Conditions: Broad Solid Tumor
Keywords: First line NSCLC
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 101
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and effectiveness of experimental medication BMS-986207 by itself, in combination with Nivolumab, and in combination with both nivolumab and ipilimumab in participants with solid cancers that are advanced or have spread.

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None

Interventions: intervention 1: BMS-986207 intervention 2: Nivolumab intervention 3: Ipilimumab
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days intervention 3: Specified dose on specified days

Protocol document:
Prot_SAP_000.pdf: 
Official Title of Study: 
Phase 1/2a First-In-Human Study of BMS-986207 Monoclonal Antibody Alone and in Combination With 
Nivolumab or With Nivolumab and Ipilimumab in Advanced Solid Tumors 
 
NCT Number: NCT02913313 
Document Date (Date in which document was last revised): 06 January 2022 


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Protocol Number: CA020002 
IND Number: 130,976 
EUDRACT Number 2016-002263-34 
Date: 12-Sep-2016 
Revised Date: 06-Jan-2022 
 
CLINICAL PROTOCOL CA020002 
Phase 1/2a First-In-Human Study of BMS-986207 Monoclonal Antibody Alone and in 
Combination with Nivolumab or with Nivolumab and Ipilimumab in Advanced Solid Tumors 
Short Title: An Investigational Immuno-therapy Study of BMS-986207 Given Alone and in 
Combination With Nivolumab or with Nivolumab and Ipilimumab 
Protocol Amendment Number: 04 
Clinical Trial Physician - Medical Monitor 
Clinical Scientist 
 
Bristol-Myers Squibb 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
Bristol-Myers Squibb 
3401 Princeton Pike 
Lawrenceville, NJ 08648 
Telephone (cell): 
Telephone (office): 
 
24-hr Emergency Telephone Number 
USA: 
International: 
 
Bristol-Myers Squibb Research and Development 
Route 206 & Province Line Road 
Lawrenceville, NJ 08543 
 
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 


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to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO). 


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DOCUMENT HISTORY 
 
Document 
Date of Issue 
Summary of Change 
 
Revision to add to Part 1C lower dose levels of BMS-986207 (≤ 600 mg 
every 3 weeks) that may be tested. In Part 2C, the triplet combination of 
BMS-986207 + nivolumab + ipilimumab will be explored in first-line 
non-small cell lung cancer (1L NSCLC) participants with PD-L1 tumor 
Protocol 
Amendment 04 
 
 
 
 
 
Protocol 
Amendment 03 
06-Jan-2022 
 
 
 
 
 
 
05-Jan-2021 
cell positive expression ≥ 1%. Additional doses lower than the dose 
declared tolerable in Part 1C may be tested for dose optimization in Part 
2C. 
Updates to contraception and pregnancy requirements in women of 
childbearing potential (WOCBP) and contraception requirements in 
males based on the available scientific evidence. 
Revised to include 2 new treatment arms: Part 1C, BMS-986207 + 
nivolumab + ipilimumab in participants with advanced solid tumors and 
Part 2C, BMS-986207 + nivolumab + ipilimumab in participants with 1L 
NSCLC with tumor PD-L1 expression ≥ 50%. 
Administrative 
Letter 05 
Administrative 
Letter 04 
Administrative 
Letter 03 
Administrative 
Letter 02 
Revised 
Protocol 02 
02-Jul-2020  Updates to staff/contact information for the Medical Monitor 
28-Aug-2018  Updates to staff/contact information for the Medical Monitor 
27-Feb-2018  Updates to staff/contact information for the Medical Monitor 
24-Aug-2017   Updates to staff/contact information for the Medical Monitor 
06-Jul-2017   Addition of q4w dosing regimen 
 
Updates to staff/contact information for Medical Monitor/Study Director 
and Clinical Scientist 
Page 20, Section 2, Table 2.2 On Treatment Schedule of Activities: 
• 
Change in PK sampling schedule. C1D56 corresponds to C2D1 
collection. C1D56 PK sample will not to be collected and will 
Administrative 
Letter 01 
16-Mar-2017 
be removed with next protocol amendment. 
• 
Removal of C1D50 as there are no assessments/treatments to be 
done for study participants on this day. 
 
