9 Rationale for Dose Selection of Regorafenib and Line of Therapy 
(in 3rd/4th Line MSS CRC) ................................................................... 
 
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 TREATMENTS ADMINISTERED .......................................................................... 
 
7.1 Schedule of Dose for Each Investigational Product ......................................... 
 
7.2 Method of Treatment Assignment .................................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.4.1 Dose-limiting Toxicities ........................................................................... 
 
7.4.2 Management Algorithms for Immuno-oncology Agents .......................... 
 
7.4.3 Dose Delays Due to Toxicity.................................................................... 
 
7.4.3.1 Criteria to Resume Treatment ......................................................... 
 
7.4.4 Exceptions to Permanent Discontinuation Criteria ................................. 
 
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7.4.5 Management of Drug-related Infusion Reactions ................................... 
 
7.4.6 Dose Modification for Regorafenib ......................................................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.5.1 Retained Samples for Bioavailability/Bioequivalence ............................. 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
 
7.7.1.1 Imaging Restriction and Precautions ............................................. 
 
7.7.2 Permitted Therapy ................................................................................... 
 
7.7.3 Palliative Local Therapy .......................................................................... 
 
7.8 Treatment After the End of the Study ............................................................... 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation from Study Treatment ............................................................ 
 
8.1.1 Post-Study Treatment Study Follow-up ................................................... 
 
8.2 Discontinuation from the Study ........................................................................ 
 
8.3 Lost to Follow-Up ............................................................................................. 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
9.1.1 Imaging Assessment for the Study............................................................ 
 
9.1.1.1 Methods of Measurement ................................................................ 
 
9.1.1.2 Imaging and Clinical Assessment ................................................... 
 
9.1.2 Clinical Outcomes Assessments ............................................................... 
 
9.1.2.1 NSCLC-SAQ .................................................................................... 
 
9.1.2.2 EQ-5D-5L ....................................................................................... 
 
9.1.2.3 FACIT GP5 ..................................................................................... 
 
9.2 Adverse Events ................................................................................................. 
 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
 
9.2.2 Method of Detecting AEs and SAEs ......................................................... 
 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
 
9.2.5 Pregnancy ................................................................................................ 
 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
 
9.2.7 Immune-Mediated Adverse Events ........................................................... 
 
9.2.8 Potential Drug-induced Liver Injury (DILI) ............................................ 
 
9.2.9 Other Safety Considerations .................................................................... 
 
9.3 Overdose ........................................................................................................... 
 
9.4 Safety ................................................................................................................ 
 
9.4.1 Physical Examinations ............................................................................. 
 
9.4.2 Vital signs................................................................................................. 
 
 
 
9.4.4 Electrocardiograms ................................................................................. 
 
9.4.5 Clinical Safety Laboratory Assessments .................................................. 
 
9.4.6 Imaging Safety Assessment ...................................................................... 
 
9.5 Pharmacokinetics and Immunogenicity Assessment ........................................ 
 
9.6 Pharmacodynamics ........................................................................................... 
 
9.7 Pharmacogenomics ........................................................................................... 
 
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Clinical Protocol
BMS-986288
CA043001
anti-CTLA-4 NF Probody mAb
Protocol Amendment No.: 03
Date: 24-Mar-2023
14
4.0
Approved
930132727
4.0
v
Approved
1.0
v

9.7.1 ADME Sampling ...................................................................................... 
 
9.8 Biomarkers ........................................................................................................ 
 
9.8.1 
 Biomarkers .................................................................. 
 
9.8.1.1 Soluble Biomarkers ......................................................................... 
 
9.8.1.2 Immunophenotyping ........................................................................ 
 
9.8.1.3 
 Analysis............................................................... 
 
9.8.1.4 
 Variants .................................................................. 
 
 
 
 
 
 
 
9.8.2.1 Characterization of Tumor Immune Microenvironment ................. 
 
9.8.2.2 Characterization of 
 ............................................. 
 
 
 
9.8.2.4 Mutational and DNA Methylation Analyses ................................... 
 
9.8.3 Biomarker Sampling Schedule ................................................................. 
 
9.8.4 Additional Research Collection ............................................................... 
 
9.9 Health Economics OR Medical Resource Utilization and Health Economics . 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Sample Size Determination ............................................................................. 
 
10.1.1 Monotherapy Dose Escalation (Part 1A) .............................................. 
 
10.1.2 The Safety Evaluation of Combination Doses of BMS-986288 with 
Nivolumab (Part 1B) ................................................................................... 
 
10.1.3 The 
 Evaluation of BMS-986288 as a Monotherapy and in 
Combination with Nivolumab 
 ................................................... 
 
10.1.4 The BMS-986288 
 Cohort Expansion (Part 2A) .............. 
 
10.1.5 The BMS-986288 in Combination with Nivolumab Cohort Expansion 
(Part 2B) ..................................................................................................... 
 
10.1.6 The BMS-986288 in Combination with Nivolumab Cohort Expansion in 
MSS CRC Participants (Part 2C) ............................................................... 
 
10.2 Populations for Analyses ................................................................................ 
 
10.3 Statistical Analyses ......................................................................................... 
 
10.3.1 Efficacy Analyses ................................................................................... 
 
10.3.2 Safety Analyses....................................................................................... 
 
10.3.3 Pharmacokinetic Analysis for BMS-986288 .......................................... 
 
10.3.4 Immunogenicity ...................................................................................... 
 
10.3.5 Biomarker Analyses ............................................................................... 
 
10.3.6 ECG Analyses ........................................................................................ 
 
10.3.7 Other Analyses ....................................................................................... 
 
10.3.8 Interim Analyses ..................................................................................... 
 
10.3.8.1 Bayesian Continuous Monitoring for Treatment-related Toxicities 
Meeting DLT Criteria in Part 2 ............................................................ 
 
11 REFERENCES ........................................................................................................ 
 
12 APPENDICES ......................................................................................................... 
 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
 
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Clinical Protocol
BMS-986288
CA043001
anti-CTLA-4 NF Probody mAb
Protocol Amendment No.: 03
Date: 24-Mar-2023
15
4.0
Approved
930132727
4.0
v
Approved
1.0
v

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 RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS ........................ 
 
APPENDIX 6 MANAGEMENT ALGORITHMS FOR IO AGENTS ........................ 
 
 
 
APPENDIX 8 SCHEDULE OF ACTIVITIES, PHARMACOKINETICS SAMPLING 
SCHEDULE, AND BIOMARKER SAMPLING SCHEDULE FOR POTENTIAL 
ALTERNATIVE DOSE SCHEDULES IN CA043001 ......................................... 
 
APPENDIX 9 ECOG PERFORMANCE STATUS ..................................................... 
 
APPENDIX 10 NYHA FUNCTIONAL CLASSIFICATION ..................................... 
 
APPENDIX 11 COUNTRY-SPECIFIC REQUIREMENTS/DIFFERENCES............ 
 
APPENDIX 12 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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Clinical Protocol
BMS-986288
CA043001
anti-CTLA-4 NF Probody mAb
Protocol Amendment No.: 03
Date: 24-Mar-2023
16
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
1
SYNOPSIS
Protocol Title: A Phase 1/2 First-in-human Study of BMS-986288 Alone and in Combination with Nivolumab 
in Advanced Malignant Tumors
Short Title: An Investigational Immunotherapy Study of BMS-986288 Alone and in Combination With Nivolumab 
in Advanced Solid Cancers 
Study Phase: Phase 1/2
Rationale:
This is a Phase 1/2, first-in-human study of BMS-986288, a non-fucosylated (NF) ProbodyTM variant of ipilimumab, 
administered alone and in combination with nivolumab in humans with select advanced solid tumors: squamous cell 
carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), cutaneous melanoma, triple-negative 
breast cancer (TNBC), renal cell carcinoma (RCC), urothelial carcinoma, gastric, esophageal, cervical, and colorectal 
cancer (CRC).
Ipilimumab is a fully human monoclonal antibody (mAb) that binds the negative immunoregulatory protein, cytotoxic 
T-lymphocyte-associated protein 4 (CTLA-4). Treatment with ipilimumab as a monotherapy or in combination with 
nivolumab (anti-programmed cell death 1 [PD-1] mAb) results in clinically meaningful anti-tumor activity in several 
malignancies; however, treatment is also associated with a high frequency of immune-related adverse events (irAEs). 
Strategies to reduce the frequency and severity of ipilimumab-associated irAEs and increase the breadth and depth of 
anti-tumor activity could improve the benefit-risk of anti-CTLA-4 containing treatment regimens.
BMS-986288 is an anti-CTLA-4 NF Probody mAb (PROBODY is a trademark of CytomX Therapeutics, Inc.). Unlike 
ipilimumab, BMS-986288 
 on the heavy chain, and is predicted 
to harbor a higher affinity for 
 and improve
. The Probody is 
made by the addition of 44 amino acids to the N-terminus of both light chains of the human anti-CTLA-4 mAb 
ipilimumab, which is designed to be activated by proteolytic cleavage at specific sites in the Probody sequence upon 
encountering proteases predominantly present in the tumor microenvironment. In this way, Probody therapeutics have 
the potential to minimize toxicities due to limited interaction of the administered (“prodrug”) form of the drug with 
its target in healthy tissues and to maintain efficacy due to interaction of protease-activated drug with its target in 
tumors.
The properties of BMS-986288 (anti-CTLA-4 NF Probody mAb) include:
 (as the Probody form) 
to human CTLA-4 protein compared to ipilimumab; 
 compared 
to ipilimumab; higher 
activity than ipilimumab in a 
 assay;
increased anti-tumor activity compared to ipilimumab in 
 tumor models; and 
peripheral 
pharmacodynamic activity compared to ipilimumab based on analysis of extratumoral 
 populations. These 
properties support the hypothesis that BMS-986288 can potentially 
 the depth and breadth of response by 
combining CTLA-4 blockade with the 
in the tumor 
microenvironment, while 
 systemic exposure to the active species and potentially reducing the risk of 
autoimmune side effects normally seen after ipilimumab treatment. This potentially improved 
 is 
especially important because of the promise of combination immunotherapy approaches, 
 
.
Based on this unique mechanism of action, this study will evaluate the safety and preliminary efficacy of BMS-986288 
alone and in combination with nivolumab.
Study Population:
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 measurable disease per Response Evaluation Criteria in 
Solid Tumors (RECIST) v1.1 and have at least 1 soft tumor tissue lesion accessible for biopsy.
Objectives and Endpoints:
The objectives and endpoints for primary, secondary, and exploratory analyses for this study are shown in Table 1.
Protocol Amendment No.: 03
Date: 24-Mar-2023
17
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 1:
Objectives and Endpoints
Objectives
Endpoints
For Part 1, 2A, 2B

Primary

To characterize the safety, tolerability, and DLTs and to 
determine the MTD/RP2D of BMS-986288 administered as 
monotherapy and in combination with nivolumab in 
participants with select advanced solid tumors

Incidence of AEs, SAEs, AEs meeting
protocol-defined DLT criteria, AEs leading 
to discontinuation, and death.
For Part 1, 2A, 2B
Secondary

To characterize the PK of BMS-986288 when administered 
alone and in combination with nivolumab 

To assess the preliminary efficacy of BMS-986288 alone 
and in combination with nivolumab in advanced solid 
tumors using RECIST v1.1 

Summary measures of PK parameters of 
BMS-986288

ORR, DOR, PFS, and TTR per RECIST 
v1.1 by Investigator assessment
For Part 1, 2A, 2B
Exploratory

To explore the potential association between anti-tumor 
activity and pharmacodynamic markers, such as, but not 
limited to,
 
 
prior to 
treatment and following administration of BMS-986288 
alone and in combination with nivolumab

To explore the associations between BMS-986288 PK, 
safety, efficacy, and clinical biomarkers

To characterize the immunogenicity of BMS-986288 and 
nivolumab

To assess the preliminary efficacy of BMS-986288 alone 
and in combination with nivolumab in select advanced solid 
tumors using iRECIST

To assess the OS in participants treated with BMS-986288 
alone and in combination with nivolumab

To assess the potential effect of BMS-986288 when 
administered 
 on the QTc interval

To characterize the PK and bioavailability of BMS-986288
when administered 

To explore the impact of treatment on NSCLC 
participant-reported symptoms and health-related quality of 
life (Part 2A and Part 2B only)

To explore participant overall perception of bother in 
relation to treatment-related symptomatic side effects (Part 
2A and Part 2B only)

To explore overall health status (Part 2A and Part 2B only)

To measure 
, and assess 
 change over time and in 
association with response

Summary measures of anti-tumor activity 
by pretreatment level of biomarkers of 
interest; correlation/measure of association 
of anti-tumor activity and change (or % 
change) from baseline in biomarkers of 
interest

Association 
measures 
between 
BMS-986288 PK levels by 
 
select outcomes, and biomarkers of interest

Incidence of ADA to nivolumab and BMS-
986288

ORR, DOR, and PFS per iRECIST by 
BICR

OSR at 1 year and 2 years

Summary measures of ECG parameters and 
changes in QTcF (ΔQTcF) from baseline

Summary 
of 
PK 
parameters 
when 
BMS-986288 is administered 
 alone or 
in combination with nivolumab

Mean NSCLC-SAQ scores and change 
from baseline scores

Proportion of participants endorsing each 
response option of the FACIT GP5

Mean EQ-5D-5L utility index scores and 
EQ-5D-VAS scores and change from 
baseline scores

Summary 
measures 
of 
 
and 
correlation/ measure of association of anti-
tumor activity and change (or % change) 
from baseline in 
Protocol Amendment No.: 03
Date: 24-Mar-2023
18
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 1:
Objectives and Endpoints
Objectives
Endpoints
For Part 2C 
Primary

To 
compare 
the 
efficacy 
of 
BMS-986288 
in 
combination with nivolumab vs regorafenib in the 3L/4L 
MSS CRC setting.

ORR per RECIST v1.1 by BICR 
For Part 2C
Secondary

To compare the efficacy of BMS-986288 in combination 
with nivolumab vs regorafenib in the 3L/4L MSS CRC 
setting

To characterize the safety and tolerability of BMS-986288 
in combination with nivolumab vs regorafenib in the 3L/4L 
MSS CRC setting

DOR and PFS per RECIST v1.1 by BICR, 
and OS

ORR, DOR, and PFS per RECIST v1.1 by 
Investigator assessment 

Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs leading 
to discontinuation, and death
For Part 2C
Exploratory

To compare the efficacy of BMS-986288 in combination 
with nivolumab vs regorafenib in the 3L/4L MSS CRC 
setting in subgroups of 

Explore the association between response with both 
baseline and pharmacodynamic markers in the 
 
 and the 

To evaluate BMS-986288 PK in the MSS CRC setting in 
combination with nivolumab

To evaluate immunogenicity of BMS-986288 and 
nivolumab when administered as combination

To explore the exposure-response relationship for 
BMS-986288 when given as combination with nivolumab 

ORR, DCR, DOR, PFS by BICR, and OS in 
the subgroups of 
 
participants

Summary measures of change (or % 
change) from baseline in parameters of 
interest 
and 
correlation/measure 
of 
association 
of 
response 
and 
pharmacodynamic markers

Summary measures of PK parameters from 
population PK analysis 

Summary 
of 
ADA 
incidence 
and 
association 
with 
PK, 
efficacy, 
hypersensitivity, 
and 
infusion-related 
safety events

Exposure-response relationship for efficacy 
endpoints including ORR and PFS.

Exposure-response relationship for safety 
endpoints including TRAE Grade 3+ and 
dose modification due to TRAE. 
Abbreviations: 3L/4L = 3rd line/4th line; ADA = anti-drug antibody; AE = adverse event; BICR = blinded independent 
central review; BMS = Bristol-Myers Squibb; CRC = colorectal cancer; DCR = disease control rate; DOR = duration 
of response; DLT = dose-limiting toxicity; ECG = electrocardiogram; EQ-5D-5L = 5-Level EQ-5D; EQ-5D-VAS = 
EQ-5D Visual Analog Scale; FACIT GP5 = Functional Assessment of Chronic Illness Therapy, General Physical 
item; IgG = immunoglobulin G; iRECIST = modified RECIST in cancer immunotherapy trials; MSS = microsatellite 
stable; MTD = maximum tolerated dose; NSCLC-SAQ = Non-small Cell Lung Cancer Symptom Assessment 
Questionnaire; ORR = objective response rate; OS = overall survival; OSR = overall survival rate; PFS = progression-
free survival; PK = pharmacokinetics; QTc = QT interval corrected; QTcF = QT interval corrected for heart rate using 
Fridericia’s formula; RECIST = Response Evaluation Criteria in Solid Tumors; RP2D = recommended Phase 2 dose;
SAE = serious adverse event; 
 TRAE = treatment-related 
adverse event; 
 TTR = time to response.
Protocol Amendment No.: 03
Date: 24-Mar-2023
19
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Overall Design:
This is a Phase 1/2, open-label study of BMS-986288, administered as a single agent and in combination with 
nivolumab in participants with select advanced solid tumors (SCCHN, NSCLC, cutaneous melanoma, RCC, CRC, 
TNBC, urothelial carcinoma, gastric, esophageal, and cervical cancer).
The study is composed of 2 parts: dose escalation (Part 1) and initial dose expansion (Part 2). In the dose-escalation 
phase, BMS-986288 will be administered intravenously (IV) alone (Part 1A) or in combination with nivolumab 
(Part 1B). 
 administration of BMS-986288 as a monotherapy or in combination with nivolumab 
may also be evaluated
. In the initial dose-expansion phase, cohorts of BMS-986288 
 
(Part 2A), and in combination with nivolumab (Part 2B and Part 2C Arm C and Arm E) will be expanded to gather 
additional safety, tolerability, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamic information in 
specific participant populations. In Part 2C, (randomized microsatellite stable [MSS] CRC cohort), Arm D standard 
of care (regorafenib) will be given. Participants in Part 2C Arm D receiving regorafenib will have the option to 
transition to BMS-986288 in combination with nivolumab (Part 2C Arm Z) after BICR-assessed progression. An
additional dose of BMS-986288 in combination with nivolumab may be open as Arm E.
All participants will complete up to 3 study periods: Screening (up to 30 days), Treatment (up to 
 cycles, 
days/cycle), and Follow-up (comprised of Safety [100 days], Imaging [up to 2 years], and Survival [up to 2 years] 
following end of treatment [EOT]). The duration of study participation will be approximately 4 years (treatment of up 
to 2 years and follow-up of up to 2 years).
Images will be submitted to a central imaging vendor and may undergo Blinded Independent Central Review at any 
time during the study. Prior to scanning first participant, sites should be qualified and understand the image acquisition 
guidelines and submission process as outlined in the CA043001 Imaging Manual provided by the central imaging 
vendor.
Number of Participants: 
The approximate total number of evaluable participants will be up to 
, as shown below:

Part 1 - Escalation Phase: Up to approximately 
DLT-evaluable participants may be treated, including:

Part 1A - Safety Evaluation of BMS-986288 Monotherapy Escalation: Up to 
evaluable participants

Part 1B - Safety Evaluation of BMS-986288 in Combination with Nivolumab: Up to 
evaluable 
participants

 Evaluation of BMS-986288 as a Monotherapy and in Combination with Nivolumab: 
Up to 
 evaluable participants

Part 2 - Initial Expansion Phase: Up to 
evaluable participants may be treated, including:

Part 2A Cutaneous Melanoma - BMS-986288 
 Cohort Expansion: Up to 
participants with 
cutaneous melanoma 

Part 2A NSCLC - BMS-986288 
Cohort Expansion: Up to 
 participants with NSCLC will be 
treated. If more than 1 dose level is evaluated, additional participants (up to 
 participants per dose level) 
may be enrolled, up to 
 participants (eg, 
 participants 2 arms) 

Part 2B - BMS-986288 in Combination with Nivolumab Cohort Expansion: Up to 
 participants with 
NSCLC will be treated. If more than 1 dose level is evaluated, additional participants (up to 
 participants 
per dose level) may be enrolled, up to 
 participants (eg,
 participants 2 arms) 

Part 2C randomized MSS CRC cohort:

Arm C - BMS-986288 in combination with nivolumab: up to 
 participants will be treated.

Arm D - standard of care: up to 
 participants will be treated with regorafenib. Participants will have 
the option to transition to BMS-986288 in combination with nivolumab upon progression (Arm Z).

If more than 1 dose level is evaluated, additional participants (up to 
 participants) may be enrolled in 
a separate arm (Arm E) in Part 2C.
Protocol Amendment No.: 03
Date: 24-Mar-2023
20
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Treatment Arms and Duration:
Part 1: The Dose-Escalation Phase is where the dose of BMS-986288 will be administered IV alone (Part 1A) or in 
combination with nivolumab (Part 1B).
 administration of BMS-986288 as a monotherapy (Arm A) or in 
combination with nivolumab (Arm B) may also be evaluated 

The BMS-986288 Monotherapy Escalation (Part 1A) will escalate the dose of BMS-986288 to determine the 
monotherapy maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Specifically, the Part 1A dose 
escalation will evaluate different doses of BMS-986288 starting at 
mg, followed by 
 
. If it appears that a planned dose level is associated with 
an unacceptable frequency of toxicities, then an intermediate dose or alternative administration schedule may be 
evaluated, and will not initially exceed a dose determined to be tolerable. After preliminary evaluation of safety 
and PK data from these intermediate dose or alternative administration schedules, re-escalating doses of 
BMS-986288 may be initiated. The study will first evaluate the safety and tolerability of BMS-986288 
monotherapy based on dose-limiting toxicities (DLTs), using a Bayesian Logistic Regression Model (BLRM) 
employing the escalation with overdose control (EWOC) principle, and overall assessment of available safety, 
PK, and pharmacodynamic data.

The Safety Evaluation of BMS-986288 in Combination with Nivolumab (Part 1B) will evaluate the safety and 
tolerability of various doses of BMS-986288 in combination with nivolumab to determine the combination 
MTD/RP2D. Treatment in Part 1B will be initiated in a staggered manner relative to the BMS-986288 
Monotherapy Escalation (Part 1A). Specifically, Part 1B can be initiated upon the decision to escalate when at 
least 2 dose levels in Part 1A have cleared the DLT period in accordance with dose escalation rules, after which 
dose escalation in Part 1A and Part 1B will proceed in parallel. At no point will the dose of BMS-986288 
administered in combination with nivolumab in Part 1B exceed the highest safe dose in ongoing monotherapy 
dose escalation in Part 1A or the highest dose determined to be tolerated in Part 1A. In Part 1B, the dose of 
BMS-986288 will be escalated, whereas the dose of nivolumab will be 
. However, if it 
appears that a planned dose level is associated with an unacceptable frequency of toxicities, then an intermediate 
dose, additional cohorts of alternative BMS-986288 administration schedules, or de-escalating doses of 
nivolumab may be evaluated, and potential re-escalating doses of BMS-986288 may then be initiated. The safety 
and tolerability of the BMS-986288 combination with nivolumab will be evaluated using a BLRM-copula
employing the EWOC principle, and an overall assessment of available safety, PK, and pharmacodynamic data.

The 
 Evaluation of BMS-986288 as a Monotherapy and/or in Combination with Nivolumab 
 may be conducted to obtain preliminary data on the safety, tolerability, PK, bioavailability, and 
pharmacodynamics of BMS-986288 alone or in combination with nivolumab when
 
will be initially composed of a single cohort for BMS-986288 monotherapy (Arm A) and/or BMS-986288 in 
combination with nivolumab (Arm B). The dose and administration schedule of BMS-986288 alone or in 
combination with nivolumab selected for 
 will be determined by evaluation of the available clinical 
safety, PK, and pharmacodynamic data from Part 1A and Part 1B, 
 
. BMS-986288 may be combined with the 
 depending on the dose 
selected (Arm A and/or Arm B). Nivolumab in combination with 
 may also be administered (Arm B).
The BMS-986288 dose in 
 will not exceed the highest dose equivalent determined to be tolerated in Part 
1A and/or Part 1B. 
 may be used to inform 
 dose selection in The Initial 
Expansion Phase (Part 2).
Part 2: The Expansion Phase is where cohorts of BMS-986288 
 (Part 2A) and Combination With 
Nivolumab (Part 2B) are expanded to gather additional safety, tolerability, preliminary efficacy, PK, and 
pharmacodynamic information in specific participant populations.

One or more dose regimens of BMS-986288 alone and in combination with nivolumab selected for Part 2 cohort 
expansion will be selected from the range of doses assessed as tolerable in Part 1, and which do not exceed the 
MTD or highest dose administered. These dose(s) will be selected based on evaluating the recommendation from 
BLRM and an overall assessment of available safety, PK, pharmacodynamics, and efficacy data from Part 1.

Part 2 is currently comprised of signal-seeking expansion cohorts in cutaneous melanoma, NSCLC, and a 
randomized MSS CRC cohort in comparison with regorafenib; additional tumors or potential arms will be 
included upon evaluation of available safety, PK, pharmacodynamic, and efficacy data from Part 1.
Protocol Amendment No.: 03
Date: 24-Mar-2023
21
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb

In Part 2C, the efficacy and safety of BMS-986288 
with nivolumab will be assessed in 
participants with MSS CRC who have progressed or relapsed on at least 2 prior standard therapies. Participants 
must not have received prior anti-CTLA-4, anti-PD-(L)1 therapy in the advanced or metastatic setting. The 
dose(s) to be evaluated in Part 2C will be selected from the range of doses assessed as tolerable in Part 1B, and 
which do not exceed the MTD or highest dose administered that has cleared safety. The dose(s) will be selected 
based on the totality of available safety, tolerability, efficacy, PK, and PD data. Regardless of whether or not 
 
 status is known, all participants will be tested during screening for extended RAS (Kirsten rat sarcoma 
virus [KRAS] and 
 and 
 status. The 
Sponsor may elect to prioritize enrollment of participants based on 
 status as well as presence of liver 
metastasis at screening. In Part 2C, participants will be treated 
 for up to 2 calendar years regardless of 
treatment delays. This cohort will have a standard of care control arm using regorafenib at 
 mg, or in 
accordance with locally approved prescribing information, orally once daily for 21 days of each 28-day cycle. 
Study Treatment: An overview of study treatment is shown in Table 2.
Table 2:
Study Treatment for CA043001
Medication
Potency
IP/Non-IP
BMS-986288 Powder for Solution for Injection
 mg per vial
IP
Nivolumab (BMS-986558) Solution for Injection
 mg (10 mg/mL)
IP
 mg (1 mg/mL)
IP
Regorafenib Tabletb
40 mgc
IP
Abbreviations: IP = investigational product; 
.
b These products may be obtained by investigational sites as local commercial product in certain countries if allowed 
by local regulations. In these cases, products may be a different pack size/potency than listed in the table. These 
products should be prepared/stored/administered in accordance with the package insert or SmPC.
c May include other commercially available strengths.
The study design schematics are shown in Figure 1 and Figure 2.
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anti-CTLA-4 NF Probody mAb
Figure 1:
Study Design Schematic
Abbreviations: 3L/4L = 3rd/4th line; BMS = Bristol-Myers Squibb; CRC = colorectal cancer; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; IRT = 
Interactive Response Technology; IV = intravenous; MSS = microsatellite stable; NSCLC = non-small cell lung cancer; PK = pharmacokinetics; 
 
 RCC = renal cell carcinoma; 
 RP2D = recommended Phase 2 dose; 
; SCCHN = 
squamous cell carcinoma of the head and neck; TBD = to be determined; TNBC = triple-negative breast cancer.
a Prior anti-PD-(L)1 therapy allowed. Anti-CTLA-4 naive required.
b Additional doses and dose schedules may be explored using data obtained from 
 administration.
c Part 1B will not start until demonstration of acceptable safety in at least 2 cohorts from Part 1A. Subsequently, treatment in both parts will occur in parallel.
d Doses(s) will be identified upon clinical evaluation of available safety, PK, pharmacodynamics, and efficacy data in Part 1A and/or Part 1B. 
 
 may be used in combination with BMS-986288 or nivolumab, depending on the determined dose. Details will be 
provided through a protocol amendment.
e Part 2 will be initiated upon evaluation of available safety, PK, pharmacodynamics, and efficacy data from Part 1 and may include IV or 
 administration.
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f Alternative assignment: In Part 2A 
 and Part 2B Combination Expansion, Part 2A and Part 2B may be open concurrently. In this case, treatment 
assignments will alternate between Part 2A and Part 2B. Multiple doses may be open concurrently in each part. In that case, treatment assignments will alternate 
between the dose levels, with consecutively treated participants assigned to different parts through IRT whenever possible. If there are no openings available in 
the dose level to which the participant would be assigned by this algorithm, then the participant will be assigned to the next open dose. 
g Intermediate dose level. 
Figure 2:
Study Design Schematic for Expansion Part 2C
Abbreviations: 3L/4L = 3rd/4th line; BICR = blinded independent central review; CRC = colorectal cancer; IRT, Interactive Response Technology; MSS = 
microsatellite stable; 
.
a Efficacy analyses based on the treated population may be performed for interim analyses.
b Stratification by liver metastasis status and a cap of 50% participants with liver metastases in each arm. Once enrolled in IRT, participants who have met all 
eligibility criteria for Part 2C will be randomized in a 2:1 ratio to nivolumab in combination with BMS-986288 (Arm C) or regorafenib (Arm D) and stratified 
by liver metastasis status. An additional dose of BMS-986288 (
 mg or 
 mg) in combination with nivolumab may be opened as Arm E. 
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Screening: The screening period will be up to 30 days and begins by establishing the participant’s initial eligibility 
and signing of the informed consent form. Within a given disease type, participants meeting all eligibility criteria will 
be enrolled in the study using an Interactive Response Technology according to the part and treatment arm availability.
Treatment: The initial dosing regimen of BMS-986288 is 
. All participants will be treated for up to 2 calendar 
years. Continuous safety evaluation and tumor assessment occurring in Part 1 and Part 2 
 of 
treatment and then 
thereafter), will guide the decision to treat a participant with additional 
cycles of study therapy if the participant has confirmed clinical benefit (up to a maximum of 2 years).

For the BMS-986288 Monotherapy Escalation (Part 1A) and the Expansion Phase BMS-986288 
 
(Part 2A), BMS-986288 will be infused over approximately 30 minutes. 

Shorter infusion times may be used for the initial dose cohorts and longer infusion times (approximately 
) may be used for the higher dose levels. 

For the Safety Evaluation of BMS-986288 in Combination with Nivolumab (Part 1B) and the Expansion Phase 
BMS-986288 in Combination with Nivolumab (Part 2B and Part 2C Arm C, Arm E, and Arm Z), BMS-986288 
and nivolumab will each be infused over approximately 30 minutes. 

When both BMS-986288 and nivolumab are given in combination, nivolumab will be given first, over 
 followed by BMS-986288 
, beginning at least 30 minutes after completion of the 
infusion of nivolumab.

Shorter infusion times for BMS-986288 may be used for the initial dose cohorts and longer infusion times 
 may be used for the higher dose levels.

Depending on the dose(s) selected for the 
 Evaluation of BMS-986288 as a Monotherapy and/or in 
Combination with Nivolumab 
 BMS-986288 and nivolumab may each be 
 with the 
. 

 of study treatment should be administered 
. Different 
 sites should be used if both BMS-986288 
 and nivolumab 
 are being administered (Arm B), 
with nivolumab being given first, followed by BMS-986288. 
 should not occur into or around an 
infected or acutely inflamed area because of the danger of spreading a localized infection. Clinical judgement 
should be used in determining the best site for 
 drug administration. 

For the 
 BMS-986288 in combination with nivolumab portion of the study, participants will receive the 
 dose of 
 mg 
 with the selected BMS-986288 dose 
 
administration will be permitted when 
 is not possible upon confirmation with the Sponsor. 
 the infusion will be the same as described below). 
The starting dose will be 
 mg of BMS-986288. A possible additional arm with a to-be-determined dose of 
BMS-986288 may be added based on an evaluation of the entirety of the safety, PK, PD, and anti-tumor activity 
data from Part 1B. When both BMS-986288 and nivolumab are given in 
, the infusion will be 
given approximately over 
. For participants weighing < 40 kg, the total infusion volume will be limited 
to 80 mL. For the 
 Arm D, the participants will receive regorafenib at 
 mg orally once daily for 21 
days of each 
-day cycle until disease progression, toxicity, withdrawal of consent, or death, whichever occurs 
first.

Refer to the Pharmacy Manual for additional dose preparation details for BMS-986288, nivolumab, 
, 
and regorafenib (if applicable).

Tumor progression and response endpoints will be assessed using RECIST v1.1.
Follow-up:

Safety Follow-up Period:

Upon completion of study therapy (up to a maximum of 2 years, if applicable) or once the decision is made 
to discontinue the participant from treatment, that is, at EOT, all participants will enter a Safety Follow-up 
Period.

All participants will be evaluated for any new AEs for at least 100 days after the EOT visit. Follow-up visits 
should occur at Days 30, 60, and 100 (7 days for all study visits) after the EOT visit. All participants should 
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anti-CTLA-4 NF Probody mAb
complete the 3 clinical safety follow-up visits regardless of whether new anti-cancer therapy is started, except 
those participants who will withdraw consent for study participation.

Imaging Follow-up Period:

Participants will continue to have radiologic and clinical tumor assessments after treatment discontinuation. 
Imaging assessments will continue to occur 
 (1 week) from the date of first treatment until Week 48, 
then continue 
 (1 week) thereafter. The duration of the Imaging Follow-up Period will be for a total 
of 2 years following EOT, or until initiation of another anti-cancer treatment, or death, whichever occurs 
first. Radiological assessments for participants who have ongoing clinical benefit may continue to be 
collected after participants complete the Survival Follow-up Period of the study. Participants who have 
disease progression after an initial course of study therapy will be evaluated beyond the EOT visit and will 
be allowed to receive other tumor-directed therapy as required.

Survival Follow-up Period:

In parallel with the Safety Follow-up Period, all participants will start the Survival Follow-up Period. 
Participants will be followed by telephone Q12W (2 weeks) from EOT for 2 years or until death, loss to 
follow-up, withdrawal of consent, or conclusion of the study, whichever comes first. Participants will have 
both the Imaging Follow-up Period and Survival Follow-up Period occur simultaneously. The duration of 
this follow-up is up to 2 years after EOT, although a longer follow-up period could be considered in selected 
cases if an efficacy signal is apparent. Subsequent therapies will also be recorded in this Survival Follow-up 
Period.
Data Monitoring Committee: No.
BMS has developed a multi-layered process to ensure safety monitoring 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. To support safety 
oversight, BMS has established ongoing processes for collection, review, analysis, and submission of individual 
adverse event reports and their aggregate analyses. Because this is an open-label study, WWPS, the BMS Medical
Monitor, and the Investigators will have access to all data necessary for safety evaluation.
BMS WWPS is an internal group that operates independently from the clinical team to monitor safety across all BMS 
protocols, and analyze all data in an unblinded fashion. Within BMS, an SMT is established for investigational 
therapies under clinical development, and a member of WWPS chairs this team. In addition, 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 (Chairman of the SMT) and WWPS single-case review physician, the study 
Medical Monitor(s) (or designee), the study biostatistician, and epidemiologist, all of whom analyze the data in an 
unblinded fashion. Furthermore, the SMT routinely monitors for actual or potential issues related to participant safety 
that could result in a significant change in the medical benefit-risk balance associated with the use of study 
treatment(s).
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anti-CTLA-4 NF Probody mAb
2
SCHEDULE OF ACTIVITIES
Study assessments and procedures are shown in Table 2-1, Table 2-2, and Table 2-3.
In limited instances, scheduled events (including events other than safety assessments) can occur 
outside of the indicated timeframes but the Sponsor should first be notified.
If a participant has a delay in study drug administration for any reason, then assessments and
laboratory tests (with the exception of any tests needed to ensure participant safety) should be
correspondingly delayed, with the exception of tumor assessments. Tumor assessments continue
per protocol schedule regardless of any treatment delay incurred.
The pharmacokinetic (PK), pharmacodynamic, and safety profiles of BMS-986288 are being 
elucidated; modifications to the procedures (ie, reduction in PK, pharmacodynamic sampling, 
timing of procedures, dose schedules) currently outlined in Section 2 and Section 9 may be 
required. These modifications will not include the addition of new procedures and will be 
documented in a note to file or administrative letter.
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Table 2-1:
Screening Schedule of Activities for All Study Parts
Procedure
Screening Visit 
(Days -30 to -1)
Notes
Eligibility Assessments
Informed Consent
X
A participant is considered enrolled only when a protocol-specific ICF is signed.
IRT Participant Assignment
X
After the participants meet all eligibility criteria, sites will use IRT for participant number 
assignment. Subsequent visits will be registered into the IRT system for drug supply 
(see Section 5.1.1). 
Inclusion/Exclusion Criteria
X
See Section 6.1 and Section 6.2.
Medical History
X
Include all medical history relevant to the disease under study (including, but not limited to,
liver metastasis status of Part 2C participants), any toxicities or allergies related to previous 
treatments, and SARS-CoV-2 vaccines more than 30 days prior to first study treatment.
Prior Cancer Therapies
X
Specify systemic and local therapy, particularly local liver-directed therapy for Part 2C 
participants.
Concomitant Medications
X
Within 14 days prior to treatment assignment.
Vaccine use within 30 days prior to first study treatment.
ECOG Performance Status
X
ECOG Performance Status of 0 or 1 is required for eligibility.
Safety Assessments
PE
X
If the screening PE is performed within 72 hours prior to dosing on Day 1, then a single 
examination may count as both the screening and predose evaluation.
Physical Measurements
X
Includes height and weight.
Vital Signs
X
Includes body temperature, respiratory rate, and seated/supine 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.
Oxygen Saturation
X
Pulse oximetry collected at rest.
ECG
X
ECGs should be recorded after the participant has been supine for at least 5 minutes and prior to 
blood draws (see Section 9.4.4).
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Table 2-1:
Screening Schedule of Activities for All Study Parts
Procedure
Screening Visit 
(Days -30 to -1)
Notes
Laboratory Tests
X
See Clinical Laboratory Assessments in Section 9.4.5 and Table 9.4.5-1.
Urinalysis
X
Microscopic urine reflex only for urinalysis positive for blood/protein/leukocytes.
Serology
X
Includes hepatitis C Ab, hepatitis B surface antigen, and HIV-1 and HIV-2 antibody 
(see Section 9.4.5 and Table 9.4.5-1).
Pregnancy Test
X
For WOCBP only. Serum to be collected at screening and within 24 hours prior to dosing. 
Serum pregnancy test may be taken on the first day of treatment, provided results are available 
prior to starting study therapy. If pregnancy test is taken within 24 hours of dosing (C1D1), a 
further pregnancy test is not required.
FSH
X
Women only, as needed to document postmenopausal status. Females under the age of 55 years 
must have a serum FSH level > 40 mIU/mL to confirm menopause.
Adverse Event Reporting
Assessment of Signs/Symptoms/
Clinical Complaints
X
Monitor for SAEs
X
All SAEs must be collected from the date of participant’s written consent until 100 days after 
discontinuation of dosing.
All AEs (SAEs or nonserious AEs) associated with SARS-CoV-2 infection collected from time 
of consent.
Tumor Assessments
Body Imaging
X
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected sites 
of disease, within 30 days prior to first dose. For participants with cancer of the head and neck, 
a CT or MRI of the neck is required. For participants with TNBC without measurable lesions 
outside of the breast, contrast-enhanced MRI of the breasts should be performed. See Section 
9.1.1 for further details.
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anti-CTLA-4 NF Probody mAb
Table 2-1:
Screening Schedule of Activities for All Study Parts
Procedure
Screening Visit 
(Days -30 to -1)
Notes
Brain Imaging
X
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 30 days of anticipated first study drug 
administration. Refer to imaging assessment details in Section 9.1.1.
Bone Scan
X
As clinically indicated per local standards (see Section 9.1.1).
Biomarker Assessment
Collection of 
X
All study parts: Consent for 
 
 is required for enrollment.
 are
optional for Part 2C regorafenib Arm D and Arm Z participants. For participants in Part 
2C Arm D who elect to crossover to Arm Z, 
 are mandatory in 
order to provide pre-treatment information.
 
obtained within 3 months prior to the initiation of study treatment (without any intervening 
systemic anti-cancer therapy during that time) must be submitted to the central laboratory. 
 
 
 
Instructions for the collection and processing 
 will be provided in the Laboratory 
Manual.
Abbreviations: AE = adverse event; BMS = Bristol-Myers Squibb; C1D1 = Cycle 1 Day 1; CT = computed tomography; ECG = electrocardiogram; ECOG = 
Eastern Cooperative Oncology Group; FSH = follicle stimulating hormone; HIV = human immunodeficiency virus; ICF = informed consent form; IgG = 
immunoglobulin G; IRT = Interactive Response Technology; MRI = magnetic resonance imaging; PE = physical examination; SAE = serious adverse event; 
SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TNBC = triple-negative breast cancer; WOCBP = women of childbearing potential.
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anti-CTLA-4 NF Probody mAb
Table 2-2:
On-Treatment - Schedule of Activities for All Study Parts
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
 days in length)
Cycles 3 and Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
Safety Assessments
ECOG Performance 
Status
X
X
X
X
PE
X
X
X
X
Symptom-directed PE
X
X
X
X
X
X
Weight
X
X
X
X
Vital Signsd
X
X
X
X
X
X
X
X
X
X
Oxygen Saturationd
X
X
X
ECGe
X
X
X
X
Triplicate ECGs performed 
at predose and EOI on 
C1D1 and C4D1 for 
Part 1A only. Single safety 
ECGs to be performed for 
all other time points and 
cohorts.
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anti-CTLA-4 NF Probody mAb
Table 2-2:
On-Treatment - Schedule of Activities for All Study Parts
Procedure
Cycle 1
 days in length)
Cycle 2
(
 days in length)
Cycles 3 and Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
Laboratory Tests
X
X
X
X
X
X
X
X
X
X
There will be a 72-hour 
window for collection of 
laboratory tests on D1. 
If screening laboratory 
tests are within 72 hours of 
C1D1, laboratory tests 
performed at screening can 
be used for C1D1. 
Coagulation assessment at 
screening only. See Section 
9.4.5 and Table 9.4.5-1.
Urinalysis
X
X
As clinically 
indicated 
Microscopic urine reflex 
only for urinalysis positive 
for blood/protein/leukocyte 
esterase.
Pregnancy Test 
(WOCBP only)h
X
X
X
X
Adverse Event Reporting and Concomitant Medication Assessments
Monitor for Non-SAEs
Non-SAEs will be collected continuously starting with the first dose of study medication 
and through 100 days following last dose of study treatment.
See Appendix 3 and 
Section 9.2.
All AEs (SAEs or 
nonserious AEs) including 
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CA043001
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anti-CTLA-4 NF Probody mAb
Table 2-2:
On-Treatment - Schedule of Activities for All Study Parts
Procedure
Cycle 1
 days in length)
Cycle 2
(
 days in length)
Cycles 3 and Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
those associated with 
SARS-CoV-2 infection 
must be collected 
continuously during the 
treatment period.
Monitor for SAEs
All SAEs must be collected continuously from the date of the participant’s written consent 
until 100 days following last dose of study treatment.
See Appendix 3 and 
Section 9.2.
All AEs (SAEs or 
nonserious AEs) including 
those associated with 
SARS-CoV-2 infection 
must be collected 
continuously during the 
treatment period.
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
PK Assessments
 
.
Immunogenicity (ADA)
Assessments
See Table 9.5-2, Table 9.5-3, and Table 9.5-4 for the PK and immunogenicity sampling schedule and 
Section 9.5.
 
See Table 9.8.3-1 and Table 9.8.3-2 for the biomarker sampling schedule and Section 9.8.
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anti-CTLA-4 NF Probody mAb
Table 2-2:
On-Treatment - Schedule of Activities for All Study Parts
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
 days in length)
Cycles 3 and Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
Imaging Assessments
Body Imagingi
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected sites of 
disease should occur 
 (7 days) starting from the first dose up until Week 48. Imaging 
assessments should then occur 
 (7 days). 
For participants with cancer of the head and neck, a CT or MRI of the neck is required.
For participants with TNBC without measurable lesions outside of the breast, contrast-enhanced MRI 
of the breasts should be performed. See Section 9.1.1 for further details.
Brain Imaging
Participants with history of brain metastasis should have surveillance MRI performed approximately 
every 12 weeks from first dose or sooner if clinically indicated. CT of the brain without and with 
contrast can be performed if MRI is contraindicated. See Section 9.1.1.1 for further details.
Bone Scan
As clinically indicated per local standards (see Section 9.1.1). 
Biomarker Assessments
See Section 9.5, 
Section 9.8, and 
Table 9.8.3-1 and Table 
9.8.3-2.
X
Mandatory 
 
must be performed at 
C2
(± 3 days), except 
for Part 2C participants 
enrolled in the regorafenib 
arm (Part 2C Arm D) and 
cross-over (Part 2C Arm 
Z).
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CA043001
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anti-CTLA-4 NF Probody mAb
Table 2-2:
On-Treatment - Schedule of Activities for All Study Parts
Procedure
Cycle 1
 days in length)
Cycle 2
(
 days in length)
Cycles 3 and Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
A 
 is required, if medically feasible, upon confirmation of PD (within 7 days) except 
for: 1) participants who have an 
 and progress within 4 cycles; 2) participants 
who will be imminently (within 4 weeks) enrolling in a subsequent clinical research study that 
requires a screening 
; 3) participants who consent to be treated beyond progression will require 
the 
 only at the subsequent confirmation of progression; and 4) participants in Part 2C, unless 
the participant elects to crossover to Arm Z.
 