 
 
 
Revised 
Protocol 01 
24-Oct-2016 
Incorporates Amendment 02 
Revisions/clarifications to protocol language: 
• 
Treatment of participants beyond initial progression modified to 
include radiographic assessment at 4-6 weeks to confirm initial 
Amendment 02 
24-Oct-2016 
disease progression (Section 8.1.1.1); 
• 
Required separate consent for retreatment of participants with 
progressive disease in follow-up (Section 5.1.3.4) 
• 
Inclusion Criteria for HCC participants: 
 


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Document 
Date of Issue 
Summary of Change 
 
radiographic evidence acceptable at enrollment with histologic 
confirmation required prior to initiation of study therapy; active 
hepatitis C infection with any viral load permitted, provided 
participants on anti-viral therapy; Participants must be ineligible for 
ablative techniques or liver transplant; Those who progressed after 
locoregional therapy, locoregional therapy must be completed at 
least 4 weeks prior to the baseline scan (Section 6.1). 
• 
Addition of d 29 safety ECG and removal of Day 50 timepoint from 
On Treatment Schedule of Activities Table and Clarification of 
Laboratory assessments in follow-up (Section 2); Confirmation of 
On Treatment C1D29 PK collection at hour 04:00 and PK 
collections in Retreatment (Tables 9.5-2 
) 
• 
Clarified mandatory requirement for archived 
 
• 
Addition of 60 minute monitoring post infusion of BMS 986207 for 
all 4 doses in Cycle 1 (section 7.1 and Schedule of Activities Table 
-section 2) 
• 
Added section: Discontinuation Due to Hypersensitivity (section 
7.4.6) 
• 
Clarification of DLT criteria for Hypersensitivity Reaction to ≥ 
Grade 4 or Grade 3 that does not resolve to Grade 1 in < 6 hours 
(section 7.4.1.4) 
• 
Addition Preliminary Safety Cohort to Study Design (Appendix 13 
and related study design text) 
• 
Clarified conditions for determination of MTD/RP2D (section 
10.1.1). 
Original Protocol 
12-Sep-2016 
Not applicable 


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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 04: 
Key changes in this protocol amendment are the addition to Part 1C of lower dose levels of BMS- 
986207 (≤ 600 mg every 3 weeks) that may be tested in order to better estimate the tolerability of 
the optimal dose level of BMS-987207 in combination with nivolumab and ipilimumab. In 
addition, the triplet combination of BMS-986207 + nivolumab + ipilimumab will be explored in 
first-line non-small cell lung cancer (1L NSCLC) participants with PD-L1 tumor cell positive 
expression ≥ 1% (Part 2C). Additional doses lower than the dose declared tolerable in Part 1C may 
be tested for dose optimization in Part 2C. This will be examined in order to further develop the 
BMS-986207 program. 
This protocol amendment also updates contraception and pregnancy requirements in women of 
childbearing potential (WOCBP) and contraception requirements in males based on the available 
scientific evidence. 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Synopsis 
Revised to reflect the revisions in the body of the 
protocol. 
For consistency throughout the 
protocol 
Table 2-1: Screening 
- Schedule of 
Activities 
Removed 
from 
screening. 
Align with Table 2-4 
that this test should be done on C1D1 
instead. 
Table 2-1: Screening 
- Schedule of 
Activities 
Section 6.1: 
Inclusion Criteria 
Changed current description of PD-L1 
immunohistochemistry (IHC) results for Part 2C 
enrollment to increase clarity. 
For better clarity for all global sites. 
Section 3.1: Study 
Rationale 
Section 3.2.1.4: 
Preliminary Clinical 
Safety Profile 
Section 3.3: 
Benefit/Risk 
Assessment 
Figure 5.1.2.2-2: 
Treatments Cohorts 
in CA020002 
Section 5.1.2.6: 
Safety Evaluation 
Phase of Part 1C 
Section 5.1.2.7: 
Cohort Expansion 
Revised to reflect current knowledge regarding 
the safety and dose of BMS-986207. 
Clarification language added where necessary. 
To reflect current knowledge regarding 
the safety and dose of BMS-986207. 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & 
Title 
Description of Change 
Brief Rationale 
(Parts 2A, 2B, and 
2C) 
Table 4.1: 
Objectives and 
Endpoints 
Figure 5.1.2.2-2: 
Treatments Cohorts 
in CA020002 
5.5.2.2: Nivolumab 
Dose for BMS-986207 changed from 1200 mg to 
600 mg. 
Due to the safety profile observed in 
participants in Part 1C who were 
treated with 1200 mg BMS-986207 
Q3W + 360 mg nivolumab Q3W + 1 
mg/kg ipilimumab Q6W (see Section 
3.2.1.4). 
Section 5.1.2.2: 
Treatment in Part 1C 
and Part 2C 
Text revised to include current testing dose of 
600 mg BMS-986207 Q3W and that additional 
lower doses may be used. 
 
Figure 5.1.2.2-2: 
Treatments Cohorts 
in CA020002 
Section 5.4.8: 
Rationale for Dose 
Escalation Phase 
Design 
Additional doses lower than 
the dose declared tolerable in Part 1C may be 
tested for dose optimization in Part 2C. 
Figure 5.1.2-2 updated to reflect dose of 600 mg 
BMS-986207 in Part 1C and the RP2D dose(s) 
of BMS-986207 in Part 2C. 
Section 7.4: Dosage 
Modification 
Intra-participant dosage modification has been 
clarified. 
Section 5.2: Number 
of Participants 
Participant numbers revised. 
To align with statistical size 
determinations as discussed in Section 
10: Statistical Considerations. 
Section 5.2: Number 
of Participants 
Section 7.2: Method 
of Treatment 
Assignment 
Section 10.1.3.2: 
Cohort Expansion in 
Part 2C 
Language revised to clarify handling of 
unconfirmed pre-existing PD-L1 results. 
To clarify language about discordant 
test results that may be seen in Part 
2C. 
Section 5.4.4 
Rationale for the 
Language added to justify inclusion of 
Inclusion of 
will promote 
enrollment and capture the potential 
Combination of 
BMS-986207, 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Nivolumab and 
Ipilimumab in 
NSCLC 
Table 5.4.7-1: 
Rationale for Tumor 
Selection 
Language revised to clarify PD-L1 positive 
expression in NSCLC tumors. 
benefit of BMS-986207 in a larger 
population. 
Section 5.4.4: 
Rationale for the 
Combination of 
BMS-986207, 
Nivolumab, and 
Ipilimumab in 
NSCLC 
Section 5.5.2.1: 
BMS-986207 
Table 7.1-2: 
Selection and 
Timing of Dose 
Updates and reorganization of Section 5.4.4. 
Updated Section 5.5.2.1 with latest safety 
information on Part 1C at 1200 mg Q3W BMS- 
986207. 
Added additional doses of BMS-986207 to Table 
7.1-2. 
Added footnote to Table 7.1-2 for dose de- 
escalation of BMS-986207. 
Clarify further why the Triplet 
Combination is being examined in this 
study. 
Data from Part 1C indicated that the 
dose of 1200 mg Q3W BMS-986207 
with nivolumab and ipilimumab was 
not tolerable in some participants and a 
lower dose was warranted. 
Section 6.1: 
Inclusion Criteria 
4)b) & 4)d) Updated WOCBP contraception 
criteria. 
4)f) Updated male contraception criteria. 
Added 4)g) - 4)j). 
Based on the available scientific 
evidence and regulatory guidance 
(FDA: International Council on 
Harmonisation [ICH] S6 [R1]), 
nivolumab, ipilimumab and BMS- 
986207 are not expected to have 
genotoxic potential. 
Section 7.6.1: 
Prohibited and/or 
Restricted 
Treatments 
Added sentence to clarify the non-live SARS- 
CoV-2 vaccination as a simple concomitant 
medication. 
To provide increased clarity to study 
sites. 
Section 9.2.5: 
Pregnancy 
Appendix 4: Women 
of Childbearing 
Potential Definitions 
and Methods of 
Contraception 
Guidance revised to notification of pregnancy 
for 5 months following product administration. 
Additional guidance for completion of protocol 
procedures added. Removal of guidance to report 
pregnancy in female partners of male 
participants. 
End of relevant systemic exposure is 
the time point where the 
Investigational Medicinal Product 
(IMP) or any active major metabolites 
have decreased to a concentration that 
is no longer considered to be relevant 
for human teratogenicity or 
fetotoxicity. This should be evaluated 
in context of safety margins from the 
no-observed-adverse-effect level, or 
the time required for 5 half-lives of the 
IMP to pass. In this study, nivolumab 
has the longest half-life of 25 days 
compared to BMS-986207 (half-life of 
14 days), and ipilimumab (half-life of 
20 days). Using the half-life of 
nivolumab, the end of relevant 
systemic exposure is 125 days which is 
over 4 months. In order to simplify the 