 
Sampling
See Table 9.8.3-1 and Table 9.8.3-2 for details of biomarker assessments.
See Section 9.5, 
Section 9.8, 
Table 9.8.3-1, and Table 
9.8.3-2 and refer to 
Laboratory Manual.
Exploratory Biomarker Assessments
See Section 9.5, 
Section 9.8, Table 9.8.3-1,
and Table 9.8.3-2.
Clinical Treatment Supplies
BMS-986288 Planned 
Administration 
k
X
X
X
BMS-986288 to be 
supplied by BMS.
Does not apply for Part 2C 
Arm D.
Nivolumab 
Administration 
 
(Part 1B, 
 
Arm B, Part 2B, Part 
2C Arm C, Arm E, and 
Arm Z)
X
X
X
Nivolumab to be supplied 
by BMS.
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 2-2:
On-Treatment - Schedule of Activities for All Study Parts
Procedure
Cycle 1
 days in length)
Cycle 2
(
 days in length)
Cycles 3 and Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
Regorafenib (
mg)
Part 2C Arm Dl
See notes
Orally, once daily for the 
first 21 days (D1 to D21) 
of each 
-day cycle.
Clinical Outcomes Assessments (Part 2A and Part 2B Only)
NSCLC-SAQ
X
X
X
X
Clinical outcomes 
assessments to be 
administered in Part 2A and 
Part 2B only. NSCLC-SAQ 
will only be administered to 
NSCLC participants. Data 
will be collected using 
electronic devices. See 
Section 9.1.2.
FACIT GP5
X
X
X
X
X
X
X
X
X
X
EQ-5D-5L
X
X
X
X
Abbreviations: ADA = anti-drug antibody; BMS = Bristol-Myers Squibb; C = cycle; CT = computed tomography; CXDY = Cycle X Day Y, as an example; 
D = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOT = end of treatment; 
EQ-5D-5L = 5-Level EQ-5D; FACIT GP5 = Functional Assessment of Chronic Illness Therapy, General Physical item; hCG = human chorionic gonadotropin; 
IgG = immunoglobulin G; MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer; NSCLC-SAQ = Non-small Cell Lung Cancer Symptom 
Assessment Questionnaire; PD = progressive disease; PE = physical examination; PK = pharmacokinetic; 
 RECIST = Response Evaluation 
Criteria in Solid Tumors;
 SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome 
coronavirus 2; 
 TNBC = triple-negative breast cancer; WOCBP = women of childbearing potential.
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a EOT is defined as the visit where the decision is made to discontinue the participant from treatment. Evaluations will be performed prior to study discharge, or
for participants who are prematurely discontinued.
b For participants who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C26D1)
and 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 most recent 
on-treatment visit (with all available safety and response data); it does not need to be repeated and will be considered as the start of the safety follow-up period.
c
d Vital signs will be obtained before the IV infusion of BMS-986288 and then every 15 minutes (5 minutes) until 60 minutes after completion of the infusion 
for first 3 doses of study treatment on C1D1, C2D1, and C3D1; oxygen saturation to also be performed in conjunction with vital signs monitoring on these days.
For all cycles after C3 and for the nivolumab infusion, vital signs and oxygen saturation are to be taken before the infusion and at the end of infusion. If any 
vital sign is abnormal (based upon clinician assessment) at the final check, the participant must be observed further for a period of time, as clinically indicated.
e ECGs should be recorded after the participant has been supine for at least 5 minutes and prior to blood draws (see Section 9.4.4).
g Eye exam is to be performed as clinically indicated, starting with Cycle 3 (ie, Cycle 3, Cycle 5, etc.) and at EOT.
h Serum/urine to be collected within 24 hours prior to dosing. Pregnancy test may be completed on the first day of treatment, provided the results are available
before the start of study therapy. Serum or urine pregnancy test must be performed within 24 hours prior to administration of study treatment (urine pregnancy
test: minimum sensitivity 25 IU/L or equivalent units of hCG).
i
The same imaging modality is to be used for all assessments, per RECIST v1.1 (Appendix 5). Tumor assessment to be performed prior to initiating next cycle
of treatment.
j
Pre-treatment screening
 can be performed on C1D1. Mandatory 
 must be performed at C2D8 (± 3 days), except for the Part 2C participants 
enrolled in the regorafenib arm (Part 2C Arm D). Bone lesion 
 are unacceptable for submission. 
k Refer to Appendix 8 (if applicable) for potential alternative schedules that may be explored following evaluation of preliminary safety, PK, and 
pharmacodynamic data from 
 administration. Decisions to initiate exploration of these alternative dose schedules will be made after discussion and 
agreement between the Investigators and the BMS Medical Monitor (or designee). If a cohort with a more frequent schedule of administration is explored, the 
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dose level will be based on the PK data obtained from the 
 dosing schedule and will not exceed a dose equivalent determined to be tolerable. Implementation 
of these alternative dose schedules will not include the addition of new procedures and will be documented in a note to file or administrative letter. 
l
For participants who transition from regorafenib (Part 2C Arm D) to receive BMS-986288 in combination with nivolumab, PK, biomarker, physical 
examinations, vital sign measurements, and clinical laboratory evaluations will be performed on the same schedule of combination therapy starting at C1D1 and 
moving forward. A biomarker sample should be collected at the time of initial documented disease progression as the requirement at EOT visit and will be 
treated as screening sample in Part 2C Arm Z. Efficacy and safety data obtained after starting the combination therapy will be analyzed separately; however, 
safety data from these participants will be considered among the totality of data used for safety evaluation.
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Table 2-3:
Follow-up Procedural Outline for All Study Parts
Procedure
Safety Follow-up
(relative to the last dose of study treatment 
or date of discontinuation, whichever is later)
Imaging 
Follow-up
Survival Follow-
up
(assessed every 12 
weeks for 2 years 
from EOT)
Notes
Follow-up 1
30 Days
(7 Days)
Follow-up 2
60 Days
(7 Days)
Follow-up 3
100 Days
(7 Days)
Safety Assessments
PE
X
X
X
Vital Signs
X
X
X
Includes body temperature, seated/supine 
blood pressure, and heart rate.
Laboratory Tests
X
X
X
Laboratory tests also as clinically indicated.
See laboratory assessments in Section 9.4.5
and Table 9.4.5-1.
Urinalysis
As clinically indicated (see Section 9.4.5).
Pregnancy Test
X
X
X
For WOCBP, serum/urine pregnancy test is 
to be performed (urine pregnancy test: 
minimum sensitivity 25 IU/L or equivalent 
units of hCG; see Section 9.2.5).
Adverse Event Reporting and Concomitant Medication Assessments
Monitor for Non-SAEs
X
X
X
See Notes
Nonserious AEs will be collected
continuously starting with the first dose of 
study treatment and through 100 days after 
last dose of study treatment (see Appendix 3 
and Section 9.2).
Monitor for SAEs
X
X
X
See Notes
All SAEs must be collected continuously 
from the date of the participant’s written 
consent until 100 days after last dose of 
study treatment (see Appendix 3 and Section 
9.2).
Monitor for SARS-
CoV-2-related 
X
X
See Notes
Participants will be followed for all SAEs 
and all AEs (SAEs and nonserious AEs) 
associated with confirmed or suspected 
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Table 2-3:
Follow-up Procedural Outline for All Study Parts
Procedure
Safety Follow-up
(relative to the last dose of study treatment 
or date of discontinuation, whichever is later)
Imaging 
Follow-up
Survival Follow-
up
(assessed every 12 
weeks for 2 years 
from EOT)
Notes
Follow-up 1
30 Days
(7 Days)
Follow-up 2
60 Days
(7 Days)
Follow-up 3
100 Days
(7 Days)
Nonserious AEs and 
SAEs
SARS-CoV-2 infection until resolution, the 
condition stabilizes, the event is otherwise 
explained, the event is deemed irreversible, 
the participant is lost to follow-up (as 
defined in Section 8.3), or for suspected 
cases, until SARS-CoV-2 infection is ruled-
out.
Concomitant 
Medications
X
X
X
Sample Collection
PK Assessments
See Table 9.5-2, Table 9.5-3, and Table 9.5-4 for the PK and immunogenicity 
sampling schedule and Section 9.5.
Immunogenicity 
(ADA) Assessments
See Table 9.5-2, Table 9.5-3, and Table 9.5-4 for the PK and immunogenicity 
sampling schedule and Section 9.5.
Efficacy Assessments
Body Imaging
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or 
suspected sites of disease should occur 
 (7 days) starting from the 
first dose, up until Week 48. Imaging assessments should then occur 
 
 (7 days).
The duration of the Imaging Follow-up Period will be for a total of 2 years 
following EOT, initiation of another anti-cancer treatment, or death, whichever 
occurs first.
For participants with cancer of the head and neck, a CT or MRI of the neck is 
required.
For participants with TNBC without measurable lesions outside of the breast, 
contrast-enhanced MRI of the breasts should be performed. See Section 9.1.1 for 
further details.
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Table 2-3:
Follow-up Procedural Outline for All Study Parts
Procedure
Safety Follow-up
(relative to the last dose of study treatment 
or date of discontinuation, whichever is later)
Imaging 
Follow-up
Survival Follow-
up
(assessed every 12 
weeks for 2 years 
from EOT)
Notes
Follow-up 1
30 Days
(7 Days)
Follow-up 2
60 Days
(7 Days)
Follow-up 3
100 Days
(7 Days)
Brain Imaging
Participants with a history of brain metastasis should have surveillance MRI 
performed approximately every 12 weeks from first dose or sooner if clinically 
indicated. CT of the brain without and with contrast can be performed if MRI is 
contraindicated. See Section 9.1.1.
Bone Scan
See Section 9.1.1. As clinically indicated per local standards.
Subsequent Treatments 
(anti-cancer)
X
X
X
X
Assessment of 
Participant Survival 
Status
X
Participant status will be assessed by any 
documented clinic visit or telephone contact 
every 12 weeks.
Clinical Outcomes Assessments (Part 2A and Part 2B Only)
NSCLC-SAQ
X
X
X
X
Clinical outcomes assessments to be 
administered in Part 2A and Part 2B only. 
NSCLC-SAQ will only be administered to
NSCLC patients. Data will be collected 
using electronic devices, and EQ-5D-5L data
can be collected via telephone for the 
Survival Follow-up Period. See Section
9.1.2.
EQ-5D-5L
X
X
X
X
FACIT GP5
X
X
X
X
Abbreviations: ADA = anti-drug antibody; AE = adverse event; CT = computed tomography; EOT = end of treatment; EQ-5D-5L = 5-Level EQ-5D; FACIT GP5 =
Functional Assessment of Chronic Illness Therapy, General Physical item; hCG = human chorionic gonadotropin; IgG = immunoglobulin G; MRI = magnetic 
resonance imaging; NSCLC-SAQ = Non-small Cell Lung Cancer Symptom Assessment Questionnaire; PE = physical examination; PK = pharmacokinetics; SAE = 
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anti-CTLA-4 NF Probody mAb
serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TNBC = triple-negative breast cancer; WOCBP = women of childbearing 
potential.
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In the event of multiple procedures are required at a single time point, the electrocardiogram (ECG)
may be obtained up to 15 minutes earlier, vital signs may be obtained up to 10 minutes earlier or 
later, and clinical laboratory samples may be obtained up to 5 minutes earlier than the nominal 
time point, ensuring the PK samples can be collected on time.
3
INTRODUCTION
Ipilimumab is a fully human monoclonal antibody (mAb)
that binds the negative 
immunoregulatory protein, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Treatment 
with ipilimumab as a monotherapy or in combination with nivolumab (anti-programmed cell 
death 1 [PD-1] mAb) results in clinically meaningful anti-tumor activity in several malignancies;
however, treatment is also associated with a high frequency of immune-related adverse events 
(irAEs). Strategies to reduce the frequency and severity of ipilimumab-associated irAEs and 
increase the breadth and depth of anti-tumor activity could improve the benefit-risk of 
anti-CTLA-4 containing treatment regimens. CA043001 is a Phase 1/2, first-in-human (FIH) study 
of BMS-986288, a non-fucosylated (NF) ProbodyTM variant of ipilimumab, administered alone 
and in combination with nivolumab, in humans with select advanced solid tumors: squamous cell 
carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), cutaneous 
melanoma, triple-negative breast cancer (TNBC), renal cell carcinoma (RCC), urothelial 
carcinoma, gastric, esophageal, cervical, and colorectal cancer (CRC).
3.1
Study Rationale
Anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab) are approved immunotherapies for the 
treatment of select malignancies. Ipilimumab was the first immunotherapy to show a survival 
advantage in late-stage metastatic melanoma and has also demonstrated a significant 25% 
reduction in risk of recurrence or death in the melanoma adjuvant treatment setting. Blockade of 
CTLA-4 by ipilimumab has demonstrated anti-tumor activity in other malignancies, including lung 
cancer, prostate cancer, and RCC. However, no significant activity as a monotherapy was observed 
in urothelial carcinoma, colorectal, esophageal, gastric, and triple-negative breast cancer. 
Ipilimumab is also approved and in clinical development in combination with nivolumab. The 
combination was associated with a greater benefit in melanoma compared to each single agent. 
Benefit with the combination has also been observed in NSCLC, RCC, and microsatellite 
instability high (MSI-H) CRC, and is currently under evaluation in several other malignancies. 
The activation of a pre-existing but attenuated immune response to cancer by checkpoint blockade 
is associated with an adverse event (AE) profile that is inherent to immune activation. Ipilimumab 
treatment-related AEs can involve multiple organ systems (digestive, skin, and endocrine) and can 
require cessation of drug and treatment with corticosteroids. The combination regimen is 
associated with an increased incidence of AEs compared to nivolumab monotherapy, but a similar 
overall AE profile. Developing a new anti-CTLA-4 antibody with a more manageable AE profile 
and an 
 breadth and depth of response could improve the 
of 
anti-CTLA-4 containing treatment regimens.
BMS-986288 is an anti-CTLA-4 NF Probody mAb (PROBODY is a trademark of CytomX 
Therapeutics, Inc.). The Probody is made by the addition of 44 amino acids to the N-terminus of 
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both light chains of the human anti-CTLA-4 mAb ipilimumab. These amino acids form a masking 
peptide with a protease-cleavable linker containing sites for specific enzymes that are more active 
in tumors than in peripheral tissues. Probody therapeutics are prodrug forms of mAb-based 
therapeutics. Similar to prodrug strategies that have been successfully applied to small-molecule 
pharmaceuticals, the premise of the “Probody technology” is to create mAbs that are administered 
in a form that has a significantly reduced ability to bind to a mAb’s cognate antigen and maintains 
this form while in circulation and when encountering normal healthy tissue. The Probody 
therapeutic is designed to be activated by proteolytic cleavage at specific sites in the Probody 
sequence upon encountering proteases predominantly present in the tumor microenvironment. In 
this way, Probody therapeutics have the potential to minimize toxicities due to limited interaction 
of the administered (“prodrug”) form of the drug with its target in healthy tissues and to maintain 
efficacy due to interaction of protease-activated drug with its target in tumors. By widening the 
therapeutic window, Probody therapeutics are expected to be most useful for therapies where 
clinical utility is limited by significant on-target toxicities caused by antibody binding to target 
outside of the tumor. The hypothesis that a Probody version of ipilimumab (BMS-986249) will 
have a more tolerable safety profile than ipilimumab is currently being tested in a Phase 1 clinical 
trial (clinicaltrials.gov, NCT03369223).
The rest of the BMS-986288 amino acid sequence is exactly the same as ipilimumab; however, 
BMS-986288 is expressed in a 
, and 
therefore 
. In addition to the 
CTLA-4 blocking activity of ipilimumab, BMS-986288, via this
, is predicted to 
harbor 
. Data from 
 
models suggests that 
 increases the anti-tumor efficacy of 
CTLA-4 antibodies.1
Indeed, 
 studies with BMS-986288 show 
 
 compared to ipilimumab, correlating with more 
profound 
 at the tumor site (but not the periphery).
 play 
an important role in 
 the anti-tumor immune response by 
 
 in the tumor microenvironment. 
 present in tumors express higher levels of 
CTLA-4, and part of ipilimumab’s mechanism of action may be related to 
 triggered 
by 
; however, the data supporting this potential functionality is currently inconclusive. The 
hypothesis that a 
 version of ipilimumab (BMS-986218) will have increased anti-tumor activity 
to ipilimumab is currently being tested in a Phase 1 clinical trial (clinicaltrials.gov, 
NCT03110107). 
The properties of BMS-986288 (anti-CTLA-4 NF Probody mAb) are summarized below:

 (as the Probody form) to human 
 (masking efficiency of 
30) compared to ipilimumab

Comparable binding to 
compared to ipilimumab

 activity than ipilimumab in a 
 assay

Increased anti-tumor activity compared to ipilimumab in 
 tumor models
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
 peripheral pharmacodynamic activity compared to ipilimumab based on analysis of 
extratumoral 
The above properties support the hypothesis that BMS-986288 can potentially 
 the depth 
and breadth of response by combining CTLA-4 blockade with the 
 
 in the tumor microenvironment, while 
 systemic exposure to the active species
and potentially reducing the risk of autoimmune side effects normally seen after ipilimumab
treatment. This potentially improved 
 is especially important because of the 
promise of combination immunotherapy approaches, 
 
.
Based on this unique mechanism of action, this study will evaluate the safety and preliminary 
efficacy of BMS-986288 alone and in combination with nivolumab. 
3.2
Background
A detailed description of the chemistry, pharmacology, efficacy, and safety of BMS-986288 is 
provided in the Investigator’s Brochure (IB).2
3.2.1
BMS-986288
BMS-986288 has shown promising characteristics as a combination of both of the Probody
(BMS-986249) and NF (BMS-986218) second generation anti-CTLA-4 strategies and may
decrease irAEs while maximizing clinical benefits. The masked antibody exhibits reduced binding 
to CTLA-4 and 
 functional activity in vitro. When tested in 
 syngeneic tumor 
models, BMS-986288 has 
 systemic pharmacodynamic markers of 
anti-CTLA-4 activity, such as Ki-67 and ICOS upregulation on 
 and 
 in 
peripheral lymphoid organs. At the same time, BMS-986288 has consistently shown 
 
anti-tumor activity to BMS-986218, and 
 levels of 
 at the tumor site. 
These data confirm the ability of the Probody to preferentially target the tumor site for antigen 
binding activity and 
while reducing the systemic exposure to active antibody
and serves as the basis for BMS-986288, the Probody version of the fully human anti-CTLA-4 NF 
mAb, BMS-986218, and is shown in Figure 3.2.1-1.
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Figure 3.2.1-1:
Schematic of BMS-986288
3.2.1.1
Generation of an Anti-human-CTLA-4 NF Probody mAb
BMS-986288 was selected for dosage form development and is also referred to as BMS-986288-01
or anti-CTLA-4 NF Probody mAb. BMS has partnered with CytomX to use their Probody mAb 
approach, which takes advantage of increased protease activity in tumor tissues to remove a 
masking peptide and reveal the antigen binding site of the Ab. Hence, BMS-986288 has a masking 
peptide attached to the N-terminus of the 2 light chains of the anti-CTLA-4 NF mAb, 
BMS-986218. BMS-986218 is therefore the parent molecule and active form of BMS-986288.
BMS-986288 is produced from cell culture using a 
.
3.2.1.2
BMS-986288 Nonclinical Pharmacology
BMS-986288 binds CTLA-4 with an approximately 
-fold 
 (ie, less potent) half-maximal 
effective concentration (EC50) than the parent molecule BMS-986218, when the masking peptide 
is intact.3 The 
 in binding affinity also results in a 
 in functional activity. In a 
human 
 functional assay using 
to stimulate interleukin 
(IL)-2 production, BMS-986218 induced approximately -fold
levels of IL-2 compared to 
BMS-986288 at the highest concentration tested.4
induced by BMS-986288 was also 
 compared to BMS-986218.5
In the 
 syngeneic tumor model, dose titrations of both BMS-986218 and 
BMS-986288 
 tumor growth to a similar extent at all 3 identical dose levels (
 
 g) examined, and resulted in 
 tumor regressions 
 at 
the 2 highest dose levels.6 At the lowest dose level examined, BMS-986288 treatment resulted in 
a 
 regressions than BMS-986218
. A similar trend was 
observed between ipilimumab and BMS-986249, with comparable inhibition of tumor growth at 
the 2 highest dose levels and reduced anti-tumor activity of BMS-986249 at the lowest dose level. 
At the 
-g dose level, BMS-986218 and BMS-986288 exhibited a more robust anti-tumor 
activity compared to ipilimumab and BMS-986249. Immune monitoring of 
 populations 
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anti-CTLA-4 NF Probody mAb
indicated that BMS-986288 
 similarly to BMS-986218, with a 
 
and 
 reduction, respectively. Systemic pharmacodynamic markers of CTLA-4 activity, such 
as increased Ki-67 and ICOS levels on 
 subsets in the spleen, were 
. 
BMS-986288, therefore, has been shown to 
 anti-tumor activity and tumoral 
pharmacodynamic effects while 
 systemic pharmacodynamic effects.7
In summary, the in vitro and in vivo data indicate that BMS-986288 has 
 activity outside 
of the tumor site compared to ipilimumab and the parent molecule BMS-986218, while preserving 
the 
 of BMS-986218, supporting the development of this antibody for 
the treatment of cancer.
3.2.1.3
BMS-986288 Nonclinical Pharmacokinetics
The PK properties of BMS-986288, a Probody of BMS-986218 (NF-ipilimumab), were evaluated 
in mice and cynomolgus monkeys.
In human CTLA-4 
 tumors, following a -mg/kg IP dose of BMS-986288, 
the area under the concentration-time curve from 0 to 7 days (AUC[0-7d]) for total antibody in 
 was 
 g•h/mL, comparable to that of the parent molecule BMS-986218 
(
g•h/mL) administered at the same dose. The active species were formed over time, and the 
AUC(0-7d) of the active species was determined to be 
gh/mL. As a result, the AUC(0-7d) 
ratio between the active species and the total antibody in mice up to 7 days post IP dose was 
. 
Similar to mice, after 
-mg/kg weekly IV doses to monkeys for 
, the 
 
concentration-time profile of the total antibody superimposed on that of BMS-986218 given at the 
same dose. The AUC(0-7d) ratio between the active species and the total antibody after the first 
dose was 
, with the active species increasing following subsequent doses on a 
 
schedule. PK modeling of monkey repeat-dose data revealed that the total body 
 clearance 
(CLT) of the intact Probody was 
mL/d/kg, 
 than that of the total antibody 
(
mL/d/kg), suggesting that the Probody undergoes protease-mediated clearance in addition to 
the typical mAb elimination. The steady-state volume of distribution (Vss, 
 mL/kg) was 
estimated to be the same for the intact Probody and the total antibody. As a result, the estimated 
terminal half-life of the intact Probody 
, based on the PK model, was ~2-fold 
shorter than that of the total antibody 
. In addition, after a single IV dose, the AUC (INF)
ratio of the intact Probody, 
 species vs total antibody in monkeys,
estimated using the PK model, was
, respectively, demonstrating the 
conversion of the Probody to 
 species.
Anti-drug antibody (ADA) formation was observed in 
 monkeys; however, the 
formation of ADAs did not appear to affect the PK of BMS-986288 in monkeys. Furthermore, the 
tissue concentrations of the total antibody and the active species were evaluated in monkeys on 
Day 21 after the first IV dose. The concentrations of the total antibody in the liver, spleen, and 
colon were similar and 
lower than the 
 concentration. The active species were
detected in these tissue samples, with the concentrations being 
 of the total antibody.
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3.2.1.4
BMS-986288 Nonclinical Toxicology
In a 1-month toxicity study in monkeys 
 at weekly doses of 
 mg/kg 
, 
mg/kg 
, or 
mg/kg
 U/mL 
) of BMS-986288 resulted in profound 
dose-dependent 
 of 
 activation (ranging from 
) was 
observed at all doses following 
 
 consistent with the 
pharmacology of BMS-986288.8 BMS-986288 was clinically tolerated by monkeys when 
administered 
 
once 
 
for 
1 
month 
at 
mg/kg/week 
(mean 
AUC[0-T] =
gh/mL) with findings generally limited to minimal lymphohistiocytic 
 
 
 
 
 
 
. 
At 
mg/kg/week 
 
 
 
(mean 
AUC[0-T] =
gh/mL or 
 gh/mL, respectively), BMS-986288 administration 
resulted in 
on Days
, due to 
 clinical 
condition, primarily resulting from 
 
 (correlating with increased BUN, creatinine, and chloride), 
 
. In 
addition, there were mild to marked decreases in 
 and 
 
mg/kg/week 
 BMS-986288 was 
. With the 
exception of the  recovery monkeys that required 
 during the recovery period, most 
BMS-986288-related changes were partially or fully reversible. Based on tolerability and lack of 
severe toxicity at the low dose, the highest non-severely toxic dose (HNSTD) in this study was 
considered to be 
mg/kg/week (
gh/mL).
In comparison, the HNSTD for BMS-986218 in a similar 1-month IV monkey toxicity study was 
 mg/kg/week (
gh/mL), with moribundity occurring at the next 
highest dose level of 
 mg/kg/week (
gh/mL).9 Thus, BMS-986288 
appeared to reduce the systemic immune toxicities of BMS-986218 in both a 
 
-dependent manner. BMS-986288 administration also resulted in reduced toxicological effects 
compared to ipilimumab over a comparable dose range. Although the HNSTD of ipilimumab was 
also 
 mg/kg/week (mean AUC[0-168h] = 
gh/mL) in a similar 1-month study, there 
was a higher incidence and wider tissue distribution of inflammatory infiltrates in the ipilimumab 
groups compared to BMS-986288 groups across and within studies.10,11 These results were 
consistent with the proposed masking properties of the Probody linker on BMS-986288 and 
support the potential of BMS-986288 to offer an improved and/or differentiated safety profile 
relative to BMS-986218 and ipilimumab.
The BMS-986288 HNSTD corresponds to exposure (AUC) multiples of approximately 
 
 
µgh/mL) and highest projected dose for the FIH study (
 mg 
 
µgh/mL), respectively. 
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In vitro incubation of human PBMCs with dry-coated BMS-986218 as well as an isotype-matched 
control mAb (anti-KLH IgG1nf) led to significant 
 activation (as measured by increased 
CD25 and CD69 expression) at 
µg/well.12,13 Additionally, 
 of IL-1, IL-6, 
IL-8, interferon gamma (IFN-), and tumor necrosis factor alpha (TNF-α) relative to the 
phosphate-buffered saline (PBS) control occurred in a 
 of incubation 
with either dry-coated BMS-986218 or anti-KLH IgG1nf, due to non-target mediated engagement 
of the NF Fc tail. Despite the 
 and 
 observed with BMS-986218 and the 
isotype control under these superphysiologic conditions, clinical trial data from BMS-986218 and 
similar NF IgG1 constructs indicate that these antibodies do not have significant non-target related 
cytokine release in humans. No adverse cytokine release has been noted following IV 
administration of BMS-986218 at up to 
 mg/dose every 
 in patients with 
advanced cancers.14
 
 
Furthermore, in physiologically relevant whole-blood assays, clinically relevant concentrations of 
BMS-986218 in solution induced a 
 activation in a few donors at concentrations 
 µg/mL, and 
 cytokine release potential similar to that of ipilimumab.12,13,16,17
Therefore, BMS-986288 is also not expected to elicit adverse cytokine release in humans.
Overall, BMS-986288 has demonstrated an acceptable pharmacologic, nonclinical PK, 
pharmacodynamics, and risk profile to support initiation of a FIH clinical study in cancer patients.
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). 
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.18
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-986288 and nivolumab have not been 
conducted and are not required by the International Council on Harmonisation (ICH) S9 Note for 
Guidance on Nonclinical Evaluation for Anticancer Pharmaceuticals.19 The safety of the 
combination will be carefully monitored in the planned clinical trial.
The overall clinical safety experience with nivolumab, as either monotherapy or in combination 
with other therapeutics, is based on experience in approximately 17,700 participants.18 Nivolumab 
monotherapy is approved in multiple regions, including the United States (US) and Europe (EU), 
for unresectable or metastatic melanoma, previously treated metastatic NSCLC, previously treated 
advanced RCC, previously treated relapsed or refractory classical Hodgkin lymphoma, previously 
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treated advanced or metastatic urothelial carcinoma, and for the treatment of previously treated 
recurrent or metastatic SCCHN; it is also approved for previously treated CRC, previously treated 
hepatocellular carcinoma (HCC), and the adjuvant treatment of melanoma in the US. In addition, 
nivolumab has been approved for use in combination with ipilimumab for RCC in the US and 
unresectable melanoma in multiple countries, including the US and EU.18
Details on the clinical safety and PK profile of nivolumab, including results from other clinical 
studies, are summarized in the nivolumab IB.18
3.2.3
Ipilimumab
Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the 
activation and proliferation of tumor-infiltrating T-effector cells. Inhibition of CTLA-4 signaling 
can also reduce T-regulatory cell (Treg) function, which may contribute to a general increase in 
T-cell responsiveness, including the anti-tumor response.
Ipilimumab (BMS-734016, MDX010, and MDX-CTLA-4) is a fully human monoclonal IgG1κ 
specific for human CTLA-4 (CD152). Ipilimumab is a mAb that binds to CTLA-4 and blocks the 
interaction of CTLA-4 with its ligands, CD80/CD86. Ipilimumab has been administered to more 
than 22,571 participants (total number of participants enrolled in ipilimumab studies) in several 
cancer types in completed and ongoing studies, as well as a compassionate use program. 
Ipilimumab has been approved for use in over 47 countries including the US (Mar-2011), the 
European Union (Jul-2011), and Australia (Jul-2011).
The focus of the monotherapy clinical program has been in melanoma, with advanced melanoma 
and adjuvant melanoma being the most comprehensively studied indications. Ipilimumab is being 
investigated in combination with other modalities, such as chemotherapy, radiation therapy, and 
other immunotherapies in multiple tumor types. 
The safety profile of ipilimumab is generally consistent across studies, with: a) the majority of 
AEs being inflammatory in nature, which is consistent with the proposed mechanism of action of 
ipilimumab; b) the same types of such immune-related adverse events (irAEs) in the 
gastrointestinal (GI) tract, skin, liver, and endocrine system being reported; and c) most of these 
events being manageable with immune-suppressive therapies.
In patients with advanced melanoma who received 3 mg/kg ipilimumab monotherapy in a Phase 3 
study (MDX010-20), the most frequently reported adverse reactions (10% of participants) were 
diarrhea, rash, pruritus, fatigue, nausea, vomiting, decreased appetite, and abdominal pain. The 
majority of AEs were mild to moderate (Grade 1 or 2) and treatment was discontinued for adverse 
reactions in 10% of participants.
Dose-dependent toxicity as well as the relative efficacy of ipilimumab 3 mg/kg vs 10 mg/kg were 
established in a Phase 3 study in advanced melanoma (CA184169). Ipilimumab resulted in a 
median OS of 15.70 months in patients treated with 10 mg/kg and 11.53 months in patients treated 
with 3 mg/kg. Ipilimumab 10 mg/kg demonstrated statistically a significant improvement in OS 
(primary efficacy endpoint) compared with ipilimumab 3 mg/kg (HR = 0.84: 95% CI: 0.70, 0.99; 
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P-value = 0.0400). Best overall response rate was 15.3% (95% CI: 11.8, 19.5) for 10 mg/kg and
12.2% (95% CI: 9.0, 16.0) for 3 mg/kg.20
Ipilimumab monotherapy prolongs survival in patients with pretreated and previously untreated 
advanced melanoma and has demonstrated anti-tumor activity in other malignancies, including 
lung cancer, prostate cancer, and RCC.21
Additional details on the safety profile and clinical benefit of ipilimumab alone and in combination 
with nivolumab, including results from clinical studies in melanoma, prostate, lung, kidney, 
bladder, or triple-negative breast tumors are summarized in the ipilimumab and nivolumab 
IBs.18,21
3.2.4
Nivolumab Combined with Ipilimumab
Multiple clinical studies have evaluated nivolumab (OPDIVO®) combined with ipilimumab
(YERVOY®) at different doses and schedules. Based on phase 3 data showing improved survival
over standard of care therapies, nivolumab combined with ipilimumab has been approved in
multiple countries for the treatment of patients with unresectable or metastatic melanoma,
intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC), malignant 
pleural mesothelioma, NSCLC (PD-L1 ≥ 1%), and microsatellite instability-high or mismatch 
repair deficient metastatic colorectal cancer (mCRC). Details of the clinical activity in these 
various malignancies are provided in the USPI and summary of product characteristics (SmPC).
The combination of ipilimumab and nivolumab is currently FDA approved at 2 different dosing 
regimens: 1) 3 mg/kg ipilimumab and 1 mg/kg nivolumab Q3W for 4 doses in patients with 
unresectable or metastatic melanoma; and 2) 1 mg/kg ipilimumab and 3 mg/kg nivolumab Q3W
for 4 doses in patients with intermediate or poor risk, previously untreated advanced RCC and in 
patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mCRC
that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.22
In CA209032 (CheckMate 032), a Phase 1/2, open-label study of nivolumab monotherapy or 
nivolumab combined with ipilimumab in participants with advanced or metastatic solid tumors, 
the safety and anti-cancer efficacy of N3 Q2W, N+I at N1I1, N1I3, and I3N1 Q3W 4 followed 
by N3 Q2W were evaluated in 216 participants with SCLC who had received at least 1 prior 
platinum-containing regimen. Responses were seen in 10 (10%) of 98 participants treated with N3, 
1 (33%) of 3 treated with N1I1, 14 (23%) of 61 who received N1I3 and 10 (19%) of 54 who 
received N3I1. Grade 3 or 4 treatment-related AEs occurred in 13 (13%) participants in the N3 
cohort, 18 (30%) in the N1I3 cohort, and 10 (19%) in the N3I1 cohort; none of the 3 participants 
treated with N1I1 experienced treatment-related Grade 3 or higher AEs.23
CA209016 (CheckMate 016) was a Phase 1 study of nivolumab plus sunitinib, pazopanib, or 
ipilimumab in participants with metastatic renal cell carcinoma (RCC). Three different N+I 
regimens were assessed: N3I3, N1I3, and N3I1 given Q3W for 4 cycles followed by N3 Q3W. 
The N3I3 arm was closed due to poor tolerance. The N3I1 and the N1I3 arm accrued 
47 participants each, and Grade 3 to 4 treatment-related AEs were reported in 38.3% and 61.7% 
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of the participants in the N3I1 and N1I3 arms, respectively. At a median follow-up of 22.3 months, 
the confirmed objective response rate (ORR) was 40.4% in both arms, with ongoing responses in 
42.1% and 36.8% of participants in the N3I1 and N1I3 arms, respectively. The 2-year OS was 
67.3% and 69.6% in the N3I1 and N1I3 arms, respectively.24
Based on CheckMate 016, a randomized trial (CA209214; CheckMate 214) of nivolumab 
combined with ipilimumab (N3I1 Q3W 4 followed by N3 Q2W) vs sunitinib monotherapy was 
conducted in participants with previously untreated, advanced, or metastatic RCC. After a 
minimum follow up of 17.5 months, improved ORRs (41.6% vs 26.5%, p < 0.0001) and median 
PFS (11.6 vs 8.4 months, p = 0.0331) were seen in intermediate and high-risk RCC participants 
treated with nivolumab and ipilimumab (n = 425) compared to sunitinib (n = 422), respectively. 
Drug-related AEs in the entire study population (including participants with low risk RCC) were 
observed in 509 of 547 participants (93% any Grade, 46% Grade 3 to 4) with 
nivolumab + ipilimumab vs 521 of 535 participants (97% any Grade, 63% Grade 3 to 5) with 
sunitinib. Death occurred in 159 N+I participants (7 [1%] drug-related) and 202 sunitinib 
participants (4 [1%] drug-related).25
CA209012 (CheckMate 012) was a Phase 1, multiple-cohort study of nivolumab as monotherapy, 
in combination with ipilimumab, or in combination with chemotherapy or targeted therapy, in 
chemotherapy-naive adult (18 years) participants with stage IIIB/IV NSCLC or recurrent 
disease, assessing the safety, tolerability, ORR, and PFS rate (PFSR) at 24 weeks based on 
immune-related response criteria assessment. Cohort P included 38 participants who received 
nivolumab 3 mg/kg Q2W + ipilimumab 1 mg/kg every 12 weeks (Q12W), while Cohort Q 
included 39 participants who received nivolumab 3 mg/kg Q2W + ipilimumab 1 mg/kg every 
6 weeks (Q6W). Confirmed objective responses were achieved in 18 (47% [95% CI: 31, 64]) 
participants in the ipilimumab Q12W cohort and 15 (38% [95% CI: 23, 55]) participants in the 
ipilimumab Q6W cohort. Median duration of response (DOR) was not reached in either cohort, 
with median follow-up times of 12.8 months (interquartile range [IQR]: 9.3, 15.5 months) in the 
ipilimumab Q12W cohort and 11.8 months (IQR: 6.7, 15.9 months) in the ipilimumab Q6W 
cohort. The safety profiles in Cohorts P and Q were similar; no new types of AEs were observed 
and AEs were manageable with established algorithms. There were no deaths due to study drug 
toxicity. The rate of treatment-related AEs in the Q12W (82%) and Q6W (72%) arms were 
comparable to monotherapy (69%). In the study, Grade 3 to 4 treatment related AEs were 37%, 
33%, and 19% for the Q12W, Q6W, and nivolumab monotherapy arms, respectively. 
Treatment-related SAEs occurred in 32% and 28% of participants in the Q12W and Q6W cohorts, 
respectively, compared to 19% to nivolumab monotherapy.26,27
When nivolumab 1 mg/kg was administered in combination with ipilimumab 3 mg/kg, the 
clearance (CL) of nivolumab was increased by 29%, and the CL of ipilimumab was unchanged 
compared to nivolumab administered alone. When nivolumab 3 mg/kg was administered in 
combination with ipilimumab 1 mg/kg, the CL of nivolumab and ipilimumab were unchanged. 
When nivolumab was administered in combination with ipilimumab, the presence of anti-
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nivolumab antibodies increased the CL of nivolumab by 20% and the CL of ipilimumab was 
unchanged in the presence of anti-ipilimumab antibodies.
3.3
Benefit-Risk Assessment
Patients who have advanced solid tumors have a poor prognosis and few curative options.
Immunotherapy with ipilimumab or nivolumab has demonstrated clinical activity in patients with
advanced melanoma, NSCLC, RCC, SCCHN, and other tumors. Treatment-related AEs include 
those associated with autoimmune activation, such as colitis, pneumonitis, thyroiditis, hepatitis, 
and adrenal insufficiency.
There is no prior human experience with BMS-986288; therefore, clinical benefit has not been 
established in patients with advanced cancer. However, nonclinical models are suggestive of at 
least similar anti-tumor activity that has been observed with ipilimumab.
In the absence of clinical studies with BMS-986288, the evaluation of risk is based primarily on 
the potential effects based on the proposed mechanism of action, as well as on information from 
nonclinical studies with BMS-986288 in monkeys (Section 3.2.1), and clinical evidence from 
ipilimumab therapy. In addition, BMS is evaluating an anti-CTLA-4 NF mAb (clinical trials.gov, 
NCT03110107) and an anti-CTLA-4 Probody mAb (clinicaltrials.gov, NCT03369223) in separate 
clinical trials. Emerging data from these programs may inform the safety profile of BMS-986288.
The nonclinical assessment based on Good Laboratory Practice (GLP) toxicology studies of 
BMS-986288 has demonstrated a dose related toxicity profile of irAEs and cytokine release 
potential compatible with the expected mechanism of action (see Section 3.2.1). 
For the combination of BMS-986288 and nivolumab, as observed with ipilimumab and nivolumab 
combination therapy, it is possible that a higher incidence of irAEs may occur. The safety profile 
of nivolumab monotherapy and the combination of ipilimumab and nivolumab are characterized 
based on experience with more than 17,700 participants as either monotherapy or in combination 
therapy. The frequency and types of immune-mediated adverse reactions are similar across 
multiple types of tumors and are described in the Reference Safety Information in the current 
nivolumab and ipilimumab IBs.18,21 Unanticipated side effect events may also occur.
The proposed clinical studies of BMS-986288 have been designed to minimize the overall risk to 
participants; measures will include those described below.
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Continuous safety assessments will be utilized by the Investigators and Sponsor to determine 
whether additional safety measures, or termination of the study is required at any time. In addition, 
AEs and serious adverse events (SAEs) will be reviewed on an ongoing basis by the BMS Medical 
Monitor (or designee) and Worldwide Patient Safety (WWPS) representatives to monitor for any 
safety signals or trends. As BMS-986288 is an experimental agent, it is possible that unforeseen, 
unknown, or unanticipated reactions may occur. However, based on the nonclinical safety profile 
of BMS-986288 built into the planned starting dose of 
mg (equivalent to approximately 
mg/kg), the potential safety risks are expected to be minimized. 
The administration will occur at infusion centers with medical monitoring and the capability to 
manage infusion reactions or anaphylaxis. The protocol provides a treatment algorithm for infusion 
reactions. In addition to conventional safety measures for infusion of biologic agents, all 
participants administered study drug IV will undergo observation and assessment for signs of 
infusion reaction for a 60-minute period after the completion of the infusion for the first 3 doses 
for each participant.
 
 
 Furthermore, to assess for potential effects of lymphocyte 
activation, a sentinel participant will be monitored for 5 days at each dose level. The sentinel 
participant approach is used to closely monitor early-onset safety events in the monotherapy and 
combination therapy arms because the doses are escalated in a staggered manner.
Management algorithms for ipilimumab/nivolumab-induced AEs involving GI, renal, pulmonary, 
hepatic, endocrinopathy, skin, neurologic, and cardiac systems are included in the protocol 
(see Appendix 6).
Participants who develop imAEs may require prolonged treatment with high-dose corticosteroids 
and other immunosuppressive agents. This could increase the risk of opportunistic infections. The 
imAE management algorithms in the protocol recommend antibiotic prophylaxis against 
opportunistic infections in such situations.
Complete blood counts (CBCs) and chemistry (including liver enzyme) tests will be carried out 
prior to administration of study therapy and on a weekly basis during the first  weeks of treatment 
in monotherapy and the first  weeks of the combination between BMS-986288 and nivolumab. 
In addition, complete physical examinations (PEs) will be conducted on Day 1 of each new cycle, 
along with weekly symptom-directed targeted PEs during the first 
 weeks of treatment.
 
 Safety assessments are outlined in Section 2 and
Section 9.4. Due to the potential risk of exaggerated inflammatory response, participants with 
autoimmune disorders, chronic viral infections, or who are at risk for flare of autoimmunity will 
be excluded.
The mandated 
 pose limited risk to the participant and include discomfort, pain, and 
bleeding. 
gives guidance on lesions that are appropriate for a 
, and 
participants where a 
 is attempted but who are not able to undergo the
 with an 
acceptable risk can participate in some situations and upon agreement with the Study
Director/Medical Monitor (or designee). Because of the need for development of predictive 
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biomarkers for participants treated with BMS-986288 in future studies or the clinical setting, the 
limited risk of a 
 in selected (low-risk) participants is considered appropriate in an 
early phase research setting.
The amount of 
 poses limited risk to the participant and includes discomfort, pain, 
and bleeding. The amount of total blood is reduced to the minimal quantity required to address the 
need of safety monitoring, standard of care, PK/ADAs, and biomarker needs and is below the 
recommended daily limits for each treatment day.
Patients with mCRC after progression on 2 lines of standard systemic chemotherapy have a very 
poor prognosis.30 There is a need to develop treatments that can be effective in later lines of 
therapy. Nivolumab as a monotherapy is not an effective treatment for proficient mismatch repair 
(pMMR)/microsatellite stable (MSS) colon cancer, but has demonstrated safety and activity in 
multiple solid tumors including MSI-H colon cancer.31 The combination of nivolumab and BMS-
986288 has the potential to allow treatment in the broader group of MSS mCRC patients and 
tolerable over the Part 1B dose range in a variety of solid tumors, including mCRC. The available 
evidence supports the safe addition of a randomized Phase 2 expansion cohort in MSS CRC 
participants (see Section 5.4.3). In Part 1B, current data indicate that the combination of 
BMS-986288 with nivolumab is safe and the overall benefit/risk assessment for this study is 
favorable.2 Regorafenib is approved globally for the treatment of mCRC and is recognized 
standard of care treatment for 3rd/4th line treatment of mCRC.32,33 This will be used as the 
comparator in the expansion cohort. To mitigate risks associated with the use of regorafenib, the
protocol allows for dose adjustment. A weekly hepatic laboratory value and more frequent
international normalized ratio (INR) monitoring in warfarin-treated participants is recommended
as per institutional guidelines to minimize potential risk to study participants.
In conclusion, the potential direct benefit to participants who participate in this study is that both 
single-agent and combined therapies with these investigational agents may result in a greater 
proportion of participants with stabilization of disease, objective response, PFS, OS, or increased 
DOR than those observed with standard therapy or other investigational immunotherapy.
The potential for direct benefit described above warrants evaluating BMS-986288 both as a single 
agent and in combination with nivolumab in this Phase 1/2 clinical study with the risk mitigation 
described above. 
More detailed information about the known and expected benefits and risks and reasonably 
anticipated AEs of BMS-986288 may be found in the IB.2
The global coronavirus disease 2019 (COVID-19) pandemic has been identified as a potential risk 
to clinical trial participants in general. Whether administration of BMS-986288 alone or in 
combination with nivolumab 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 recent or acute infections will be excluded or delay start of treatment 
as defined in Section 6.2 and Section 7.4. If a participant has a confirmed SARS-CoV-2 infection 
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while on study treatment, dose delay or interruption of study treatment is required as described in 
Section 7.4.
The study has been designed with study visits that allow for close monitoring of participants’ safety 
throughout the clinical trial (Section 2), and participants are encouraged to contact the investigator 
if an intercurrent illness develops between study visits. Testing for SARS-CoV-2 to inform 
decisions about clinical care during the study should follow local standard practice.
Non-live SARS-CoV-2 vaccination is considered a simple concomitant medication within the 
study. However, the efficacy and safety of non-live vaccines (including non-live SARS-CoV-2
vaccines) in participants receiving BMS-986288 or nivolumab is unknown.
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4
OBJECTIVES AND ENDPOINTS
The objectives and endpoints for this study are shown in Table 4-1.
Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
For Part 1, 2A, 2B

Primary

To characterize the safety, tolerability, and DLTs and to 
determine the MTD/RP2D of BMS-986288 administered as 
monotherapy and in combination with nivolumab in 
participants with select advanced solid tumors

Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs 
leading to discontinuation, and death.
For Part 1, 2A, 2B
Secondary

To characterize the PK of BMS-986288 when administered 
alone and in combination with nivolumab 

To assess the preliminary efficacy of BMS-986288 alone and 
in combination with nivolumab in advanced solid tumors using 
RECIST v1.1 

Summary measures of PK parameters of
BMS-986288

ORR, DOR, PFS, and TTR per 
RECIST v1.1 by Investigator 
assessment
For Part 1, 2A, 2B
Exploratory

To explore the potential association between anti-tumor 
activity and pharmacodynamic markers, such as, but not 
limited to,
 
 
prior to treatment and 
following administration of BMS-986288 alone and in 
combination with nivolumab

To explore the associations between BMS-986288 PK, safety, 
efficacy, and clinical biomarkers

To characterize the immunogenicity of BMS-986288 and 
nivolumab

To assess the preliminary efficacy of BMS-986288 alone and
in combination with nivolumab in select advanced solid tumors 
using iRECIST

To assess the OS in participants treated with BMS-986288 
alone and in combination with nivolumab

To assess the potential effect of BMS-986288 when 
administered 
 on the QTc interval

To characterize the PK and bioavailability of BMS-986288
when

To 
explore 
the 
impact 
of 
treatment 
on 
NSCLC 
participant-reported symptoms and health-related quality of 
life (Part 2A and Part 2B only)

To explore participant overall perception of bother in relation 
to treatment-related symptomatic side effects (Part 2A and Part 
2B only)

To explore overall health status (Part 2A and Part 2B only)

Summary 
measures 
of 
anti-tumor 
activity by pretreatment level of 
biomarkers 
of 
interest; 
correlation/measure of association of 
anti-tumor activity and change (or % 
change) from baseline in biomarkers of 
interest

Association 
measures 
between 
BMS-986288 PK levels by 
, 
select outcomes, and biomarkers of 
interest

Incidence of ADA to nivolumab and 
BMS-986288

ORR, DOR, and PFS per iRECIST by 
BICR

OSR at 1 year and 2 years

Summary measures of ECG parameters 
and changes in QTcF (ΔQTcF) from 
baseline

Summary of PK parameters when 
BMS-986288 is 
 alone 
or in combination with nivolumab

Mean NSCLC-SAQ scores and change 
from baseline scores

Proportion of participants endorsing 
each response option of the FACIT GP5
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints

To measure 
, and assess 
 change over time and in 
association with response

Mean EQ-5D-5L utility index scores 
and EQ-5D-VAS scores and change 
from baseline scores

Summary measures of 
 and 
correlation/ measure of association of 
anti-tumor activity and change (or % 
change) from baseline in 
For Part 2C 
Primary

To compare the efficacy of BMS-986288 in combination with 
nivolumab vs regorafenib in the 3L/4L MSS CRC setting.

ORR per RECIST v1.1 by BICR
For Part 2C
Secondary

To compare the efficacy of BMS-986288 in combination with 
nivolumab vs regorafenib in the 3L/4L MSS CRC setting

To characterize the safety and tolerability of BMS-986288 in 
combination with nivolumab vs regorafenib in the 3L/4L MSS 
CRC setting

DOR and PFS per RECIST v1.1 by 
BICR, and OS

ORR, DOR, and PFS per RECIST v1.1 
by Investigator assessment

Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs 
leading to discontinuation, and death
For Part 2C
Exploratory

To compare the efficacy of BMS-986288 in combination with 
nivolumab vs regorafenib in the 3L/4L MSS CRC setting in 
subgroups of 
 and mutant tumors

Explore the association between response with both baseline 
and pharmacodynamic markers in the 
 

To evaluate BMS-986288 PK in the MSS CRC setting in 
combination with nivolumab

To evaluate immunogenicity of BMS-986288 and nivolumab 
when administered as combination

To 
explore 
the 
exposure-response 
relationship 
for 
BMS-986288 when given as combination with nivolumab 

ORR, DCR, DOR, PFS by BICR, and 
OS in the subgroups of 
 
and 
 participants

Summary measures of change (or % 
change) from baseline in parameters of 
interest and correlation/measure of 
association 
of 
response 
and 
pharmacodynamic markers

Summary measures of PK parameters 
from population PK analysis 

Summary of ADA
incidence
and 
association 
with 
PK, 
efficacy,
hypersensitivity, and infusion-related 
safety events

Exposure-response 
relationship 
for 
efficacy endpoints including ORR and 
PFS.

Exposure-response 
relationship 
for 
safety 
endpoints 
including 
TRAE 
Grade 3+ and dose modification due to 
TRAE.
Abbreviations: 3L/4L = 3rd line/4th line; ADA = anti-drug antibody; AE = adverse event; BICR = blinded independent 
central review; BMS = Bristol-Myers Squibb; CRC = colorectal cancer; DCR = disease control rate; DOR = duration 
of response; DLT = dose-limiting toxicity; ECG = electrocardiogram; EQ-5D-5L = 5-Level EQ-5D; EQ-5D-VAS = 
EQ-5D Visual Analog Scale; FACIT GP5 = Functional Assessment of Chronic Illness Therapy, General Physical 
item; IgG = immunoglobulin G; iRECIST = modified RECIST in cancer immunotherapy trials; MSS = microsatellite 
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stable; MTD = maximum tolerated dose; NSCLC-SAQ = Non-small Cell Lung Cancer Symptom Assessment 
Questionnaire; ORR = objective response rate; OS = overall survival; OSR = overall survival rate; PFS = progression-
free survival; PK = pharmacokinetics; QTc = QT interval corrected; QTcF = QT interval corrected for heart rate using 
Fridericia’s formula; RECIST = Response Evaluation Criteria in Solid Tumors; RP2D = recommended Phase 2 dose;
SAE = serious adverse event; 
 TRAE = treatment-related 
adverse event; 
 TTR = time to response.
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5
STUDY DESIGN
5.1
Overall Design
This is a Phase 1/2, open-label study of BMS-986288 administered as a single agent and in 
combination with nivolumab in participants with select advanced solid tumors (SCCHN, NSCLC, 
cutaneous melanoma, RCC, CRC, TNBC, urothelial carcinoma, gastric, esophageal, and cervical 
cancer). The study is composed of 2 parts: dose escalation and initial dose expansion.
Part 1: The Dose-Escalation Phase is where the dose of BMS-986288 will be administered IV 
alone (Part 1A) or in combination with nivolumab (Part 1B). 
 administration of BMS-986288 
as a monotherapy (Arm A) or in combination with nivolumab (Arm B) may also be evaluated 
. 

The BMS-986288 Monotherapy Escalation (Part 1A) will escalate the dose of BMS-986288 
to determine the monotherapy maximum tolerated dose (MTD)/recommended Phase 2 
dose (RP2D). Specifically, the Part 1A dose escalation will evaluate different doses of 
BMS-986288 starting at 
mg, followed by 
 
. If it appears that a planned dose level is associated with an unacceptable 
frequency of toxicities, then an intermediate dose or alternative administration schedule may 
be evaluated, and will not initially exceed a dose determined to be tolerable. After preliminary 
evaluation of safety and PK data from these intermediate dose or alternative administration 
schedules, re-escalating doses of BMS-986288 may be initiated (see Table 2-2 and 
Appendix 8). The study will first evaluate the safety and tolerability of BMS-986288
monotherapy based on dose-limiting toxicities (DLTs), using a Bayesian Logistic Regression
Model (BLRM) employing the escalation with overdose control (EWOC) principle 
, and overall assessment of available safety, PK, and 
pharmacodynamic data.

The Safety Evaluation of BMS-986288 in Combination with Nivolumab (Part 1B) will 
evaluate the safety and tolerability of various doses of BMS-986288 in combination with 
nivolumab to determine the combination MTD/RP2D. Treatment in Part 1B will be initiated 
in a staggered manner relative to the BMS-986288 Monotherapy Escalation (Part 1A). 
Specifically, Part 1B can be initiated upon the decision to escalate when at least 2 dose levels 
in Part 1A have cleared the DLT period in accordance with dose escalation rules, after which
dose escalation in Part 1A and Part 1B will proceed in parallel (see Section 7.2). At no point 
will the dose of BMS-986288 administered in combination with nivolumab in Part 1B exceed
the highest safe dose in ongoing monotherapy dose escalation in Part 1A or the highest dose
determined to be tolerated in Part 1A. In Part 1B, the dose of BMS-986288 will be escalated, 
whereas the dose of nivolumab will be 
mg 
. However, if it appears that a
planned dose level is associated with an unacceptable frequency of toxicities then an 
intermediate dose level, additional cohorts of alternative BMS-986288 administration 
schedules, or de-escalating doses of nivolumab may be evaluated, and potential re-escalating 
doses of BMS-986288 may then be initiated (see Table 2-2 and Appendix 8).The safety and 
tolerability of the BMS-986288 combination with nivolumab will be evaluated using a 
BLRM-copula employing the EWOC principle, and an overall assessment of available safety,
PK, and pharmacodynamic data.
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
The 
 of BMS-986288 as a Monotherapy and/or in Combination with 
Nivolumab 
 may be conducted to obtain preliminary data on the safety, tolerability, 
PK, bioavailability, and pharmacodynamics of BMS-986288 alone or in combination with 
nivolumab when 
 will be initially composed of a single cohort for 
BMS-986288 monotherapy (Arm A) and/or BMS-986288 in combination with nivolumab
(Arm B). The dose and administration schedule of BMS-986288 alone or in combination with 
nivolumab selected for 
 will be determined by evaluation of the available safety, PK, 
and pharmacodynamic data from Part 1A and Part 1B, 
 
. BMS-986288 may be combined with 
depending on the dose 
selected (Arm A and/or Arm B). Nivolumab in combination with 
 may also be 
administered (Arm B). The BMS-986288 dose in 
 will not exceed the highest dose
equivalent determined to be tolerated in Part 1A and/or Part 1B.
 may be used to 
inform 
 dose selection in The Initial Expansion Phase (Part 2).
Part 2: The Expansion Phase is where cohorts of BMS-986288 
 (Part 2A) and 
Combination with Nivolumab (Part 2B) are expanded to gather additional safety, tolerability, 
preliminary efficacy, PK, and pharmacodynamic information in specific participant populations.

One or more dose regimens of BMS-986288 alone and in combination with nivolumab selected 
for Part 2 cohort expansion will be selected from the range of doses assessed as tolerable in 
Part 1, and which do not exceed the MTD or highest dose administered. These dose(s) will be 
selected based on evaluating the recommendation from BLRM and an overall assessment of 
available safety, PK, pharmacodynamic, and efficacy data from Part 1.

Part 2 is currently comprised of signal-seeking expansion cohorts in cutaneous melanoma,
NSCLC, and a randomized MSS CRC cohort in comparison with regorafenib; additional 
tumors or potential arms will be included upon evaluation of available safety, PK, 
pharmacodynamic, and efficacy data from Part 1.
All participants will complete up to 3 study periods: Screening (up to 30 days), Treatment (up to 
 cycles, 
 days/cycle), and Follow-up (comprised of Safety [100 days], Imaging [up to 2 years], 
and Survival [up to 2 years] following end of treatment [EOT]). The duration of study participation 
will be approximately 4 years (treatment of up to 2 years and follow-up of up to 2 years).
Images will be submitted to a central imaging vendor and may undergo blinded independent 
central review (BICR) at any time during the study. Prior to scanning first participant, sites should 
be qualified and understand the image acquisition guidelines and submission process as outlined 
in the CA043001 Imaging Manual provided by the central imaging vendor.
The study design schematic is presented in Figure 5.1-1. A detailed schematic for study period and 
participant flow is presented in Figure 5.1-2.
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Figure 5.1-1:
Study Design Schematic
Abbreviations: 3L/4L = 3rd/4th line; BMS = Bristol-Myers Squibb; CRC = colorectal cancer; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; IRT = 
Interactive Response Technology; 
 MSS = microsatellite stable; NSCLC = non-small cell lung cancer; PK = pharmacokinetics; 
 
 RCC = renal cell carcinoma; 
 RP2D = recommended Phase 2 dose; 
 SCCHN = 
squamous cell carcinoma of the head and neck; TBD = to be determined; TNBC = triple-negative breast cancer.
a Prior anti-PD-(L)1 therapy allowed. Anti-CTLA-4 naive required.
b Additional doses and dose schedules may be explored using data obtained from 
 administration.
c Part 1B will not start until demonstration of acceptable safety in at least 2 cohorts from Part 1A. Subsequently, treatment in both parts will occur in parallel.
d Doses(s) will be identified upon clinical evaluation of available safety, PK, pharmacodynamics, and efficacy data in Part 1A and/or Part 1B. 
 
 may be used in combination with BMS-986288 or nivolumab, depending on the determined dose. Details will be 
provided through a protocol amendment.
e Part 2 will be initiated upon evaluation of available safety, PK, pharmacodynamics, and efficacy data from Part 1 and may include 
 administration. 
f Alternative assignment: In Part 2A 
 and Part 2B Combination Expansion, Part 2A and Part 2B may be open concurrently. In this case, treatment 
assignments will alternate between Part 2A and Part 2B. Multiple doses may be open concurrently in each part. In that case, treatment assignments will alternate 
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between the dose levels, with consecutively treated participants assigned to different parts through IRT whenever possible. If there are no openings available in 
the dose level to which the participant would be assigned by this algorithm, then the participant will be assigned to the next open dose.
g Intermediate dose level (Section 5.1.2.1). 
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Figure 5.1-2:
Study Design Schematic for Expansion Part 2C
Abbreviations: 3L/4L = 3rd/4th line; BICR = blinded independent central review; CRC = colorectal cancer; IRT, Interactive Response Technology; 
MSS = microsatellite stable; 
.
a Efficacy analyses based on the treated population may be performed for interim analyses (see further details in Section 10).
b Stratification by liver metastasis status and a cap of 50% participants with liver metastases in each arm. Once enrolled in IRT, participants who have met all 
eligibility criteria for Part 2C will be randomized in a 2:1 ratio to nivolumab in combination with BMS-986288 (Arm C) or regorafenib (Arm D) and stratified 
by liver metastasis status. An additional dose of BMS-986288 (
 mg or 
 mg) in combination with nivolumab may be opened as Arm E.
 (see 
further details in Section 5.4.8).
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Figure 5.1-3:
Study Period and Participant Flow
5.1.1
Screening Period
The screening period will be up to 30 days and begins by establishing the participant’s initial 
eligibility and signing of the informed consent form (ICF). The screening assessments are shown 
in Table 2-1. If a participant exceeds the 30-day screening period due to a study-related procedure 
(eg, scheduling of a 
 or waiting for a study-related laboratory value), the participant 
must be re-consented, but does not require a new participant identification number. In this 
situation, the fewest number of procedures from the initial screening should be repeated to qualify 
the participant, while maintaining participant safety and eligibility. Within a given disease type, 
participants meeting all eligibility criteria will be enrolled in the study using an Interactive 
Response Technology (IRT) according to the part and treatment arm availability.
5.1.2
Treatment Period
The initial dosing regimen of BMS-986288 is 
. Continuous safety evaluation and tumor 
assessment occurring in Part 1 and Part 2 (
until Week 48 of treatment and 
then 
 thereafter), will guide the decision to treat a participant with additional cycles of study 
therapy if the participant has confirmed clinical benefit (up to a maximum of 2 years).
Weekly study visits will be performed for the first 8 weeks after the first dose of study treatment 
for the BMS-986288 Monotherapy Escalation (Part 1A), the Safety Evaluation of BMS-986288 in 
Combination with Nivolumab (Part 1B), the 
 of BMS-986288 as a 
Monotherapy and in Combination with Nivolumab 
, and the Initial Expansion Phase 
(Part 2), followed by study visits 
 thereafter. During the treatment period for all study parts, 
additional study visits to collect samples for intensive PK, ADA, and cytokine assessments will be 
required at Cycles 1-6, and every fourth cycle after Cycle 6 until EOT. See Section 9.5 for further 
details. 
For the BMS-986288 Monotherapy Escalation (Part 1A) and the Expansion Phase BMS-986288 
 (Part 2A), BMS-986288 will be infused over approximately 
. Shorter 
infusion times may be used for the initial dose cohorts and longer infusion times (approximately 
) may be used for the higher dose levels.
For the Safety Evaluation of BMS-986288 in Combination with Nivolumab (Part 1B) and the 
Expansion Phase BMS-986288 in Combination with Nivolumab (Part 2B and Part 2C Arm C, Arm 
Screening
30 days
Fresh 
Treatment Period
On-treatment fresh 
 
Part 1 and Part 2: 
 cycles for up to 2 years
End of 
Treatment 
(EOT)
Follow-up
Safety: Visits on Days 30, 60, and 100 
(7 days) after EOT
Imaging: Every 
 (7 days) for the 
first 
 from treatment start and 
every 
 (7 days) thereafter, until 
EOT + 2 years, death, or initiation of 
another anti-cancer treatment, whichever 
occurs first
Survival: EOT + 2 years
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E, and Arm Z), BMS-986288 and nivolumab will each be infused over approximately 30 minutes. 
When both BMS-986288 and nivolumab are given in combination, nivolumab will be given first, 
over 30 minutes, followed by BMS-986288 over 
, beginning at least 30 minutes after 
completion of the infusion of nivolumab. Shorter infusion times for BMS-986288 may be used for 
the initial dose cohorts and longer infusion times (approximately 
) may be used for the 
higher dose levels.
For the Part 2C BMS-986288 in combination with nivolumab portion of the study, participants 
will receive the 
with the selected
BMS-986288 dose 
 is 
not possible upon confirmation with the Sponsor. 
 
, the infusion will be the same as described below). The starting dose will be
mg of BMS-986288. A possible additional arm with a to-be-determined dose of BMS-986288
may be added based on an evaluation of the entirety of the safety, PK, PD, and anti-tumor activity
data from Part 1B. When both BMS-986288 and nivolumab are given 
, the 
infusion will be given approximately over 
. For participants weighing < 40 kg, the total 
infusion volume will be limited to 80 mL. For the Part 2C Arm D, the participants will receive 
regorafenib at 
 mg orally once daily for 21 days of each 
-day cycle until disease progression, 
toxicity, withdrawal of consent, or death, whichever occurs first (see Section 5.5.4.9 for details).
Depending on the dose(s) selected for the 
 of BMS-986288 as a 
Monotherapy and/or in Combination with Nivolumab 
, BMS-986288 and nivolumab 
may each be 
 with the 
 of study 
treatment should be administered in the abdomen or alternatively in the thigh. Different 
 
sites should be used if both BMS-986288 
 and nivolumab 
 are being administered (Arm B), 
with nivolumab being given first, followed by BMS-986288.
 should not occur into 
or around an infected or acutely inflamed area because of the danger of spreading a localized 
infection. Clinical judgement should be used in determining the best site for 
 drug 
administration.
See Table 2-2 for the on-treatment Schedule of Activities and Table 7.1-1 for a list of dose selection 
and timing. Refer to the Pharmacy Manual for additional dose preparation details for 
BMS-986288, nivolumab, and 
(if applicable).
Sentinel Participant
During the Dose-Escalation Phase (Part 1), a staggered dosing (sentinel participant) approach will 
be used. The first participant to be dosed at Cycle 1 Day 1 of each dose level will be observed for 
5 days, before additional participants (ie, Participant 2 onward in that cohort) receive study 
treatments in the same dose level.
Initially, 3 participants will be enrolled at the start of each cohort, in accordance with the sentinel 
participant approach cited above. However, to allow for any unforeseen discontinuations (such as 
disease progression) before the 5-week DLT period (35 days) is completed, an extra participant 
may be enrolled in each dose-escalation cohort. Therefore, there may be a total of 4 participants 
(3 + 1) at the start of each cohort, provided that the fourth participant is able to start dosing within 
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approximately 1 week of the third participant in the same dose-escalation cohort. Additional 
information on DLTs can be found in Section 5.1.2.1 and Section 7.4.1.
5.1.2.1
Dose-Escalation Decisions for the BMS-986288 Monotherapy Escalation 
(Part 1A) and the Safety Evaluation of BMS-986288 in Combination with 
Nivolumab (Part 1B)
The Dose-Escalation Phase (Part 1) of the study will evaluate the safety and tolerability of 
BMS-986288, given alone or in combination with nivolumab, based on DLTs, using a BLRM for 
both Part 1A and Part 1B. The DLT period will be 5 weeks.
During the monotherapy (Part 1A) and combination therapy (Part 1B) dose-escalation phases, a 
set of approximately 3 participants will be treated at each specified dose level. If the potential DLT 
occurring in the third evaluable participant regarding the specific dose level does not influence the 
dose escalation decision by BLRM, the next dose level may proceed without waiting for the 
third participant to complete the corresponding DLT observation period. In this situation, cohort 
tolerability assessment and subsequent dose recommendation may occur when at least evaluable 
participants within a cohort have completed a 5-week DLT period, after discussion and agreement 
between the Sponsor and Investigators. Any toxicities that occur beyond the DLT period will be 
accounted for in making dose level decisions and/or dose level modifications. Additional 
information on DLTs can be found in Section 7.4.1.
Continuous reassessment of dose recommendation, by BLRM in the BMS-986288 Monotherapy 
Dose Escalation (Part 1A) and in the Safety Evaluation of BMS-986288 in Combination with 
Nivolumab (Part 1B), will be carried out for each dose level. The planned dose regimens are shown 
in the study design schematic in Figure 5.1-1.
Prior to declaring the MTD, and in consultation with investigators, the Sponsor has the option to 
expand any dose level previously established to be tolerable (during the DLT evaluation) in order 
to obtain additional experience or to investigate dose levels intermediate to those defined in the 
protocol (hereon referred to as “backfill”). The Sponsor may choose to enroll only participants 
with certain cancer types and certain criteria, from dose escalation during backfill, based on 
emerging data. Planned dose levels may be modified (eg, alternative administration schedule, 
Appendix 8), or intermediate dose levels added, based upon the BLRM analysis and clinical 
evaluation of available safety, PK, and pharmacodynamic data in Part 1A and Part 1B. Dose 
escalation in the alternative schedule may be performed; cohort tolerability assessment and 
subsequent dose recommendation will follow the same principles as outlined for the planned 
administration schedule of 
. 
5.1.2.2
 Evaluation of BMS-986288 as a Monotherapy and in 
Combination with Nivolumab
Up to a total of 
 evaluable participants may be treated in the BMS-986288 monotherapy (Arm 
A) and/or combination (Arm B)
cohort(s)
 will be initiated
 
once an appropriate BMS-986288 monotherapy (Part 1A) or combination dose
(Part 1B) is identified from clinical evaluation of available preliminary safety, PK, 
pharmacodynamic, and efficacy data (eg, MTD/RP2D). The dose(s) selected for 
 will not 
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exceed the dose equivalent determined to be safe and tolerable in Part 1A and/or Part 1B.
Depending on the dose selected, BMS-986288 may be
with the 
 
(as a monotherapy [Arm A] or in combination [Arm B] with nivolumab 
). Participants receiving 
stration will be different from 
those receiving 
 administration, not crossed over. Treatment will be for up to calendar years. 
5.1.2.3
The Expansion Phase of BMS-986288 
 (Part 2A) 
 
Nivolumab (Part 2B and Part 2C
Arm C, Arm E, and Arm Z)
The purpose of the BMS-986288 cohort expansions is to gather preliminary efficacy information 
in specific patient populations regarding BMS-986288 alone and in combination with nivolumab.
In addition, safety, tolerability, PK, and pharmacodynamics data will be evaluated.
The Initial Expansion Phase (Part 2) will be initiated once an appropriate BMS-986288 
monotherapy (Part 1A) or combination dose (Part 1B) is identified based on recommendations 
from the BLRM and an overall assessment of available preliminary safety, PK, pharmacodynamic, 
and efficacy data (eg, MTD/RP2D). The Part 2 route of administration 
 may be informed 
from an overall assessment of available preliminary safety, PK, pharmacodynamic, and efficacy 
data from Part 1A, Part 1B, or 
. Any BMS-986288 dose selected for use in Part 2A will 
not exceed the highest dose determined to be safe in monotherapy (Part 1A). Similarly, any 
BMS-986288 dose selected for use in Part 2B and Part 2C will not exceed the highest dose 
determined to be safe in combination therapy (Part 1B). A safe dose selected for use in Part 2 in 
either part of the study requires a minimum of  safety-evaluable participants in the selected dose 
level in Part 1. 
The Expansion Phase of BMS-986288 
(Part 2A) will initially involve signal-seeking 
expansion cohorts in participants with advanced cutaneous melanoma and NSCLC with disease 
relapse/recurrence or progression after prior immunotherapy treatment with an anti-PD-(L)1 
containing regimen. Participants with cutaneous melanoma must not have received prior 
anti-CTLA-4 therapy.
The Expansion Phase of BMS-986288 in Combination with Nivolumab (Part 2B) will initially
involve signal seeking expansion cohorts in participants with advanced NSCLC with disease 
relapse/recurrence or progression after prior immunotherapy treatment with an anti-PD-(L)1 
containing regimen.
In Part 2C, the efficacy and safety of BMS-986288 
 with nivolumab will be 
assessed in participants with MSS CRC who have progressed or relapsed on at least 2 prior 
standard therapies. Participants must not have received prior anti-CTLA-4, anti-PD-(L)1 therapy 
in the advanced or metastatic setting. The dose(s) to be evaluated in Part 2C will be selected from 
the range of doses assessed as tolerable in Part 1B, and which do not exceed the MTD or highest 
dose administered that has cleared safety. The dose(s) will be selected based on the totality of 
available safety, tolerability, efficacy, PK, and PD data. Regardless of whether or not 
 
mutation status is known, all participants will be tested during screening for 
 
 
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and 
 status. The Sponsor may elect to prioritize enrollment of participants based 
on mutation status as well as presence of liver metastasis at screening. In Part 2C, participants will 
be treated 
 for up to 2 calendar years regardless of treatment delays. This cohort will have a 
standard of care control arm using regorafenib at 
 mg, or in accordance with locally approved 
prescribing information, orally once daily for 21 days of each 
-day cycle. 
Additional tumor types considered may include those in which ipilimumab monotherapy has failed 
to prove sufficient efficacy, in participants who have progressed or relapsed after anti-PD-(L)1 
therapy, or tumors in which a high level of 
 correlates with worse prognosis.
Participants with unconfirmed progressive disease (PD), stable disease (SD), partial response (PR), 
or complete response (CR) at the end of a given cycle will continue to the next treatment cycle. 
Participants will be allowed to continue study treatment until the first occurrence of any of the 
following:

Completion of the maximum 2 calendar years of study therapy 

PD defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Appendix 5),
unless participants meet criteria for treatment beyond progression (Section 5.1.4)

Clinical deterioration suggesting that no further benefit from treatment is likely

Intolerability to therapy

Participant meets criteria for discontinuation of study treatment as shown in Section 8.1
5.1.2.4
Visit Windows
A 2 day window is permitted to accommodate study participants and schedules during and 
between cycle visit days for all treatment visits, except for Cycle 1 Day 1.
5.1.3
Follow-up
5.1.3.1
Safety Follow-up Period
Upon completion of study therapy (up to a maximum of 2 years, if applicable) or once the decision 
is made to discontinue the participant from treatment, that is, at EOT, all participants will enter a 
Safety Follow-up Period.
All participants will be evaluated for any new AEs for at least 100 days after the EOT visit. 
Follow-up visits should occur at Days 30, 60, and 100 (7 days for all study visits) after the EOT 
visit. All participants should complete the 3 clinical safety follow up visits regardless of whether 
new anti-cancer therapy is started, except those participants who will withdraw consent for study 
participation. Refer to Table 2-2 and Table 2-3.
5.1.3.2
Imaging Follow-up Period
Participants will continue to have radiologic and clinical tumor assessments after treatment 
discontinuation. Imaging assessments will continue to occur 
(1 week) from the date of first
treatment until Week 48, then continue 
(1 week) thereafter. The duration of the Imaging 
Follow-up Period will be for a total of 2 years following EOT, or until initiation of another 
anti-cancer treatment, or death, whichever occurs first. Radiological assessments for participants 
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who have ongoing clinical benefit may continue to be collected after participants complete the 
Survival Follow-up Period of the study. Participants who have disease progression after an initial 
course of study therapy will be evaluated beyond the EOT visit and will be allowed to receive 
other tumor-directed therapy as required.
5.1.3.3
Survival Follow-up Period
In parallel with the Safety Follow-up Period, all participants will start the Survival Follow-up 
Period. Participants will be followed by telephone Q12W (± 2 weeks) from EOT for 2 years or 
until death, loss to follow-up, withdrawal of consent, or conclusion of the study, whichever comes 
first. Participants will have both the Imaging Follow-up Period and Survival Follow-up Period 
occur simultaneously. The duration of this follow-up is up to 2 years after EOT, although a longer 
follow-up period could be considered in selected cases if an efficacy signal is apparent. Subsequent 
therapies will also be recorded in this Survival Follow-up Period.
5.1.4
Treatment Beyond Progression
Tumor progression and response endpoints will be assessed using RECIST v1.1 criteria 
(Appendix 5). Treatment beyond progression may be allowed in selected participants with initial 
RECIST v1.1 defined PD after discussion and agreement with the BMS Medical Monitor (or 
designee), if the benefit-risk assessment favors continued administration of study treatment. 
Participants will be permitted to continue treatment beyond initial RECIST v1.1 defined 
progressive disease (PD), as assessed by the Investigator, as long as the following criteria are 
considered:

Investigator-assessed clinical benefit.

Tolerance of study drug.

Stable performance status.

Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, central nervous system [CNS] metastases).
Participants must be re-consented with an ICF addendum or similar document to continue 
treatment beyond progression and prior to receiving additional treatment with the study drug 
regimen. All other elements of the main consent including description of reasonably foreseeable 
risks or discomforts, or other alternative treatment options will still apply. Continue radiographic 
assessment/scan(s) in accordance with the Section 2 Schedule of Activities for the duration of the 
treatment beyond progression and submit to the central imaging vendor. Balance the assessment 
of clinical benefit with clinical judgment as to whether the participant is clinically deteriorating 
and unlikely to receive any benefit from continued treatment with study regimens.
If the Investigator feels that the participant continues to achieve clinical benefit by continuing 
treatment, the participant could remain on the trial and should continue to receive monitoring 
according to the Section 2 (Schedule of Activities). Radiographic assessment, by compute 
tomography (CT; preferred) or magnetic resonance imaging (MRI) described in Section 5.1.4.1
and Section 9.1.1, is required when participants continue post-progression treatment and should 
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be performed for the duration of the treatment beyond progression and should be submitted to the 
central imaging vendor. Participants in Part 2C Arm D receiving regorafenib will have the option 
to transition to BMS-986288 in combination with nivolumab (Part 2C Arm Z) after BICR-assessed 
progression.
5.1.4.1
Discontinuation Due to Further Progression (Confirmed Progression)
Participants that meet the above criteria and continue on study therapy beyond initial PD must 
discontinue BMS-986288 (and nivolumab, if part of the combination cohorts) upon the next 
documented event of PD. 
A follow-up scan should be performed within 6 weeks 5 days of original progressive disease to 
determine whether there has been a decrease in the tumor size, or continued progression of disease. 
For participants who continue study therapy beyond progression, further progression is defined as 
an additional 10% increase in tumor burden with a minimum of 5 mm absolute increase from time 
of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the 
diameters of new measurable lesions compared to the time of initial PD. 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 which become measurable, these new lesions must demonstrate an absolute increase 
of at least 5 mm.
For statistical analyses that include the Investigator-assessed progression date, participants who 
continue treatment beyond initial Investigator-assessed, RECIST v1.1 defined progression will be 
considered to have Investigator-assessed PD at the time of the initial progression event.
5.1.5
Criteria for Transition From Regorafenib (Part 2C Arm D) to BMS-
986288 in Combination with Nivolumab
Participants in the regorafenib arm (Part 2C Arm D) may receive BMS-9864288 in combination 
with nivolumab provided that the criteria below are met:

The participant has PD per RECIST v1.1 (as assessed by BICR).

The participant has completed at least 2 cycles of regorafenib.

At least 
 days have elapsed since the last dose of regorafenib.

AEs have returned to Grade 1 or baseline, except clinically insignificant laboratory values 
which must have returned to Grade 2 or to baseline.

Provided participants still meet physical and laboratory test findings inclusion criteria (see 
Section 6.1 Inclusion Criterion 3)).

Participant does not have any condition, including active or uncontrolled infection, or the
presence of laboratory abnormalities, which places the participant at unacceptable risk.
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
Participant provides written informed consent prior to receiving additional treatment. 
For Part 2C Arm D participants who elect to crossover to Part 2C Arm Z to receive BMS-986288
in combination with nivolumab, a collection 
 is mandatory in order to provide 
pre-treatment information. These participants may continue treatment at the next scheduled 
treatment visit and will be followed on study for up to 2 years from the last dose of study 
intervention.
5.1.6
Data Monitoring Committee and Other External Committees
BMS has in place a multi-layered process for ensuring patient safety through close collaboration 
of study site Investigators, the BMS study team, and the BMS 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 (Chairman of the SMT) and WWPS single-case review physician, the study 
Medical Monitor(s) (or designee), the study biostatistician, and epidemiologist. The SMT monitors 
actual or potential issues related to patient safety that could result in a significant change in the 
medical benefit-risk balance associated with the use of study treatment(s). Furthermore, 
Investigators will be kept updated of important safety information, such as DLTs, during 
teleconferences between Investigators and the BMS clinical team, which will be held at least 
 
during dose escalation and at least monthly during cohort 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 study, the BMS Medical Monitor and the Investigators will have access to all data 
necessary for safety evaluation.
All participants in this study represent individuals with high unmet medical need because the 
prognosis for advanced/metastatic solid tumors is generally very poor.
Relative to the exploratory nature of this Phase 1/2 study and the robust experience that already 
exists around use of ipilimumab, BMS has elected not to use a Data Monitoring Committee (DMC) 
for this study. In addition to the comprehensive safety monitoring plan outlined above, the 
following key points were considered for this decision:

This is an open-label study.

The eligibility criteria exclude participants with disease characteristics that could predispose 
to higher risk of morbidity (eg, history of interstitial lung disease).
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
Exclusion of participants with known autoimmunity also applies because they could be at risk 
for exacerbation of their condition by the administration of therapies that relieve immune 
suppression such as BMS-986288 and nivolumab.

Participants will be observed frequently for clinical evaluation and blood counts during dose 
escalation.

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.

For the combination therapy with nivolumab management algorithms for immune-related
events are well established based on the clinical experiences from the over 17,700 patients who 
were exposed to nivolumab as either monotherapy or in combination with other agents, in the 
past as well as in ongoing studies.
5.2
Number of Participants
The approximate total number of evaluable participants treated will be up to 
, as shown below:

Part 1 - Escalation Phase: Up to approximately 
DLT-evaluable participants may be treated, 
including:

Part 1A - Safety Evaluation of BMS-986288 Monotherapy Escalation: Up to 
evaluable 
participants

Part 1B - Safety Evaluation of BMS-986288 in Combination with Nivolumab: Up to 
evaluable participants 

 of BMS-986288 as a Monotherapy and in 
Combination with Nivolumab: Up to 
evaluable participants

Part 2 - Initial Expansion Phase: Up to 
evaluable participants may be treated, including:

Part 2A - BMS-986288 
 Cohort Expansion
Part 2A Cutaneous Melanoma: Up to 
participants with cutaneous melanoma
Part 2A NSCLC: Up to 
 participants with NSCLC will be treated. If more than 1
dose level is evaluated, additional participants (up to 
 participants per dose level) 
may be enrolled, up to 
 participants (eg,
 participants 2 arms)

Part 2B - BMS-986288 in Combination with Nivolumab Cohort Expansion: Up to 
participants with NSCLC will be treated. If more than 1 dose level is evaluated, 
additional participants (up to 
 participants per dose level) may be enrolled, up to 
 
participants (eg,
 participants 2 arms).

Part 2C randomized MSS CRC cohort:
Arm C - BMS-986288 in combination with nivolumab: up to 
 participants will be 
randomized.
Arm D - standard of care: up to 
 participants will be randomized to receive 
regorafenib. Participants will have the option to transition to BMS-986288 in 
combination with nivolumab upon progression (Arm Z).
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If more than 1 dose level is evaluated, additional participants (up to 
 participants) 
may be treated in a separate arm (Arm E) in Part 2C.
For additional details on sample size determination, see Section 10.1.
5.3
End of Study Definition
The start of the study for the trial is defined as the first visit for the first participant screened. The 
end of the study for the trial is defined as the last visit or scheduled procedure shown in the 
Schedule of Activities (see Section 2) for the last participant. Primary study completion is defined 
as the final date on which data for the primary endpoint are expected to be collected.
A participant is considered to have completed the study if he/she has completed the last procedure 
shown in the Schedule of Activities.
5.4
Scientific Rationale for Study Design
BMS-986288 is being investigated as a monotherapy and in combination with nivolumab in 
humans with select advanced solid tumors (SCCHN, NSCLC, cutaneous melanoma, RCC, CRC, 
TNBC, urothelial carcinoma, gastric, esophageal, and cervical cancer). These indications were 
chosen based on a higher prevalence of 
and 
 
 (internal data at BMS). 
play an important role in 
impairing the anti-tumor immune response by 
 function. NF 
increases the affinity of BMS-986288 for 
, enhancing 
 of target expressing cells; this
increase in effector function may mediate specific 
 at the 
tumor site. CTLA-4 is expressed on a subset of activated T cells on which it acts as a negative 
regulator of 
 activity. Blockade of CTLA-4 has been shown to augment 
 activation and 
proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. 
Inhibition of CTLA-4 signaling can also reduce 
 function, which may contribute to a general 
increase in 
 responsiveness. The amount of 
 and CTLA-4 expression in tumor samples 
will be assessed in this study. The study design includes the following:

30-day screening period

Up to 2 calendar year treatment period

Dose-escalation phases in monotherapy and combination with nivolumab

Cohort-expansion phase

Safety follow-up period of 100 days from EOT

Imaging/survival follow-up period of up to  years from EOT
The rationale for the individual elements of the study design are given below. 
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5.4.1
Rationale for BMS-986288 Monotherapy Dose Escalation (Part 1A) and 
the Safety Evaluation of BMS-986288 in Combination with Nivolumab 
(Part 1B)
The safety of CTLA-4 blockade with ipilimumab has been extensively characterized in more than 
22,571 participants with different cancer types (refer to the ipilimumab IB for further details21). 
Modifying the ipilimumab structure with enhanced 
 may result in a different dose/effect 
relationship and AE profile; however, the addition of the protease cleavable masking peptide may 
abrogate the affinity for CTLA-4 and minimize systemic effects. BMS is evaluating an 
anti-CTLA-4 NF mAb (clinical trials.gov, NCT03110107) and an anti-CTLA-4 Probody mAb 
(clinicaltrials.gov, NCT03369223) in separate clinical trials. Emerging data from these programs 
may help inform the dose effect and AE profile of BMS-986288. In addition, in nonclinical 
experiments,
BMS-986288
was tolerated at doses up to 
mg/kg, with evidence of 
pharmacodynamic effects at all doses. The 
mg (
mg/kg) of BMS-986288 in the 
monotherapy dose escalation (Part 1A) is lower than the dose safely tested in animals, and will 
allow an accurate evaluation of the tolerability of BMS-986288. 
Furthermore, the study plans to evaluate different dose escalations of BMS-986288 in combination 
with nivolumab (Part 1B). The combination of ipilimumab and nivolumab is approved for RCC in 
the US and unresectable melanoma in multiple countries, including the US and EU. Information 
regarding safety and efficacy can be found in the nivolumab IB.18 The combination of nivolumab 
and ipilimumab is also currently under investigation in various doses, schedules of administration, 
and additional tumor types. Different doses and schedules of administration were evaluated with 
different outcomes in terms of safety, tolerability, and efficacy depending on tumor type.18 The 
combination study design and the doses are based on the results of safety data from clinical trials 
evaluating nivolumab and ipilimumab combinations (see Section 3.2.4 and the nivolumab IB18)
and will evaluate BMS-986288 in combination with nivolumab 
 mg 
 as outlined in 
the study design schematic in Figure 5.1-1.
In addition, NSCLC patients poorly tolerated certain doses and schedules of ipilimumab and 
nivolumab combination therapy, while alternative dosing schedules resulted in a more manageable 
AE profile, as demonstrated by the results in CA209012.34 Given the CA209012 safety data and 
to minimize the introduction of bias in initial dose escalation, for Part 1B participants with NSCLC 
will not be included in a BMS-986288 + nivolumab dosing cohort during the initial DLT 
evaluation period. However, given the ipilimumab and nivolumab combination efficacy data in 
NSCLC, after a BMS-986288 + nivolumab dose level is determined to be tolerable, participants 
with NSCLC will then be allowed to enroll and will be evaluated to determine if NSCLC patients 
have a similar tolerability and efficacy profile. Data from the NSCLC participant population will 
therefore be available for utilization in subsequent dose selection and MTD/RP2D determination.
Modifying the ipilimumab structure into an NF Probody mAb has the potential to offer decreased 
systemic exposure, which may translate into better tolerability while increasing efficacy at the 
tumor site when administered alone or in combination, and may be a more effective CTLA-4 
regimen for a larger number of patients in different tumor types. PK and pharmacodynamic data 
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will be evaluated to ensure there is evidence of decreased systemic absorption and activation in 
relation to effects in the tumor microenvironment.
The BLRM with an overdose control principle escalation was selected as an appropriate design for 
this study. It offers more accuracy and efficiency in determining the true MTD compared to rule 
based methods (such as 3 + 3 design) by incorporating external information from pre-clinical 
studies as well as 
 clinical trials. The EWOC principle limits the risk of exposing 
participants in the next cohort to an intolerable or toxic dose. Hence, it ensures that safety is not 
compromised during dose escalation. Simulation results demonstrate that BLRM allows fast 
escalation when the expected toxicity is very low, and limits participants treated at sub-therapeutic 
doses, which is attributed to the adaptive Bayesian learning from previous doses. In addition, 
BLRM has greater applicability to the combination therapy setting compared to other model-based 
methods. The drug-associated dose toxicity profiles from the BMS-986288 Monotherapy Dose 
Escalation (Part 1A) will be characterized and incorporated as prior knowledge into the Safety 
Evaluation of Combination Doses of BMS-986288 with Nivolumab (Part 1B), the 
 
Administration of BMS-986288 as a Monotherapy and Combination with Nivolumab 
, 
the initial drug expansion phase of the study (Part 2), or used in future studies.
5.4.2
Rationale for Tumor Selection in Part 1
Specific tumor types (SCCHN, NSCLC, cutaneous melanoma, RCC, CRC, TNBC, urothelial 
carcinoma, gastric, esophageal, and cervical cancer) were selected in Part 1 to evaluate the safety 
and potential therapeutic effect of BMS-986288 monotherapy and in combination with nivolumab 
based on the following rationale:

Previously assessed safety and efficacy profile of ipilimumab alone or in combination with 
nivolumab.