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Section Number & 
Title 
Description of Change 
Brief Rationale 
contraception and pregnancy reporting 
guidance, 5 half-lives was updated to 5 
months following product 
administration. 
Based on the available scientific 
evidence and regulatory guidance 
(FDA: International Council on 
Harmonisation [ICH] S6 [R1]), 
nivolumab, ipilimumab and BMS- 
986207 are not expected to have 
genotoxic potential. 
Section 10.1.3.2: 
Cohort Expansion in 
Part 2C 
Table 10.1.3.2-1: 
Operating 
characteristics of 
criteria for antitumor 
activity by ORR 
Table 10.1.3.2-2: 
Potential ORR in 1L 
NSCLC (≥ 1% PD- 
L1) and Exact 80% 
CI 
Table 10.2-1: 
Population for 
Analyses 
Table 10.3.1-1: 
Efficacy - Statistical 
Analysis 
Updated 
Updated to include that one or two doses are 
planned to be evaluated in Part 2C and a 
minimum of 20 participants are enrolled per dose 
level of BMS-986207. 
Statistical tables updated to reflect the change. 
To align with changes to study 
rationale for Part 2C. 
Throughout 
Minor typographical errors corrected, or 
revisions made to increase readability. 
Minor, therefore have not been 
summarized. 


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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
1 
DOCUMENT HISTORY.............................................................................................. 
3 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 04: ............................ 
5 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04................ 
5 
TABLE OF CONTENTS.............................................................................................. 
9 
1 SYNOPSIS................................................................................................................. 
13 
2. SCHEDULE OF ACTIVITIES................................................................................. 
24 
3. INTRODUCTION .................................................................................................... 
44 
3.1 Study Rationale ................................................................................................. 
44 
3.2 Background ....................................................................................................... 
47 
3.2.1 BMS-986207 ............................................................................................ 
47 
3.2.1.1 Nonclinical Pharmacology ............................................................. 
47 
3.2.1.2 Nonclinical Pharmacokinetics ........................................................ 
48 
3.2.1.3 Nonclinical Toxicology ................................................................... 
48 
3.2.1.4 Preliminary Clinical Safety Profile ................................................ 
49 
3.2.2 Nivolumab ................................................................................................ 
51 
3.2.3 Ipilimumab ............................................................................................... 
51 
3.2.4 Nivolumab Combined with Ipilimumab Clinical Activity ........................ 
52 
3.3 Benefit/Risk Assessment .................................................................................. 
52 
4. OBJECTIVES AND ENDPOINTS .......................................................................... 
55 
5. STUDY DESIGN...................................................................................................... 
57 
5.1 Overall Design .................................................................................................. 
57 
5.1.1 Screening Period...................................................................................... 
57 
5.1.2 Treatment Period ..................................................................................... 
57 
5.1.2.1 Treatment in Parts 1A, 1B, 2A, and 2B........................................... 
57 
5.1.2.2 Treatment in Part 1C and Part 2C ................................................. 
58 
5.1.2.3 Preliminary Safety Cohort & Dose Escalation (Part 1A and 1B) .. 
61 
5.1.2.4 Dose Escalation Decisions for Monotherapy and Combination 
(Parts 1A and 1B) ................................................................................. 
63 
5.1.2.5 Dose Limiting Toxicities in Dose Escalation Phases (Parts 1A and 
1B)......................................................................................................... 
64 
5.1.2.6 Safety Evaluation Phase of Part 1C................................................ 
64 
5.1.2.7 Cohort Expansion (Parts 2A, 2B, and 2C) ..................................... 
67 
5.1.2.8 Treatment with Additional Cycles Beyond 24 Weeks (Parts 1A, 1B, 
2A, and 2B) ........................................................................................... 
68 
5.1.3 Follow-up ................................................................................................. 
68 
5.1.3.1 Safety Follow-up Period ................................................................. 
68 
5.1.3.2 Response Follow-up Period (Parts 1A, 1B, 1C, 2A, 2B, and 2C) .. 
69 
5.1.3.3 Survival Follow-up Period.............................................................. 
69 
5.1.3.4 Retreatment During Follow-up Periods (Parts 1A, 1B, 2A, and 2B) 
............................................................................................................... 
69 
5.1.4 Treatment Beyond Progression................................................................ 
70 
5.1.5 Data Monitoring Committee and Other External Committees ................ 
71 
5.2 Number of Participants ..................................................................................... 
71 


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5.3 End of Study Definition .................................................................................... 
72 
5.4 Scientific Rationale for Study Design............................................................... 
72 
5.4.1 Rationale for BMS-986207 Monotherapy in Colorectal Cancer Cancer 
and Other Cancers Associated with Fusobacterium Nucleatum ................ 
73 
5.4.2 Rationale for the Combination of BMS-986207 and Nivolumab............. 
73 
5.4.3 Rationale for the Combination of BMS-986207, Nivolumab, and 
Ipilimumab .................................................................................................. 
73 
5.4.4 Rationale for the Combination of BMS-986207, Nivolumab and 
Ipilimumab in NSCLC................................................................................. 
74 
5.4.5 Rationale for Treatment Duration ........................................................... 
75 
5.4.6 Rationale for Treatment Beyond Progression ......................................... 
75 
5.4.7 Rationale for Tumor Selection ................................................................. 
76 
5.4.8 Rationale for Dose Escalation Phase Design .......................................... 
77 
5.5 Justification for Planned Dose Selection .......................................................... 
77 
5.5.1 The current study is a FIH study.............................................................. 
77 
5.5.1.1 Introduction..................................................................................... 
77 
5.5.1.2 Nonclinical Pharmacokinetics and Efficacy ................................... 
78 
5.5.1.3 Nonclinical Toxicity Data ............................................................... 
79 
5.5.1.4 Rationale for Starting Dose in Humans.......................................... 
80 
5.5.2 Rationale for Dosing Schedule ................................................................ 
80 
5.5.2.1 BMS-986207 ................................................................................... 
80 
5.5.2.2 Nivolumab ....................................................................................... 
82 
5.5.2.3 Ipilimumab ...................................................................................... 
82 
5.5.2.4 Rationale for Infusion Times........................................................... 
83 
6. STUDY POPULATION ........................................................................................... 
84 
6.1 Inclusion Criteria .............................................................................................. 
84 
6.2 Exclusion Criteria ............................................................................................. 
88 
6.3 Lifestyle Restrictions ........................................................................................ 
92 
6.4 Screen Failures.................................................................................................. 
92 
6.4.1 Retesting During Screening or Lead-In Period ....................................... 
92 
7. TREATMENT .......................................................................................................... 
93 
7.1 Treatments Administered.................................................................................. 
93 
7.2 Method of Treatment Assignment .................................................................... 
95 
7.3 Blinding............................................................................................................. 
95 
7.4 Dosage Modification......................................................................................... 
95 
7.4.1 Dose Limiting Toxicities .......................................................................... 
96 
7.4.1.1 Hepatic Dose-Limiting Toxicity ...................................................... 
96 
7.4.1.2 Hematologic Dose-Limiting Toxicity .............................................. 
97 
7.4.1.3 Dermatologic Dose-Limiting Toxicity ............................................ 
97 
7.4.1.4 Other Dose-Limiting Toxicities....................................................... 
97 
7.4.2 Management Algorithms for Immuno-Oncology Agents ......................... 
98 
7.4.3 Dose Delays Due To Toxicity .................................................................. 
98 
7.4.3.1 Criteria for Dose Delay Secondary to Changes in AST or ALT for 
Participants with HCC.......................................................................... 
99 
7.4.3.2 Protocol-Specific Recommendation for Management of Hepatic 
Events in HCC Participants.................................................................. 
99 