Tumors associated with higher prevalence of 
and 
 
 (internal data at BMS).35

Tumors for which 
 has been correlated with worse prognosis.
Nonclinical data suggests that BMS-986288 
activity at the tumor site and 
 
peripheral systemic exposure to CTLA-4 blockade compared with ipilimumab. Hence, 
BMS-986288 alone and in combination with nivolumab may potentially improve the 
 
 previously seen with ipilimumab treatment in the aforementioned tumor types.
5.4.3
Rationale for Tumor Selection in Part 2C
Nivolumab administered as monotherapy has demonstrated remarkable clinical benefit in several 
solid tumor types, including MSI-H CRC. However, MSS CRC is highly immunosuppressive, and 
inhibits the activation of anti-tumor immune responses that allow T-cells to engage with the 
tumor.36 Single-agent immunotherapies are largely ineffective in pMMR/MSS CRC, which 
represents approximately 85%-96% of the CRC patient population.37,38,39 Preclinical and clinical 
evidence suggests synergy between nivolumab and ipilimumab, which target distinct mechanisms 
that limit T-cell activation, PD-1, and CTLA-4, respectively. In vitro combinations of nivolumab 
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plus ipilimumab increase IFN-γ production 2- to 7-fold over either agent alone in a mixed 
lymphocyte reaction. The combination of nivolumab and ipilimumab has been shown to be more 
effective than either agent in monotherapy in the treatment of a variety of tumors including 
melanoma, lung, and renal cell carcinoma.40,41,42,43 Most relevant, this combination has also 
demonstrated meaningful clinical efficacy (Checkmate 142) in MSI-H CRC of improved efficacy 
compared to immuno-oncology monotherapy. In a murine melanoma vaccine model, blockade 
with either CTLA-4 or PD-1 antibodies increased the proportion of CTLA-4 and PD-1-expressing 
CD4/CD8 tumor infiltrating T effector cells, and dual blockade increased tumor infiltration of T 
effector cells and decreased intratumoral T regulatory cells, as compared to either agent alone.44
Despite minimal activity observed in MSS CRC with the combination of nivolumab and 
ipilimumab, clinical activity with next generation anti-CTLA4s was seen in the form of reductions 
in tumor volume, including objective responses in MSS CRC.45,46 Similar results are also observed
when participants with MSS CRC are treated with BMS-986218, a Fc-enhanced ipilimumab, in 
combination with nivolumab.14 BMS-986288 is an enhanced Fc ipilimumab with Probody mAb 
(PROBODY is a trademark of CytomX Therapeutics, Inc.) and is designed to provide a well 
tolerable safety profile. Modifying the ipilimumab structure with enhanced Fc engagement may 
result in a different dose/effect relationship; however, the addition of the protease cleavable 
masking peptide may minimize systemic effects (details in Section 5.4.1).2 This combination has 
an added mechanism of action compared to ipilimumab in combination with nivolumab. These 
data collectively support the further investigation of BMS-986288 in combination with nivolumab 
in MSS CRC participants.
5.4.4
Rationale for Randomization in Part 2C
The overall sample size in Arm C (containing BMS-986288) is 
 participants to allow for 
sufficient sizing for safety and subgroup efficacy analyses. To maintain a suitable number of total 
participants, the randomization ratio is 2:1. The sample size of the comparator cohort is up to 
 
participants; in addition, to up to
 
(see Section 5.4.8). The clinical data from another Fc-enhanced
anti-CTLA-4 inhibitor demonstrated higher clinical benefit in MSS CRC patients without liver 
metastasis.44 To minimize the potential for imbalances across treatment arms, there will be a 
stratification factor utilized in this trial: liver metastasis status (yes [which includes locally treated 
liver metastasis] or no). The prognostic implications of liver metastasis status is well established;
participants in the current trial will therefore be stratified by liver metastasis as the effect on 
response to nivolumab and BMS-986288 combination therapies is not yet known.
5.4.5
Rationale for BMS-986288 in Participants Previously Treated with 
Immunotherapy
Cancer immunotherapies that target the immunosuppressive checkpoint receptors CTLA-4 or 
PD-1 and its ligand, PD-L1, have changed the landscape of anti-cancer immunotherapy. In 
particular, checkpoint inhibitors targeting PD-1 and PD-L1 have demonstrated unprecedented 
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clinical efficacy in more than 15 cancer types, including melanoma, NSCLC, RCC, urothelial 
carcinoma, SCCHN, and Hodgkin’s lymphoma.47 Nevertheless, primary resistance to anti-PD-1 
therapies is common, affecting up to 60% of patients in some cancer types. Furthermore, it is now 
becoming apparent that encouraging initial responses observed among some patients can be 
undone by their development of acquired resistance to anti-PD-1 therapies, leading to disease 
relapse.48 In the current understanding of mechanisms contributing to the development of 
resistance to anti-PD-1 therapy, overexpression of other immune checkpoints (TIM-3, LAG-3, and 
CTLA-4) and influx of 
(which co-express these molecules) have been demonstrated to 
promote either primary or acquired resistance to anti-PD-1 therapy.49,50
A transcriptional signature associated with resistance to PD-1 immunotherapy, termed as Innate 
PD-1 RESistance (IPRES) was reported. Notably, over 30% of patients whose melanomas 
expressed the IPRES signature responded to CTLA-4 blockade (ipilimumab), suggesting that the 
IPRES signature does not indicate resistance to every immunotherapy.51
Targeting CTLA-4 and 
 could present a valuable mechanism to overcome 
anti-PD-1 resistance, especially in tumors where a high level of 
 correlates with 
poor prognosis. Including participants with cutaneous melanoma and NSCLC will therefore enable 
this hypothesis to be assessed in tumor types with established responsiveness to ipilimumab, and 
in those where ipilimumab monotherapy did not demonstrate a sufficient level of efficacy, 
respectively.
5.4.6
Rationale for Two Years Fixed Duration with Checkpoint Blockade
The optimal duration of immunotherapy is an important question and continues to be investigated. 
Accumulating data suggest that 2 years of PD-1 checkpoint inhibitor treatment may be sufficient 
for long-term benefit. CA209003, a dose-escalation cohort expansion trial evaluating the safety 
and clinical activity of nivolumab in participants with previously treated advanced solid tumors 
(including 129 participants with NSCLC), specified a maximum treatment duration of 2 years. 
Among 16 participants with NSCLC who discontinued nivolumab after completing 2 years of 
treatment, 12 participants were alive for > 5 years and remained progression-free without any 
subsequent therapy. In the CA209003 NSCLC cohort, the OS curve begins to plateau after 2 years, 
with an OSR of 25% at 2 years and 18% at 3 years.52 These survival outcomes are similar to 
Phase 3 studies in previously treated NSCLC, in which nivolumab treatment was continued until 
progression or unacceptable toxicity (2-year OSRs of 23% and 29%, and 3-year OSRs of 16% and 
18% for squamous and non-squamous NSCLC, respectively).53
Taken together, these data suggest that treatment beyond 2 years is unlikely to confer additional 
clinically meaningful benefit and that the risk of progression after discontinuing treatment at 
2 years is low.
In contrast, a shorter duration of nivolumab of only 1 year was associated with increased risk of 
progression in previously treated participants with NSCLC, suggesting that treatment beyond 
1 year is likely needed. In CA209153, participants with previously treated advanced NSCLC who 
completed 1 year of nivolumab therapy were randomized to either continue or stop treatment, with 
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the option of retreatment upon progression. Among 163 participants still on treatment at 1 year 
and without progression, those who were randomized to continue nivolumab had significant 
improvement in PFS compared to those who were randomized to stop treatment, with median PFS 
(post-treatment allocation) not reached vs 10.3 months, respectively; HR = 0.42 (95% CI: 0.25,
0.71). With a median follow-up of 14.9 months post-treatment allocation, there also was a trend 
for participants on continued treatment to live longer (OS HR = 0.63 [95% CI: 0.33, 1.20]). Of
note, the PFS curves in both groups plateau approximately 1 year after treatment allocation (ie, 2 
years after treatment initiation), suggesting that there may be minimal benefit in extending 
treatment beyond a total of 2 years.54
Collectively, these data suggest that there is minimal, if any, benefit derived from continuing 
immuno-oncology (I-O) treatment beyond 2 years in advanced tumors. However, even though 
immunotherapy can be well tolerated, participants will be at risk for additional toxicity with 
longer-term treatment. 
The role of immune check-point inhibitors in MSS or pMMR CRC is under investigation to 
validate the hypothesis of evoking immunogenic responses.55 Although the optimal duration of 
checkpoint blockade in MSS or pMMR CRC is not yet defined, the data presented above indicate 
that the duration of 2 years in solid tumors, including MSS or dMMR CRC, would achieve an 
optimal risk/benefit ratio. Therefore, in this study, nivolumab and BMS-986288 treatment will be 
given for up to 2 years in the absence of disease progression or unacceptable toxicity. There is no 
maximum treatment duration for Part 2C Arm D (regorafenib). Treatment with regorafenib may 
continue until progression of disease or unacceptable toxicity (see Section 8.1) in accordance with 
locally approved prescribing information.
5.4.7
Rationale for Quality of Life Evaluation
The evaluation of patient-reported outcomes (PROs) is an increasingly important aspect of clinical 
efficacy in oncology trials. Such data provide an understanding of the impact of treatment from 
the participant’s perspective and offer insights into patient experience that may not be captured 
through physician reporting. Additionally, generic health-related quality of life (HRQoL) 
measures provide data needed for calculating utility values to inform health economic models.
The 5-Level EQ-5D (EQ-5D-5L) will be used to assess general health status, the Functional 
Assessment of Chronic Illness Therapy, General Physical item (FACIT GP5) will be used to assess 
the overall bother of side effects, and the Non-small Cell Lung Cancer Symptom Assessment 
Questionnaire (NSCLC-SAQ) will be used to assess symptoms and overall HRQoL in this patient 
population.
These PROs will only be administered in Part 2 of this protocol. Part 2C is excluded from PROs.
5.4.8
Rationale for Using a 
 Arm
In Part 2C of this study, a 
 arm is planned. A portion (up to
participants) of the 
control cohort will be 
 
 
.56 The use of a 
 arm allows optimizing the usage of participant 
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data by 
 the number of participants in control groups. As such, more patients will have 
access to potentially new effective medicines during clinical development.
To establish the appropriate assessment of the treatment effect between the experimental arms and 
the 
 arm, 2 approaches will be taken:

The baseline eligibility (inclusion/exclusion criteria) from the current study recapitulates the 
 randomized control trial planned to be used as the 
 
. This ensures the consistency of the overall target population of the intended 
indication to enhance the confidence of any conclusions drawn (see further details in Section 
10.1.6).

During the study, it is possible that there may still be differences between the current study and 
the 
 external control due to the sampling mechanism. 
 
using baseline prognostic information will be applied to further reduce the potential bias. 
Details of the 
 method will be described in the statistical analysis 
plan. 
5.4.9
Rationale for Not Blinding
The study will be open label. The Site and Sponsor will be unblinded to BMS-986288 treatment 
assignment. This is to facilitate safety monitoring by the Sponsor and to ensure adequate ability of 
the clinical trial physician to monitor and discuss the management of the participants with the 
investigators.
5.5
Justification for Dose
5.5.1
Rationale for BMS-986288 Starting Dose in Humans
Introduction 
The starting dose of BMS-986288 for this FIH study was selected to be a
-mg 
 initially 
administered 
. 
The BMS-986288 starting dose was determined by taking into consideration: 
1) The GLP toxicology studies, which utilized the HNSTD identified from a 1-month repeat-dose 
toxicity 
study 
in 
cynomolgus 
monkeys 
and 
demonstrated 
 
systemic 
immune-activating pharmacodynamic responses and toxicities in cynomolgus monkeys 
compared to ipilimumab. 
2) The nonclinical pharmacology-based method, which evaluated BMS-986288 in a human 
CTLA-4 
 model, and demonstrated 
 in 
comparison with ipilimumab. In addition, human PK projection suggested that BMS-986288 
will slowly convert to the fully active species in systemic circulation with the steady-state 
exposure 
 of ipilimumab, and may result in a more tolerable safety profile.
3) The known clinical safety experience data of ipilimumab. Because BMS-986288 is a Probody 
of the NF form of ipilimumab, it is predicted to have the same type of irAEs as ipilimumab 
that have been well defined and managed in clinic. BMS is also evaluating an anti-CTLA-4 
NF mAb (BMS-986218) and an anti-CTLA-4 Probody mAb (BMS-986249) in separate 
clinical trials (clinicaltrials.gov, NCT03110107 and NCT03369223, respectively). Emerging 
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data from these programs may help inform BMS-986288 clinical trial design and AE 
management.
The BMS-986288 starting dose of 
 mg (approximately 
 mg/kg) was derived from the known 
ipilimumab clinical safety profile and supported by preliminary clinical data from the anti-CTLA-4 
NF mAb (BMS-986218; clinical trials.gov, NCT03110107) and the anti-CTLA-4 Probody mAb 
(clinicaltrials.gov, NCT03369223) programs. Importantly, this dose is about 
 below 
the starting dose calculated from toxicology- and pharmacology-based methods and is also 
supported by the no-effect level from the in vitro cytokine release assay. Therefore, 
mg/kg 
converted to a 
 mg, 
, is recommended as the FIH starting 
dose for BMS-986288.
Collectively, the proposed strategy for FIH starting dose selection represents the intent of ensuring 
adequate patient safety while limiting the number of cancer patients receiving sub-therapeutic 
doses.
Starting Dose Selection Supported by the HNSTD in Monkeys
The HNSTD of BMS-986288 from a GLP 1-month repeat-dose toxicity study in monkeys was 
determined to be 
 mg/kg.8 Using the standard body weight (BW) conversion to the human 
equivalent dose and applying a safety factor of 
, the human starting dose was calculated to 
be 
 mg/kg (or 
 mg 
 for 
). In addition, the total antibody exposure 
(AUC[0-168h]) observed at the HNSTD, after the 4th dose, was 
gh/mL. Based on the 
monkey HNSTD exposure and the predicted human clearance of the total antibody (
 mL/d/kg),
the FIH starting dose, after applying a safety factor of 
, was estimated to be 
 mg/kg 
(or
mg 
 for 
). However, the actual proposed FIH starting dose (
mg, 
or approximately 
 mg/kg), based on additional considerations described below, is 
 
lower than that supported by this HNSTD-based approach, providing an additional safety factor.
Starting Dose Selection Supported by BMS-986288 Nonclinical Pharmacology 
In nonclinical pharmacology and toxicology studies described in previous sections, BMS-986288 
compared to ipilimumab and BMS-986218 demonstrated reduced in vitro activities, in vivo 
systemic active drug exposure and pharmacodynamic responses, and yet maintained comparable 
anti-tumor activity in the human CTLA-4 
 tumor model. The key differentiation 
between BMS-986288, ipilimumab, and BMS-986218 is summarized below.

BMS-986288 binds human CTLA-4 expressed on 
 --CTLA-4/CD3 cells with 
approximately 
-fold higher EC50 than BMS-986218 and ipilimumab 
 
 but similar to BMS-986249 
 nM). These differential binding affinities translate 
to lower IL-2 secretion by BMS-986288 vs ipilimumab and BMS-986218 and slightly higher 
IL-2 secretion vs BMS-986249 in 
human 
functional assay.

In the FcR-mediated 
 assay, the ranking of activity by the antibodies was as follows: 
BMS-986218 > ipilimumab > BMS-986288 > BMS-986249. These data are consistent with 
the expectation that the NF version of ipilimumab is more potent, and that the addition of the 
Probody masking peptide reduces functional 
 activity.
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
PK of BMS-986288 in mice and cynomolgus monkeys suggests that the intact Probody is 
slowly converted to 
 species in vivo. The projected systemic exposure 
of the 
 Probody, which is equally active as BMS-986218, is predicted to be 
 
of BMS-986218 exposure when BMS-986288 is administered at the same dose as 
BMS-986218 in patients. For comparison, the conversion efficiency of BMS-986288 to its 
active species in monkeys was similar to BMS-986249.

In human CTLA-4 
 tumors, BMS-986288 had similar anti-tumor 
activity to BMS-986218 in the 
 model at all 3 dose levels tested, and both 
antibodies demonstrated greater activity than ipilimumab and BMS-986249 at the 2 lower dose 
levels. BMS-986288-treated mice also had similar levels of 
 reduction, 
indicating that the drug has similar pharmacodynamic activity at the tumor site. Analysis of 
peripheral 
 populations in the spleen indicated that the levels of the activation markers 
Ki-67 and ICOS on 
 and 
 in BMS-986288-treated animals were 
 compared to ipilimumab and BMS-986218-treated animals. The 
 in 
peripheral pharmacodynamic activity by the Probody is consistent with the goal of the Probody
therapeutic to 
 CTLA-4 binding activity outside of the tumor site.

In a non-GLP investigative 3-week monkey investigative study, BMS-986288 at 
 mg/kg 
exhibited 
systemic 
/pharmacodynamic responses when compared to 
BMS-986218 or ipilimumab at the same dose in a time-dependent manner, corresponding with 
a delayed conversion of BMS-986288 to its active forms. By the end of the dosing period, the 
magnitude of change for pharmacodynamic activity for most endpoints was generally 
BMS-986218 > ipilimumab ≥ BMS-986288.
Assuming the in vitro activities, in vivo systemic active drug exposure, and pharmacodynamic
responses of BMS-986288 relative to ipilimumab and BMS-986218 in nonclinical studies translate 
to cancer patients, BMS-986288 at the starting dose of 
mg may provide similar efficacy as 
ipilimumab, but with reduced systemic active drug exposure and pharmacodynamic responses that 
may be responsible for its irAEs.
Starting Dose Selection Based on Ipilimumab Clinical Exposure and Response of Safety 
Analysis in Melanoma Patients
BMS-986288 is the NF Probody form of ipilimumab. The AEs of ipilimumab in cancer patients 
are mostly irAEs, which have been well defined in terms of their incidence, severity, time to onset 
and resolution. An exposure-response of safety analysis conducted with ipilimumab data from 
previously treated advanced melanoma patients showed that, the probability of Grade 3+ irAEs 
occurred at approximately 3% in patients receiving 0.3 mg/kg.57 The probability of Grade 3+ 
irAEs increased to 11% and 23% at ipilimumab doses of 3 mg/kg and 10 mg/kg, respectively. In 
advanced melanoma patients, the irAEs of ipilimumab at 3 mg/kg Q3W for 4 cycles occurred in 
approximately 60%-65% of the patients. These AEs were mostly Grade 1 or Grade 2 and affected 
primarily the skin (in 43%-45% of patients) and gastrointestinal tract (in 29%-32% of patients), 
followed by the liver and endocrine system (in 6%-8% of patients). The vast majority of these 
irAEs occurred within 12 weeks of initial dosing, with a median time of Grade 2-4 irAEs occurring 
at 4.6 weeks.58 In addition, a low incidence of infusion-related reaction of ipilimumab was also 
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reported in 2.2% and 4.3% patients treated at 3 mg/kg and 10 mg/kg infused over 90 minutes, 
respectively, and can be treated by premedication with diphenhydramine.59 Management of irAEs 
attributed to ipilimumab treatment have been well established as the Risk Evaluation and 
Mitigation Strategy (REMS) Guidelines approved by FDA.60
The BMS-986288 FIH starting dose was selected to be 
mg 
 (approximately 
mg/kg). Considering the preclinical similarities between BMS-986288 and ipilimumab 
(specifically the HNTSD of BMS-986288 was 
 as ipilimumab, the preclinical peripheral 
pharmacodynamic activity for ipilimumab was 
 to BMS-986288, while the 
preclinical anti-tumor activity was 
 for BMS-986288 than for ipilimumab), the 
BMS-986288 FIH starting dose was selected to be similar to the ipilimumab dose that produced
minimal Grade 3+ irAEs in the clinic. In addition, the FIH starting dose is supported by the 
preliminary clinical experience from the anti-CTLA-4 NF mAb (BMS-986218; clinical 
trials.gov, NCT03110107) and the anti-CTLA-4 Probody mAb (clinicaltrials.gov, NCT03369223) 
programs.
5.5.2
Rationale for BMS-986288 Maximum Dose
At the time of this Protocol Amendment 02, the preliminary clinical safety profile of BMS-986288 
as a single agent (
 mg to
 mg 
) and in combination with nivolumab (BMS-986288 
mg + nivolumab 
 mg 
) is well tolerated and clinically manageable. The MTD for 
BMS-986288 has not been reached. 
 reported were Grade 
, and 
 were 
reported with monotherapy or combination therapy. Therefore, 
additional dose levels (
 mg 
 and 
 mg 
) have been added to Part 1A to further explore the MTD for monotherapy, 
while maintaining the projected safety exposure margin greater than
for Cmax and 
for AUC). In addition, 
 mg 
 and 
 mg 
 of BMS-986288 in combination with 
 
mg 
 nivolumab have been added to Part 1 B to explore the MTD for the combination therapy.
The dose of BMS-986288 to be explored in Part 1B will not exceed the safe and tolerable BMS-
986288 dose identified in Part 1A.
5.5.3
Rationale for BMS-986288 Dose Selection in Part 2C
For Part 2C Arm C, a safe dose of 
mg BMS-986288 in combination with 
 mg nivolumab
will be used. Depending on the emerging PK, PD, safety, and preliminary efficacy results 
from Part 1B and Part 2B, an additional dose of BMS-986288 in combination with nivolumab may 
be evaluated in Part 2C as Arm E. The additional dose level will not exceed the dose level that has 
been evaluated and determined to be safe in Part 1B.
The selection of 
 mg BMS-986288 in combination with
 mg nivolumab
is based on 
the clinical safety and 
from Part 1A, Part 1B, and Part 2B, as described in the 
investigator brochure.2
As expected, all AEs observed in participants receiving BMS-986288 in combination with 
 mg 
nivolumab were qualitatively similar to those seen with ipilimumab.
Aforementioned safety observations suggest that 
 mg BMS-986288 in combination with 
mg nivolumab is safe and tolerable. The 
 shows
 mg is the optimized dose 
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level. The benefit-risk balance will be continuously evaluated and compared among 
 mg 
BMS-986288 in combination with 
mg nivolumab, 
 mg BMS-986288 in combination with 
 mg nivolumab, and 
 mg BMS-986288 in combination with 
 mg nivolumab with 
emerging data. An additional dose of BMS-986288 
 mg or 
mg) in combination with 
nivolumab may be added to Part 2C.
5.5.4
Rationale for 
 Selection and Dosing Schedule
5.5.4.1
BMS-986288
A 
 (mg) of BMS-986288 will be used in this study instead of a 
 
dose. Therapeutic mAb doses have been routinely calculated on a 
body size basis. This practice assumes that 
 significantly reduces variability in 
therapeutic mAb exposure.61 However, recent analyses of marketed and experimental mAbs have 
demonstrated that 
-based dosing did not always offer advantages over 
 in 
reducing exposure variability. Many mAbs are target-specific with a relatively large therapeutic 
window that increases the tolerability of exposure variability. Additionally, patient-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, 
 dosing could result in higher mAb 
concentrations in the heaviest participants (eg, 90th percentile), whereas 
 could lead to 
higher mAb concentrations in the lightest participants (eg, 10th percentile). Body weight 
distribution data from a clinical trial database of over 2500 adults with solid or hematologic cancers 
suggested a log-normal distribution of body weight with median, 10th percentile, and 
90th percentile of 78 kg, 56 kg, and 112 kg, respectively.62
In addition to the above rationale, 
 offers practical advantages over 
 
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 
 
 calculations.61 Because the magnitude of the impact 
 on the human PK of 
BMS-986288 is not yet determined, the PK and safety data from the Phase 1/2 study will be 
evaluated to validate the 
 approach. If appropriate, based on the totality of the data, the 
Sponsor will consider a revision of the 
 strategy.
BMS-986288 will initially be administered 
. This dosing frequency is supported by the 
projected human T-HALF for BMS-986288 of 
. In addition, it complements the 
 
dosing regimen planned in the Safety Evaluation of Combination Doses of BMS-986288 with 
Nivolumab (Part 1B), the 
 Evaluation of BMS-986288 as a Monotherapy and in 
Combination with Nivolumab 
and the BMS-986288 in Combination with Nivolumab 
Cohort Expansion (Part 2B), thereby simplifying study logistics for both participants and 
Investigators. An alternative dosing schedule may implemented upon evaluation of available 
safety, PK, and pharmacodynamic data from 
 administration (refer to Table 2-2 and 
Appendix 8).
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5.5.4.2
Rationale for 
 Administration of BMS-986288 with or 
without Nivolumab
 has the potential to reduce infusion time and provide greater convenience and 
comfort for oncology patients. The 
 facilitates 
 
 as demonstrated by several 
 biologic therapies already 
approved in the US, EU, and other countries (eg, trastuzumab and rituxumab). As of 15-Nov-2018, 
 and other 
 have been administered to 1592 participants in 
30 clinical studies conducted under 
 or in postmarketing Phase 4 studies. In 
these studies, individual doses have ranged from 
. Across all studies, 
 
 of 
were generally well-tolerated in healthy participants, dehydrated pediatric 
participants, hospice and palliative care participants, participants with type 1 and type 2 diabetes, 
and participants with rheumatoid arthritis. 
 alone or in combination with 
lactated Ringer’s, normal saline, co-injected drugs (morphine, ceftriaxone, insulin, and insulin 
analogs), or biologic products (IgG and adalimumab) have been well-tolerated in all clinical trials. 
Most AEs were mild, transient 
 reactions, including erythema, pain, bruising, pruritus, 
burning, tenderness, edema, induration, irritation, paresthesia, numbness, and rash. Moderate 
 reactions, which have occurred less frequently, include burning, erythema, pain, and 
numbness. Mild-to-moderate headache was also commonly reported. AEs in these trials have 
otherwise generally reflected the adverse reaction profiles of the 
 drug or have 
been associated with the rapid introduction of a relatively large volume of fluid in the 
.
In addition, a large safety database exists for approved products coformulated with 
 
.
Studies have consistently shown that the bioavailability (BA) of monoclonal antibodies following 
 approximates 
 with lower Cmax, a delayed and decreased Tmax, 
a comparable trough-observed plasma concentration (Ctrough) compared to 
 administration, 
and comparable overall exposure. Comparable efficacy (ORR, complete response rate, PFS, EFS, 
and OS in various studies) for 
 routes was also demonstrated. The mAb dose ranges 
evaluated in these studies ranged from  mg to 
mg when administered with or without 
BMS-986288 will be studied in the dose range of 
 mg to 
 mg. Clinical 
evaluation of nivolumab 
 with and without 
 is currently ongoing
(clinicaltrials.gov, 
).
Overall, these data suggest that 
 of BMS-986288 and 
 of 
nivolumab, at a dose exposure previously shown to be safe intravenously, should be feasible and 
tolerable. Additionally, as part of a 1-month toxicity study in monkeys, weekly 
 
of 
mg/mL BMS-986288 and 
 U/mL
 resulted in no significant skin irritation or 
local tolerance issues. In a separate nonclinical toxicity study in monkeys, nivolumab administered 
at 
 mg/kg 
 U/mL) was also shown to be well-tolerated with no 
clinical observations and no local tolerance issues at the 
 sites. The use and dose of 
 will be determined following evaluation of preliminary data from Part 1A and Part 1B. 
Potential risks will be further mitigated through a sentinel participant dosing strategy. The PK data 
from this 
 cohort will inform BA in comparison to 
 formulation and may help in 
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determining 
 for the initial expansion phase (Part 2). The participants 
receiving the 
 administration will be different from those receiving IV administration, not 
crossed over. It is anticipated that the cleavage of the Probody to active species will be relatively 
slow and, as a result, there may be accumulation after repeat dosing. In addition, there may be
potential of cleavage at the 
 site before absorption into lymphatic system. The presence 
of multiple and different processes may complicate an accurate assessment of the BA. Separate 
 cohorts will facilitate safety assessment attributed to these different dosing routes.
5.5.4.3
Rationale for Nivolumab 30-minute Infusions
Nivolumab is currently approved for IV administration over 30 minutes for select indications. The 
impact of infusion time on nivolumab safety was assessed in a substudy conducted as part of an 
ongoing community based trial (ie, CheckMate 153) in participants with previously treated 
advanced or metastatic NSCLC.68 In the substudy, 322 participants received nivolumab 3 mg/kg 
IV Q2W as a 30-minute infusion, and 355 participants received the same nivolumab regimen as a 
60-minute infusion. As detailed in the nivolumab IB,18 nivolumab can be safely administered as a 
30-minute infusion, with a low incidence of irAEs. Given these findings, 30-minute infusions are 
being implemented across nivolumab development programs, including the FIH study CA043001.
5.5.4.4
Rationale for 
 of Nivolumab
A nivolumab 
 dose of 
 mg every 2 weeks (Q2W) was approved in the US as monotherapy 
for unresectable or metastatic melanoma, metastatic NSCLC, advanced RCC, locally advanced or 
metastatic urothelial carcinoma, MSI-H or mismatch repair deficient (dMMR) mCRC, HCC, and 
as maintenance therapy for unresectable or metastatic melanoma after induction therapy with 
nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses. In addition, 
nivolumab 
 mg 
 infused over 30 minutes was Food and Drug Administration (FDA) 
approved in Mar-2018 for the majority of the approved indications. The European Medicines 
Agency’s Committee for Medicinal Products for Human Use (CHMP) has also recommended 
adding the option of a 4-week dosing schedule to the label for nivolumab for the treatment of 
patients with advanced melanoma and previously treated RCC. 
The benefit-risk profiles of nivolumab 
 mg 
 and 
 mg 
 are expected to be 
comparable to  mg/kg 
. This assessment is based on a comprehensive characterization of 
nivolumab PK, safety, efficacy, and E-R relationships across indications. Given that nivolumab 
has linear PK over a dose range of 0.1 to 10 mg/kg across multiple tumor types, the 
 mg 
 
regimen was selected based on the approximate 
 for subjects treated 
in nivolumab clinical trials. The 
 mg 
 regimen was selected as it translates to a 
 
of the 
 mg 
. With reduced dosing frequency from 
, the 
average nivolumab exposure with 
 mg 
 is expected to be comparable to that from  mg/kg 
 mg 
. Additional details are provided in the current version of the nivolumab 
IB.18
Given the PK, safety, and efficacy data for nivolumab monotherapy (mg/kg dosing) and the 
simulated 
 exposure data described above, a nivolumab 
 mg 
 will 
be examined in combination with BMS-986288 in this study.
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5.5.4.5
Rationale for 
Long 
 times place a burden on patients and treatment centers. Establishing that nivolumab 
and BMS-986288 can be safely administered using shorter 
 times of approximately 
 in participants will diminish the burden provided no change in safety profile. 
 
 However, 
 may result in 
2 Therefore, any 
potential safety differences between 
 and 
 regimens would be expected 
to be limited to infusion reactions. 
versus 
 is not expected to impact 
the overall safety profile. Overall, infusion reactions including high-grade hypersensitivity 
reactions have been uncommon across nivolumab or BMS-986288 clinical studies 
 
.
5.5.4.6
Rationale for Choice of Standard of Care Treatment in Part 2C
Regorafenib is a standard late line therapy for patients with mCRC who have been previously 
treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF 
therapy, and anti-epidermal growth factor receptor (EGFR) therapy (if KRAS wild type). 
Regorafenib is approved by regulatory authorities in many regions of the world for patients with 
mCRC who have failed at least 2 prior lines of therapy (no more than 4 prior lines). Regorafenib 
was chosen to be the standard of care treatment in Part 2C, in accordance with practice guidelines
that advise that regorafenib may provide benefit when used in the 3L+ setting.69,30 In the 3L 
setting, approved therapies are used interchangeably due to their similarity in treatment benefit. A 
single therapy (regorafenib) was chosen as a comparator in the Part 2C cohort due to its 
cross-country and regional availability and because matched studies utilizing regorafenib are 
available to enable use of a 
 in this cohort. Participants in Arm D (regorafenib) can 
transition to BMS-986288 and nivolumab after disease progression (Arm Z).
5.5.4.7
Rationale for KRAS Testing
Activating mutations of the KRAS gene have been reported to occur in 35% to 40% of colorectal 
cancers.70
Although the prognostic value of KRAS mutations in CRC (independent of anti-EGFR therapy) is 
unclear due to conflicting data, KRAS mutations are predictive for a lack of response and clinical 
benefit from anti-EGFR mAbs in patients with mCRC based on several large clinical trials.71
All participants with metastatic colorectal cancer should have tumor genotyped for RAS (KRAS 
and NRAS), and after lines of treatment to address RAS status changes and to collect real-time 
data on RAF/RAS genetics. Participants with any known KRAS or NRAS mutation should not be 
treated with EGFR-targeting monoclonal antibodies.72
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5.5.4.8
Rationale for 
 Testing
 are observed in 5% to 10% of CRC, with 80% to 90% of 
 being 
 
Given the poor prognosis associated with 
mutations, these patients 
will be excluded.
5.5.4.9
Rationale for Dose Selection of Regorafenib and Line of Therapy (in 
3rd/4th Line MSS CRC)
Recommended starting dose for regorafenib (
 mg) is selected based on approved product labels 
across various regions. Local product label and institutional guidelines for regorafenib starting 
dose can be considered in consultation with BMS Medical Monitor/designee.
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 who 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 or their legally acceptable representative (see Appendix 2) must sign the 
ICF prior to the performance of any study-related procedures that are not considered part 
of standard of care.
b) The participant or their legally acceptable representative (see Appendix 2) must sign the 
consent for pretreatment, on treatment, and upon progression 
 
. 
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
measurable disease per RECIST v1.1 (Appendix 5) and have at least 1 soft-tissue tumor 
lesion accessible for biopsy.
b) Eastern Cooperative Oncology Group Performance Status of 0 or 1 (Appendix 9).
c) The BMS-986288 Dose Escalation Phase (Part 1)
i)
Participants with 
 proven NSCLC, SCCHN, CRC, RCC, TNBC, urothelial 
cancer, gastric cancer (including gastro-esophageal junction), esophageal cancer, 
cervical cancer, and cutaneous melanoma will be permitted during dose escalation, 
except for participants with tumors with CNS metastases as the only site of active 
disease.
(1) Part 1B participants with NSCLC will not be permitted as part of the initial DLT 
assessment; instead, Part 1B NSCLC participants will be evaluated only as part of 
additional participant enrollment to a previously tested tolerable cohort.
ii) All Part 1 participants must be anti-CTLA-4 naive. Prior anti-PD-1 or anti-PD-L1 
exposure is allowed.
iii) Participants with Gastric or Esophageal Cancer:
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(1) Must have received, and then progressed, relapsed, or been intolerant to, at least 
1 standard treatment regimen in the advanced or metastatic setting (or have 
progressed within 6 months of adjuvant therapy).
(2) Participants with human epidermal growth factor receptor 2 (HER2)-positive 
gastric cancer must have received prior treatment with a HER2 inhibitor 
(eg, trastuzumab).
iv) Participants with Urothelial Carcinoma:
(1) Must have received, and then progressed, relapsed, been intolerant to, or 
ineligible for, at least 1 platinum-containing chemotherapy regimen
OR
Within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment with a 
platinum agent in the setting of cystectomy for localized muscle-invasive 
urothelial cancer.
v) Participants with NSCLC:
(1) Must have received, and then progressed, relapsed, or been intolerant to, at least 
1 standard treatment regimen in the advanced or metastatic setting
OR 
Must have recurrent or progressive disease within 6 months after completing 
platinum based chemotherapy for local disease.
(2) Not Applicable as of Amendment 02. See 2.c.v.3 below: Participants with 
adenocarcinoma must have known epidermal growth factor receptor (EGFR), 
anaplastic lymphoma kinase (ALK) status, and ROS1 mutational status. 
(a) Must have been offered mutation-directed therapy, if indicated, that has 
proven survival benefit. This must be documented in the medical record.
(3) All participants with adenocarcinoma must have known EGFR, ALK, KRAS, and 
ROS1 status (when testing is available as per country/region standard of care 
practices); participants with an activating EGFR mutation, ALK translocation, or 
ROS1 mutation must have received appropriate inhibitor therapy (as available per 
country/region standard of care). Note: If KRAS results are not known, then a 
sample 
 
 should be sent for testing locally. 
 may be used 
if 
 results are not feasible, with prior Sponsor approval.
(a) Must have been offered mutation-directed therapy, if indicated, that has 
proven survival benefit. This must be documented in the medical record.
vi) Participants with CRC:
(1) Participants must have received and then progressed on or after, or have been 
intolerant or refractory to, at least 1 standard systemic therapy for metastatic 
and/or unresectable disease (or have progressed within 6 months of adjuvant 
therapy).
(a) Prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan given as a 
single regimen or over multiple regimens is required.
(b) Prior treatment with an anti-angiogenic therapy (eg, bevacizumab) is required.
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(2) Participants must have known MSI or mismatch repair status. 
 
status, if known, should be documented.
(a) If 
, prior treatment with an anti-EGFR therapy (eg, cetuximab 
or panitumumab) is required.
vii)Participants with RCC:
(1) Participants must have received at least 1 but not more than 2 prior 
anti-angiogenic therapy regimens (including but not limited to sunitinib, 
sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or 
metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-), vaccine therapy, or 
treatment with cytotoxics is allowed.
(2) Not Applicable as of Amendment 02: Participants must have received no more 
than 3 total prior systemic treatment regimens in the advanced or metastatic 
setting and must have evidence of progression on or after the last treatment 
regimen received and within 6 months prior to study enrollment.
viii)
Participants with SCCHN:
(1) Histologically confirmed, recurrent, or metastatic SCCHN (oral cavity, pharynx, 
larynx), and not amenable to local therapy with curative intent.
(a) Any other cancers of the head and neck, including salivary gland and 
neuroendocrine tumors, are excluded.
(2) Participants who progressed on or after, or were intolerant to, a 
platinum-containing regimen.
(3) Prior curative radiation therapy must have been completed at least 4 weeks prior 
to first study drug administration. Prior local palliative radiotherapy must have 
been completed at least 2 weeks before study drug administration.
(4) Documentation of p16 is sufficient to determine HPV status of tumor for SCCHN 
of the oropharynx. If results are not available, then a sample 
 
 should be 
sent to the central laboratory for analysis.
ix) Participants with TNBC:
(1) Males and females with histologically confirmed TNBC as defined by American 
Society of Clinical Oncology/College of American Pathologists guidelines.
(2) Participants must have had at least 1 chemotherapeutic regimens for the treatment 
of metastatic or locally advanced and unresectable disease.
(3) Participants must have been considered for all other potentially efficacious 
therapies.
x) Participants with Cervical Cancer:
(1) Must have received, and then progressed, relapsed, or been intolerant to, at least 
1 standard treatment regimen in the advanced or metastatic setting, if such a 
therapy exists.
xi) Participants with cutaneous melanoma:
(1) Participants must have received, and then progressed, relapsed, or been intolerant 
to, at least 1 standard treatment regimen in the advanced or metastatic setting.
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(a) If anti-PD-(L)1 therapy is approved then participants are eligible to receive 
this treatment as part of the Part 1B combination regimen in this study prior to 
having completed the 1 prior systemic therapy regimen, after discussion and 
agreement with the Medical Monitor (or designee). 
(2) Participants must have known BRAF status.
d) The Expansion Phase of BMS-986288
(Part 2A):
i)
Participants with cutaneous melanoma:
(1) Histologically confirmed cutaneous melanoma that is unresectable or metastatic.
(a) Participants with ocular or mucosal melanoma are excluded.
(2) Must have radiologically or clinically documented progressive or recurrent 
disease occurring either during treatment with or within 3 months of 
discontinuing anti-PD-(L)1 therapy when administered as either monotherapy or 
as part of a combination.
(a) No more than 1 intervening therapy is allowed but not required between prior 
anti-PD-(L)1 containing regimen and enrollment. 
(b) No more than 70% of participants should have had progression of disease 
within a period of 6 months of start of therapy with 
 agent. 
(3) Must not have received prior anti-CTLA-4 therapy in the advanced or metastatic 
setting. 
(4) Participants must have known BRAF status. 
(a) Must have been offered mutation-directed therapy, if indicated, that has 
proven survival benefit. This must be documented in the medical record. 
ii) Participants with histologically or cytologically documented metastatic or recurrent
NSCLC:
(1) Must have received, and then progressed, relapsed, or been intolerant to, at least 
1 standard treatment regimen in the advanced or metastatic setting
OR 
Must have recurrent or progressive disease within 6 months after completing 
platinum based chemotherapy for local disease.
(2) All participants with adenocarcinoma must have known EGFR, ALK, KRAS, and 
ROS1 status (when testing is available as per country/region standard of care 
practices); participants with an activating EGFR mutation, ALK translocation, or 
ROS1 mutation must have received appropriate inhibitor therapy (as available per 
country/region standard of care). Note: If KRAS results are not known, then a 
sample 
 
 should be sent for testing locally. 
 may be used 
if 
 results are not feasible, with prior Sponsor approval.
(a) Must have been offered mutation-directed therapy, if indicated, that has 
proven survival benefit. This must be documented in the medical record. 
(3) Must have radiologically or clinically documented progressive or recurrent 
disease occurring either during treatment with or within 3 months of 
discontinuing anti-PD-(L)1 therapy when administered as either monotherapy or 
as part of a combination.
(a) No more than 1 intervening systemic anti-cancer regimen is allowed but not 
required between prior anti-PD-(L)1 containing regimen and enrollment. 
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(b) Prior anti-CTLA-4 therapy is not allowed.
(4)
 available from screening 
 will be sent for analysis for 
 
. If adequate 
 is unavailable, then 
prior outside genomic or other testing result from 
 from within 
3 months and no intervening therapy prior to enrollment on this study may be 
used for this purpose only.
(5) The Sponsor may elect to prioritize enrollment of participants with BOR of SD, 
PR, or CR > than 6 months’ duration in response to prior anti-PD-1/anti-PD-L1 
treatment.
e) The Expansion Phase of BMS-986288 in Combination with Nivolumab (Part 2B)
i)
Participants with histologically or cytologically documented metastatic or recurrent 
NSCLC:
(1) Must have received, and then progressed, relapsed, or been intolerant to, at least 
1 standard treatment regimen in the advanced or metastatic setting
OR 
Must have recurrent or progressive disease within 6 months after completing 
platinum based chemotherapy for local disease.
(2) All participants with adenocarcinoma must have known EGFR, ALK, KRAS, and 
ROS1 status (when testing is available as per country/region standard of care 
practices); participants with an activating EGFR mutation, ALK translocation, or 
ROS1 mutation must have received appropriate inhibitor therapy (as available per 
country/region standard of care). Note: If KRAS results are not known, then a 
sample 
 
should be sent for testing locally. 
 may be used 
if 
 results are not feasible, with prior Sponsor approval.
(a) Must have been offered mutation-directed therapy, if indicated, that has 
proven survival benefit. This must be documented in the medical record. 
(3) Must have radiologically or clinically documented progressive or recurrent 
disease occurring either during treatment with or within 3 months of 
discontinuing anti-PD-(L)1 therapy when administered as either monotherapy or 
as part of a combination. 
(a) No more than 1 intervening systemic anti-cancer regimen is allowed but not 
required between prior anti-PD-(L)1 containing regimen and enrollment. 
(b) Prior anti-CTLA-4 therapy is not allowed.
(4)
 available from screening 
 will be sent for analysis for 
 
. If adequate 
 is unavailable, then 
prior outside genomic or other testing result from 
 from within 
3 months and no intervening therapy prior to enrollment on this study may be 
used for this purpose only.
(5) The Sponsor may elect to prioritize enrollment of participants with BOR of SD, 
PR, or CR > than 6 months’ duration in response to prior anti-PD-1/anti-PD-L1 
treatment.
f)
The Randomized cohort of BMS-986288 in Combination with Nivolumab versus 
Regorafenib (Part 2C)
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i)
Histologically or cytologically confirmed previously treated patients with mCRC with 
adenocarcinoma histology, pMMR/MSS and in Stage IV per American Joint 
Committee on Cancer (Edition 7.0) at study entry.
(1) Microsatellite status should be performed per local standard of practice, IHC and/or 
PCR. If the MSI molecular test and MMR IHC test results are both available, then 
both MSS and MMR proficiency will be required for study entry. Patients with 
MSI-high or MSI-low or MMR deficiency will not be eligible.
(2) KRAS and NRAS (extended RAS) and 
 status should be verified 
based on available local testing results as part of medical history. Regardless of 
whether or not RAS mutation status is known, all participants will be tested during 
screening for extended RAS (NRAS and KRAS) and BRAF mutation status. 
Results from this testing at screening is not required prior to receiving treatment on 
study (except 
). Note: If results are not known, then a sample 
 
 should be 
sent for testing locally. 
 may be used if 
 
results are not feasible, with prior Sponsor approval. The proportion of participants 
with 
 will be monitored on an ongoing basis. The sponsor may limit 
the number of 
 participants after discussion with the investigators. 
Patients with 
 are not eligible for the study.
(3) Participants with 3L/4L mCRC must have progressed or been intolerant to 2 prior 
lines of chemotherapy in the metastatic disease setting, which must include at least 
oxaliplatin- and irinotecan-containing regimens. 
(a) Participants who received FOLFOXIRI (or equivalent) in the 1L setting may be 
considered for enrollment in the second line setting. 
(b) Prior therapies containing anti-VEGF agents and/or anti-EGFR agents are 
permitted.
(c) Disease recurrence within 6 months after the last dose of the 
adjuvant/neoadjuvant therapy is permitted and will be considered as 1 line of 
prior therapy for study entry. Disease recurrence beyond 6 months after the last 
dose of the adjuvant/neoadjuvant therapy is also permitted but will NOT be 
considered as 1 line of prior therapy for study entry.
(d) Disease progression must have occurred during or within 3 months following 
the last dose of approved standard therapies
(4) Participants must have measurable disease per RECIST 1.1 (Appendix 5). 
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.
(5) Participants with or without liver metastasis. Participants post local liver metastasis 
therapy (surgery, selective internal radiation therapy, etc) will be categorized as 
participants with liver metastasis. Side of primary tumor needs to be documented if 
known. Participants with or without active carcinoembryonic antigen tumor marker
are eligible. If feasible, the Sponsor aims to prioritize participants without liver
metastasis, including 
 and at study entry, in each arm to achieve 50% 
treated participants without liver metastasis through enrollment.
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(6) Be able to swallow and absorb oral tablets.
(7) Anticipated life expectancy greater than 3 months.
3) Physical and Laboratory Test Findings
a) Adequate hematologic function for participants as defined by the following:
i)
Neutrophils 1,500/L.
ii) Platelets 100 103/L (transfusion to achieve this level is not permitted within 
2 weeks of first study treatment administration).
iii) Hemoglobin 9 g/dL (transfusion to achieve this level is not permitted within 2 weeks 
of first study treatment administration).
iv) WBC 2000/L.
b) Adequate hepatic function for participants as defined by the following:
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).
c) Normal thyroid function or stable on hormone supplementation per Investigator 
assessment.
d) 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 1.00
72 serum creatinine in mg/dL
e) 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 hCG) within 24 hours 
prior to the start of study treatment.
c) Women must not be breastfeeding.
d) WOCBP who are continuously not heterosexually active are also exempt from 
contraceptive requirements but should still undergo pregnancy testing as described in this 
section.
e) WOCBP must agree to follow instructions for method(s) of contraception (Appendix 4) for 
the duration of BMS-986288 combination therapy treatment, plus 5 months post treatment 
completion. WOCBP receiving monotherapy treatment with BMS-986288 must agree to 
follow instructions for method(s) of contraception for the duration of monotherapy 
treatment with BMS-986288, plus 3 months post treatment completion. Local laws and 
regulations may require use of alternative and/or additional contraception methods. 
See Appendix 4. 
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f)
Not Applicable as of Amendment 02: Males who are sexually active with WOCBP must 
agree to follow instructions for method(s) of contraception and fetal protection (Appendix 
4) for the duration of BMS-986288 combination treatment, plus 5 half-lives of nivolumab, 
plus 90 days (duration of sperm turnover), for a total of 215 days post treatment completion. 
Males who are sexually active with WOCBP must agree to follow instructions for methods 
of contraception during monotherapy treatment with BMS-986288, plus 5 half-lives of 
BMS-986288, plus 90 days (duration of sperm turnover), for a total of 165 days post 
treatment completion. In addition, male participants must be willing to refrain from sperm 
donation during this time. See Appendix 4. 
g) WOCBP who are continuously not heterosexually active are exempt from contraceptive 
requirements, and still must undergo pregnancy testing as described in this section.
h) WOCBP must agree to follow instructions for method(s) of contraception (Appendix 4) for 
the duration of treatment, plus 2 months after last dose of regorafenib (or local guidelines).
Local laws and regulations may require use of alternative and/or additional contraception 
methods. See Appendix 4.
Investigators shall counsel 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, tumors with CNS metastases as the only site 
of disease, 
 brain metastases, or leptomeningeal metastasis will be excluded.
However, participants with 
 metastases are eligible. 
 