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7.4.3.3 Criteria to Resume Treatment......................................................... 
7.4.4 Exceptions to Permanent Discontinuation Criteria................................. 
7.4.5 Management of Drug-related Infusion Reactions.................................... 
7.4.6 Discontinuation Due to Hypersensitivity ................................................. 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
7.5.1 Retained Samples for Bioavailability / Bioequivalence ........................... 
7.6 Treatment Compliance...................................................................................... 
7.6.1 Prohibited and/or Restricted Treatments................................................. 
7.7 Treatment After the End of the Study............................................................... 
7.7.1 Permitted Therapy ................................................................................... 
8. DISCONTINUATION CRITERIA .......................................................................... 
8.1 Discontinuation from Study Treatment ............................................................ 
8.1.1 Discontinuation Due to Further Progression (Confirmed Progression). 
8.1.2 Assessment Schedule for Participants with Post-progression Treatment 
8.1.3 Post study Treatment Study Follow-up .................................................... 
8.2 Discontinuation from the Study ........................................................................ 
8.3 Lost to Follow-up.............................................................................................. 
9. STUDY ASSESSMENTS AND PROCEDURES.................................................... 
9.1 Efficacy Assessments........................................................................................ 
9.2 Adverse Events ................................................................................................. 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
9.2.2 Method of Detecting AEs and SAEs......................................................... 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
9.2.4 Regulatory Reporting Requirements for SAEs......................................... 
9.2.5 Pregnancy ................................................................................................ 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
9.2.7 Potential Drug-induced Liver Injury (p-DILI) ........................................ 
9.2.8 Other Safety Considerations .................................................................... 
9.3 Overdose ........................................................................................................... 
9.4 Safety ................................................................................................................ 
9.4.1 Physical Examinations............................................................................. 
9.4.2 Vital Signs ................................................................................................ 
9.4.3 Electrocardiograms ................................................................................. 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
9.4.5 Imaging Assessment for the Study............................................................ 
9.5 Pharmacokinetics and Immunogenicity ............................................................ 
9.5.1 Pharmacokinetic Sample Analyses .......................................................... 
9.5.2 Immunogenicity Sample Analysis ............................................................ 
 