 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) For Part 2C:
i)
Participants with 
 mutant 
.
(1) Verify 
 status based on available local testing results as part of 
medical history prior to study treatment. 
 
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) Noncytotoxic 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 is shorter than 4 weeks, agreement with the Sponsor/Medical Monitor 
(or designee) is mandatory.
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c) Prior immunotherapy treatments, unless at least 4 weeks or 5 half-lives (whichever is 
shorter) have elapsed from the last dose of immune therapy and initiation of study therapy. 
See Section 6.1 for additional requirements for prior immunotherapy treatments.
d) Any botanical preparation (eg, herbal supplements or traditional Chinese medicines) 
intended to treat the disease under study within 4 weeks prior to treatment. If less than 
4 weeks have elapsed from the last botanical supplement and the initiation of study 
treatment, the participant can be treated at the Investigator’s discretion and in agreement 
with the Sponsor/Medical Monitor (or designee).
i)
Use of marijuana and its derivatives for treatment of symptoms related to cancer or 
cancer treatment are permitted if obtained by medical prescription or if its use 
(even without a medical prescription) has been legalized locally.
e) Participants who have received live/attenuated vaccine within 30 days of first treatment.
i)
The use of inactivated seasonal influenza vaccines (eg, Fluzone) will be permitted 
on study without restriction.
f)
Previous SARS-CoV-2 vaccine within 7 days of Cycle 1 Day 1 (C1D1). For vaccines 
requiring more than 1 dose, the full series (eg, both doses of a 2-dose series) should be 
completed prior to enrollment when feasible and when a delay in enrollment would not put 
the study participant at risk.
g) Treatment with complementary medications (eg, herbal supplements or traditional Chinese 
medicines) to treat the disease under study within 2 weeks prior to first study treatment. 
Such medications are permitted if they are used as supportive care. Refer to Section 7.7.1 
for prohibited therapies.
h) Concomitant participation in treatment period of any clinical vaccine studies.
i)
Prior radiotherapy must be completed at least 2 weeks prior to treatment allocation. 
Participants must have recovered from all radiation-related toxicities.
j)
For Part 2C: 
i)
Prior treatment with an 
 antibody.
3) Medical History and Concurrent Disease
a) Prior malignancy active within the previous 3 years except for locally curable cancers that 
have been apparently cured, 
 
.
i)
In Part 2, the BMS-986288 Cohort Initial Expansion Phase, participants with 
concurrent malignancies that do not require treatment and are clinically stable and 
anticipated to be followed in an active surveillance manner for the next 12 months are 
eligible. Treatment should not be required at timing of consent and not be expected to 
be needed not only for the concurrent malignancy, but also for complications caused 
by it. The Investigator should inform the participant that the study treatment is not 
intended and not expected to be considered as treatment for the concurrent malignancy.
b) Participants with other active malignancy requiring concurrent intervention.
c) Prior organ allograft.
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d) Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless 
the toxicity is resolved, returned to baseline or Grade 1, or deemed irreversible.
i)
Any active neuropathy > Grade 2 (National Cancer Institute [NCI] Common 
Terminology Criteria for Adverse Events [CTCAE] v5.0).
e) Participants with the following:
i)
Active, known, or suspected autoimmune disease, including history of uveitis or 
autoimmune ocular 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.
(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 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 antibody or drug specifically targeting 
 
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 corticosteroids > 10 mg daily prednisone 
equivalent within 14 days or other immunosuppressive medications within 30 days of 
study treatment administration. Inhaled or topical steroids and adrenal replacement 
steroid doses of ≥10 mg daily prednisone equivalent are permitted in the absence of 
active autoimmune disease.
(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 torsades de pointes).
(4) Not Applicable as of Amendment 03. See 3.e.iv.9 below: 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).
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(5) History of myocarditis, regardless of etiology.
(6) Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
(7) QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation 
> 480 msec, except for right bundle branch block.
(8) History of other clinically significant heart disease (eg, cardiomyopathy, congestive 
heart failure with New York Heart Association functional classification II, III, or 
IV [Appendix 10], pericarditis, or significant pericardial effusion).
v) Not Applicable as of Amendment 02. See 3.e.xiii and xiv below: History of chronic 
hepatitis as evidenced by the following:
(1) Positive test for hepatitis B surface antigen (HBsAg).
(2) Positive test for qualitative hepatitis C viral load by polymerase chain reaction 
(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.
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)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.
viii)
Receipt of packed red blood cells or platelet transfusion within 2 weeks of the first 
dose of study treatment.
ix) 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.
x) Not Applicable as of Amendment 02. See 3.e.xv below: Positive test for human 
immunodeficiency virus (HIV).
Note: Testing for HIV must be performed at sites where mandated by local 
requirements.
xi) Interstitial lung disease that is symptomatic or may interfere with the detection or 
management of suspected treatment-related pulmonary toxicity.
xii)WOCBP who are pregnant or breastfeeding.
xiii)
Any positive test result for hepatitis B virus (HBV) indicating presence of virus, 
eg, HBsAg, Australia antigen positive.
xiv)
Any positive test result for hepatitis C virus (HCV) indicating presence of active 
viral replication (detectable HCV-RNA). Note: Participants with positive HCV 
antibody and an undetectable HCV RNA are eligible to enroll.
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xv) Known human immunodeficiency virus (HIV) positive with an AIDS-defining 
opportunistic infection within the last year, or a current CD4 count < 350 cells/uL.
Participants with HIV are eligible if:
a) they have received antiretroviral therapy (ART) for at least 4 weeks prior to treatment 
assignment, as clinically indicated, while enrolled on study
b) they continue on ART as clinically indicated while enrolled on study
c) CD4 counts and viral load are monitored per standard of care by a local health care 
provider.
NOTE: Testing for HIV must be performed at sites where mandated locally. HIV-
positive participants must be excluded where mandated locally.
xvi)
Participants with serious or uncontrolled medical disorders.
xvii)
Participant has any condition, including active or uncontrolled infection, or the 
presence of laboratory abnormalities, which places the participant at unacceptable risk 
if he/she were to participate in the study.
xviii)
Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic 
infections or 20 days for severe/critical illness prior to screening or predose C1D1.
(1) 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.
xix)
For MSS CRC Part 2C
(1) Any evidence of active bleeding, or hemorrhage or bleeding event ≥ NCI-CTCAE 
version 5.0 Grade 3 within 4 weeks prior to the start of study medication.
(2) Arterial or venous thrombotic or embolic events such as cerebrovascular accident 
(including transient ischemic attacks), deep vein thrombosis, or pulmonary 
embolism within 6 months before the start of study medication (except for 
adequately treated catheter-related venous thrombosis occurring more than 1 month 
before the start of study medication). 
(3) Prior or current gastrointestinal perforation or fistula.
(4) Non-healing wound, non-healing ulcer, or non-healing bone fracture.
4) Allergies and Adverse Drug Reactions
a) History of allergy to study treatment(s) or any of its components.
b) History of severe hypersensitivity reaction to any mAb.
5) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific 
circumstances, and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply, and BMS approval is required.)
b) Participants who are compulsorily detained for treatment of either a psychiatric or a 
physical (eg, infectious disease) illness.
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Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
Not applicable. No restrictions are required.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, 
to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, as 
applicable, and to respond to queries from regulatory authorities. Minimal information includes 
date of consent, demography, screen failure details, eligibility criteria, and any serious AEs.
6.4.1
Retesting During Screening or Lead-In Period
This study permits the re-enrollment of a participant who has discontinued the study as a 
pretreatment failure (ie, participant has not been treated). 
Retesting of laboratory parameters and/or other assessments during the extended screening period 
will be allowed. The most current result prior to treatment allocation is the value by which study 
inclusion will be assessed, as it represents the participant’s most current clinical state.
Laboratory parameters and/or assessments that are included in Table 2-1 may be repeated in an 
effort to find all possible well qualified participants. Consultation with the Medical Monitor 
(or designee) may be needed to identify whether repeat testing of any particular parameter is 
clinically relevant.

Testing for asymptomatic SARS-CoV-2 infection by reverse transcription polymerase chain 
reaction (RT-PCR) or viral antigen is not required. However, some participants may develop 
suspected or confirmed symptomatic SARS-CoV-2 infection or be discovered to have 
asymptomatic SARS-CoV-2 infection during the screening period. In such cases, participants 
may be considered eligible for the study after meeting all inclusion/exclusion criteria related 
to active infection, and after meeting the following criteria: 

At least 10 days (20 days for severe/critical illness) have passed since symptoms first 
appeared or positive RT-PCR 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 medical monitor approval. Any 
screening tests already performed which could potentially be affected by the SARS-CoV-2 
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infection or its complications on an individual basis and agreed upon with the Medical Monitor
(eg, safety labs, oxygen saturation, chest CT scan) should be repeated.
7
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 treatment 
allocation.
An investigational product (IP), also known as investigational medicinal product (IMP) in some 
regions, is defined as a pharmaceutical form of an active substance or placebo being tested or used 
as a reference in a clinical study, including products already with a marketing authorization but 
used or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered non-IPs.
In this protocol, IPs are the following:

BMS-986288

Nivolumab

Regorafenib
All 4 drugs used in this open-label study qualify as IPs, as per previous text, and their description 
and storage information are shown in Table 7-1.
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Table 7-1:
Investigational Product Description for CA043001
Product Description / 
Class and Dosage Form
Potency
IP/Non-
IP
Blinded or 
Open Label
Packaging / 
Appearance
Storage Conditions
(per label)
Nivolumab
(BMS-936558)
Solution for Injection
 mg
(10 
mg/mL)
IP
Open label
Vial
Refer to the label on 
container and/or 
Pharmacy Manual
BMS-986288
Powder for Solution for 
Injection
mg
per vial
IP
Open label
Vial
Refer to the label on 
container and/or 
Pharmacy Manual
 mg
(1 
mg/mL)
IP
Open label
Vial
Refer to the label on 
container and/or 
Pharmacy Manual
Regorafenib Tabletb
40 mgc
IP
Open Label
Bottle
Refer to the label on 
container and/or 
Pharmacy Manual
Abbreviations: IP = investigational product; 
b These products may be obtained by investigational sites as local commercial product in certain countries if allowed 
by local regulations. In these cases, products may be a different pack size/potency than listed in the table. These 
products should be prepared/stored/administered in accordance with the package insert or SmPC.
c May include other commercially available strengths.
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7.1
Schedule of Dose for Each Investigational Product
The dosing schedule for each IP is detailed below in Table 7.1-1 for all study parts. Planned dose 
levels may be modified (eg, change in administration schedule) or intermediate dose levels may 
be added, based upon the BLRM analysis and clinical evaluation of available safety, PK, and 
pharmacodynamic data.
All participants will be monitored continuously for AEs while on study treatment. Treatment 
modifications (eg, dose delay or discontinuation) will be based on specific laboratory and AE 
criteria, as described in Section 7.4. 
Table 7.1-1:
Selection and Timing of Dosea
Study Treatment
Planned Unit Dose Strength(s)/
Dosage Level(s)
Planned Dosage 
Formulation
Frequency of 
Administration
Route of 
Administration
BMS-986288
, and 
mg
IV
Nivolumab
mg
IV
BMS-986288/
Nivolumab
mga/
 mg
BMS-986288 + 
See noteb
Nivolumab + 
See noteb
Regorafenib Tablet
 mgc
Oral
Abbreviations: IV = intravenous; 
 
Note: Additional dose levels and/or administration schedules may be explored. BMS-986288 doses from 
 mg to 
mg should be administered 
, BMS-986288 doses of 
mg to 
mg should be 
administered 
, and BMS-986288 doses of 
 mg to 
 mg should be administered
 
. The 
 of 
mg of BMS-986288 in combination with 
 mg of nivolumab should
be administered 
. For participants weighing < 40 kg, 
 
will be limited to 80 mL.
a Potential additional dose levels of BMS-986288 (
 mg and 
 mg) could be 
 with 
 mg of 
nivolumab
b Dose(s) for BMS-986288 alone (Arm A) or in combination with nivolumab (Arm B) for 
 will be selected 
based on preliminary data from Part 1A and Part 1B. 
 
 
 
c See dose modification of regorafenib (Section 7.4.6).
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For Part 2C Arm D dosing, please refer to local product label and institutional guidelines for further 
details.
The recommended dose of regorafenib is 
 mg (four 40-mg tablets) taken orally once daily for 
the first 21 days of each 28-day cycle. Continue treatment until disease progression, unacceptable 
toxicity, withdrawal of consent, or the study ends, whichever occurs first. The participant should 
take regorafenib at the same time each day. Swallow tablet as a whole with water after a low-fat 
meal that contains less than 600 calories and less than 30% fat. The participant should not take 
2 doses of regorafenib on the same day to make up for a missed dose from the previous day. Any 
missed doses reported by the participant should be recorded in the participant’s source documents 
and in the participant’s diary.
Initiation of the next treatment cycle:
1. The next cycle will be initiated 
with regorafenib dosing.
2. If regorafenib dosing is delayed, the next cycle will start if at least 4 weeks have passed from 
the first dose in the current cycle to dosing re-initiation.
3. The next treatment cycle may be initiated within a ± 3-day window of scheduled dose due to 
scheduling conflict.
See Table 2-2 for treatment related Schedule of Activities. Refer to the Pharmacy Manual for 
additional dose preparation details for BMS-986288, nivolumab, and 
 (if applicable).
7.2
Method of Treatment Assignment
During the screening visit for all study parts, the investigative site will call into the enrollment 
option of the IRT designated by BMS for assignment of a 5-digit participant number that will be 
unique across all sites. Enrolled participants, including those not dosed, will be assigned sequential 
participant numbers starting with 
. The participant 
identification 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 
. Specific instructions for using the IRT system will be provided to the 
investigational sites in a separate document.
Participants will not be replaced if they are discontinued from the study secondary to an AE unless 
the AE can be determined to be unrelated to treatment.
During dose escalation, all participants will be assigned to Part 1A until the decision is made to 
escalate to the third dose cohort. Subsequently, treatment in Part 1B will be initiated, and dose 
escalation in the 2 parts will occur in parallel. 
 will be initiated once an appropriate 
BMS-986288 monotherapy or combination dose is identified, will be incorporated through a 
protocol amendment, and may run in parallel with Part 1A and Part 1B. Treatment assignments 
for participants eligible for Part 1A, Part 1B, or 
will alternate between the 3 parts
(if open), with consecutively treated participants assigned to different parts through IRT whenever 
possible according to the corresponding inclusion criteria. If there are no openings available in the 
part to which the participant would be assigned by this algorithm, then the participant will be 
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assigned to the next open part/cohort. Prioritization of participants eligible for both Part 1A and 
Part 1B may be modified to ensure the dose of BMS-986288 in the Safety Evaluation of
BMS-986288 in Combination with Nivolumab (Part 1B) does not exceed the highest dose
evaluated in the BMS-986288 Monotherapy Dose Escalation (Part 1A).
In Part 2A and Part 2B Combination Expansion, multiple doses may be open concurrently. In that 
case, treatment assignments will alternate between the dose levels, with consecutively treated 
participants assigned to different parts through IRT whenever possible. If there are no openings 
available in the dose level to which the participant would be assigned by this algorithm, then the 
subject will be assigned to the next open dose. Study treatment will be dispensed at the study visits 
as listed in the Schedule of Activities (Section 2) or Appendix 8 (if applicable).
Part 2C
Part 2C is a randomized, open-label study with 2 treatment arms, nivolumab in combination with
BMS-986288 (Arm C) versus regorafenib (Arm D). Once enrolled in IRT, participants who have 
met all eligibility criteria for Part 2C will be randomized in a 2:1 ratio to nivolumab in combination 
with BMS-986288 (Arm C) or regorafenib (Arm D) and stratified by liver metastases status. 
Participants in Part 2C Arm D receiving regorafenib will have the option to transition to 
BMS-986288 in combination with nivolumab (Part 2C Arm Z) after BICR-assessed progression.
An additional dose of BMS-986288 
 mg or 
 mg) in combination with nivolumab may be 
opened in Part 2C (as Arm E). This additional dose level will not be randomized with Arm C and 
Arm D.
7.3
Blinding
This is an open-label study (open to sponsor and site/participant; not treated as sponsor-blind); 
however, the specific treatment to be taken by a participant will be assigned using an IRT. The site 
will contact the IRT prior to the start of study treatment administration for each participant. The 
site will record the treatment assignment on the applicable case report form, if required. Designated 
staff of BMS can have access to treatment assignments prior to database lock to facilitate data 
analysis, as well as the bioanalytical analysis of PK and immunogenicity samples. 
See Section 10.3.8 for details of interim analysis. A bioanalytical scientist in the Bioanalytical 
Sciences department of BMS Research & Development (or a designee in the external central 
bioanalytical laboratory) and/or Clinical Pharmacology groups may obtain the treatment 
assignments in order to minimize unnecessary bioanalytical analysis of samples. This access to the 
treatment codes will not impact the data integrity of the study.
7.4
Dosage Modification
Intra-participant dose escalation/reduction of BMS-986288 or nivolumab is not permitted in this 
study in order to allow better evaluation of the safety and efficacy at individual dose levels and 
schedules. Regorafenib starting dose modification can be considered in consultation with BMS 
Medical Monitor/designee. For AEs that are deemed to be related to regorafenib by the 
investigator, refer to local product label and institution guidelines for further detail in addition to 
the recommendation provided in Section 7.4.6.
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7.4.1
Dose-limiting Toxicities
For the purpose of guiding dose escalation, all AEs will be assessed and DLTs will be defined 
based on the incidence, intensity, and duration of the AEs for which no clear alternative cause is 
identified. The DLT period will be 5 weeks (35 days) in both BMS-986288 monotherapy and 
combination dose escalation (Part 1A and Part 1B). Any toxicities that occur beyond the DLT 
period will be accounted for in making final dose level decisions. Participants who have
discontinued due to a DLT or who have received 2 doses of BMS-986288 monotherapy or in 
combination with nivolumab and have completed the 5-week DLT period will be considered as 
DLT-evaluable participants. Participants who withdraw from the study during the DLT evaluation 
period or have received less than 2 doses for reasons other than a DLT in both monotherapy and 
combination therapy will not be considered as DLT-evaluable participants and may be replaced 
with a new participant at the same dose level. Participants who are dose delayed during the DLT 
evaluation period for reasons other than a DLT in both monotherapy and combination therapy will 
be considered as DLT-evaluable participants if they received at least 2 doses of therapy within 
8 weeks.
For the purpose of participant management, any drug related AE that meets DLT criteria, 
regardless of the cycle or cohort in which it occurs, will lead to discontinuation of study treatment. 
AEs will be graded according to the NCI CTCAE v5.0.
Continuous evaluation of toxicity events in the 
 Evaluation of BMS-986288 
 and BMS-986288 Cohort Expansion Combination Therapy (Part 2) will be performed. 
If at any time, the aggregate rate of treatment-related toxicities meeting DLT criteria in a 
BMS-986288 containing cohort exceeds 33% across patients treated in a cohort, the findings will 
be discussed with the Investigators and further enrollment may be interrupted. If a cohort is 
discontinued due to toxicity, a new cohort at a previously tested alternative dose level which was 
found to be safe in Part 1A or Part 1B may be considered based on the aggregate safety experience 
and in consultation and agreement between Investigators and Sponsor. An alternative dose or 
administration schedule may also be initiated in a specific 
 or Part 2 cohort upon 
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assessment of available safety, PK, pharmacodynamics, and efficacy data from that cohort. 
A protocol amendment reflecting any such new cohort will be submitted prior to enrollment to the 
cohort.
7.4.2
Management Algorithms for Immuno-oncology Agents
I-O agents are associated with imAEs that can differ in severity and duration from AEs caused by 
other therapeutic classes. BMS-986288 and nivolumab are considered I-O agents in this protocol. 
Early recognition and management of imAEs associated with I-O agents may mitigate severe 
toxicity. Management algorithms have been developed from extensive experience with 
ipilimumab and nivolumab to assist Investigators in assessing and managing the following groups 
of imAEs:

GI

Renal

Pulmonary

Hepatic

Endocrinopathies

Skin

Neurological (including encephalitis)

Cardiac
The clinical nature of AEs noted with BMS-986288 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 imAEs in this protocol are in Appendix 6.
7.4.3
Dose Delays Due to Toxicity
If an event is attributed to BMS-986288 or nivolumab, alone or in combination, then all study 
drugs must be delayed until treatment can resume (see Section 7.4.3.1). Delay administration of 
both nivolumab and BMS-986288 if any of the delay criteria in Table 7.4.3.1-1 are met. Tumor 
assessments for all participants should continue per protocol even if dosing is delayed. 
Participants who experience the following must have all study treatment(s) withheld:

Potential DLTs, until DLT relatedness is defined.

Drug-related select AEs and laboratory abnormalities in Table 7.4.3.1-1.

AE, laboratory abnormality, or concurrent illness that, in the judgment of the Investigator, 
warrants delaying study treatment administration.

Confirmed SARS-CoV-2 infection.
Participants who require a delay of study drug should be re-evaluated weekly or more frequently 
if clinically indicated. For participants receiving a combination (eg, Part 1B, 
, Part 2B), 
if dosing is delayed, then study drugs must be delayed together. If dosing with both study drugs is 
to be resumed after a delay, then both must be resumed on the same day. Criteria for participants 
who are required to permanently discontinue study treatments are listed in Section 8.2. In addition, 
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all AEs should be evaluated and managed per the toxicity management algorithms in Appendix 6. 
Participants not meeting guidelines for permanent discontinuation will be permitted to resume 
therapy based on the criteria specified below in Section 7.4.3.1. Participants eligible to resume 
study therapy will resume study therapy at the nominal treatment visit after their last received 
study medication dose.
7.4.3.1
Criteria to Resume Treatment
Subsequent dosing with study therapy may resume once drug-related non-DLT AEs resolve to 
Grade 1 or baseline. When criteria to resume treatment are met, resume both nivolumab and 
BMS-986288 on the same day.

Participants experiencing AEs not meeting criteria for permanent discontinuation may resume 
treatment with study intervention(s) if they have completed AE management (eg, 
corticosteroid taper) or are on ≤ 10 mg prednisone or equivalent and meet the requirements per 
Table 7.4.3.1-1.

Prior to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks (unless 
the exceptions in Table 7.4.3.1-1 are met), 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 
or more frequently if 
clinically indicated during such dosing delays.

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.
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Table 7.4.3.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of 
Nivolumab and/or BMS-986288
Drug-Related Adverse 
Event (AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and 
Resume Criteria
Gastrointestinal
Colitis or Diarrhea
Grade 2 
Delay dose
Dosing may resume when AE 
resolves to baseline. Grade 2 colitis 
> 5 days is a DLT.
Grade 3 
Permanently 
discontinue
Grade 4 
Permanently 
discontinue
Hematologic
Anemia
Grade 4
Delay or 
permanently 
discontinue
For first occurrence: Delay dose 
until recovery. If event recurs, 
permanently discontinue.
Dose delay during Cycle 1 is 
considered a DLT.
Hemolysis
Grade ≥ 3
Permanently 
discontinue
Neutropenia
Grade 3
Delay dose
Delay dose until recovery; resume 
treatment when AE resolves to 
Grade ≤ 1 or baseline. 
Grade 3 with duration ≥ 7 days 
during Cycle 1 is considered a DLT; 
resume treatment once AE resolves, 
as described above.
Grade 4 or febrile 
neutropenia
Delay or 
permanently 
discontinue
If duration < 7 days, delay until 
recovery.
If duration ≥7 days or for 
neutropenic fever of any duration, 
permanently discontinue.
Dose delay during Cycle 1 is 
considered a DLT. 
Thrombocytopenia
Grade 3 
thrombocytopenia > 
7 days or associated 
with Grade ≥ 2 
hemorrhage
Delay or 
permanently 
discontinue
If duration ≤ 7 days, delay until 
recovery. If duration > 7 days or 
associated with clinically significant 
bleeding, permanently discontinue. 
Grade 4
Permanently 
discontinue
Renal
Serum Creatinine Increased
Grade 2 or 3 
Delay dose
Dosing may resume when AE 
resolves to Grade ≤1 or baseline 
value.
Grade 4 
Permanently 
discontinue
Pulmonary
Pneumonitis
Grade 2 
Delay dose
Dosing may resume after 
pneumonitis has resolved to ≤ Grade 
1.
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Table 7.4.3.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of 
Nivolumab and/or BMS-986288
Drug-Related Adverse 
Event (AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and 
Resume Criteria
Grade 2 pneumonitis that does not 
respond to dose delay and systemic 
steroids within 14 days is a DLT.
Grade 3 or 4 
Permanently 
discontinue
Hepatic
Aspartate aminotransferase 
(AST), alanine 
aminotransferase (ALT), or 
total bilirubin (T.bili) 
increased
AST or ALT > 3x 
and ≤5x upper limit 
of normal (ULN) or 
T.Bili > 1.5x and ≤3x 
ULN, regardless of 
baseline value
Delay dose
Dosing may resume when 
laboratory values return to baseline.
AST or ALT > 5 x 
ULN or T. bili > 3 x 
ULN, regardless of 
baseline value
Delay dose or 
Permanently 
discontinue 
In most cases of AST or ALT > 5 x 
ULN, study treatment will be 
permanently discontinued. If the 
investigator determines a possible 
favorable benefit/risk ratio that 
warrants continuation of study 
treatment, a discussion between the 
investigator and the Medical 
Monitor/ designee must occur and 
approval from Medical Monitor 
prior to resuming therapy.
Concurrent AST or 
ALT > 3 x ULN and 
T.bili > 2 x ULN, 
regardless of baseline 
value
Permanently 
discontinue 
Endocrinopathy
Adrenal Insufficiency
Grade 2 adrenal 
insufficiency
Delay dose
Dosing may resume after adequately 
controlled with hormone 
replacement.
Grade 3 or 4 adrenal 
insufficiency or 
adrenal crisis
Delay dose or 
permanently 
discontinue
Mandatory discussion with and 
approval from the Medical Monitor 
needed prior to resuming therapy. If 
adrenal insufficiency resolves or is 
adequately controlled with 
physiologic hormone replacement, 
participant may not require 
discontinuation of study drug.
Hyperglycemia
Hyperglycemia 
requiring initiation or 
change in daily 
management (Grade 
2 or 3)
Delay dose
Dosing may resume if 
hyperglycemia resolves to Grade ≤1 
or baseline value, or is adequately 
controlled with glucose-controlling 
agents.
Grade 4
Delay dose or 
permanently 
discontinue
Mandatory discussion with and 
approval from the Medical Monitor 
needed prior to resuming therapy. If 
hyperglycemia resolves, or is 
adequately controlled with glucose-
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Table 7.4.3.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of 
Nivolumab and/or BMS-986288
Drug-Related Adverse 
Event (AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and 
Resume Criteria
controlling agents, participant may 
not require discontinuation of study 
drug.
Hypophysitis/Hypopituitarism 
Symptomatic Grade 
1-3 that is also 
associated with 
corresponding 
abnormal lab and/or 
pituitary scan
Delay dose 
Dosing may resume if 
endocrinopathy resolves to be 
asymptomatic, or is adequately 
controlled with only physiologic 
hormone replacement.
Grade 4
Delay dose or 
permanently 
discontinue
Mandatory discussion with and 
approval from the Medical Monitor 
needed prior to resuming therapy. If 
endocrinopathy resolves or is 
adequately controlled with 
physiologic hormone replacement, 
participant may not require 
discontinuation of study drug.
Hyperthyroidism or
Hypothyroidism
Grade 2 or 3
Delay dose
Dosing may resume if 
endocrinopathy resolves to be 
asymptomatic, or is adequately 
controlled with only physiologic 
hormone replacement or other 
medical management.
Grade 4
Delay dose or 
permanently 
discontinue
Mandatory discussion with and 
approval from the Medical Monitor 
needed prior to resuming therapy. If 
endocrinopathy resolves or is 
adequately controlled with 
physiologic hormone replacement or 
other medical management, 
participant may not require 
discontinuation of study drug.
Skin
Rash
Grade 2 rash 
covering > 30% body 
surface area or Grade 
3 rash 
Delay dose 
Dosing may resume when rash 
reduces to ≤10% body surface area.
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Table 7.4.3.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of 
Nivolumab and/or BMS-986288
Drug-Related Adverse 
Event (AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and 
Resume Criteria
Suspected Stevens-
Johnson syndrome 
(SJS), toxic 
epidermal necrolysis 
(TEN), or drug 
reaction with 
eosinophilia and 
systemic symptoms 
(DRESS)
Discontinue or delay 
dose
Dosing may resume if SJS, TEN, or 
DRESS is ruled out and rash 
reduces to ≤10% body surface area.
Grade 4 rash or 
confirmed SJS,TEN, 
or DRESS
Permanently 
discontinue
Neurological
Guillain-Barre Syndrome 
(GBS)
Any Grade
Permanently 
discontinue
Myasthenia Gravis (MG)
Any Grade
Permanently 
discontinue
Encephalitis
Any Grade 
encephalitis
Delay dose 
After workup for differential 
diagnosis, (ie, infection, tumor-
related), if encephalitis is not drug 
related, then dosing may resume 
when AE resolves.
Any Grade drug-
related encephalitis 
Permanently 
discontinue
Myelitis
Any Grade myelitis
Delay dose
After workup for differential 
diagnosis, (ie, infection, tumor-
related), if myelitis is not drug 
related, then dosing may resume 
when AE resolves.
Any Grade drug-
related myelitis
Permanently 
discontinue
Neurological (other than GBS, 
MG, encephalitis, or myelitis)
Grade 2
Delay dose
Dosing may resume when AE 
resolves to baseline.
Grade 3 or 4
Permanently 
discontinue
Myocarditis
Myocarditis
Symptoms induced 
from mild to 
moderate activity or 
exertion
Delay dose
Dosing may resume after 
myocarditis has resolved.
Severe or life 
threatening, with 
symptoms at rest or 
with minimal activity 
or exertion, and/or 
where intervention 
indicated.
Permanently 
discontinue
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Table 7.4.3.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of 
Nivolumab and/or BMS-986288
Drug-Related Adverse 
Event (AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and 
Resume Criteria
Other Clinical AE
Pancreatitis: 
Amylase or Lipase increased
Grade 3 with 
symptoms
Delay dose
Note: Grade 3 increased amylase or 
lipase without signs or symptoms or 
radiographic evidence of 
pancreatitis does not require dose 
delay. 
Dosing may resume when patient 
becomes asymptomatic.
Grade 4
Permanently 
discontinue
Grade 4 increased amylase or lipase 
without signs or symptoms or 
radiographic evidence of 
pancreatitis does not require 
permanent discontinue.
Uveitis, episcleritis, iritis, eye 
pain, or blurred vision
Grade 2 
Delay dose
Dosing may resume with response 
to topical therapy (eye drops) and 
after resolution to Grade ≤ 1 or 
baseline. If patient requires oral 
steroids, then permanently 
discontinue study drug. 
Grade 3 or 4 
Permanently 
discontinue
Other Drug-related AE (not 
listed above)
Grade 2 non-skin 
AE, except fatigue
Delay dose
Dosing may resume when AE 
resolves to Grade ≤ 1 or baseline 
value.
Grade 3 AE - First 
occurrence lasting ≤ 
7 days
Delay dose
Dosing may resume when AE 
resolves to Grade ≤ 1 or baseline 
value.
Grade 3 AE- First 
occurrence lasting > 
7 days
Permanently 
discontinue
Recurrence of Grade 
3 AE of any duration
Permanently 
discontinue
Exception to permanent 
discontinuation: 
Grade 3 fatigue < 7 days in any 
cycle does not require permanent 
discontinuation.
Grade 3 tumor flare (defined as 
pain, irritation, or rash that localizes 
to sites of known or suspected 
tumor).
Grade 3 fever not associated with 
hemodynamic compromise (eg, 
hypotension, clinical, or laboratory 
evidence of impaired end-organ 
perfusion).
Grade 3 nausea, vomiting, or 
abdominal pain that returns to Grade 
1 or baseline within 48 hours, either 
spontaneously or with medical 
intervention.
Grade 4 or Life-
threatening adverse 
reaction
Permanently 
discontinue
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Table 7.4.3.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of 
Nivolumab and/or BMS-986288
Drug-Related Adverse 
Event (AE) per CTCAE v5
Severity 
Action Taken
Clarifications, Exceptions, and 
Resume Criteria
Other Lab abnormalities 
Other Drug-Related lab 
abnormality (not listed 
above)
Grade 3
Delay dose 
Exception: No delay required for 
Grade 3 lymphopenia.
Grade 4
Permanently 
discontinue
Exceptions: The following events 
do not require discontinuation of 
study drug: 
Grade 4 lymphopenia or 
leukopenia. Grade 4 lymphopenia 
or leukopenia that lasts > 7 day is 
a DLT.
Grade 3 or 4 isolated electrolyte 
imbalances/abnormalities that are 
not associated with clinical 
sequelae and are responding to 
supplementation/appropriate 
management within 72 hours of 
their onset.
Infusion Reactions (manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, 
hypertension, bronchospasm, or other allergic-like reactions.)
Hypersensitivity reaction or 
infusion reaction
Grade 3 or 4
Permanently 
discontinue
Refer to Section 7.4.5 on Treatment 
of Related Infusion Reactions 
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7.4.4
Exceptions to Permanent Discontinuation Criteria
Any drug-related AE occurring at any time that meets DLT criteria as outlined in Section 7.4.1
will require permanent discontinuation, with the exceptions detailed in Table 7.4.3.1-1 and the 
following:

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 (or designee) must be consulted. Tumor 
assessments should continue as per protocol even if dosing is delayed. Periodic study visits 
to assess safety and laboratory studies should also continue 
, 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 
(or designee). Prior to re-initiating treatment in a participant with a dosing delay lasting 
> 8 weeks, the BMS Medical Monitor (or designee) must be consulted.
Even if the criteria to resume treatment are met, the consideration to re-initiate study therapy under 
the following exception will be made on a case-by-case basis after considering the overall 
benefit/risk profile and in consultation between the Investigator and the Sponsor. Any AE with 
clinical risk will be assessed on a case-by-case basis with the Investigator and the BMS Medical 
Monitor (or designee) to determine the risks and benefits of continuing on therapy following 
resolution vs discontinuing therapy permanently.
7.4.5
Management of Drug-related Infusion Reactions
Because BMS-986288 and nivolumab contain only human Ig protein sequences, they are unlikely 
to be immunogenic and induce infusion or hypersensitivity reactions. However, based on the non-
clinical toxicology evaluation of BMS-986288, infusion reactions due to 
 activation and 
cytokine release may occur in both monotherapy and combination with nivolumab. 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. Report all 
Grade 3 or 4 infusion reactions within 24 hours as an SAE if it meets the criteria. 
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), recommendations are as follows:

Remain at bedside and monitor participant until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1,000 mg at least 30 minutes before 
study treatment administrations.
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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), recommendations are as follows:

Stop the study treatment infusion, begin an IV infusion of normal saline, and treat the 
participant 
with 
diphenhydramine 
50 
mg 
IV 
(or 
equivalent) 
and/or 
acetaminophen/paracetamol 325 to 1,000 mg; remain at bedside and monitor participant until 
resolution of symptoms. Corticosteroid and/or bronchodilator therapy may also be 
administered as appropriate. If the infusion is interrupted, then restart the infusion at 50% of 
the original infusion rate when symptoms resolve; if no further complications ensue after 
30 minutes, then the rate may be increased to 100% of the original infusion rate. Monitor 
participant closely. If symptoms recur, then no further BMS-986288 or nivolumab will be 
administered at that visit.

For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1,000 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.
Grade 3 or 4 infusion reactions require permanent discontinuation of both study treatments. 
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 after initial 
improvement; hospitalization indicated for other clinical sequelae [eg, renal impairment, 
pulmonary infiltrates]; Grade 4: life-threatening; pressor or ventilatory support indicated), 
recommendations are as follows:

Immediately discontinue 
 study treatment. Begin an IV infusion of normal saline 
and treat the participant as follows: recommend bronchodilators, epinephrine 0.2 to 1 mg of a 
1:1,000 solution for SC administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly 
for IV administration, and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV 
(or equivalent), as needed. Participant should be monitored until the Investigator is comfortable 
that the symptoms will not recur. 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).
7.4.6
Dose Modification for Regorafenib
If dose modifications are required, reduce the dose in 40 mg (one tablet) increments; the lowest 
recommended daily dose of regorafenib is 80 mg daily. The following dose modification is 
provided as a recommendation. Local product labels and/or institutional guidelines should be 
followed if they are more conservative than the recommendations below.
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Interrupt regorafenib for the following:

Grade 2 hand-foot skin reaction (HFSR) (palmar-plantar erythrodysesthesia syndrome) that is 
recurrent or does not improve within 7 days despite dose reduction; interrupt therapy for a 
minimum of 7 days for Grade 3 HFSR. If restarting treatment, decrease dose by 40 mg.

Symptomatic Grade 2 hypertension.

Any Grade 3 or 4 adverse reaction.

Worsening infection of any grade.
Reduce the dose of regorafenib to 
 mg:

For the first occurrence of Grade 2 HFSR of any duration.

After recovery of any Grade 3 or 4 adverse reaction except infection.

For Grade 3 AST/ALT elevation, only resume if the potential benefit outweighs the risk of 
hepatotoxicity.
Reduce the dose of regorafenib to 80 mg: 

For re-occurrence of Grade 2 HFSR at the 120-mg dose.

After recovery of any Grade 3 or 4 adverse reaction at the 120-mg dose (except hepatotoxicity 
or infection).
Discontinue regorafenib permanently for the following: 

Failure to tolerate 80-mg dose.

Any occurrence of AST or ALT more than 20 × ULN.

Any occurrence of AST or ALT more than 3 × ULN with concurrent bilirubin more than 
2 × ULN.

Re-occurrence of AST or ALT more than 5 × ULN despite dose reduction to 120 mg.

Gastrointestinal perforation or fistula.

Severe or life-threatening hemorrhage.

Reversible posterior leukoencephalopathy syndrome.

Wound dehiscence.

Any event that leads to delay in dosing for > 8 weeks from the previous dose requires 
discontinuation with the following exception: dosing delays > 8 weeks that occur for 
non-drug-related reasons may be allowed 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. Tumor assessments should continue as per protocol even if dosing 
is delayed.

Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
investigator, presents a substantial clinical risk to the participant with continued treatment.
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
For any Grade 4 adverse reaction, only resume if the potential benefit outweighs the risks.
7.5
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 package insert.
IP documentation (whether supplied by BMS or not) must be maintained that includes all processes 
required to ensure drug is accurately administered. This includes documentation of drug storage, 
administration and, as applicable, storage temperatures, reconstitution, and use of required 
processes (eg, required diluents, administration sets).
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.

Further guidance and information for final disposition of unused study treatment are provided 
in Appendix 2 and the Pharmacy Manual.
Please refer to the current version of the IBs2,18,
and/or Pharmacy Manual for complete 
preparation, storage, and handling information.
When study treatments nivolumab and BMS-986288 are to be administered on the same day, 
nivolumab is to be administered first. Nivolumab infusion must be promptly followed by a flush 
of diluent to clear the line of nivolumab before starting the BMS-986288 infusion. The second 
infusion will always be the BMS-986288 study treatment and will start after the infusion line has 
been flushed, filters changed, and the participant has been observed to ensure no infusion reaction 
has occurred.
7.5.1
Retained Samples for Bioavailability/Bioequivalence
Not applicable.
7.6
Treatment Compliance
Not applicable.
7.7
Concomitant Therapy
7.7.1
Prohibited and/or Restricted Treatments
The following medications are prohibited during the study (unless utilized to treat a drug-related 
AE):

Immunosuppressive agents.
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
Immunosuppressive doses of systemic corticosteroids (except as stated in Section 6.2).

Any concurrent approved or investigational anti-neoplastic therapy (eg, chemotherapy, 
immunotherapy, extensive, non-palliative radiation therapy). Palliative hormonal therapy will 
be permitted when indicated.

Any botanical preparation (eg, herbal supplements or traditional Chinese medicines) intended 
to treat the disease under study. Use of marijuana and its derivatives for treatment of symptoms 
related to cancer or cancer treatment are permitted if obtained by medical prescription or if its 
use (even without a medical prescription) has been legalized locally.

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. 

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.

Participants may receive authorized or approved SARS-CoV-2 vaccines while continuing on 
study treatment at the discretion of the Investigator. 
7.7.1.1
Imaging Restriction and Precautions
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history, renal status), the appropriate imaging modality and contrast 
regimen per imaging study. Imaging contraindications and contrast risks are to be considered in 
this assessment. Participants with renal insufficiency are to be assessed as to whether or not they 
should receive contrast, and if so, which contrast agent and dose is appropriate. Specific to MRI, 
participants with severe renal insufficiency (ie, estimated glomerular filtration rate [eGFR] 
< 30 mL/min/1.73 m2) are at increased risk of nephrogenic systemic fibrosis; therefore, MRI 
contrast is contraindicated. In addition, participants may be excluded from MRI if they have 
tattoos, metallic implants, pacemakers, etc. This will be outlined in the Image Acquisition Manual.
Gentle hydration before and after IV contrast should follow local standard of care. The ultimate 
decision to perform MRI in an individual participant in this study rests with the site radiologist, 
the Investigator, and standards set by the local Ethics Committee.
7.7.2
Permitted Therapy
Participants are permitted the use of the following treatments:

Topical, ocular, intra-articular, intra-nasal, and inhalational corticosteroids (with minimal 
systemic absorption).

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).

Supportive care: For participants receiving regorafenib, follow local product label, institutional 
guidelines, or relevant regional guidelines (eg, American Society of Clinical Oncology or 
European Society for Medical Oncology) to manage expected toxicities. Supportive care 
includes, but is not limited to, hematologic support and management of diarrhea, 
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nausea/vomiting, skin toxicities, as well as prophylactic or therapeutic administration of 
appropriate therapies.
7.7.3
Palliative Local Therapy
Palliative and supportive care for disease-related symptoms may be offered to all participants on 
the study. 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 5.1.4) prior to re-initiating study treatment. Participants 
receiving palliative radiation of target lesions will have the evaluation of ORR just prior to 
radiotherapy, but 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 2 weeks before (if elective) and 2 weeks after surgery, or until the 
participant recovers from the procedure, whichever is longer. Participants undergoing major 
surgery for any reason while on study should have study treatment(s) held for at least 4 weeks after 
surgery. Prior to resuming study treatment wound healing must be evaluated by the surgeon, 
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.
7.8
Treatment After the End of the Study
At the conclusion of the study, participants who continue to demonstrate clinical benefit will be 
eligible to receive BMS-supplied study treatment up to a maximum duration of 2 years. Study 
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treatment will be provided via an extension of the study, a rollover study requiring approval by 
responsible health authority and ethics committee or through another mechanism at the discretion 
of BMS.
BMS reserves the right to terminate access to BMS supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of BMS-986288 is 
terminated for other reasons, including but not limited to lack of efficacy and/or not meeting the 
study objectives; or 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 5) unless participants 
meet criteria for treatment beyond progression (Section 5.1.4).

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 7.4.1
will require permanent discontinuation. Exceptions to permanent discontinuation are listed in 
Section 7.4.4. 

Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information.

Any clinical AE, laboratory abnormality or intercurrent illness which, in the opinion of the 
Investigator, indicates that continued participation in the study is not in the best interest of the 
participant.

Termination of the study by BMS.

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances, and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply and 
BMS approval is required.)

Inability to comply with protocol.

Discretion of the Investigator.

Pregnancy.

Individual participants with confirmed CR will be given the option to discontinue study therapy 
on a case-by-case basis after specific consultation and agreement between the Investigator and
BMS Medical Monitor (or designee) in settings where benefit/risk justifies discontinuation of 
study therapy.
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
Any event that leads to delay in dosing lasting > 8 weeks from the previous dose requires 
discontinuation, with the following exceptions:

Dosing delays for prolonged steroid tapers to manage drug-related AEs are allowed. 

Dosing delays lasting > 8 weeks from the previous dose that occur for non-drug-related 
reasons may be allowed if approved by the BMS Medical Monitor (or designee). 

If a participant in any of the BMS-986288 in combination with nivolumab arms meets criteria 
for discontinuation, the participant should discontinue both nivolumab and BMS-986288, as it 
may not be possible to determine whether the event is related to one or both study treatments.
Refer to the Schedule of Activities (Section 2) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that can be completed.
In the case of pregnancy, the Investigator must immediately, within 24 hours of awareness of the 
pregnancy, notify the BMS Medical Monitor/designee of this event. In most cases, the study 
treatment will be permanently discontinued in an appropriate manner (eg, dose tapering if 
necessary for participant safety). Refer to Section 9.2.5 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.
Regorafenib Dose Discontinuation
Discontinue regorafenib permanently for any of the following (local product label and institutional 
guidelines should be followed if they are more conservative):

Failure to tolerate 80-mg dose

Any occurrence of AST or ALT > 20× ULN

Any occurrence of AST or ALT > 3× ULN with concurrent bilirubin > 2× ULN, except in 
participants with Gilbert’s syndrome

Re-occurrence of AST or ALT > 5× ULN despite dose reduction to 120 mg

Gastrointestinal perforation or fistula

Severe or life-threatening hemorrhage

Reversible posterior leukoencephalopathy syndrome

Wound dehiscence

For any Grade 4 adverse reaction; only resume if the potential benefit outweighs the risks

Any event that leads to delay in dosing for > 8 weeks from the previous dose requires 
discontinuation with the following exception:
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
Dosing delays > 8 weeks that occur for non-drug-related reasons may be allowed 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. Tumor 
assessments should continue as per protocol even if dosing is delayed.

Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
investigator, presents a substantial clinical risk to the participant with continued treatment.
8.1.1
Post-Study Treatment Study Follow-up
In this study, safety and efficacy are key endpoints of the study. Post study follow-up is of critical 
importance and is essential to preserving participant safety and the integrity of the study. 
Participants who discontinue study treatment must continue to be followed (in this study or a 
rollover study) for collection of outcome and/or survival follow-up data as required and in line 
with Section 5.3 until death or the conclusion of the study.
8.2
Discontinuation from the Study
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol specified follow-up procedures. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 

Participants should notify the Investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.

The withdrawal of consent should be explained in detail in the medical records by the 
Investigator, as to whether the withdrawal is from further treatment with study treatment only 
or also from study procedures and/or post treatment study follow-up, and entered on the 
appropriate CRF page.

In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.

If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.
8.3
Lost to Follow-Up

All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of three
documented phone calls, faxes, or emails as well as lack of response by participant to one 
registered mail letter. All attempts should be documented in the participant’s medical records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If Investigator’s use of 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 
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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 (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
(Section 2), 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 treatment allocation. 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 (Section 2).
Additional measures, including non-study required laboratory tests, should be performed as 
clinically indicated or to comply with local regulations. Laboratory toxicities (eg, suspected drug 
induced liver enzyme evaluations) will be monitored during the follow-up phase via on-site/local 
laboratories until all study drug-related toxicities resolve, return to baseline, or are deemed 
irreversible.
If a participant shows pulmonary-related signs (eg, hypoxia, fever) or symptoms (eg. dyspnea, 
cough, fever) consistent with possible pulmonary AEs, the participant should be immediately 
evaluated to rule out pulmonary toxicity, according to the suspected pulmonary toxicity 
management algorithm in the 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
Efficacy Assessments
Efficacy assessments for the anti-tumor activity of BMS-986288 alone, BMS-986288 in 
combination with nivolumab, and 
will be based on tumor measurements, using 
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RECIST v1.1. Efficacy evaluation of BMS-986288 alone and in combination with nivolumab per 
modified RECIST in cancer immunotherapy trials (iRECIST) using BICR is an exploratory 
objective.
Only data for the procedures and assessments specified in this protocol should be submitted to the 
Sponsor or Designee on a CRF. Additional procedures and assessments may be performed as part 
of standard of care. However, data for these assessments should remain in the participant’s medical 
record and should not be provided to the Sponsor or Designee, unless specifically requested from 
BMS or Designee.
9.1.1
Imaging Assessment for the Study
Images for all study participants will be submitted to a central imaging vendor and collected 
images from Part 2C participants will undergo BICR review. All other images may undergo BICR 
review at any time during the study. Prior to scanning first participant, sites should be qualified 
and understand the image acquisition guidelines and submission process as outlined in the 
CA043001 Imaging Manual provided by the central imaging vendor.
Refer to Schedule of Activities (Section 2) for timing of tumor assessments.
Any additional CT/MRI images performed either at unscheduled time points and/or at an outside 
institution, which may demonstrate tumor response or progression per RECIST v1.1 should be 
submitted to the central imaging vendor. X-rays, bone scans, and FDG PET scans which clearly 
demonstrate interval progression of disease, for example most commonly as unequivocal lesions,
that are unmistakably new since the prior CT/MRI, should also be submitted to central imaging
vendor.
9.1.1.1
Methods of Measurement
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected sites 
of disease should be performed for tumor assessments. Images should be acquired with slice 
thickness of 5 mm or less with no intervening gap (contiguous). Every attempt should be made to 
image each participant using an identical acquisition protocol on the same scanner for all imaging
time points. Tumor measurements should be made by the same Investigator or radiologist for each 
assessment, whenever possible. Change in tumor measurements and tumor response to guide 
ongoing study treatment decisions will be assessed by the Investigator using the RECIST v1.1 
criteria.
For participants with cancer of the head and neck, a CT or MRI scan of the neck is required.
For participants with TNBC without measurable lesions outside of the breast, contrast-enhanced 
MRI of the breasts should be performed.
In case of a contraindication for either contrast agent or MRI (eg, incompatible pacemaker) it is 
recommended to use the following guidance: 
If a participant has a contraindication for CT IV contrast, then a non-contrast CT of the chest and 
a contrast-enhanced MRI of the abdomen, pelvis, and other known/suspected sites of disease 
should be obtained.
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If a participant has a contraindication for both MRI and CT IV contrasts, then a non-contrast CT 
of the chest and a non-contrast MRI of the abdomen, pelvis, and other known/suspected sites of 
disease should be obtained. 
If a participant has a contraindication for MRI in addition to contraindication to CT IV contrast, 
then a non-contrast CT of the chest, abdomen, pelvis, and other known/suspected sites of disease 
is acceptable.
Use of CT component of a positron emission tomography (PET)-CT scanner: Combined 
modality scanning, such as with PET-CT, is increasingly used in clinical care, and is a 
modality/technology that is in rapid evolution; therefore, the recommendations outlined here may 
change rather quickly with time. At present, low dose or attenuation correction CT portions of a 
combined PET-CT are of limited use in anatomically-based efficacy assessments, and it is 
therefore suggested that they should not be substituted for dedicated diagnostic contrast-enhanced 
CT scans for anatomically-based RECIST v1.1 measurements. However, if a site can document 
that the CT performed as part of a PET-CT is of identical diagnostic quality to a diagnostic CT 
(with IV and oral contrast), then the CT portion of the PET-CT can be used for RECIST v1.1 
measurements. Note, however, that the PET portion of the CT introduces additional data which 
may bias an Investigator if it is not routinely or serially performed.
Bone scan or PET scan are not adequate for assessment of RECIST v1.1 response in target lesions. 
In selected circumstances where such modalities are the sole modality used to assess certain 
non-target organs, those non-target organs may be evaluated less frequently. For example, bone 
scans may need to be repeated only when CR is identified in target disease or when progression in 
bone is suspected.
Bone scans may be collected per local standards, as clinically indicated.
MRI of the brain should be acquired as outlined in the Schedule of Activities (Section 2). CT of 
the brain (without and with contrast) can be performed if MRI is contraindicated.
9.1.1.2
Imaging and Clinical Assessment
Tumor assessments should continue on the protocol defined imaging schedule regardless if dosing 
is delayed or discontinued. Changes in tumor measurements and tumor responses should be 
assessed by the same Investigator using RECIST v1.1 criteria. Investigators will report the number 
and size of new lesions that appear while on study. The time point of tumor assessments will be 
reported on the eCRF based on the Investigator’s assessment using RECIST v1.1 criteria (see 
Appendix 5 for specifics of RECIST v1.1 criteria to be used in this study). Assessments of PR and 
CR must be confirmed at least 4 weeks after initial response. A Best Response of SD can only be 
made after the participant is on study for a minimum of 49 days from the date of treatment initiation 
(ie, first dose).
9.1.2
Clinical Outcomes Assessments
The evaluation of the participant’s experience in the evaluation of biopharmaceutical treatments is 
important to fully understand the impact of such products on how participants feel and function. 
PROs have been incorporated in oncology trials in order to more fully understand the participant’s 
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experience. In addition, there is an increased focus from the clinical community on the specific 
concepts that are influenced by therapeutic products, including disease-related symptoms, 
symptomatic AEs, and physical functioning. When used in tandem with traditional clinical 
measures, the Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) 
can provide additional context for safety and efficacy results. In the current trial, the participant’s 
experience will be directly measured through the NSCLC-SAQ, the FACIT GP5, and the 
EQ-5D-5L. The Center for Drug Evaluation and Research has determined that the NSCLC-SAQ 
demonstrated adequate evidence of content validity and cross-sectional measurement properties 
(ie, internal consistency reliability, test-retest reliability, convergent validity, and known-groups 
validity) to measure symptoms of NSCLC in the context of the participant population being studied 
in this trial. Other indication-specific PROs will be included through a protocol amendment if other 
indications are included in the study.
The NSCLC-SAQ, FACIT GP5, and EQ-5D-5L will be collected during Part 2A and Part 2B only
using electronic devices. The EQ-5D-5L may be collected using a validated telephone script in 
Survival Follow-up Period. However, if exceptional circumstances preclude the continued 
administration of measures using planned modalities, then alternate administration methods may 
be required, after consultation with Sponsor or the Sponsor’s representative.
9.1.2.1
NSCLC-SAQ
The NSCLC-SAQ is a 7-item PRO measure intended for use in advanced NSCLC clinical trials to 
support medical product labeling.75 The NSCLC-SAQ uses a 7-day recall period and verbal rating 
scale. It was developed in accordance with the US FDA’s PRO Guidance and scientific best 
practices, and the resulting qualitative interview data provide evidence of content validity. The 
NSCLC-SAQ total score measures overall severity of the following NSCLC symptoms: cough, 
pain, dyspnea, fatigue, and appetite. The NSCLC-SAQ has been qualified for exploratory use to 
measure symptoms of NSCLC in drug development programs. Further evaluation is needed on the 
instrument’s longitudinal measurement properties and the interpretation of clinically meaningful 
within-patient change in score. After the NSCLC-SAQ’s longitudinal measurement properties and 
the interpretation of clinically meaningful within-patient change have been evaluated, the 
NSCLC-SAQ total score is intended to support labeling claims related to change in overall 
symptoms of NSCLC. The NSCLC-SAQ will be administered electronically to NSCLC 
participants only in Part 2 (see Section 2 Schedule of Activities).
9.1.2.2
EQ-5D-5L
The EQ-5D-5L was introduced by the EuroQoL Group to improve the instrument’s sensitivity and 
to reduce ceiling effects, as compared to the 3-Level EQ-5D (EQ-5D-3L). Participants’ reports of 
general health status will be assessed using the EQ-5D-5L, which has 2 components, the 
EQ-5D-5L descriptive system and the EQ-5D Visual Analog Scale (EQ-5D-VAS).76 The 
EQ-5D-5L has been shown to be reliable in cancer patient populations.77
The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, 
usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no 
problems, slight problems, moderate problems, severe problems, and extreme problems. The 
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participant is asked to indicate his or her health state by ticking the box next to the most appropriate 
statement in each of the 5 dimensions. This decision results in a 1-digit number that expresses the 
level selected for that dimension. A total of 3125 possible health states are defined in this way. 
Each state is referred to in terms of a 5-digit code. For example, state 11111 indicates no problems 
on any of the 5 dimensions, while state 12345 indicates no problems with mobility, slight problems 
with washing or dressing, moderate problems with doing usual activities, severe pain or 
discomfort, and extreme anxiety or depression. EQ‑5D‑5L health states, defined by the 
EQ‑5D‑5L descriptive system, may be converted into a single summary index by applying a 
formula that attaches values (also called weights) to each of the levels in each dimension. The 
index can be calculated by deducting the appropriate weights from 1, the value for full health (ie, 
state 11111). This is referred to as the EQ‑5D-5L utility index. Currently, there are no published 
minimally important differences for change in scores for the EQ-5D-5L utility index score in a 
cancer population.
The EQ‑5D‑5L VAS records the respondent’s self-rated health on a scale from 0 (Worst 
imaginable health state) to 100 (Best imaginable health state); higher scores represent better self-
rated health. A change of 7 points is considered a clinically meaningful change and will be used 
to aid interpretation of change from baseline scores.
The EQ-5D-5L will be administered electronically to all participants in Part 2, except Part 2C (see 
Section 2 Schedule of Activities).
9.1.2.3
FACIT GP5
A single item drawn from the FACIT measurement system (item GP5) will be administered to 
assess the overall extent of perceived bother due to symptomatic AEs. Evidence exists for the 
validity of this single item and its usefulness as an overall measure of burden due to symptomatic 
treatment toxicities.78
The FACIT GP5 will be administered electronically to all participants in Part 2 (see Section 2 
Schedule of Activities).
9.2
Adverse Events
The definitions of an AE or SAE can be found in Appendix 3. Use CTCAE v5 definitions and 
grading for safety reporting of all AE and SAEs on the case report form.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study. 
Contacts for SAE reporting specified in Appendix 3.
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For regorafenib, refer to local product labels for safety profile, including Warnings and 
Precautions.
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
The continuous collection of nonserious AE information (with the exception of nonserious AEs 
related to SARS-CoV-2 infection [see below]) should begin at initiation of study treatment until
100 days after last dose of study treatment administration, at the time points specified in the 
Schedule of Activities (see Section 2).

All SAEs must be collected continuously from the time of signing the consent, including those 
thought to be associated with protocol-specified procedures and within 100 days of last dose
of study treatment must be collected, except in cases where a study participant has started a 
new anti-neoplastic treatment. However, any SAE occurring after the start of a new anti-
neoplastic treatment that is suspected to be related to study treatment by the Investigator should 
be reported as an SAE.

The Investigator must report any SAE that occurs after these time periods and that is believed 
to be related to study drug or protocol-specified procedure, (eg, a follow-up 
).

Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF module.

All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 

The Investigator will submit any updated SAE data to the sponsor or designee within 24 hours
of updated information being available.
All SAEs and all AEs (SAEs and nonserious AEs) associated with confirmed or suspected SARS-
CoV-2 infection must be collected from the date of the participant’s written consent until 100 days 
following discontinuation of study treatment. Investigators are not obligated to actively seek AEs 
or SAEs in former study participants. However, if the Investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the study, and he/she considers the 
event reasonably related to the study treatment or study participation, the Investigator must 
promptly notify the sponsor.
The method of evaluating and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3.
9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AE and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
adverse events, when appropriate for the program or protocol.
Every AE must be assessed by the Investigator with regard to whether it is considered 
immune-mediated. For events which are potentially immune-mediated, additional information will 
be collected on the participant’s CRF.
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9.2.3
Follow-up of AEs and SAEs

Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study treatment as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.
After the initial AE/SAE report, the Investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and nonserious AEs of special interest (as defined in 
Section 9.2) will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).

After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and AEs associated with confirmed or 
suspected SARS-CoV-2 infection will be followed until resolution, the condition stabilizes, 
the event is otherwise explained, the event is deemed irreversible, the participant is lost to 
follow-up (as defined in Section 8.3) or for suspected cases, until SARS-CoV-2 infection is 
ruled-out.
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 (IRB)/Independent Ethics 
Committee (IEC), if appropriate according to local requirements.
Sponsor or designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws including European Directive 2001/20/EC and FDA Code of 
Federal Regulations 21 CFR Parts 312 and 320. A suspected, unexpected serious adverse reaction
(SUSAR) is a subset of SAEs and will be reported to the appropriate regulatory authorities and 
Investigators following local and global guidelines and requirements.
9.2.5
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including  months after BMS-
986288 combination therapy,
 months after BMS-986288 monotherapy administration, and 2 
months after the last dose of regorafenib, 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. 
Please call the BMS Medical Monitor (or designee) within 24 hours of awareness of the pregnancy.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
participant.
If, for whatever reason, the pregnancy has ended, confirmed by negative serum pregnancy test, 
treatment may be resumed (at least 3 weeks after the pregnancy has ended), following approvals 
of participant/sponsor/IRB/EC, as applicable.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
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 vs low hemoglobin value).
9.2.7
Immune-Mediated Adverse Events
Immune-mediated adverse events (imAEs) are AEs consistent with an immune-mediated 
mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection 
or tumor progression) have been ruled out. imAEs can include events with an alternate etiology 
which were exacerbated by the induction of autoimmunity. Information supporting the assessment 
will be collected on the participant’s case report form.
9.2.8
Potential Drug-induced Liver Injury (DILI)
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, meeting 
the defined criteria, must be reported as SAEs (see Section 9.2 and Appendix 3 for reporting 
details).
Potential DILI is defined as: 
1) Aminotransaminases (ATs; ALT or AST elevation > 3 times upper limit of normal [ULN])
AND
2) Total bilirubin > 2 ULN, without initial findings of cholestasis (elevated serum ALP)
AND
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3) No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
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: (i) Timely evaluation and triaging of p-DILI cases; (ii) Expedited reporting of 
p-DILI cases; and (iii) 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, the following: infectious diseases (such as active hepatitis A, B, and C), 
congenital diseases (such as Gilbert’s syndrome), neoplastic diseases, autoimmune diseases (such 
as primary 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 nonserious or serious AE, as appropriate, and reported accordingly.
9.3
Overdose
For this study, any dose of BMS-986288 or nivolumab greater than the assigned dose and 
considered excessive and medically important by the Investigator will be considered an overdose
(see Appendix 3).
In the event of an overdose the Investigator/treating physician should:
1) Contact the Medical Monitor (or designee) immediately.
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2) Closely monitor the participant for AEs/SAEs and laboratory abnormalities until BMS-986288 
or nivolumab can no longer be detected systemically (at least 125 days).
3) Obtain a serum sample for PK if requested by the Medical Monitor/designee (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 (or designee) based on the clinical 
evaluation of the participant.
For regorafenib overdose, please refer to local product label.
9.4
Safety
Safety assessments will be based on reported AEs and the measurement results of vital signs, 
ECGs, PEs, and clinical laboratory tests. AEs will be coded using the most current version of 
Medical Dictionary for Regulatory Activities (MedDRA), 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 100 days after last dose of study treatment. 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 v5.0. Collection of AEs and severity 
will also include local 
 reactions after 
 administration and IV-related infusion 
reactions.
Planned time points for all safety assessments are listed in the Schedule of Activities (Section 2).
9.4.1
Physical Examinations
Refer to Schedule of Activities (Section 2).
9.4.2
Vital signs
Refer to Schedule of Activities (Section 2).
9.4.4
Electrocardiograms
Refer to Schedule of Activities (Section 2) for timing of assessments.
The effect of BMS-986288 on the QTc interval will be evaluated by a central reader using ECG 
data collected in triplicate along with time-matched PK during the BMS-986288 Monotherapy 
Dose Escalation (Part 1A) only (eg, 1 ECG test equals 3 consecutive individual 12-lead ECGs 
performed approximately 5 minutes apart). For the purposes of monitoring participant safety (all 
other ECG assessments), the Investigators will review the 12-lead ECGs using their site’s standard 
ECG machines throughout the study. The QTcF will be applied to each ECG reading.
9.4.5
Clinical Safety Laboratory Assessments

Investigators must document their review of each laboratory safety report.
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
A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests performed on Day -1 must be available prior to dosing.

The laboratory tests that will be performed for study participants are shown in Table 9.4.5-1.

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 9.4.5-1:
Clinical Laboratory Assessments
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Prothrombin time, activated partial thromboplastin time, and international normalized ratio (at screening only)
Coagulation (screening only. Monitor INR levels more frequently in participants on regorafenib and participants
receiving warfarin according to institutional guidelines)
Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin (reflexa)
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Creatinine
Creatine kinase/Creatine phosphokinase
C-reactive protein
Blood Urea Nitrogen (BUN)
Uric acid
Glucose
Lipase
Amylase
Gamma glutamyl transferase (reflex onlyb)
Thyroid stimulating hormone (TSH)
Free T3 and T4 (screening and reflex onlyc)
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatinine clearance (Cockcroft-Gault method; 
screening only)
Troponin
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase and/or white blood cell (WBC)
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Table 9.4.5-1:
Clinical Laboratory Assessments
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive on the dipstick
Serology
Serum for hepatitis C antibody, hepatitis B surface antigen, HIV-1 and HIV-2 antibody (at screening, and as 
mandated by local requirement)
Other Analyses
Pregnancy test (WOCBP only: screening, predose, discharge)
Follicle stimulating hormone (FSH) (screening only for women only) 
a Reflex testing to be performed only if total bilirubin is abnormal.
b Reflex testing to be performed only if liver function test is abnormal.
c Reflex testing to be performed only if TSH is abnormal.
9.4.6
Imaging Safety Assessment
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the study Investigator as per standard 
medical/clinical judgment. 
9.5
Pharmacokinetics and Immunogenicity Assessment
The PK of BMS-986288 will be derived from plasma concentration-time data. The PK parameters 
that will be assessed following serial PK collection are shown in Table 9.5-1. Sparse nivolumab 
serum samples will be collected and may be used in an integrated PPK or ER analysis along with 
data from other nivolumab studies, which would be the subject of a separate report. Separate 
samples will be collected for PK and ADA assessments using validated methods.
Plasma samples for BMS-986288 ADA and serum samples for nivolumab ADA and cytokines 
will be collected from all participants at specified time points (see Table 9.5-2, Table 9.5-3, and 
Table 9.5-4). PK samples may be analyzed by validated and exploratory methods that measure 
different forms of the Probody mAb for exploratory purposes; exploratory results may be reported. 
Immunogenicity samples will be analyzed by validated methods and may also be analyzed for 
neutralizing antibodies. Blood samples designated for PK or biomarker assessments may also be 
used for immunogenicity analysis if required (eg, insufficient volume for complete 
immunogenicity assessment or to follow up on suspected immunogenicity-related AEs), and vice 
versa.
Additionally, residual bioanalytical samples will be archived and may be used for potential 
exploratory bioanalysis (including, but not limited to, analysis of drug-ADA immune complexes, 
metabolite analyses, etc) and/or for additional method purposes (including, but not limited to, 
cross-validation, ADA/PK selectivity, cut point, etc).
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Table 9.5-1:
BMS-986288 Pharmacokinetic Analyses
Parameters
Definition
Cmax
Maximum observed concentration
Tmax
Time of maximum observed concentration
AUC(0-T)
Area under the 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 concentration-time curve in one dosing interval
Ctau
Observed concentration at the end of a dosing interval
Ctrough
Trough observed concentrations (this includes predose concentrations [C0] and Ctau)
Parameters That May be Assessed Following the Dose Administration in Cycle 4
CLT
Total body clearance
Cavgss
Average 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 maximum observed concentration [Cmax])
T-HALF
Terminal half-life if data permit (Cycle 4)
Individual participant PK parameter values will be derived by noncompartmental methods using a 
validated PK analysis program. Actual times will be used for all formal analyses. For participants 
enrolled in 
 receiving 
 administration, a non-compartmental or PPK approach will be 
used to assess the PK data, and parameters such as Cmax, AUC(0-T), and bioavailability (F) will 
be assessed as feasible and applicable. 
Table 9.5-2, Table 9.5-3, and Table 9.5-4 list the sampling schedule to be followed for the 
assessment of PK.
 PK and ADA sample collection schedules 
 
. Further details of blood collection and processing will be provided to the site 
in the Laboratory Manual.
On-treatment PK samples are intended to be drawn relative to actual dosing days. If a dose occurs 
on a different day within the cycle due to delays or minor schedule adjustments, PK samples 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, then an additional predose sample should not be collected. A PK 
and ADA sample may be taken in the event of a Grade 3 infusion reaction or hypersensitivity 
reaction. Further details of sample collection, processing, and shipment will be provided in the 
Laboratory Manual.
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Table 9.5-2:
PK and ADA Sampling Schedule for BMS-986288 IV 
 
Monotherapy in Dose Escalation (Part 1A) and BMS-986288 IV 
 
 Cohort Expansion (Part 2A)
Study Day of 
Sample Collection
(1 Cycle = 
)
Event
Time (Relative to 
Start of BMS-986288 
Infusion) Hr:Mina
BMS-986288 PK 
 Sample 
BMS-986288 ADA
Sample 
C1D1
Predoseb
00:00
X
X
EOI
See notec
X
X
C1D
X
C1D (1 day)
X
C1D (2 days)
X
C1D
(2 days)
X
C1D
(2 days)
X
C2D1
Predoseb
00:00
X
X
EOI
See notec
X
C2D d (3 days)
168:00
X
C3D1
Predoseb
00:00
X
X
EOI
See notec
X
C4D1
Predoseb
00:00
X
X
EOI
See notec
X
X
C4D
X
C4D
X
C4D
X
C4D
X
C4D
X
C5D1
Predoseb
00:00
X
X
C6D1
Predoseb
00:00
X
X
Every fourth cycle 
after C6 until EOT 
(C10D1, C14D1, 
C18D1, etc until 
EOT)
Predoseb
00:00
X
X
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Table 9.5-2:
PK and ADA Sampling Schedule for BMS-986288 IV 
 
Monotherapy in Dose Escalation (Part 1A) and BMS-986288 IV 
 
 Cohort Expansion (Part 2A)
Study Day of 
Sample Collection
(1 Cycle = 
)
Event
Time (Relative to 
Start of BMS-986288 
Infusion) Hr:Mina
BMS-986288 PK 
 Sample 
BMS-986288 ADA
Sample 
EOT
X
X
30-day follow-up
X
X
60-day follow-up
X
X
100-day follow-up
X
X
Grade 3+ infusion 
reaction
X
X
Abbreviations: ADA = anti-drug antibody; C = cycle; D = day; EOI = end of infusion; EOT = end of treatment; 
Hr = hour; Min = minute; 
; PK = pharmacokinetics;
.
a Every effort should be taken to collect the sample as close to the designated time as possible. The actual time of 
collection should be recorded.
b All predose samples should be taken within 30 minutes prior to the start of the infusion.
c EOI PK samples should be collected when all study drug has been infused. If a flush is administered to clear the IV 
lines of the drug and to ensure delivery of the entire drug dose, then draw the EOI PK sample within approximately 
15 minutes after end of the flush. Do not draw EOI samples from the same IV access through which the drug was 
administered. Refer to the Pharmacy Manual for infusion duration. If the EOI is delayed beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly.
d Sample should be collected with 
 (see Table 9.8.3-1).
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Table 9.5-3:
PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with Nivolumab IV 
 in 
Dose Escalation (Part 1B) and BMS-986288 IV 
 in Combination with Nivolumab IV 
 Cohort 
Expansion (Part 2B)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to 
Start of Nivolumab
Infusion) Hr:Mina
BMS-986288 PK
 Sample 
Nivolumab PK 
 Sample 
BMS-986288 ADA 
 Sample 
Nivolumab ADA 
 Sample 
C1D
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
X
C1D
X
C1D
X
C1D
X
C1D
X
C1D
X
C2D1
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
C2D8d (3 days)
168:00
X
X
C3D1
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
C4D1
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
04:00
X
C4D2
24:00
X
C4D4 (1 day)
72:00
X
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Table 9.5-3:
PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with Nivolumab IV 
 in 
Dose Escalation (Part 1B) and BMS-986288 IV 
 in Combination with Nivolumab IV 
 Cohort 
Expansion (Part 2B)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to 
Start of Nivolumab
Infusion) Hr:Mina
BMS-986288 PK
 Sample 
Nivolumab PK 
 Sample 
BMS-986288 ADA 
 Sample 
Nivolumab ADA 
 Sample 
C4D8 (2 days)
168:00
X
C4D15 (2 days)
336:00
X
C4D22 (2 days)
504:00
X
C5D1
Predoseb
00:00
X
X
X
X
C6D1
Predoseb
00:00
X
X
X
X
Every fourth cycle 
after C6 until EOT 
(C10D1, C14D1, 
C18D1, etc until EOT)
Predoseb
00:00
X
X
X
X
EOT
X
X
X
X
30-day follow-up
X
X
X
X
60-day follow-up
X
X
X
X
100-day follow-up
X
X
X
X
Grade 3+ infusion 
reaction
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = cycle; D = day; EOI = end of infusion; EOT = end of treatment; Hr = hour; Min = minute; IV = intravenous; PK = 
pharmacokinetics;
.
a Every effort should be taken to collect the sample as close to the designated time as possible. The actual time of collection should be recorded.
b All predose samples should be taken within 30 minutes prior to the start of the first drug (eg, nivolumab) infusion.
c EOI PK samples should be collected when all study drug has been infused. If a flush is administered to clear the IV lines of the drug and to ensure delivery of 
the entire drug dose, then draw the EOI PK sample within approximately 15 minutes after end of the flush. Do not draw EOI samples from the same IV access 
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through which the drug was administered. Refer to the Pharmacy Manual for infusion duration. If the EOI is delayed beyond the nominal infusion duration, the 
collection of this sample should also be delayed accordingly.
d Sample should be collected with 
 (see Table 9.8.3-1).
Table 9.5-4:
PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with Nivolumab IV 
 
Cohort Expansion (Part 2C Arm C, Arm E, and Arm Z)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to 
Start of Nivolumab 
Infusion) Hr:Mina
BMS-986288 PK 
 Sample 
Nivolumab PK 
 Sample 
BMS-986288 ADA 
 Sample 
Nivolumab ADA 
Sample 
C1D1
Predoseb
0:00
X
X
X
X
EOI
See notec
X
X
C1D2
24:00:00
X
X
C2D1
Predoseb
0:00
X
X
X
X
EOI
See notec
X
X
C3D1
Predoseb
0:00
X
X
C4D1
Predoseb
0:00
X
X
X
X
C6D1
Predoseb
0:00
X
X
X
X
Every fourth cycle after 
C6 until EOT (C10D1, 
C14D1, C18D1, etc 
until EOT)
Predoseb
0:00
X
X
X
X
EOT
X
X
X
X
30-day follow-up
X
X
X
X
60-day follow-up
X
X
X
X
100-day follow-up
X
X
X
X
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Table 9.5-4:
PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with Nivolumab IV 
 
Cohort Expansion (Part 2C Arm C, Arm E, and Arm Z)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to 
Start of Nivolumab 
Infusion) Hr:Mina
BMS-986288 PK 
Sample 
Nivolumab PK 
Sample 
BMS-986288 ADA 
 Sample 
Nivolumab ADA 
 Sample 
Grade 3+ infusion 
reaction
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = cycle; D = day; EOI = end of infusion; EOT = end of treatment; Hr = hour; IV = intravenous; Min = minute; PK = 
pharmacokinetics;
.
a Every effort should be taken to collect the sample as close to the designated time as possible. The actual time of collection should be recorded.
b All predose samples should be taken within 30 minutes prior to the start of the first drug (eg, nivolumab) infusion.
c EOI PK samples should be collected when all study drug has been infused. If a flush is administered to clear the IV lines of the drug and to ensure delivery of 
the entire drug dose, then draw the EOI PK sample within approximately 15 minutes after end of the flush. Do not draw EOI samples from the same IV access
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9.6
Pharmacodynamics
Details on pharmacodynamic biomarker assessments are included in Section 9.8.
9.7
Pharmacogenomics
Not applicable.
9.7.1
ADME Sampling
Not applicable.
9.8
Biomarkers
For all participants, biomarker measures of baseline, on-treatment, and upon disease progression 
, serum, and tumor samples will be used, if sufficient material collected, to identify 
pharmacodynamic markers associated with treatment. Additional biomarkers related to 
mechanisms of action, such as, but not limited to, safety biomarkers, and associations with 
response to BMS-986288 alone and in combination with nivolumab will be explored.
 will be collected prior to therapy, on treatment, and upon disease 
progression (
 are not required for participants 
enrolled in the regorafenib arm [Part 2C Arm D], but 
 are required for 
participants that elect to join the cross-over arm [Part 2C Arm Z] in order to provide pre-treatment 
information). 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 in Table 9.8.3-1 and 
Table 9.8.3-2. Further details of 
 collection and processing will be 
provided to the site in the Procedure Manual.
9.8.1
 Biomarkers
A variety of factors that may impact the immunomodulatory properties and efficacy of 
BMS-986288 will be investigated in 
 specimens taken from all participants prior 
to or during treatment at the time points indicated in Table 9.8.3-1 and Table 9.8.3-2. Results from 
these investigations will be evaluated for associations with dose, response, survival, and/or safety 
(AE) data. Several analyses will be completed and are described briefly below.
9.8.1.1
Soluble Biomarkers
 samples as well as 
 samples used for PK analysis may also be used to evaluate 
, over the course of the treatment. 
 
 
 and quantified by immunoassays in serum. Analyses may include, but not 
necessarily be limited to, soluble 
 
.
9.8.1.2
Immunophenotyping
The proportion of specific lymphocyte subsets 
 
 preparations will be quantified by flow 
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cytometry. Analyses may include, but not necessarily be limited to, the proportion of 
 
; as well as expression 
levels of 
.
9.8.1.3
 Analysis
The 
 of the peripheral 
 compartment and changes over the course of treatment with 
immunotherapeutic agents may be related to the mechanism of action of BMS-986288. In order to 
explore whether a 
 is associated with response to therapy, next generation, 
high-throughput, deoxyribonucleic acid (DNA) sequencing will be performed on DNA or RNA
isolated from 
 and 
 to quantitate the composition of the 
 
 prior to and during therapy.
9.8.1.4
 Variants
Whole blood will be collected from all participants prior to treatment to generate genomic DNA 
for single nucleotide polymorphism (SNP) analyses 
 
. These genomic analyses will include 
assessment of 
 
79 to determine if natural variation within those genes is associated 
with response to BMS-986288 and/or with AEs during treatment.
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9.8.2.1
Characterization of Tumor Immune Microenvironment
IHC will be used to assess the number and composition of immune infiltrates in order to define 
the immune cell subsets present within 
. These 
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IHC analyses may include, but will not necessarily be limited to, the following markers: 
 
.
9.8.2.2
Characterization of 
As described above, 
 may be performed on pre- and post-treatment 
 
to assess the composition of the 
. DNA will be isolated 
from the 
and/or 
.
 that are collected at screening and on treatment will be examined for 
messenger RNA gene expression by RNA sequencing, quantitative real-time PCR, or other 
technologies to characterize gene expression profiles associated with immune modulation, 
, or outcome following treatment with BMS-986288.
9.8.2.4
Mutational and DNA Methylation Analyses
DNA from 
 will be collected and analyzed using whole-exome sequencing to 
determine the number and identity of mutations found 
. 
 
 
 
 
 
DNA may also be analyzed to assess methylation status of genes of interest, including, but not 
limited to, 
.
9.8.3
Biomarker Sampling Schedule
The biomarker sampling schedule is outlined in Table 9.8.3-1 and Table 9.8.3-2.
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Table 9.8.3-1:
Biomarker Sampling Schedule for 
 Dosing Schedule for Part 1, Part 2A, Part 2B, and 
Part 2C Arm C, Arm E, and Arm Z
Study Day of 
Sample 
Collection
 
Time (Relative to 
BMS-986288 
Dose) Hr:Min
Screening
Xc
Xd
C1D1
00:00e
X
X
X
X
X
X
C1D2
24:00
X
X
C1D8
(2 days)
168:00
X
X
X
C1D15
(2 days)
336:00
X
X
X
C2D1
00:00e
X
X
X
C2D8b,
(3 days)
168:00
X
X
X
X
X
Xf
C2D15 (2 
days)
336:00
X
C3D1
00:00e
X
X
C4D1
X
X
EOT or at 
progression
X
X
X
Abbreviations: C = cycle; 
 D = day; EOT = end of treatment; KRAS = Kirsten rat sarcoma virus; 
 
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a Instructions for the collection and processing 
 will be provided in the Laboratory Manual. 
b Pre-treatment (screening) 
 can be performed on C1D1. Mandatory on-treatment 
 to be performed at C2D8; specimens may be collected 
within 3 days of the time point and must be obtained prior to administration of study treatments. C2D8 biomarker collections should occur at the same time as 
. Adjust the biomarker collection in accordance with the 
 collection. An optional additional 
 can be collected on treatment 
if the Investigator and the Medical Monitor (or designee) find it indicated. A 
 is required, if medically feasible, upon confirmation of PD (within 7 
days) except for: 1) participants who have an 
 within 4 cycles; 2) participants who will be imminently (within 4 weeks) enrolling 
in a subsequent clinical research study that requires a screening 
; 3) participants who consent to be treated beyond progression will require the 
 
only at the subsequent confirmation of progression; and 4) participants in Part 2C, unless the participant elects to crossover to Arm Z.
 are 
unacceptable for submission. 
c For Part 2C. Sample only needed if other available options for assessing KRAS are not viable, and KRAS testing must be recent (following prior lines of therapy)
and not from diagnosis as KRAS testing can change with treatment.
d For the cross-over arm, a 
 is required 
in order to provide pre-treatment information. This 
 can be from EOT 
 in Table 9.8.3-2
e All predose samples should be taken prior to the start of the infusion/administration.
f Optional collection for cross-over participants.
Table 9.8.3-2:
Biomarker Sampling Schedule for 
 Dosing Schedule for Part 2C Arm D
Study Day of 
Sample Collection
 
Time (Relative to 
BMS-986288 Dose) 
Hr:Min
Screening
Xc
X
C1D1
00:00d
X
X
X
X
X
C1D15 (2 days)
336:00
X
X
C2D1
00:00d
X
X
C3D1
00:00d
X
X
X
X
C4D1
00:00d
X
X
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Table 9.8.3-2:
Biomarker Sampling Schedule for 
 Dosing Schedule for Part 2C Arm D
Study Day of 
Sample Collection
 
Time (Relative to 
BMS-986288 Dose) 
Hr:Min
EOT or at 
progression
X
X
X
Xb
Abbreviations: C = cycle; 
 D = day; EOT = end of treatment; KRAS = Kirsten rat sarcoma virus; Q4W = every 
4 weeks; TCR = T-cell receptor.
a Instructions for the collection and processing 
 will be provided in the Laboratory Manual. 
b
 can be performed on C1D1. A new
 is required for participants that elect to cross-over to study treatment in order 
to provide pre-treatment information. For participants that do not cross-over to Arm Z, an EOT 
 is optional. 
 
c For Part 2C. Sample only needed if other available options for assessing KRAS are not viable.
d All predose samples should be taken prior to the start of the infusion/administration.
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9.8.4
Additional Research Collection
This protocol will include residual sample storage for additional research (AR). All PK, biomarker, 
cytokine, and residual samples will be stored for AR. 
For All US Sites:
AR participation is required for all investigational sites in the US.
AR is required for all study participants, except where prohibited by IRBs/ethics committees, or 
academic/institutional requirements. Where 1 or more of these exceptions occurs, participation in 
the AR should be encouraged but will not be a condition of overall study participation.

If the IRB/ethics committees and site agree to the mandatory AR retention and/or collection, 
then the study participant must agree to the mandatory AR as a requirement for inclusion in 
the study.

If optional participation is permitted and approved, then the study participants may opt out of 
the AR retention and/or collection.
For Non-US Sites:
AR is optional for all study participants, except where retention and/or collection is prohibited by 
local laws or regulations, ethics committees, or institutional requirements.
Sample retention for AR is intended to expand the translational Research & 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 patients. This may also include genetic/genomic exploration aimed at exploring disease 
pathways, progression and response to treatment etc. 
Sample Collection and Storage
All requests for access to samples or data for AR will be vetted through a diverse committee of the 
study sponsor’s senior leaders in Research & Development (or designee) to ensure the research 
supports appropriate and well-defined scientific research activities.
Samples kept for future research will be stored at the BMS Biorepository in 
 or 
an independent, BMS-approved storage vendor.
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than
 
years after the end of the study or the maximum allowed by applicable law.
Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
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No additional sampling is required for supplementary testing. Further details of sample collection 
and processing will be provided to the site in the Procedure Manual. See Table 9.8.4-1 for time 
points for retention of each sample type.
Table 9.8.4-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time points for which residual samples will be retained
PK/ADA
All
 biomarker 
samples
All
All
9.9
Health Economics OR Medical Resource Utilization and Health 
Economics
Health economics/medical resource utilization and health economics parameters will not be 
evaluated in this study.
10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination 
10.1.1
Monotherapy Dose Escalation (Part 1A)
Dose escalation during BMS-986288 Monotherapy Escalation (Part 1A) will be guided by BLRM 
employing the EWOC principle
. The BLRM method is fully adaptive, makes 
use of all the information available at the time of each dose assignment, not just data from the 
current dose level, and directly addresses the ethical need to control the probability of overdosing. 
Furthermore, the BLRM uses the knowledge gained from participants treated with ipilimumab 
(for Part 1A) or ipilimumab and nivolumab (for Part 1B). The targeted toxicity rate in this study 
is in the range of (16%, 33%). The boundary is similar to the toxicity boundary used by a rule-based 
design (ie, 3 + 3 design) in that a minimum is set at 16% (~ 1 in 6) DLT rate and a maximum at 
33% (~ 2 in 6) DLT rate. The use of the EWOC principle limits the risk of exposing patients in the 
next cohort to an intolerable dose by ensuring the posterior probability of the DLT rate at or 
exceeding 33% at any dose is capped at 35%. 
In order to understand operational characteristics of the BLRM, the total maximum number of 
participants for the simulation will be set to 
. Simulation studies with various scenarios show 
that the expected number of DLT-evaluable participants needed for BLRM is no more than 
approximately 
.
For the trial, approximately 4 participants (3+1) will be treated at the starting dose levels of 
BMS-986288. While the BLRM will use DLT information from the DLT period, clinical 
assessment will take into consideration of the totality of available data including 
PK/pharmacodynamic from all treated participants in assigning a dose level for the next cohort.
AEs meeting DLT criteria outside of the 5-week DLT period may also be incorporated into the 
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BLRM and dose de-escalation may be considered as appropriate based on the BLRM 
recommendation.
At 
least 
 
DLT-evaluable 
participants 
will 
be 
treated 
at 
the 
BLRM-recommended MTD (BLRM-MTD). A maximum of 
DLT-evaluable participants will 
be treated at each dose level. Once the BLRM-MTD is identified, then additional participants may 
be treated at the BLRM-MTD or any dose level below the BLRM-MTD for further evaluation of 
safety, PK, or pharmacodynamic parameters as required without exceeding a total of 
 evaluable 
participants.
The BLRM-MTD is the dose that satisfies the following 3 conditions:
1) The empirical posterior probability that the “DLT rate of 16% to < 33%” is greater than a 
pre-specified value (ie, 50%);
2) This probability needs to be the largest among the dose levels that satisfy the EWOC condition 
(ie, the probability that the “DLT rate ≥33%” must be no greater than 35%);
3) A minimum number of participants (ie, 6) were treated at this dose level.
The final recommended MTD/RP2D will be based on the recommendation from the BLRM and 
overall clinical assessment of available safety, PK, pharmacodynamic, and efficacy data. Lower 
doses or alternative administration schedules of BMS-986288 may be tested if none of the planned 
doses are found to be tolerable as monotherapy. Such decisions will be made after discussion and 
agreement between the Investigators and the BMS Medical Monitor (or designee).
10.1.2
The Safety Evaluation of Combination Doses of BMS-986288 with 
Nivolumab (Part 1B)
In the Safety Evaluation Combination Doses of BMS-986288 with Nivolumab (Part 1B), the 
starting dose of BMS-986288 will be at least 1 dose level lower than the current monotherapy dose 
level of BMS-986288 demonstrating an acceptable safety profile, and will be administered in 
combination with nivolumab at the planned 
 mg 
. Dose escalation and 
determination of MTD for the Safety Evaluation of Combination Doses of BMS-986288 with 
Nivolumab (Part 1B) will be guided by BLRM-copula with EWOC principle. Subsequent dose 
selection of the combination will be based on evaluating the recommendation from BLRM-copula 
and an overall assessment of available safety and PK/pharmacodynamic data. BLRM-copula will 
incorporate historical information from ipilimumab and nivolumab studies and the DLT 
information from the DLT period from both ipilimumab arms and nivolumab arms to estimate 
dose-toxicity surface, and will provide guidance for dose adjustment of either drug as needed.
While guided by the BLRM-copula, clinical assessment will take into consideration the totality of 
available data including PK/pharmacodynamics from all treated participants in assigning a dose 
level for the next cohort. AEs meeting DLT criteria outside of the 5-week DLT period may also 
be incorporated into the BLRM and dose de-escalation may be considered as appropriate based on 
the BLRM-copula recommendation. At least  DLT-evaluable participants will be treated at the 
BLRM-copula recommended MTD (BLRMc-MTD). A maximum of 
DLT-evaluable 
participants will be treated at each dose level. Once the BLRMc-MTD is identified, then additional 
participants may be treated at the BLRMc-MTD or any dose level below the BLRMc-MTD for 
further evaluation of safety, PK, or pharmacodynamic parameters as required without exceeding a 
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total of 
 evaluable participants. A combination with a higher dose level of either drug may be 
considered if recommended per BLRM-copula, after consideration of available safety, and 
PK/pharmacodynamic data. At no time will the dose of BMS-986288 in the Safety Evaluation of 
Combination Doses of BMS-986288 with Nivolumab (Part 1B) exceed the highest tolerated dose
equivalent in the BMS-986288 Monotherapy Escalation (Part 1A).
The BLRMc-MTD is the dose that satisfies the following 3 conditions:
1) The empirical posterior probability that the “DLT rate of 16% to < 33%” is greater than a 
pre-specified value (ie, 50%);
2) This probability needs to be the largest among the dose levels that satisfy the EWOC condition 
(ie, the probability that the “DLT rate ≥33%” must be no greater than 35%);
3) A minimum number of participants (ie, 6) were treated at this dose level.
The final recommended MTD/RP2D will be based on the recommendation from the BLRM-copula 
and overall clinical assessment of available safety, PK, pharmacodynamic, and efficacy data. 
Lower doses or alternative administration schedules of BMS-986288 + nivolumab may be tested 
if none of the planned doses are found to be tolerable as a combination. Such decisions will be 
made after discussion and agreement between the Investigators and the BMS Medical Monitor 
(or designee).
10.1.3
The 
 Evaluation of BMS-986288 as a Monotherapy and in 
Combination with Nivolumab 
Sample size calculations for the
 of BMS-986288 as a Monotherapy and 
in Combination with Nivolumab 
 are based on width of the confidence interval (CI) for
the geometric mean ratio (GMR) of exposure measures for
dosing. For each dose to
be tested in
, the PK parameters are assumed to be distributed log-normally, with an
inter-participant coefficient of variation of 
, and an intra-participant correlation of the log
transformed values of 0.6. With
participants, the lower bound for the 90% CI is
of the point
estimate for the GMR and the upper bound for the 90% CI is
of the point estimate. Up to 
evaluable participants will be treated in 
 (eg, 
 evaluable participants for 
BMS-986288 monotherapy [Arm A]; 
evaluable participants for BMS-986288 in combination 
with nivolumab [Arm B]).
10.1.4
The BMS-986288 
 Cohort Expansion (Part 2A)
The primary purpose of the BMS-986288 
 Cohort Expansion (Part 2A) is to evaluate 
preliminary efficacy of BMS-986288. The sample size calculation will be based on the ORR.
The preliminary efficacy of BMS-986288 as a monotherapy will be evaluated in participants with 
advanced cutaneous melanoma and NSCLC with disease relapse/recurrence or progression after 
prior immunotherapy treatment with an anti-PD-1 or anti-PD-L1 containing regimen. Up to 
 
cutaneous melanoma participants will be treated. For NSCLC, initial evaluation of efficacy signal 
(ORR) will be based on approximately the first 
 treated participants at a dose level. Based on 
the results of this initial evaluation, additional participants for a total of up to 
 participants may 
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be treated at a dose level. If more than 1 dose level is evaluated, up to 
 participants (eg,
 
participants 2 arms) may be enrolled. Other tumor types may be explored in the future.
With 
 treated participants in each BMS-986288 arm, the lower limit of the 2-sided 80% Clopper 
Pearson CI for ORR estimate will be 
 assuming ORR estimate size of 
 
 respectively. With 
 treated participants in each BMS-986288 arm, the lower limit 
of the 2-sided 80% Clopper Pearson CI for ORR estimate will be 
 assuming 
ORR estimate size of 
 respectively. 
10.1.5
The BMS-986288 in Combination with Nivolumab Cohort Expansion 
(Part 2B)
The purpose of the BMS-986288 Expansion Combination Therapy (Part 2B) is to gather additional 
data including safety, tolerability, and preliminary efficacy for combination therapy of BMS-
986288 with nivolumab in NSCLC. The sample size calculation will be based on the ORR.
Approximately 
 participants will be treated. Initial evaluation of efficacy signal (ORR) will be 
based on approximately the first 
 treated participants at a dose level and will be descriptive based 
on a point estimate and an 80% Clopper Pearson CI for ORR. In order for an 80% CI to exclude a 
 ORR (as reported for ipilimumab with nivolumab in similar population), at least responders 
(
 ORR) will need to be observed in the first 
 participants evaluated at this dose. If  
responders are observed 
, the 80% CI will equal 
. Based on the results 
of this initial evaluation, additional participants for a total of up to 
 participants may be treated 
at a dose level. If more than 1 dose level is evaluated, up to 
 participants (eg,
 participants 
arms) may be enrolled.
In addition, if 
 participants are evaluated at a dose level, there will be approximately 80% power 
to detect a difference between the null hypothesis assuming ORR of 
 and the alternative 
assuming ORR of 
, based on a one group χ2 test with a 0.10 one-sided significance alpha 
level.
10.1.6
The BMS-986288 in Combination with Nivolumab Cohort Expansion in 
MSS CRC Participants (Part 2C)
Part 2C of the study uses a 
 arm. A portion of the 
 cohort will be 
 
 
 These 
 studies will have a similar design and 
population to Part 2C (ie, similar enrolment methods, randomized population, similar inclusion 
and exclusion criteria, and baseline characteristics). Approximately 
 participants will be 
randomized in Part 2C. These 
 participants will be randomized in a 2:1 ratio for the experimental 
arm (Arm C) and control arm (Arm D) (
 participants for the experimental arm and 
participants for the control arm). An additional dose may be open in Part 2C as Arm E (see Section 
7.2). If multiple doses are open, no multiple comparison adjustments will be performed.
For each interim analysis of efficacy signal (ORR), no formal statistical comparison will be 
performed with a small administrative alpha of 0.0001. Interim analyses may be performed when 
at least 
participants in the experimental arm have at least 1 post-treatment tumor assessment
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(after 49 days). This will be a descriptive evaluation based on a point estimate. The study may be 
stopped early if the number of responders in the treatment arm is less than the number of 
responders in the control arm at interim analysis. For example, using this futility criteria, Bayesian 
predictive probability of success (with delta ORR of 
) is 
, with 
responders out of 
participants in the experimental arm and  responder out of 
participants in the control arm.
Based on the results of this initial evaluation, additional participants for a total of up to 
 
participants may be randomized to each existing experimental arm. See Section 10.3.8 for further 
information regarding interim analyses.
At the final analysis, there will be approximately 
 randomized participants in each experimental 
arm and 
 participants in the 
 arm (
 participants from the randomized control 
arm and 
 participants from the
 control data). This will provide approximately 80% 
power to detect the delta ORR of 
 with a two-sided alpha of 0.1. The trial can reach statistical 
significance when the delta ORR is 
 or larger. If it is not possible to borrow information 
from 
data or studies, approximately 
 randomized participants in the experimental arm 
and 
 participants from the randomized control arm will be evaluated. This will provide 
approximately 73% power to detect the delta ORR of 
 with a two-sided alpha of 0.1 and 
unpooled variance assumption.
10.2
Populations for Analyses
For purposes of analysis, the populations are defined in Table 10.2-1.
Table 10.2-1:
Populations for Analyses
Population
Description
Enrolled 
All participants who sign informed consent and are registered into the 
Interactive Response Technology (IRT)
Treated
All participants who take at least 1 dose of study treatment
Response-evaluable
All treated participants with measurable disease at baseline and 1 of the 
following: (a) at least 1 post baseline tumor assessment; (b) clinical progression; 
and (c) death
Pharmacokinetic
All treated participants who have evaluable concentration-time data
Immunogenicity
All treated participants who have baseline and at least 1 post-baseline 
pre-infusion immunogenicity assessment
Biomarker
All treated participants with available biomarker data
Clinical outcomes population 
(Part 2A and Part 2B only)
All treated participants who have a valid clinical outcomes assessment at 
baseline and at least 1 matched on-treatment post-baseline assessment
10.3
Statistical Analyses
The Statistical Analysis Plan will be developed and finalized before database lock, and 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.
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10.3.1
Efficacy Analyses
The primary efficacy analyses (Table 10.3.1-1) will be performed on the treated population for the 
final analysis. Efficacy analyses based on the treated population may be performed for interim 
analyses when the minimum follow-up period is less than sufficient to warrant adequate 
interpretation of the result. Details of the censoring scheme on time-to-event endpoints such as 
DOR, PFS, TTR, and OSR will be described in the Statistical Analysis Plan.
Analysis of exploratory endpoints using iRECIST by BICR (ORR, DOR, and PFS) will also be 
performed.
Table 10.3.1-1:
Efficacy - Statistical Analyses
Endpoint
Statistical Analysis Methods
ORR is defined as the proportion of all treated 
participants whose BOR is either CR or PR by 
Investigator (Part 2A/Part 2B) and BICR (Part 2C) per 
RECIST v1.1.
BOR for a participant will be assessed per 
RECIST v1.1 by Investigator (Part 2A/Part 2B) and 
BICR (Part 2C), unless otherwise specified.
Estimate of ORR and corresponding 2-sided exact 
95% CI using the Clopper-Pearson method by 
treatment for each tumor type.
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.
Estimate by the Kaplan-Meier method and 
corresponding 2-sided 95% CI using Brookmeyer and 
Crowley methodology (using log-log transformation) 
by treatment for each tumor type.
PFS
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. 
Estimate by the Kaplan-Meier method and 
corresponding 2-sided 95% CI using Brookmeyer and 
Crowley methodology (using log-log transformation)
by treatment for each tumor type.
TTR
TTR for a participant is defined as the time from the first 
dosing date to the date of the first confirmed response 
(CR or PR) per RECIST v1.1.
Listing of TTR will be provided.
OSR
OSR at a certain time point is defined as the proportion 
of subjects alive at that time point since the first dosing 
date.
Estimate by the Kaplan-Meier method and 
corresponding 2-sided 95% CI using Brookmeyer and 
Crowley methodology (using log-log transformation) 
by treatment for each tumor type.
Abbreviations: BICR = blinded independent central review; BOR = best overall response; CI = confidence interval; 
CR = complete response; DOR = duration of response; ORR = objective response rate; OSR = overall survival rate; 
PFS = progression-free survival; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; 
TTR = time to response.
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10.3.2
Safety Analyses
All safety analyses (see Table 10.3.2-1) will be performed on the treated population.
Table 10.3.2-1:
Safety - Statistical Analyses
Endpoint
Statistical Analysis Methods
Incidence of DLTs, AEs, SAEs, AEs leading to 
discontinuation, and death.
AEs will be graded according to CTCAE v5.0.
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 
system organ class level, and (3) once in the ‘total 
participant’ row at their worst CTC grade, regardless of 
system organ class or PT
Laboratory abnormalities.
Laboratory values will be graded according to 
CTCAE v5.0.
Laboratory shift table using the worst CTC grade 
on-treatment per participant
Abbreviations: AE = adverse event; DLT = dose-limiting toxicity; CTC = common terminology criteria; 
CTCAE = common terminology criteria for adverse events; PT = preferred term; SAE = serious adverse event.
10.3.3
Pharmacokinetic Analysis for BMS-986288
See Table 10.3.3-1 for PK statistical analyses.
Table 10.3.3-1:
Pharmacokinetic ‑ Statistical Analyses
Endpoint
Statistical Analysis Methods
Cmax, AUC(0-T), AUC(TAU), Ctau, CLT, Css-avg, 
AI_Cmax, AI_AUC, and T-HALF
Summary statistics: geometric means and coefficients of 
variation
Cmax, AUC(0-T), AUC(TAU)
Scatter plots vs dose for each cycle measured; dose 
proportionality based on a power model and a CI around 
the power coefficient
Tmax
Summary statistics: medians and ranges
Ctrough 
Summary statistics to assess attainment of steady state: 
geometric means and coefficients of variation, by 
treatment and by day; plots vs time by dose
Abbreviations: AI_AUC = ratio of an exposure measure at steady state to that after the first dose (exposure measure 
includes AUC[TAU]); AI_Cmax = ratio of an exposure measure at steady state to that after the first dose (exposure 
measure includes Cmax); AUC(0-T) = area under the plasma 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; CLT = total body 
clearance; Cmax = maximum observed concentration; 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; 
Ctrough = trough observed serum concentrations (this includes predose concentrations [C0] and Ctau); 
T-HALF = terminal serum half-life; Tmax = time of maximum observed plasma serum concentration. 
A non-compartmental or PPK approach will be used to assess the PK data and parameters such as 
Cmax, AUC(0-T), and bioavailability (F) will be assessed as feasible and applicable. PK 
concentration-time data for BMS-986288, and sparse plasma concentration-time for nivolumab 
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may be pooled with data from other studies for integrated PPK and ER analyses, which will be 
presented in a separate report.
10.3.4
Immunogenicity
Endpoint
Statistical Analysis Methods
Incidence of anti-drug antibodies (ADAs)
Baseline ADA-positive participant is defined as a participant 
who has an ADA-detected sample at baselinea,b
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
a Baseline sample is the last sample before initiation of the treatment.
b Details of the immunogenicity data analysis, including ADA titers, will be provided in the Statistical Analysis Plan.
10.3.5
Biomarker Analyses
Endpoint
Statistical Analysis Methods
Summary measures of change (or % change) from baseline in 
various biomarkers in the 
Summary statistics/plots by planned study day 
and dose in each arm 
Plots of the time course of biomarkers
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 mixed
effect model, if appropriate. The details of ECG data analysis will be provided in the Statistical 
Analysis Plan.
10.3.7
Other Analyses
Pharmacodynamic biomarker exploratory analyses and exploratory analyses of clinical outcomes 
assessments will be described in detail in the Statistical Analysis Plan finalized before database 
lock. OSR at 1 year and 2 years will be analyzed similarly to PFS. The population PK/ER and 
pharmacodynamic analyses may be presented separately from the main Clinical Study Report. 
10.3.8
Interim Analyses 
Interim analyses will be performed for administrative purposes or publication. No formal 
inferences requiring any adjustment to statistical significance level will be performed. 
Preliminary efficacy may be assessed for Part 2 to determine an initial signal, and enrollment may 
be paused, prior to enrolling additional participants. If an inadequate signal is detected from a 
preliminary analysis, then enrollment may be closed for that cohort.
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10.3.8.1
Bayesian Continuous Monitoring for Treatment-related Toxicities 
Meeting DLT Criteria in Part 2
A Bayesian continuous monitoring framework80 will be used to ascertain safety signals that occur 
during Part 2 that may lead to suspension or evaluation of toxicity by the Sponsor/Medical Monitor 
in BMS-986288 as a monotherapy and/or in combination with nivolumab participants. Incidence 
rates of treatment-related toxicities meeting DLT criteria (defined in Section 7.4.1) are compared 
to 33%.
The Bayesian safety monitoring boundaries are established using a noninformative prior, Beta 
(0.5, 0.5). The posterior distribution is Beta (0.5+n, 0.5+[m-n]), where m is number of treated 
Part 2 participants per dose level and n is the subset of these m participants who experience 
treatment-related toxicities meeting DLT criteria. All treated Part 2 participants are considered 
evaluable. The criterion for not continuing for future participants is based on the posterior 
probability of (treated Part 2 participants who experience treatment-related toxicities meeting DLT 
criteria > 33% | cumulative data) > 0.80. This criterion implies that continuation of BMS-986288 
as a monotherapy and/or in combination with nivolumab at that dose level in Part 2 will be re-
evaluated if there is greater than 80% probability that the number of participants with treatment-
related toxicities meeting DLT criteria is larger than 33%, corresponding to a final boundary of 
16 out of 40 total participants. When the stopping boundaries shown in Table 10.3.8.1-1 are met, 
further enrollment at that expansion dose level will be temporarily halted. Recommendations from 
interim calculations, and the totality of the data will be reviewed by the independent SMT. Based 
on the SMT’s review, the current dose level may be permanently discontinued, and a lower dose 
level will be evaluated in the remaining study part. Similar continuous safety monitoring will be 
applied to the new dose level being evaluated.
Table 10.3.8.1-1:
Monitoring Boundaries for Treatment-related Toxicities Meeting 
DLT Criteria in Part 2 
Number of Evaluable Participants: Treated Part 2 
Participants (Cumulative)
Critical Region: At or Above Number of Part 2 
Participants Who Experience Treatment-related 
Toxicities Meeting the DLT Criteria (Defined in 
Section 7.4.1) 
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Table 10.3.8.1-1:
Monitoring Boundaries for Treatment-related Toxicities Meeting 
DLT Criteria in Part 2 
Number of Evaluable Participants: Treated Part 2 
Participants (Cumulative)
Critical Region: At or Above Number of Part 2 
Participants Who Experience Treatment-related 
Toxicities Meeting the DLT Criteria (Defined in 
Section 7.4.1) 
Abbreviation: DLT = dose-limiting toxicity.
These boundaries can be applied on a continuous basis and are intended to assist the clinical 
interpretation. Other parameters may be considered and other posterior probabilities and 
boundaries may be calculated. Recommendations from interim monitoring calculations are not 
binding, and the totality of the data will be considered for decisions by SMT.
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11
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27 Final clinical study report for CA209012. A multi-arm phase 1 safety study of nivolumab in 
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35 Siemers NO, Holloway JL, Chang H, et al. Genome-wide association analysis identifies 
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38 Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N 
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40 CA209012: Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, 
Pemetrexed/Cisplatin, 
Carboplatin/Paclitaxel, 
Bevacizumab 
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Erlotinib, 
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41 CA209016: Nivolumab (BMS-936558; MDX-1106) in Combination With Sunitinib, 
Pazopanib, or Ipilimumab in Participants With Metastatic Renal Cell Carcinoma (RCC) 
(CheckMate 016). NCT01472081. 
42 Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in 
untreated melanoma. N Engl J Med 2015;372:2006-17. 
43 CA209067: Phase 3 Study of Nivolumab or Nivolumab Plus Ipilimumab Versus Ipilimumab 
Alone in Previously Untreated Advanced Melanoma (CheckMate 067). NCT01844505.
44 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 U S A 2010;107:4275-80. 
45 Wilky B, El-Khoueiry A, Bullock A, et al. 778 Botensilimab, a novel innate/adaptive immune 
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tumors. J Immunother Cancer 2022;10:doi: 10.1136/jitc-2022-SITC2022.0778.
46 Bullock AJ, Grossman JE, Fakih MG, et al. Botensilimab, a novel innate/adaptive immune 
activator, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable 
colorectal cancer. Annals of Oncology 2022;33:S376.
47 Sharma 
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challenges. Nat Rev Cancer 2016;16(2):121-6.
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expression dictates therapeutic response to anti-PD-1. Cancer Res 2015;75(18):3800-11.
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53 Felip E et al. Three-year follow-up from Checkmate 017/057: Nivolumab versus docetaxel in 
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54 Spigel DR, et al. Randomized results of continuous vs 1-year fixed-duration in patients with 
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Treated or Untreated Subjects with Advanced Melanoma. Bristol-Myers Squibb Company, 
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58 Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies 
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59 Momtaz P, Park V, Panageas KS, et al. Safety of Infusing Ipilimumab Over 30 Minutes. J Clin 
Oncol. 2015 Oct 20; 33(30): 3454–3458.
60 Bristol-Myers Squibb Company. Risk evaluation and mitigation strategy (REMS). FDA 
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62 Bai S, Jorga K, Xin Y, et al. A guide to rational dosing of monoclonal antibodies. Clin 
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30-Minute Infusion: Analysis of Data from CheckMate 153. ASCO poster #3059.
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69 Shitara K, Arita S, Shirakawa T, et al. REVERCE: randomized phase II study of regorafenib 
followed by cetuximab versus the reverse sequence for metastatic colorectal cancer patients 
previously treated with fluoropyrimidine, oxaliplatin, and irinotecan. J Clin Oncol 
2019;36:557.
70 Normanno N, Tejpar S, Morgillo F, et al. Implications for KRAS status and EGFR-targeted 
therapies in metastatic CRC. Nat Rev Clin Oncol 2009;6:519-27.
71 Rajagopalan H, Bardelli A, Lengauer C, et al. Tumorigenesis: RAF/RAS oncogenes and 
mismatch-repair status. Nature 2002;418:934.
72 National Comprehensive Cancer Network. https://www.nccn.org/guidelines/category_1.
75 McCarrier KP, Atkinson TM, DeBusk KP, et al. Patient-reported Outcome Consortium and 
Non–Small Cell Lung Cancer Working Group, 2016. Qualitative development and content 
validity of the Non–Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-
SAQ), a patient-reported outcome instrument. Clin Ther 2016;38:794-810.
76 Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-
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77 Pickard AS, De Leon MC, Kohlmann T, et al. Psychometric comparison of the standard EQ-
5D to a 5 level version in cancer patients. Med Care 2007;45:259-63.
78 Pearman TP, Beaumont JL, Mroczek D, et al. Validity and usefulness of a single-item measure 
of patient-reported bother from side effects of cancer therapy. Cancer 2018;124:991-7.
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1994;50:337-49.
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12
APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
3L/4L
3rd/4th line
ADA
anti-drug antibody
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
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
ALK
anaplastic lymphoma kinase
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AR
additional research
ART
antiretroviral therapy
AST
aspartate aminotransferase
AT
aminotransaminase
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of the 
last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
BA
bioavailability
BICR
blinded independent central review
BLRM
Bayesian Logistic Regression Model
BLRMc-MTD
Bayesian Logistic Regression Model-copula recommended maximum 
tolerated dose
BLRM-MTD
Bayesian Logistic Regression Model-recommended maximum tolerated 
dose
BMS
Bristol-Myers Squibb
BOR
best overall response
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Term
Definition
BUN
blood urea nitrogen
BW
body weight
C
Cycle
Cavg
average concentration
Cavgss
average steady-state concentration
CBC
complete blood count
CD
cluster of differentiation
CFR
Code of Federal Regulations 
CHMP
Committee for Medicinal Products for Human Use
CI
confidence interval
CL
clearance
CLT
total body clearance
Cmax
maximum observed concentration
Cmin
minimum observed concentration
CNS
central nervous system
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CR
complete response
CRC
colorectal cancer
CrCl
creatinine clearance
CRF
case report form
CT
computed tomography
CTAg
Clinical Trial Agreement
Ctau
concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.)
CTCAE
Common Terminology Criteria for Adverse Events
CTLA-4
cytotoxic T-lymphocyte-associated protein 4
Ctrough
trough-observed plasma concentration
D
Day
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Term
Definition
DILI
drug-induced liver injury
DLT
dose-limiting toxicity
DMC
Data Monitoring Committee
dMMR
mismatch repair deficient
DNA
deoxyribonucleic acid
DOR
duration of response
DRESS
drug reaction with eosinophilia and systemic symptoms
EC50
half-maximal effective concentration
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
eg
exempli gratia (for example)
eGFR
estimated glomerular filtration rate
EGFR
epidermal growth factor receptor
ELISA
enzyme-linked immunosorbent assay
EOI
end of infusion
EOT
end of treatment
EQ-5D-VAS
EQ-5D Visual Analog Scale
EQ-5D-3L
3-Level EQ-5D
EQ-5D-5L
5-Level EQ-5D
ER
exposure-response
EU
European Union
EWOC
escalation with overdose control
FACIT GP5
Functional Assessment of Chronic Illness Therapy, General Physical 
item
FcR
Fc gamma receptor
FDA
Food and Drug Administration
FIH
first in human
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Term
Definition
FSH
follicle stimulating hormone
GBS
Guillain-Barre Syndrome
GCP
Good Clinical Practice
GI
gastrointestinal
GLP
good laboratory practice
GMR
geometric mean ratio
h
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
hCG
human chorionic gonadotrophin
HCV
hepatitis C virus
HER2
human epidermal growth factor receptor 2
HFSR
hand-foot skin reaction
HIV
human immunodeficiency virus
HNSTD
highest non-severely toxic dose
HPV
human papilloma virus
HR
hazard ratio
HRQoL
health-related quality of life
IB
Investigator Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation 
ie
id est (that is)
IEC
Independent Ethics Committee
IFN
interferon
Ig
immunoglobulin
IgG
immunoglobulin G
IL
interleukin
imAE
immune-mediated adverse event
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Term
Definition
IMP
investigational medicinal product
INR
international normalized ratio
I-O
immuno-oncology
IP
investigational product
IPRES
Innate PD-1 RESistance
IQR
interquartile range
irAE
immune-related adverse event
IRB
Institutional Review Board
iRECIST
modified Response Evaluation Criteria in Solid Tumors in cancer 
immunotherapy trials
IRT
Interactive Response Technology
IU
International Unit
IUS
intrauterine hormone-releasing system
IV
intravenous
kg
kilogram
KLH
keyhole limpet hemocyanin
KRAS
Kirsten rat sarcoma virus
L
liter
LAM
lactation amenorrhea method
LDH
lactate dehydrogenase
mAb
monoclonal antibody
mCRC
metastatic colorectal cancer
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
MG
Myasthenia Gravis
min
minute
mL
milliliter
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Term
Definition
MMR
measles, mumps, rubella
MRI
magnetic resonance imaging
MSI-H
microsatellite instability high
MSS
microsatellite stable
MTD
maximum tolerated dose
g
microgram
N
number of participants or observations
NCI
National Cancer Institute
NF
non-fucosylated
ng
nanogram
NSCLC
non-small cell lung cancer
NSCLC-SAQ
Non-small Cell Lung Cancer Symptom Assessment Questionnaire
ORR
objective response rate
OS
overall survival
OSR
overall survival rate
PBMC
peripheral blood mononuclear cell
PBS
phosphate buffered saline
PCR
polymerase chain reaction
PD
progressive disease
PD-1
programmed cell death 1
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
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Term
Definition
PFS
progression-free survival
PFSR
progression-free survival rate
PI
prediction interval
PID
participant identification number
PK
pharmacokinetics
pMMR
proficient mismatch repair
PPK
population pharmacokinetics
PR
partial response
PRO
patient-reported outcome
Q2W
every 2 weeks
Q3W
every 3 weeks
Q6W
every 6 weeks
Q12W
every 12 weeks
QTc
QT interval corrected
QTcF
QT interval corrected for heart rate using Fridericia’s formula
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors
REMS
Risk Evaluation and Mitigation Strategy
RNA
ribonucleic acid
RP2D
recommended Phase 2 dose
RT-PCR
reverse transcription polymerase chain reaction
SAE
serious adverse event
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCCHN
squamous cell carcinoma of the head and neck
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Term
Definition
SD
stable disease
SJS
Stevens-Johnson syndrome
SmPC
summary of product characteristics
SMT
Safety Management Team
SNP
single nucleotide polymorphism
SUSAR
suspected, unexpected serious adverse reaction
T.bili
total bilirubin
TEN
toxic epidermal necrolysis
T-HALF
half-life
Tmax
time of maximum observed concentration
TNBC
triple-negative breast cancer
TNF-
tumor necrosis factor alpha
TRAE
treatment-related adverse event
Treg
T-regulatory cell
TSH
thyroid stimulating hormone
TTR
time to response
ULN
upper limit of normal
US
United States
USPI
United States Prescribing Information
Vss
apparent volume of distribution at steady state
Vz
volume of distribution of terminal phase (if IV and if multi-exponential 
decline)
WBC
white blood cell
WOCBP
women of childbearing potential
WWPS
Worldwide Patient Safety
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the eCRF is intended to refer to a person 
(Participant) who has consented to participate in the clinical research study.
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:

Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines, and Good Clinical Practice (GCP), 

as defined by the International Council on Harmonisation (ICH)

in accordance with the ethical principles underlying European Union Directive 2001/20/EC

United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 

applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to 
affect, to a significant degree, 1 or more of the following: (1) the physical, safety, or mental 
integrity of 1 or more subjects/particpants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, participant recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects/participants. The 
investigator or BMS should also provide the IRB/IEC with a copy of the Investigator Brochure or 
product labeling information to be provided to subjects/participants and any updates. 
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The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects/participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant  approval/favorable opinion(s) the deviation or change will be submitted, as 
soon as possible to:

IRB/IEC

Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
subjects/participants currently enrolled in the study if they are affected by the amendment; and 
(3) the new form must be used to obtain consent from new subjects/participants prior to 
enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
FINANCIAL DISCLOSURE
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that subjects/participants are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer 
to participate. 
In situations where consent cannot be given by subjects/participants, their legally acceptable 
representatives (as per country guidelines) are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which the participant 
volunteers to participate. 
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Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form which will include all elements required by ICH, GCP and applicable 
regulatory requirements. The sample informed consent form will adhere to the ethical principles 
that have their origin in the Declaration of Helsinki.
Investigators must:

Provide a copy of the consent form and written information about the study in the language in 
which the participant is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 

Allow time necessary for participant or participant's legally acceptable representative to 
inquire about the details of the study.

Obtain an informed consent signed and personally dated by the participant or the participant's 
legally acceptable representative and by the person who conducted the informed consent 
discussion. 

Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects/participants, prior to the beginning of 
the study, and after any revisions are completed for new information.
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant.
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects'/participants’ signed ICF and, in the US, the subjects’/participants’ signed HIPAA 
Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
The rights, safety, and well-being of the study subjects/participants are the most important 
considerations and should prevail over interests of science and society.
BMS COMMITMENT TO DIVERSITY IN CLINICAL TRIALS
The mission of BMS is to transform patients’ lives through science by discovering, developing, 
and delivering innovative medicines that help them prevail over serious diseases. 
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BMS is committed to doing its part to ensure that patients have a fair and just opportunity to 
achieve optimal health outcomes.
BMS is working to improve the recruitment of a diverse participant population with the goal that 
the clinical trial becomes more reflective of the real-world population and the people impacted by 
the diseases studied.
DATA PROTECTION, DATA PRIVACY, AND DATA SECURITY
BMS collects and processes personal data of study participants, patients, health care providers, 
and researchers for biopharmaceutical research and development to advance innovative, high-
quality medicines that address the medical needs of patients. BMS ensures the privacy, protection, 
and confidentiality of such personal data to comply with applicable laws. To achieve these goals, 
BMS has internal policies that indicate measures and controls for processing personal data. BMS 
adheres to these standards to ensure that collection and processing of personal data are limited and 
proportionate to the purpose for which BMS collects such personal data. This purpose is clearly 
and unambiguously notified to the individual at the time of collection of personal data. In the true 
spirit of science, BMS is dedicated to sharing clinical trial information and data with participants, 
medical/research communities, the media, policy makers, and the general public. This is done in a 
manner that safeguards participant privacy and informed consent while respecting the integrity of 
national regulatory systems. Clinical trial data, health-related research, and pharmacovigilance 
activities on key-coded health data transferred by BMS across national borders is done in 
compliance with the relevant data protection laws in the country and GCP requirements.
BMS protects Personal Information with adequate and appropriate security controls as indicated 
under the data protection laws. To align with the recommended security standards, BMS has 
adopted internal security standards and policies to protect personal data at every stage of 
its processing.
To supplement these standards, BMS enters into Clinical Trial Agreements (CTAgs) with 
confidentiality obligations to ensure proper handling and protection of personal data by third 
parties accessing and handling personal data.
BMS takes unauthorized access and disclosure of Personal Information very seriously. BMS has 
adopted the security standards that include National Institute of Standards and Technology 
Cybersecurity Framework for studies in the US. BMS aligns with these standards to continuously 
assess and improve its ability to protect, detect, and respond to cyber attacks and other 
unauthorized attempts to access personal data. These standards also aid in mitigating possible 
adverse effects. Furthermore, BMS Information Technology has defined 6 principles to protect our 
digital resources and information: 
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
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6) Internal Cyber Incident Investigation
SOURCE DOCUMENTS
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event tracking/reporting, protocol required assessments, and/or drug accountability 
records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
STUDY TREATMENT RECORDS
Records for study treatments (whether supplied by BMS, its vendors, or the site) must substantiate 
study treatment integrity and traceability from receipt, preparation, administration, and through 
destruction or return. Records must be made available for review at the request of BMS/designee 
or a Health Authority.
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If
Then
Supplied by BMS (or its 
vendors):
Records or logs must comply with applicable regulations and 
guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each participant, 
including unique participant identifiers

amount transferred to another area/site for dispensing or 
storage

nonstudy disposition (e.g., lost, wasted) 

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for 
bioavailability/bioequivalence/biocomparability, if 
applicable 

dates and initials of person responsible for Investigational 
Product dispensing/accountability, as per the Delegation 
of Authority Form.
Sourced by site, and not 
supplied by BMS or its 
vendors (examples include IP 
sourced from the sites stock or 
commercial 
supply, 
or 
a 
specialty pharmacy)
The investigator or designee accepts responsibility for 
documenting traceability and study treatment integrity in 
accordance with requirements applicable under law and the 
SOPs/standards of the sourcing pharmacy.
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
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be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
Sponsor or designee. 
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules in accordance with the applicable regulatory 
requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature is completed electronically through the 
BMS electronic data capture tool. The investigator must retain a copy of the CRFs including 
records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the BMS electronic data capture tool using the unique user 
account provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals
MONITORING
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as the source 
documents.
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to CRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities 
and promptly forward copies of inspection reports to Sponsor or designee. 
RECORDS RETENTION
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
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institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee. 
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials and syringes may be destroyed on site. 
If...
Then
Study treatments supplied by BMS 
(including its vendors
Any unused study treatments supplied by BMS can only 
be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study treatments 
containers must be immediately destroyed as required 
for safety, or to meet local regulations (eg, cytotoxics or 
biologics).
If study treatments will be returned, the return will be 
arranged by the responsible Study Monitor.
Study treatments sourced by site, not 
supplied by BMS (or its vendors) 
(examples include study treatments 
sourced from the sites stock or 
commercial supply, or a specialty 
pharmacy)
It is the investigator’s or designee’s responsibility to 
dispose of all containers according to the institutional 
guidelines and procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
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method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor
must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
CLINICAL STUDY REPORT
A Signatory Investigator must be selected to sign the clinical study report. 
For each CSR related to this protocol, the following criteria will be used to select the signatory 
investigator:

Participant recruitment (eg, among the top quartile of enrollers)

Regional representation (eg, among top quartile of enrollers from a specified region or country)

Other criteria (as determined by the study team)

SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTAg) governing [Study site or Investigator] participation in 
the study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTAg.
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
principal investigator, sub-investigator or any other member of the study staff without the prior 
written consent of the Sponsor.
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights and conclusion); AND 
2) Drafting the work or revising it critically for important intellectual content; AND 
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3) Final approval of the version to be published; AND 
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered. 
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
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 (6 months for studies including pediatric populations) of the end of trial in 
EU/European Economic Area and third countries.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW UP AND REPORTING
ADVERSE EVENTS
Adverse Event Definition:
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation participant administered study treatment 
and that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis.

Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae and 
should specify "intentional overdose" as the verbatim term
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
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SERIOUS ADVERSE EVENTS
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any 
dose:
Results in death
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it were 
more severe)
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE 
below)
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 

a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)

admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols)
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.8 for the definition of potential DILI.) 
Pregnancy and potential drug induced liver injury (DILI) must follow the same transmission timing 
and processes to BMS as used for SAEs (see Section 9.2.5 for reporting pregnancies).
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EVALUATING AES AND SAES
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor. However, it is very important that the 
investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to Sponsor.

The investigator may change his/her opinion of causality in light of follow-up information 
and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. (Note: 
Follow-up SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
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REPORTING OF SAES TO SPONSOR OR DESIGNEE

SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event.

SAEs must be recorded on the SAE Report Form.

The required method for SAE data reporting is through the eCRF.

The paper SAE Report Form is only intended as a back-up option when the electronic 
data capture (EDC) system is unavailable/not functioning for transmission of the eCRF 
to BMS (or designee).
In this case, the paper form is transmitted via email or confirmed facsimile (fax) 
transmission
When paper forms are used, the original paper forms are to remain on site

Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted via 
email or confirmed facsimile (fax) transmission 
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP

Premenarchal

Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Postmenopausal female

A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level 
> 40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgement in checking serum FSH levels. 

1-week minimum for vaginal hormonal products (rings, creams, gels)

4-week minimum for transdermal products

8-week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
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 
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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.
CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILD BEARING 
POTENTIAL
One of the highly effective methods of contraception listed below is required during study duration 
and until the end of relevant systemic exposure. For combination therapy with BMS-986288 plus 
nivolumab, relevant systemic exposure is defined as 125 days after the end of study treatment, plus 
30 days, for a total of 155 days post treatment completion. For monotherapy with BMS-986288, 
relevant systemic exposure is defined as 75 days after the end of study treatment, plus 30 days, for 
a total of 105 days post treatment completion.
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 (these methods of contraception cannot be used 
by WOCBP participants in studies where hormonal contraception is prohibited)b 

oral (birth control pills)

intravaginal (vaginal birth control suppositories, rings, creams, gels)

transdermal 

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 ovulationb 

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 cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited)b

Intrauterine device (IUD)c

Intrauterine hormone-releasing system (IUS; this method of contraception cannot be used 
by WOCBP participants in studies where hormonal contraception is prohibited)b,c

Bilateral tubal occlusion
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
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. 
If not, an additional highly effective method of contraception should be used. 

Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant.

Continuous abstinence must begin at least 30 days prior to initiation of study therapy.

It is not necessary to use any other method of contraception when complete abstinence is 
elected. 

WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence.

Periodic abstinence (including, but not limited to, calendar, symptothermal, post-ovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational 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 7.7.1 (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 7.7.1 
(Prohibited and/or Restricted Treatments) of the protocol.
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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

Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (this method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited)
Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus interruptus).

Spermicide only

Lactation amenorrhea method (LAM)
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and Appendix 3 Adverse Events and Serious 
Adverse Events: Definitions and Procedures for Evaluating, Follow-up and Reporting.
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APPENDIX 5
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS
1
EVALUATION OF LESIONS
Solid tumors will be evaluated using Response Evaluation Criteria In Solid Tumors version 1.1 
(RECIST v1.1) guideline with BMS modifications.1
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows:
1.1
Measurable
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of:

10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ≥2x slice thickness if 
greater than 5mm.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be 15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm).
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis 10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
1.2
Non-Measurable
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10mm or pathological lymph nodes with 10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
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1.3
Special considerations regarding lesion measurability
1.3.1
Bone lesions

Bone scan, PET scan and plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 

Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.

Blastic bone lesions are non-measurable.
1.4
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline (this means in 
instances where patients have only one or two organ sites involved a maximum of two and four 
lesions respectively will be recorded).
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum of
two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’).
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2
RESPONSE CRITERIA
2.1
Evaluation of Target Lesions

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.

Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed 
as either fully resolved or too small to measure (due to missing or poor quality images), and 
the sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above. 
2.1.1
Special Notes on the Assessment of Target Lesions
2.1.1.1
Lymph nodes
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target lesions, 
the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a normal 
lymph node is defined as having a short axis of < 10 mm. Case report forms or other data collection 
methods may therefore be designed to have target nodal lesions recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions.
2.1.1.2
Target lesions that become ‘too small to measure’
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned 
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
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small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 
default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm.
2.1.1.3
Lesions that split or coalesce on treatment
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’.
2.2
Evaluation of Non-Target Lesions
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need 
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol.

Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10mm short axis). 

Non-CR/Non-PD: Persistence of one or more non-target lesion(s)

Progressive Disease (PD): Unequivocal progression of existing non-target lesions.
2.2.1
Special Notes on Assessment of Progression of Non-Target Disease
The concept of progression of non-target disease requires additional explanation as follows:
2.2.1.1
When the patient also has measurable disease
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy A modest ‘increase’ in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. Pleural effusions, pericardial 
effusions and ascites will not be followed as target or non-target lesions and will not contribute to 
response or progression. The designation of overall progression solely on the basis of change in 
non-target disease in the face of SD or PR of target disease will therefore be extremely rare.
2.2.1.2
When the patient has only non-measurable disease
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
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disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 
if all lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the change 
in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in lymphangitic disease from localized to widespread, or may be 
described as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the 
patient should be considered to have had overall PD at that point. While it would be ideal to have 
objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore the increase must be substantial.
2.2.2
New Lesions
The appearance of new malignant lesions denotes disease progression; therefore, some comments 
on detection of new lesions are important. There are no specific criteria for the identification of 
new radiographic lesions; however, the finding of a new lesion should be unequivocal: ie, not 
attributable to differences in scanning technique, change in imaging modality or findings thought 
to represent something other than tumor (for example, some ‘new’ bone lesions may be simply 
healing or flare of pre-existing lesions). This is particularly important when the patient’s baseline 
lesions show partial or complete response. For example, necrosis of a liver lesion may be reported 
on a CT scan report as a ‘new’ cystic lesion, which it is not.
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new fluid 
collection is seen on a post-baseline imaging exam, a comment may be made, but the appearance 
of a new fluid collection alone should not result in an assessment of Progressive Disease (PD). A 
lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD).
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. While FDG-PET 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according 
to the following algorithm:
1) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion.
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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.
2.3
Response Assessment
2.3.1
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
disease progression or the last response recorded, taking into account any requirement for 
confirmation and censoring rules regarding subsequent therapy. The patient’s best overall response 
assignment will depend on the findings of both target and non-target disease and will also take into 
consideration the appearance of new lesions. Furthermore, depending on the nature of the study 
and the protocol requirements, it may also require confirmatory measurement.
2.3.2
Time Point Response
At each protocol specified time point, a response assessment occurs. Table 2.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) disease 
only, Table 2.3.2-2 is to be used. 
Table 2.3.2-1:
Time Point Response: Patients With Target (± Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable
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Table 2.3.2-2:
Time Point Response: Patients with Non-target Disease Only
Non-Target Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR = complete response, PD = progressive disease and NE = inevaluable
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.
2.3.3
Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point of 
4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as in 
Table 2.3.3-1. When SD is believed to be best response, it must meet the protocol specified 
minimum time from the date of first treatment.
For example, if the first scheduled follow-up imaging visit is Week 6 (± 7 days) for a particular 
protocol, a Best Response of SD can only be made after the subject is on-study for a minimum of 
6 weeks (42 days) minus 7 days, for an absolute minimum time on-study of 35 days from the 
reference start date (reference date is considered Day 1 on study).  If the subject is not on-study 
for at least this amount of time, any tumor assessment indicating stable disease before this time 
period will have a Best Response of NE unless PD is identified.
Special note on response assessment: When nodal disease is included in the sum of target lesions 
and the nodes decrease to ‘normal’ size (< 10 mm), they may still have a measurement reported 
on scans. This measurement should be recorded even though the nodes are normal in order not to 
overstate progression should it be based on increase in size of the nodes. As noted earlier, this 
means that patients with CR may not have a total sum of ‘zero’ on the case report form (CRF).
Table 2.3.3-1:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
CR
CR
CR
PR
SD, PD OR PRa
CR
SD
SD provided minimum criteria for SD duration met, 
otherwise, PD
CR
PD
SD provided minimum criteria for SD duration met, 
otherwise, PD
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anti-CTLA-4 NF Probody mAb
Table 2.3.3-1:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
NE
SD provided minimum criteria for SD duration met, 
otherwise, NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for SD duration met, 
otherwise, PD
PR
NE
SD provided minimum criteria for SD duration met, 
otherwise, NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and 
NE = inevaluable
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR.
2.3.4
Confirmation Scans
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a 
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation.
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease.
REFERENCES
1
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47.
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anti-CTLA-4 NF Probody mAb
APPENDIX 6
MANAGEMENT ALGORITHMS FOR IO AGENTS
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens.
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated.
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 
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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28-
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BMS-986288
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28-
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BMS-986288
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anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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BMS-986288
anti-CTLA-4 NF Probody mAb
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BMS-986288
anti-CTLA-4 NF Probody mAb
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BMS-986288
anti-CTLA-4 NF Probody mAb
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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BMS-986288
anti-CTLA-4 NF Probody mAb
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
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anti-CTLA-4 NF Probody mAb
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BMS-986288
anti-CTLA-4 NF Probody mAb
APPENDIX 8
SCHEDULE OF ACTIVITIES, PHARMACOKINETICS SAMPLING 
SCHEDULE, AND BIOMARKER SAMPLING SCHEDULE FOR 
POTENTIAL ALTERNATIVE DOSE SCHEDULES IN CA043001
Detailed in the tables below are the on-treatment schedule of activities, pharmacokinetic (PK) 
sampling schedule, and biomarker sampling schedule for potential alternative 
BMS-986288 dosing administration that may be explored in 
CA043001 following evaluation of preliminary safety, PK, and pharmacodynamic data from 
administration (Section 2). Decisions to initiate exploration of these 
alternative dose schedules will be made after discussion and agreement between the Investigators 
and the BMS Medical Monitor (or designee). If a cohort with a more frequent schedule of 
administration is explored, the dose level will be based on the PK data obtained from the 
 
dosing schedule, and will not exceed a dose equivalent determined to be tolerable. Implementation 
of these alternative dose schedules will not include the addition of new procedures and will be 
documented in a note to file or administrative letter.

Table 1: On-treatment Schedule of Activities for BMS-986288 Monotherapy Q3W Dosing 
Schedule in CA043001

Table 2: PK and ADA Sampling Schedule for BMS-986288 IV Q3W Monotherapy in Dose 
Escalation (Part 1A) and BMS-986288 IV Q3W 
 Cohort Expansion (Part 2A)

Table 3: Biomarker Sampling Schedule for BMS-986288 Monotherapy Q3W Dosing Schedule 
in CA043001

Table 4: On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in 
CA043001

Table 5: PK and ADA Sampling Schedule for BMS-986288 IV 
 (Part 1A 
and Part 2A)

Table 6: PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with 
Nivolumab IV 
 (Part 1B and Part 2B)

Table 7: Biomarker Sampling Schedule for 
 Dosing Schedule for All Study Parts in 
CA043001
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Table 1:
On-treatment Schedule of Activities for BMS-986288 Monotherapy 
 Dosing Schedule in CA043001
Procedure
Cycle 1 
(
 days in length)
Cycle 2 
(
 days in length)
Cycle 3 and Cycle 4 
(
days in length)
EOTa,b
Notes
D1
(2
days)
(2
days)
(2
days)
(2
days)
(2
days)
D1
(2 days)
Safety Assessments
ECOG Performance 
Status
X
X
X
X
PE
X
X
X
X
For the site of 
 administration in 
, 
careful observation and examination of the 
 is required.c
Symptom-directed PE
X
X
X
X
For the site of 
 administration in 
, 
careful observation and examination of the 
 is required.c
Weight
X
X
X
X
Vital Signsd
X
X
X
X
X
X
X
X
Oxygen Saturationd
X
X
X
ECGe
X
X
X
X
Triplicate ECGs performed at predose and EOI 
on C1D1 and C4D1 for Part 1A only. Single 
safety ECGs to be performed for all other time 
points.
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anti-CTLA-4 NF Probody mAb
Table 1:
On-treatment Schedule of Activities for BMS-986288 Monotherapy 
 Dosing Schedule in CA043001
Procedure
Cycle 1 
(
 days in length)
Cycle 2 
(
 days in length)
Cycle 3 and Cycle 4 
(
days in length)
EOTa,b
Notes
D1
(2
days)
(2
days)
(2
days)
(2
days)
(2
days)
D1
(2 days)
Laboratory Tests
X
X
X
X
X
X
X
X
There will be a 72-hour window for collection 
of laboratory tests on D1. If screening is within 
72 hours of C1D1, laboratory tests performed at 
screening can be used for C1D1. Coagulation 
assessment at screening only. See Section 9.4.5
and Table 9.4.5-1 in the main protocol.
Urinalysis 
X
X
For Cycle 3 and 
Cycle 4, as clinically 
indicated; 
microscopic urine 
reflex only for 
urinalysis positive for 
blood/protein/
leukocyte esterase.
X
Pregnancy Test 
(WOCBP only)g
X
X
X
X
Adverse Event Reporting and Concomitant Medication Assessments
Monitor for 
Non-SAEs
Non-SAEs will be collected continuously starting with the first dose of study 
medication and through 100 days following last dose of study treatment.
See Appendix 3 and Section 9.2 in the main 
protocol.
All AEs (SAEs or nonserious AEs) including 
those associated with SARS-CoV-2 infection 
must be collected continuously during the 
treatment period.
Monitor for SAEs
All SAEs must be collected continuously from the date of the participant’s written 
consent until 100 days following last dose of study treatment.
See Appendix 3 and Section 9.2 in the main 
protocol.
All AEs (SAEs or nonserious AEs) including 
those associated with SARS-CoV-2 infection 
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anti-CTLA-4 NF Probody mAb
Table 1:
On-treatment Schedule of Activities for BMS-986288 Monotherapy 
 Dosing Schedule in CA043001
Procedure
Cycle 1 
(
 days in length)
Cycle 2 
(
 days in length)
Cycle 3 and Cycle 4 
(
days in length)
EOTa,b
Notes
D1
(2
days)
(2
days)
(2
days)
(2
days)
(2
days)
D1
(2 days)
must be collected continuously during the 
treatment period.
Concomitant 
Medications 
X
X
X
X
X
X
X
X
PK Assessments
 
Immunogenicity 
(ADA) Assessments
See Table 2 in Appendix 8 for the PK and immunogenicity sampling schedule and 
Section 9.5 in the main protocol.
 
See Table 3 in Appendix 8 for the biomarker sampling schedule and Section 9.8 in 
the main protocol.
Imaging Assessments
Body Imagingh
See Section 9.1.1 in the main protocol. Contrast-enhanced CT of the chest, CT/MRI 
of the abdomen, pelvis, and all other known and/or suspected sites of disease should 
occur 
 (7 days) starting from the first dose up until Week 
. Imaging 
assessments should then occur 
 (7 days). 
For participants with cancer of the head and neck, a CT or MRI of the neck is 
required.
For participants with TNBC without measurable lesions outside of the breast, 
contrast-enhanced MRI of the breasts should be performed.
Brain Imaging
See Section 9.1.1 in the main protocol. Participants with history of brain metastasis 
should have surveillance MRI performed approximately every 12 weeks or sooner if 
clinically indicated. CT of the brain without and with contrast can be performed if 
MRI is contraindicated. See Section 9.1.1.1 in the main protocol for further details.
Bone Scan
As clinical indicated per local standards (see Section 9.1.1 in the main protocol).
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Table 1:
On-treatment Schedule of Activities for BMS-986288 Monotherapy 
 Dosing Schedule in CA043001
Procedure
Cycle 1 
(
 days in length)
Cycle 2 
(
 days in length)
Cycle 3 and Cycle 4 
(
days in length)
EOTa,b
Notes
D1
(2
days)
(2
days)
(2
days)
(2
days)
(2
days)
D1
(2 days)
Biomarker Assessments
See Section 9.5 and Section 9.8 in the main 
protocol and Table 3 in Appendix 8. 
X
Mandatory 
 must be performed at 
C2
; specimens may be collected within 
3 days of the time point.
Required 
Post-progression 
 
A 
 is required upon confirmation of PD (within 7 days) except for: 
1) participants who have an 
 and progress within 4 cycles; 
2) participants who will be imminently (within 4 weeks) enrolling in a subsequent 
clinical research study that requires a screening 
 and 3) participants who 
consent to be treated beyond progression will require the 
 only at the 
subsequent confirmation of progression.
See 
 in the main protocol.
Blood/Serum/Plasma 
Pharmacodynamic 
Sampling
See Table 3 in Appendix 8 for details of biomarker assessments.
See Section 9.5 and Section, 9.8 in the main 
protocol, Table 3 in Appendix 8, and refer to 
Laboratory Manual.
Exploratory Biomarker Assessments 
See Section 9.5 and Section 9.8 in the main 
protocol and Table 3 in Appendix 8.
Clinical Treatment Supplies
BMS-986288 
Administration 
X
X
X
BMS-986288 to be supplied by BMS. 
BMS-986288 to be administered for up to a 
maximum of 4 doses.
Clinical Outcomes Assessments (Part 2 Only)
NSCLC-SAQ
X
X
X
X
Clinical outcomes assessments to be administered 
in Part 2 only. NSCLC-SAQ will only be 
FACT GP5
X
X
X
X
X
X
X
X
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anti-CTLA-4 NF Probody mAb
Table 1:
On-treatment Schedule of Activities for BMS-986288 Monotherapy 
 Dosing Schedule in CA043001
Procedure
Cycle 1 
(
 days in length)
Cycle 2 
(
 days in length)
Cycle 3 and Cycle 4 
(
days in length)
EOTa,b
Notes
D1
(2
days)
(2
days)
(2
days)
(2
days)
(2
days)
D1
(2 days)
EQ-5D-5L
X
X
X
X
administered to NSCLC participants. Data will be 
collected using electronic devices. See Section 
9.1.2 in the main protocol.
Abbreviations: ADA = anti-drug antibody; BMS = Bristol-Myers Squibb; C= cycle; CT = computed tomography; CXDY = Cycle X Day Y, as an example; D = day; 
DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOT = end of treatment; EQ-5D-
5L = 5-Level EQ-5D; FACT GP5 = Functional Assessment of Cancer Therapy Item GP5; hCG = human chorionic gonadotropin; IgG = immunoglobulin G; MRI 
= magnetic resonance imaging; NSCLC = non-small cell lung cancer; NSCLC-SAQ = Non-small Cell Lung Cancer Symptom Assessment Questionnaire; PD = 
progressive disease; PE = physical examination; PK = pharmacokinetic; 
 RECIST = Response Evaluation Criteria in Solid Tumors; 
 
 SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; TNBC = triple-negative 
breast cancer; WOCBP = women of childbearing potential.
a EOT is defined as the visit where the decision is made to discontinue the participant from treatment. Evaluations will be performed prior to study discharge, or 
for participants who are prematurely discontinued.
b For participants who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C4D21) 
and 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 most recent 
on-treatment visit (with all available safety and response data); it does not need to be repeated and will be considered as the start of the safety follow-up period.
c In participants administered BMS-986288 
, the Investigator or designated study staff will assess the proposed 
 for signs of local irritation and 
inflammation. The proposed 
 will be evaluated prior to all 
 doses and approximately 
 after the
. There are pre-specified 
 reactions of interest: 
 erythema;
 pain, 
 pruritus, 
hematoma, 
, and
 
 induration. 
 reactions will be recorded as AEs on the appropriate page of the case report form. In addition, all participants will be contacted 
approximately 24 hours after each
 for reporting of 
reactions. The 
 will be also be evaluated at the next study visit.
d Vital signs will be obtained before the 
 of BMS-986288 and then every 15 minutes (5 minutes) until 
 after completion of the 
 
for first 3 doses of study treatment on C1D1, C2D1, and C3D1; oxygen saturation to also be performed in conjunction with vital signs monitoring on these days. 
For C4, vital signs and oxygen saturation are to be taken before the infusion and at the end of infusion. If any vital sign is abnormal (based upon clinician 
assessment) at the final check, the participant must be observed further for a period of time, as clinically indicated.
e ECGs should be recorded after the participant has been supine for at least 5 minutes and prior to blood draws. ECGs to be performed in triplicate in association 
with time-matched PK sampling at predose and EOI on C1D1 and C4D1 for the BMS-986288 Monotherapy Escalation (Part 1A) only (see Section 9.4.4 of main 
protocol). Single safety ECGs to be performed for all other time points.
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anti-CTLA-4 NF Probody mAb
g Serum/urine to be collected within 24 hours prior to dosing. Pregnancy test may be completed on the first day of treatment, provided the results are available 
before the start of study therapy. Serum or urine pregnancy test must be performed within 24 hours prior to administration of study treatment (urine pregnancy 
test: minimum sensitivity 25 IU/L or equivalent units of hCG).
h The same imaging modality is to be used for all assessments, per RECIST v1.1 (Appendix 5). Tumor assessment to be performed prior to initiating next cycle 
of treatment.
i
Pre-treatment (screening) 
 can be performed optionally on C1D1. Mandatory 
 must be performed at C2D8; specimens may be collected 
within 3 days of the time point and must be obtained prior to administration of study treatments. Bone lesion 
 are unacceptable for submission. 
See
 of main protocol.
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BMS-986288
anti-CTLA-4 NF Probody mAb
Table 2:
PK and ADA Sampling Schedule for BMS-986288 IV 
 
Monotherapy in Dose Escalation (Part 1A) and BMS-986288 IV 
 
 Cohort Expansion (Part 2A)
Study Day of Sample 
Collection
(1 Cycle =
)
Event
Time (Relative to Start of 
BMS-986288 
)a
Hour:Minute
BMS-986288 PK 
 Sample 
BMS-986288 ADA 
 Sample 
C1D1
Predoseb
00:00
X
X
EOI
See notec
X
X
C1
X
C1
X
C1
X
C1
X
C2
Predoseb
00:00
X
X
EOI
See notec
X
C2
d (3 days)
168:00
X
C3D1
Predoseb
00:00
X
X
EOI
See notec
X
C4D1
Predoseb
00:00
X
X
EOI
See notec
X
X
C4
X
C4
X
C4
X
C4
X
EOT
X
X
30-day follow-up
X
X
60-day follow-up
X
X
100-day follow-up
X
X
Grade 3+ Infusion 
Reaction
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion; EOT = end of treatment; 
IV = intravenous; 
.
a Every effort should be taken to collect the sample as close to the designated time as possible. The actual time of 
collection should be recorded.
b Predose: All predose samples should be taken within 30 minutes prior to the start of the infusion/administration.
c EOI PK samples should be collected when all study drug has been infused. If a flush is administered to clear the IV 
lines of the drug and to ensure delivery of the entire drug dose, then draw the EOI PK sample within approximately 
15 minutes after end of the flush. Do not draw EOI samples from the same IV access through which the drug was 
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anti-CTLA-4 NF Probody mAb
administered. Refer to the Pharmacy Manual for infusion duration. If the EOI is delayed beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly.
d Sample should be collected with 
 (see Table 3 in Appendix 8).
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anti-CTLA-4 NF Probody mAb
Table 3:
Biomarker Sampling Schedule for BMS-986288 Monotherapy 
 Dosing Schedule in CA043001
Study Day of 
Sample Collection
 
Time (Relative to 
BMS-986288 Dose)
Hour:Min
Screening
X
C1D1
00:00c
X
X
X
X
X
X
EOId
X
C1
X
X
X
C1
X
X
X
C1
X
X
X
C2D1
00:00c
X
EOId
X
C2
b (3 days)
168:00
X
X
X
X
X
X
X
C2D15 (2 days)
336:00
X
X
X
C3D1
00:00c
X
X
X
EOId
X
C3D8 (2 days)
168:00
X
X
X
C3D15 (2 days)
336:00
X
C4D1
00:00c
X
X
X
X 
EOT or at 
Progression
X
X
X
X
X
X
X
Abbreviations: C = cycle; CXDY = Cycle X Day Y, as an example; D = day; EOI = end of infusion; EOT = end of treatment; 
.
a Instructions for the collection and processing 
 will be provided in the Laboratory Manual.
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b Pre-treatment (screening) 
 can be performed optionally on C1D1. Mandatory 
 to be performed at C2D8; specimens may be 
collected within 3 days of the time point and must be obtained prior to administration of study treatments. C2D8 biomarker collections should occur at the same 
time as 
. Adjust the biomarker collection in accordance with the 
 collection. An optional additional 
 can be collected on-
treatment if the Investigator and the Medical Monitor (or designee) find it indicated. A 
 is required upon confirmation of PD (within 7 days) except 
for participants: 1) who have an 
 and progress within 4 cycles, 2) participants who will be imminently (within 4 weeks) enrolling in a 
subsequent clinical research study that requires a screening 
, and 3) participants who consent to be treated beyond progression will require the 
 only 
at the subsequent confirmation of progression. Bone lesion 
are unacceptable for submission.
c All predose samples should be taken prior to the start of the infusion/administration.
d EOI samples should be taken after the infusion/administration of study treatment. Refer to the Pharmacy Manual for infusion duration. EOI is defined as the end 
of infusion/administration.
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anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
Safety Assessments
ECOG Performance 
Status
X
X
X
X
PE
X
X
X
X
For the site of 
 
administration in 
, 
careful observation and 
examination of the 
 
 is required.c
Symptom-directed PE
X
X
X
X
X
X
For the site of 
 
administration in 
, 
careful observation and 
examination of the 
 
is required.c
Weight
X
X
X
X
Vital Signsd
X
X
X
X
X
X
X
X
X
X
Oxygen Saturationd
X
X
X
ECGe
X
X
X
X
Triplicate ECGs performed 
at predose and EOI on 
C1D1 and C5D1 for Part 1A 
only. Single safety ECGs to 
be performed for all other 
time points.
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anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(2 days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
D  
(2 
days)
D
 
(2 
days)
D
 
(2 
days)
D1 
(2 
days)
D  
(2 
days)
D
 
(2 
days)
D
 
(2 
days)
D1 
(2 days)
Laboratory Tests
X
X
X
X
X
X
X
X
X
X
There will be a 72-hour 
window for collection of 
laboratory tests on D1. If 
screening laboratory tests 
are within 72 hours of 
C1D1, laboratory tests 
performed at screening can 
be used for C1D1. 
Coagulation assessment at 
screening only. 
See Section 9.4.5 and 
Table 9.4.5-1 in the main 
protocol.
Urinalysis
X
X
As clinically 
indicated; 
microscopic 
urine reflex only 
for urinalysis 
positive for 
blood/protein/ 
leukocyte 
esterase.
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BMS-986288
anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
Pregnancy Test 
(WOCBP only)h
X
X
X
X
Adverse Event Reporting and Concomitant Medication Assessments
Monitor for Non-SAEs
Non-SAEs will be collected continuously starting with the first dose of study medication 
and through 100 days following last dose of study treatment.
See Appendix 3 and 
Section 9.2 in the main 
protocol.
All AEs (SAEs or 
nonserious AEs) including 
those associated with 
SARS-CoV-2 infection 
must be collected 
continuously during the 
treatment period.
Monitor for SAEs
All SAEs must be collected continuously from the date of the participant’s written consent 
until 100 days following last dose of study treatment.
See Appendix 3 and 
Section 9.2 in the main 
protocol.
All AEs (SAEs or 
nonserious AEs) including 
those associated with 
SARS-CoV-2 infection 
must be collected 
continuously during the 
treatment period.
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
PK Assessments
Immunogenicity 
(ADA)
Assessments
See Table 5 and Table 6 in Appendix 8 for the PK and immunogenicity sampling schedule and 
Section 9.5 in the main protocol.
 
See Table 5 and Table 6 in Appendix 8 for the biomarker sampling schedule and Section 9.8 in the 
main protocol.
Imaging Assessments
Body Imagingi
See Section 9.1.1 in the main protocol. Contrast-enhanced CT of the chest, CT/MRI of the abdomen, 
pelvis, and all other known and/or suspected sites of disease should occur 
 (7 days) 
starting from the first dose up until Week 48. Imaging assessments should then occur 
 
(7 days). 
For participants with cancer of the head and neck, a CT or MRI of the neck is required.
For participants with TNBC without measurable lesions outside of the breast, contrast-enhanced MRI 
of the breasts should be performed.
Brain Imaging
See Section 9.1.1 in the main protocol. Participants with history of brain metastasis should have 
surveillance MRI performed approximately every 12 weeks or sooner if clinically indicated. CT of 
the brain without and with contrast can be performed if MRI is contraindicated. 
Bone Scan
As clinically indicated per local standards (see Section 9.1.1 in the main protocol). 
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CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
 
X
X
A mandatory 
 
must be performed at C1D8; 
specimens may be collected 
within 3 days of the time 
point. While not preferred, 
if a 
at C1D8 is not 
collected, then a 
 at 
C3D5 (3 days) must be 
performed.
Required 
Post-progression 
A 
 is required upon confirmation of PD (within 7 days) except for: 1) participants who 
have an 
 and progress within 4 cycles; 2) participants who will be imminently 
(within 4 weeks) enrolling in a subsequent clinical research study that requires a screening 
; 
and 3) participants who consent to be treated beyond progression will require the 
 only at the 
subsequent confirmation of progression.
See 
 in the 
main protocol.
Blood/Serum/Plasma 
Pharmacodynamic 
Sampling
See Table 7 in Appendix 8 for details of biomarker assessments.
See Section 9.5 and 
Section 9.8 in the main 
protocol and refer to 
Laboratory Manual.
Exploratory Biomarker Assessments
See Section 9.5 and 
Section 9.8 in the main 
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Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
protocol and Table 7 in
Appendix 8.
Clinical Treatment Supplies
BMS-986288 
Administration 
X
X 
(Every other 
cycle starting at 
Cycle 3 [eg, C3, 
C5, C7, etc])
BMS-986288 to be supplied 
by BMS.
Nivolumab 
Administration 
 
(Part 1B, 
 
Arm B, Part 2B)
X
X
X
Nivolumab to be supplied 
by BMS.
Clinical Outcomes Assessments (Part 2 Only)
NSCLC-SAQ
X
X
X
X
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Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 4:
On-treatment Schedule of Activities for 
 Dosing Schedule for All Study Parts in CA043001
Procedure
Cycle 1
(
 days in length)
Cycle 2
(
days in length)
Cycles 3 and 
Beyond
(each cycle 
days 
in length)
EOTa,b
Notes
D1
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
(2 
days)
D1 
(2 days)
FACT GP5
X
X
X
X
X
X
X
X
X
X
Clinical outcomes 
assessments to be 
administered in Part 2 only. 
NSCLC-SAQ will only be
administered to NSCLC 
participants. Data will be 
collected using electronic 
devices. See Section 9.1.2 in 
the main protocol.
EQ-5D-5L
X
X
X
X
Abbreviations: ADA = anti-drug antibody; BMS = Bristol-Myers Squibb; C = cycle; CT = computed tomography; CXDY = Cycle X Day Y, as an example; 
D = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOT = end of treatment; 
EQ-5D-5L = 5-Level EQ-5D; FACT GP5 = Functional Assessment of Cancer Therapy Item GP5; hCG = human chorionicgonadotropin; IgG = immunoglobulin G;
MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer; NSCLC-SAQ = Non-small Cell Lung Cancer Symptom Assessment Questionnaire; PD 
= progressive disease; PE = physical examination; PK = pharmacokinetic; 
 RECIST = Response Evaluation Criteria in Solid Tumors; 
 SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2;
 TNBC = triple-negative breast cancer; WOCBP = women of childbearing potential.
a EOT is defined as the visit where the decision is made to discontinue the participant from treatment. Evaluations will be performed prior to study discharge, or
for participants who are prematurely discontinued.
b For participants who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C26D1)
and 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 most recent 
on-treatment visit (with all available safety and response data); it does not need to be repeated and will be considered as the start of the safety follow-up period.
c In participants administered BMS-986288 or nivolumab 
, the Investigator or designated study staff will assess the proposed 
 
. The proposed 
will be evaluated prior to all 
 doses and approximately 
. There are pre-
specified 
 
will be recorded as AEs on the appropriate page of the case report form. In addition, all participants will be 
contacted approximately 24 hours after each 
 for reporting of 
 reactions. The 
 will be also be evaluated at the next study 
visit.
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anti-CTLA-4 NF Probody mAb
d Vital signs will be obtained before the 
 of BMS-986288 and then every 15 minutes (5 minutes) until 
 after completion of the infusion 
for first 3 doses of study treatment on C1D1, C3D1, and C5D1; oxygen saturation to also be performed in conjunction with vital signs monitoring on these days.
For all cycles after C5 and for the nivolumab infusion, vital signs and oxygen saturation are to be taken before the infusion and at the end of infusion. If any 
vital sign is abnormal (based upon clinician assessment) at the final check, the participant must be observed further for a period of time, as clinically indicated.
e ECGs should be recorded after the participant has been supine for at least 5 minutes and prior to blood draws. ECGs to be performed in triplicate in association
with time-matched PK sampling at predose and EOI on C1D1 and C5D1 for the BMS-986288 Monotherapy Escalation (Part 1A) only (see Section 9.4.4 of the 
main protocol). Single safety ECGs to be performed for all other time points.
g Eye exam is to be performed every other cycle prior to dosing, starting with Cycle 3 (ie, Cycle 3, Cycle 5, etc.) and at EOT.
h Serum/urine to be collected within 24 hours prior to BMS-986288 or nivolumab dosing. For BMS-986299 monotherapy this would be collected prior to Day 1 
of odd cycles (eg, Cycle 1, Cycle 3, Cycle 5, etc), for BMS-986288 in combination with nivolumab this would be collected prior to Day 1 of all cycles. Pregnancy 
test may be completed on the first day of treatment, provided the results are available before the start of study therapy. Serum or urine pregnancy test must be 
performed within 24 hours prior to administration of study treatment (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG).
i
The same imaging modality is to be used for all assessments, per RECIST v1.1 (Appendix 5). Tumor assessment to be performed prior to initiating next cycle
of treatment.
j
Mandatory 
 must be performed at C1D8; specimens may be collected within 3 days of the time point. While not preferred, if a 
 at C1D8 is 
not collected, then a 
 at C3D5 (3 days) must be performed.
 are not required to be collected at both C1D8 and C3D5. Bone lesion 
are 
unacceptable for submission. See 
 of the main protocol.
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Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 5:
PK and ADA Sampling Schedule for BMS-986288 IV 
 
 (Part 1A and Part 2A)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to Start of 
BMS-986288 Infusion) 
Hr:Mina
BMS-986288 PK 
Sample
BMS-986288 ADA
 
Sample
C1D1
Predoseb
00:00
X
X
EOI
See notec
X
04:00
X
C1
X
C1
X
C1
X
C1
X
C1
X
C2D1
672:00
X
X
C2
 (2 days)
840:00
X
C3D1 
Predoseb
00:00
X
X
EOI
See notec
X
C3D5d
96:00
X
C4D1
672:00
X
X
C5D1
Predoseb
00:00
X
X
EOI
See notec
X
X
C5
X
C5
X
C5
X
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Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 5:
PK and ADA Sampling Schedule for BMS-986288 IV 
 
 (Part 1A and Part 2A)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to Start of 
BMS-986288 Infusion) 
Hr:Mina
BMS-986288 PK 
Sample
BMS-986288 ADA 
 
Sample
C5
X
C5
X
C6D1
672:00
X
C7D1
Predoseb
00:00
X
X
Every fourth cycle after C7 
until EOT (C11D1, C15D1, 
C19D1, etc until EOT)
Predoseb
00:00
X
X
EOT
X
X
30-day follow-up
X
X
60-day follow-up
X
X
100-day follow-up
X
X
Grade 3+ Infusion Reaction
X
X
Abbreviations: C = Cycle; D = Day; EOI = end of infusion; EOT = end of treatment; IV = intravenous; PK = pharmacokinetics; 
.
a Every effort should be taken to collect the sample as close to the designated time as possible. The actual time of collection should be recorded.
b Predose: All predose samples should be taken within 30 minutes prior to the start of the infusion of BMS-986288.
c EOI PK samples should be collected when all study drug has been infused. If a flush is administered to clear the IV lines of the drug and to ensure delivery of 
the entire drug dose, then draw the EOI PK sample within approximately 15 minutes after end of the flush. Do not draw EOI samples from the same IV access 
through which the drug was administered. Refer to the Pharmacy Manual for infusion duration. If the EOI is delayed beyond the nominal infusion duration, the 
collection of this sample should also be delayed accordingly.
d Sample should be collected with 
 (see Table 7 in Appendix 8). C3D5 PK sample is only collected if participant is scheduled for corresponding 
, while C1D  PK sample should be collected irrespective of corresponding 
.
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Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
Table 6:
PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with Nivolumab IV 
(Part 1B and Part 2B)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to Start of 
Nivolumab Infusion) Hr:Mina
BMS-986288 PK 
Sample 
Nivolumab PK 
 Sample
BMS-986288 ADA 
 Sample
Nivolumab ADA 
 Sample
C1D1
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
04:00
X
C1
X
C1
X
C1
X
C1
X
C1
X
C2D1
Predoseb
00:00
X
X
X
X
C2
 (2 days)
168:00
X
X
C3D1 
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
C3D5d
96:00
X
C4D1
Predoseb
00:00
X
X
X
X
C5D1
Predoseb
00:00
X
X
X
X
EOI
See notec
X
X
04:00
X
C5
X
X
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Table 6:
PK and ADA Sampling Schedule for BMS-986288 IV 
 in Combination with Nivolumab IV 
(Part 1B and Part 2B)
Study Day of Sample 
Collection
(1 Cycle = 
)
Event
Time (Relative to Start of 
Nivolumab Infusion) Hr:Mina
BMS-986288 PK 
Sample 
Nivolumab PK 
 Sample
BMS-986288 ADA 
 Sample
Nivolumab ADA 
 Sample
C5
X
C5
X
C5
X
C6D1
Predoseb
00:00
X
X
X
X
C7D1
Predoseb
00:00
X
X
X
X
Every fourth cycle 
after C7 until EOT 
(C11D1, C15D1, 
C19D1, etc until EOT)
Predoseb
00:00
X
X
X
X
EOT
X
X
X
X
30-day follow-up
X
X
X
X
60-day follow-up
X
X
X
X
100-day follow-up
X
X
X
X
Grade 3+ Infusion 
Reaction
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOI = end of infusion; EOT = end of treatment; IV = intravenous; PK = pharmacokinetics; 
.
a Every effort should be taken to collect the sample as close to the designated time as possible. The actual time of collection should be recorded.
b Predose: All predose samples should be taken within 30 minutes prior to the start of the infusion of nivolumab.
c EOI PK samples should be collected when all study drug has been infused. If a flush is administered to clear the IV lines of the drug and to ensure delivery of 
the entire drug dose, then draw the EOI PK sample within approximately 15 minutes after end of the flush. Do not draw EOI samples from the same IV access 
through which the drug was administered. Refer to the Pharmacy Manual for infusion duration. If the EOI is delayed beyond the nominal infusion duration, the 
collection of this sample should also be delayed accordingly.
d Sample should be collected with 
 (see Table 7 in Appendix 8). C3D5 PK sample is only collected if participant is scheduled for corresponding 
, while C1D  PK sample should be collected irrespective of corresponding
.
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Table 7:
Biomarker Sampling Schedule for 
 Dosing Schedule for All Study Parts in CA043001
Study Day of Sample 
Collection
(1 Cycle = 
)
Time (relative to 
BMS-986288 dose) 
Hour:Min
Screening
X
C1D1
00:00c
X
X
X
X
X
X
EOId
X
C1D2
24:00
X
X
X
C1D8b (3 days)
168:00
X
X
X
X
X
X
X
C1D15
(2 days)
336:00
X
X
X
C1D22
(2 days)
504:00
X
C2D1e
672:00
X
X
X
C2D8
(2 days)
840:00
X
X
X
C2D15
(2 days)
984:00
X
X
C2D22
(2 days)
1152:00
X
X
C3D1
00:00c
X
EOId
X
C3D5b (3 days)
96:00
X
X
X
X
X
X
X
C3D15 (2 days)
336:00
X
X
X
C3D22 (2 days)
840:00
X
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Table 7:
Biomarker Sampling Schedule for 
 Dosing Schedule for All Study Parts in CA043001
Study Day of Sample 
Collection
(1 Cycle = 
)
Time (relative to 
BMS-986288 dose) 
Hour:Min
C4D1e
672:00
X
X
X
X
C5D1 and beyond: D1
(every other cycle until 
EOT)
00:00c
X
Every 6 months from 
C1D1
EOT or at progression
X
X
X
X
X
X
30-day Follow-up
Abbreviations: C = cycle; D = Day; EOI = end of infusion; EOT = end of treatment; 
.
a Instructions for the collection and processing 
 will be provided in the Laboratory Manual.
b Mandatory on-treatment 
 to be performed at C1D8; specimens may be collected within 3 days of the time point and must be obtained prior to 
administration of study treatments. While not preferred, if a 
 at C1D8 is not collected, then a 
 at C3D5 (3 days) must be performed.
 are 
not required to be collected at both C1D8 and C3D5. An optional additional 
 can be collected on-treatment if the Investigator and the Medical 
Monitor (or designee) find it indicated. A
 is required upon confirmation of PD (within 7 days) except for participants: 1) who have an 
 and progress within 4 cycles, 2) participants who will be imminently (within 4 weeks) enrolling in a subsequent clinical research study that requires a 
screening 
, and 3) participants who consent to be treated beyond progression will require the 
y only at the subsequent confirmation of progression. 
 are unacceptable for submission.
c All predose samples should be taken prior to the start of the infusion/administration.
d EOI samples should be taken after the infusion/administration of BMS-986288. Refer to the Pharmacy Manual for infusion duration. EOI is defined as the end 
of 
 or 
 administration.
e For cohorts with BMS-986288 administered in combination with nivolumab (Part 1B, 
 Arm B, and Part 2B), nivolumab will continue to be administered 
, hence samples should be collected prior to nivolumab administration. Instructions for the collection and processing 
 will be provided in the 
Laboratory Manual.
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APPENDIX 9
ECOG PERFORMANCE STATUS
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APPENDIX 10
NYHA FUNCTIONAL CLASSIFICATION
Heart failure is usually classified according to the severity of the patient’s symptoms. The table 
below describes the most commonly used classification system, the New York Heart Association 
(NYHA) functional classification. It places patients in 1 of 4 categories based on how much they 
are limited during physical activity.
Class
Patient Symptoms
I
No limitation of physical activity. Ordinary physical activity does 
not cause undue fatigue, palpitation, or dyspnea (shortness of 
breath).
II
Slight limitation of physical activity. Comfortable at rest. Ordinary 
physical activity results in fatigue, palpitation, or dyspnea 
(shortness of breath).
III
Marked limitation of physical activity. Comfortable at rest. Less 
than ordinary activity causes fatigue, palpitation, or dyspnea.
IV
Unable to carry on any physical activity without discomfort. 
Symptoms of heart failure at rest. If any physical activity is 
undertaken, discomfort increases.
Class
Objective Assessment
A
No objective evidence of cardiovascular disease. No symptoms 
and no limitation in ordinary physical activity.
B
Objective evidence of minimal cardiovascular disease. Mild 
symptoms and slight limitation during ordinary activity. 
Comfortable at rest.
C
Objective evidence of moderately severe cardiovascular disease. 
Marked limitation in activity due to symptoms, even during 
less-than-ordinary activity. Comfortable only at rest.
D
Objective evidence of severe cardiovascular disease. Severe 
limitations. Experiences symptoms even while at rest.
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APPENDIX 11
COUNTRY-SPECIFIC REQUIREMENTS/DIFFERENCES
Section
Original Language
Country-specific Language or Differences
Section 
6.1: 
Inclusion 
Criteria
Must have received, and then 
progressed, relapsed, or been intolerant 
to, at least 1 standard treatment 
regimen in the advanced or metastatic 
setting
France: Must have received, and then 
progressed, relapsed, or been intolerant 
to, at least 1 standard chemotherapy-
based treatment regimen in the 
advanced or metastatic setting
Section 
6.1: 
Inclusion 
Criteria
All participants with adenocarcinoma 
must have known EGFR, ALK, KRAS, 
and ROS1 status (when testing is 
available as per country/region 
standard of care practices). Participants 
with an activating EGFR mutation, 
ALK translocation, or ROS1 mutation 
must have received appropriate 
inhibitor therapy (as available per 
country/region standard of care).
France: All participants with 
adenocarcinoma must have known 
EGFR, ALK, KRAS, and ROS1 status 
(when testing is available as per 
country/region standard of care 
practices). Regardless of histology, all 
participants with a known activating 
EGFR mutation, ALK translocation, or 
ROS1, or KRAS mutation must have 
received appropriate inhibitor therapy 
(as available per country/region 
standard of care).
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APPENDIX 12
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for Protocol Amendment 02, 22-Jul-2021
Key changes in this protocol amendment are the addition of new dose levels for dose escalation 
(Part 1) and the addition of clinical outcomes assessments and new indications for dose expansion 
(Part 2). 
This protocol amendment updates toxicity management based on CTCAE v5. Previously, toxicity 
management was based on CTCAE v4 and adverse event reporting was based on CTCAE v5. This 
update was made to ensure consistency with adverse event reporting and the most up-to-date 
CTCAE version. This protocol amendment also incorporates SARS-CoV-2 assessment 
requirements to address the COVID-19 pandemic with regard to study conduct. The contraceptive 
and pregnancy requirements have been updated based on the available scientific evidence and 
regulatory guidance. 
Lastly, this protocol amendment incorporates changes from the approved Administrative Letter 
02, which are not detailed in the Summary of Key Changes table below.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Title Page
Updated contact information for 
the Clinical Trial Physician -
Medical Monitor and Clinical 
Scientist
To provide current study 
information
Synopsis
Revised to match relevant 
protocol revisions below
For consistency throughout 
the protocol
Table 2-1 Screening Schedule of 
Activities for All Study Parts
Revised screening 
 
requirements 
Updated to provide 
flexibility around the 
screening sample that is 
collected and ensure that 
fresh 
 collection 
could be prioritized. If a 
fresh screening sample is 
not available, the alternative 
would be a relatively recent 
archival sample. 
 
 ensure 
enough material for 
biomarker assays.
2 Schedule of Activities
3.3 Benefit-Risk Assessment
Table 4-1 Objectives and Endpoints
6.2 Exclusion Criteria (2.f, 2.h, and 
3.e.xvi-xviii)
Added protocol text to address 
SARS-CoV-2 infection and 
vaccination during study 
participation
Added guidance to address 
serum collection and AE 
monitoring related to 
COVID-19
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
6.4.1 Retesting During Screening or 
Lead-In Period
7.4 Dosage Modification (and relevant 
subsections)
7.7.1 Prohibited and/or Restricted 
Treatments
9.2 Adverse Events (and relevant 
subsections)
Table 9.8.4-1 Biomarker Sampling 
Schedule for 
 Dosing Schedule 
for All Study Parts 
9.8.4.1 Exploratory Serum and Plasma 
Biomarkers
2 Schedule of Activities
9.2.1 Time Period and Frequency for 
Collecting AE and SAE Information
9.4 Safety
Specified that AE and SAE 
collection will be done 
“continuously” and from “last 
dose” of study treatment
For clarity, as the date of 
discontinuation of dosing 
may be different from the 
date of last dose
2 Schedule of Activities
Table 4-1 Objectives and Endpoints
5.4.5 Rationale for Quality of Life 
Evaluation
9.1.2 Clinical Outcomes Assessments 
(and relevant subsections)
Table 10.2-1 Populations for Analyses
10.3.7 Other Analyses
Added collection of clinical 
outcomes assessments in Part 2 
only 
To assess quality of life for 
new indications
3.2.3 Ipilimumab
3.2.4 Nivolumab Combined with 
Ipilimumab
Added text on ipilimumab and 
the combination of nivolumab 
and ipilimumab
Added information based on 
new scientific findings
3.3 Benefit-Risk Assessment
5.1.5 Data Monitoring Committee and 
Other External Committees
Changed Global 
Pharmacovigilance and 
Epidemiology (GPVE) to 
Worldwide Patient Safety 
(WWPS)
Changed Medical Surveillance 
Team (MST) to Safety 
Management Team (SMT)
Updated to align with 
current BMS nomenclature
5.1 Overall Design
Figure 5.1-1 Study Design Schematic
5.1.2.3 The Expansion Phase of BMS-
986288 
 (Part 2A) and 
Added 2 doses to each Part 1 
cohort 
Added text indicating that Part 2 
dosing will be selected from the 
Added to further explore the 
MTD
Updated Part 2 dosing 
regimen based on new study 
design for Part 2
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
BMS-986288 in Combination with 
Nivolumab (Part 2B)
5.5.2 Rationale for BMS-986288 
Maximum Dose
Table 7.1-1 Selection and Timing of 
Dose
7.2 Method of Treatment Assignment
range of doses that are tolerable 
in Part 1 
5.1.2.3 The Expansion Phase of BMS-
986288 
 (Part 2A) 
 
 
Nivolumab (Part 2B)
6.1 Inclusion Criteria (2.d.ii.3.b)
Removed allowance for prior 
anti-CTLA-4 therapy in up to 
20% of 
 participants
To enroll a more 
homogenous cohort 
5.1.4 Treatment Beyond Progression
9.1.1 Imaging Assessment for the 
Study 
Added instruction to continue 
radiographic assessment for the 
duration of treatment beyond 
progression
Added instruction to perform 
imaging assessments that may 
demonstrate tumor response or 
progression at unscheduled time 
points
To clarify the timing of 
follow-up requirements
Figure 5.1-1 Study Design Schematic
5.2 Number of Participants
6.1 Inclusion Criteria (2.d.ii.2 and 2.e)
10.1.4 The BMS-986288 
Cohort Expansion (Part 
2A)
10.1.5 The BMS-986288 in 
Combination with Nivolumab Cohort 
Expansion (Part 2B)
Specified number of participants 
for each Part 2 cohort and added 
inclusion criteria detail for Part 
2A and Part 2B
Updated number of 
participants and inclusion 
criteria based on new study 
design for Part 2
6.1 Inclusion Criteria (1.a and 1.b)
Added that “a legally acceptable 
representative” may also sign the 
informed consent form
Updated to allow for 
participants’ legally 
acceptable representatives to 
sign/date IRB/IEC-approved 
consent forms 
6.1 Inclusion Criteria (2.c.v.2 and 
2.c.v.3)
Added KRAS status requirement 
to participants with 
 in 
Part 1
Updated to collect baseline 
KRAS status in Part 1 
 participants due to 
the evolving treatment 
landscape
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
6.1 Inclusion Criteria (2.c.vii.2)
Removed inclusion criterion 
requiring that participants with 
 in Part 1 have no more than 
3 prior total systematic treatment 
regimens
To allow more lines of 
treatment in the current 
treatment environment
6.1 Inclusion Criteria (4.e, 4.f, and 
4.g)
9.2.5 Pregnancy
Removed language related to 
half-lives, fetal toxicity, and 
contraception requirements for 
male participants
Removed requirements for 
pregnancy and sexual activity 
reporting and surveillance in 
female partners of male 
participants 
Based on the available 
scientific evidence and 
regulatory guidance (FDA: 
International Council on 
Harmonisation [ICH] S6 
[R1]), nivolumab and 
BMS-986288 are not 
expected to have genotoxic 
potential at relevant 
systemic concentrations 
sufficient to produce a risk 
of fetal toxicity in WOCBP 
partners of male participants 
who have exposure to a 
male participant’s seminal 
fluid 
6.2 Exclusion Criteria (2.g; 2.i; 3.e.iii; 
3.e.v; 3.e.x; and 3.e.xiii through 
3.e.xv)
Revised exclusion criteria 
regarding complementary 
medicine
Revised exclusion criteria 
regarding prior radiotherapy
Revised exclusion criteria 
regarding timing of systemic 
treatment with corticosteroids or 
other immunosuppressive 
medications
Revised exclusion criteria 
regarding chronic hepatitis and 
HBV, HCV, and HIV infection
Changed complementary 
medicine criteria based on 
regulatory guidance
Clarified prior radiotherapy 
relevant exclusion
Clarified the different 
requirement of 
corticosteroids and other 
immunosuppressive 
medications
Changed viral infection 
criteria based on regulatory 
guidance
7.4 Dosage Modification (and relevant 
subsections)
Table 7.4.3.1-1 Adverse Event 
Criteria for Delay, Resume, and 
Discontinue of Nivolumab and/or 
BMS-986288
Added text specifying that when 
criteria to resume treatment are 
met, both study treatments are 
resumed on the same day 
Added table for AE criteria for 
delaying, resuming, or 
discontinuing nivolumab and/or 
BMS-986288
Clarified that both study 
treatments should resume on 
the same day for 
combination therapy
Updated study treatment 
dose delay, resumption, and 
discontinuation criteria to 
align with CTCAE v5 and 
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Added definition of DLTs and 
moved DLT information to Table 
7.4.3.1-1 
reorganized table for 
readability
Added DLT information to 
AE table for greater 
convenience
7.4.5 Management of Drug-related 
Infusion Reactions
Revised text to indicate that 
Grade 3 or 4 infusion reactions 
are to be reported through the 
standard AE/SAE reporting 
process and do not need to be 
reported separately to the BMS 
Medical Monitor
To reflect current practice
7.5 Preparation/Handling/Storage/
Accountability
Specified that when combination 
therapy is administered, 
nivolumab is to be administered 
first
Clarified the study drug 
administration procedure
9.2.3 Follow-up of AEs and SAEs
Specified that after initial 
AE/SAE report, the investigator 
must follow each participant at 
subsequent visits/contacts
Clarified the follow-up 
expectation for AEs/SAEs 
Table 9.5-2 PK and ADA Sampling 
Schedule for BMS-986288 
 
Monotherapy in Dose Escalation (Part 
1A) and BMS-986288 IV 
 
 Cohort Expansion (Part 
2A)
Table 9.5-3 PK and ADA Sampling 
Schedule for BMS-986288
 
in Combination with Nivolumab 
 
 in Dose Escalation (Part 1B) 
and BMS-986288 
 in 
Combination with Nivolumab 
 
 Cohort Expansion (Part 2B)
Revised EOI footnote to allow 
15-minute window
To reflect current practice
10.3.8.1 Bayesian Continuous 
Monitoring for Treatment-related 
Toxicities Meeting DLT Criteria in 
Part 2
Table 10.3.8.1-1 Monitoring 
Boundaries for Treatment-related 
Toxicities Meeting DLT Criteria in 
Part 2
Set up Bayesian continuous 
monitoring framework to assist 
clinical interpretation of safety 
signals in Part 2 expansion 
participants  
Provided safety monitoring 
boundaries for treatment-related 
toxicities meeting DLT criteria in 
a table 
To ascertain safety signals 
(by quantitative framework 
for monitoring DLT) that 
may occur during Part 2 
expansion in BMS-986288 
as monotherapy and/or in 
combination with 
nivolumab in study 
participants
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BMS-986288
anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Appendix 2 Study Governance 
Considerations 
Updated first paragraph for 
Monitoring section to further 
describe that details on 
monitoring can be found in the 
monitoring plan 
Added section on dissemination 
of clinical study data
Clarified expectations
Appendix 4 Women of Childbearing 
Potential Definitions and Methods of 
Contraception
Updated contraception guidance 
and removed additional measures 
required for male participants 
Aligned methods of 
contraception with updates 
made to male contraceptive 
requirements in Section 6.1 
Appendix 6 Management Algorithms 
for IO Agents
Updated the IO agent 
management algorithms to align 
with CTCAE v5
Updated toxicity 
management algorithms for 
immune-mediated AEs to 
align with CTCAE v5 and 
the updated Nivolumab IB 
Addendum 01
Appendix 8 Schedule of Activities, 
Pharmacokinetics Sampling Schedule, 
and Biomarker Sampling Schedule for 
Potential Alternative Dose Schedules 
in CA043001
Added protocol text to address 
SARS-CoV-2 infection and 
vaccination during study 
participation
Specified that AE and SAE 
collection will be done 
“continuously” and from “last 
dose” of study treatment
Added collection of clinical 
outcomes assessments in Part 2 
only. Included additional text to 
indicate that if other indications 
are included then other 
indication-specific patient-
Added guidance to address 
serum collection and AE 
monitoring related to 
COVID-19
For clarity, as the date of 
discontinuation of dosing 
may be different from the 
date of last dose
Added clinical outcomes 
assessments to assess 
quality of life for new 
indications
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BMS-986288
anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
reported outcomes will also be 
included in future protocol 
amendments
Revised EOI footnotes to allow 
15-minute window
To reflect current practice
All
Removed some instances of 
“randomization” and/or added 
“treatment allocation”
Specified participants with 
“cutaneous” melanoma for this 
study
Minor formatting and 
typographical corrections and 
additional revisions to align the 
protocol with respect to the key 
changes outlined above
For clarification. In this 
open-label study, treatment 
assignment is by allocation, 
not randomization
Updated for consistency of 
melanoma tumor subtype 
within the document
Corrections for clarity and 
consistency within the 
document were minor and 
therefore have not been 
summarized
Overall Rationale for the Revised Protocol 01, 11-Jun-2019
The primary reasons for these changes are to address questions provided by the United States Food 
and Drug Administration, incorporate Administrative Letter 01, and ensure that the protocol is 
consistent with internal BMS policies and operating procedures.
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 01
Section Number 
& Title
Description of Change
Brief Rationale
2 and Appendix 8: 
Schedule of 
Activities
Updated notes and footnotes 
 
.
Clarified expectations and timing 
 
6.1: Inclusion 
Criteria
Require additional prior 
treatments for eligible 
participants with 
 
, 
removed language pertaining 
to participant refusal from 
inclusion criteria, and 
removed option of replacing 
participants based on tumor 
mutational burden status.
Inclusion criteria updated to ensure that 
participants receive appropriate prior 
therapy.
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anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 01
Section Number 
& Title
Description of Change
Brief Rationale
6.2: Exclusion 
Criteria;
7.4.1: Dose-
limiting Toxicities;
7.4.5: Management 
of Drug-related 
Infusion 
Reactions; 9.4: 
Safety; 
10.3.2: Safety 
Analyses
Updated National Cancer 
Institute [NCI] Common 
Terminology Criteria for 
Adverse Events (CTCAE) 
from v4.03 to v5.0.
Updated NCI CTCAE criteria to current 
version 5.0.
7.1: Schedule of 
Dose for Each 
Investigational 
Product
Updated footnote “a” in Table 
7.1-1 to include additional 
details on infusion times.
Clarified infusion times for 
BMS-986288 per Administrative Letter 
01.
7.4.1.3: 
Hematologic 
Dose-Limiting 
Toxicities;
7.4.4: Exceptions 
to Permanent 
Discontinuation 
Criteria
Additional hematologic dose-
limiting toxicity criteria 
provided.
Added for participant safety.
7.4.2: Management 
Algorithms for 
Immuno-oncology 
Agents
Added encephalitis as an 
example of a neurological 
immune-mediated adverse 
event and cardiac 
management algorithms.
Added for participant safety.
9.8.5: Additional 
Research 
Collection
Provided additional details for 
additional research collection.
Clarified expectations for additional 
research collection.
Appendix 2: Study 
Governance 
Considerations
Addressed language around 
serious breach, clinical study 
report, and scientific 
publications.
Modified for clarity and consistency 
with internal BMS policies and 
operating procedures.
Appendix 6: 
Management 
Algorithms for IO 
Agents
Added treatment algorithm 
for myocarditis.
Added for participant safety.
Protocol Amendment No.: 03
Date: 24-Mar-2023
262
4.0
Approved
930132727
4.0
v
Approved
1.0
v

Clinical Protocol
CA043001
BMS-986288
anti-CTLA-4 NF Probody mAb
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 01
Section Number 
& Title
Description of Change
Brief Rationale
All
Minor formatting, 
typographical corrections, and 
additional amendments to 
align the protocol with respect 
to the key changes outlined 
above.
Corrections for clarity and consistency 
within the document were minor, and 
therefore have not been summarized.
Protocol Amendment No.: 03
Date: 24-Mar-2023
263
4.0
Approved
930132727
4.0
v
Approved
1.0
v