9.7 Pharmacogenomics ........................................................................................... 
9.7.1 ADME Sampling ...................................................................................... 
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10. STATISTICAL CONSIDERATIONS ................................................................... 
10.1 Sample Size Determination............................................................................. 
10.1.1 Dose Escalation ..................................................................................... 
10.1.2 Safety Evaluation Phase (Part 1C) ........................................................ 
10.1.3 Cohort Expansion .................................................................................. 
10.1.3.1 Cohort Expansion in Part 2A and Part 2B ................................... 
10.1.3.2 Cohort Expansion in 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 Analyses for BMS-986207, Nivolumab, and 
Ipilimumab .................................................................................................. 
10.3.4 Immunogenicity...................................................................................... 
10.3.6 ECG Analyses ........................................................................................ 
10.3.7 Other Analyses ....................................................................................... 
10.3.8 Interim Analyses for Parts 2A, 2B, and 2C............................................ 
11. REFERENCES ....................................................................................................... 
12 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERANCE CONSIDERATIONS .................................... 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW UP AND REPORTING......................................................................... 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION..................................................................... 
APPENDIX 5 RECIST 1.1 CRITERIA........................................................................ 
APPENDIX 6 MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS................................................................................................................. 
APPENDIX 7 ADME RELATED GENES .................................................................. 
APPENDIX 8 EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS ................................................................................... 
APPENDIX 9 NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION ................................................................................................ 
APPENDIX 10 CONSORT PUBLISHING REQUIREMENTS ................................. 
APPENDIX 11 CHILD-PUGH CLASSIFICATION ................................................... 
APPENDIX 12 STATISTICAL METHODOLOGY ................................................... 
APPENDIX 13 PRELIMINARY SAFETY COHORT ................................................ 
APPENDIX 14 REVISED PROTOCOL SUMMARY OF CHANGE HISTORY ...... 
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Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
 
1 
SYNOPSIS 
Protocol Title: Phase 1/2a First-In-Human Study of BMS-986207 Monoclonal Antibody Alone and in 
Combination with Nivolumab or with Nivolumab and Ipilimumab in Advanced Solid Tumors 
Short Title: An Investigational Immuno-therapy Study of BMS-986207 Given Alone and in Combination With 
Nivolumab or with Nivolumab and Ipilimumab 
Study Phase: Phase 1/2a 
Rationale: BMS-986207, an anti-T cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif 
(ITIM) domain (TIGIT) monoclonal antibody (mAb), is being studied alone and in combination with nivolumab or in 
combination with nivolumab and ipilimumab in humans with advanced solid tumors. 
Tumors modulate and evade the host immune response through a number of mechanisms, including down regulation 
of tumor-specific antigen expression and presentation, secretion of anti-inflammatory cytokines, and upregulation of 
inhibitory ligands. Immunotherapeutic approaches such as checkpoint pathway blockade have demonstrated clinical 
efficacy in several cancers, including melanoma, renal cell, lung, and hormone-refractory prostate cancers. Following 
the success of anti-cytotoxic T-lymphocyte-associated protein (CTLA-4) and anti-programmed cell death 1 (PD-1) 
pathway-targeted agents in several cancers, the field of tumor immunotherapy is rapidly expanding, recognizing the 
potential value of combination therapies. 
BMS-986207 is a fully human variant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds with high 
affinity to TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif 
domain), a negative regulatory molecule that suppresses activation and functional responses in T cells and natural 
killer (NK) cells. TIGIT upregulation has been observed in cancer patients, in particular on T cells, and is co-expressed 
with 
of T cell exhaustion. Binding of poliovirus receptor (PVR) and Nectin-2 (TIGIT ligands) to TIGIT 
results in suppression of T cell and NK cell function. These same ligands also bind with lower affinity to the 
stimulatory receptor CD226 (DNAX accessory molecule 1 [DNAM-1]) also expressed on effector T cells. Blockade 
of TIGIT with molecules like BMS-986207 therefore may increase the anti-tumor immune response both by removing 
the suppressive signal emanating from TIGIT and by freeing its ligands to bind to the stimulatory receptor CD226. 
Blockade of TIGIT-mediated inhibition of T and NK cell function is hypothesized to facilitate an increase in the 
amplitude and durability of responses against a number of malignancies. 
 
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. For Part 2C, participants must have NSCLC, be treatment-naive, and have 
pre-existing or prior PD-L1 IHC results from testing of tumor tissue. PD-L1 expression must be tumor cell positive 
≥ 1% for a participant to be eligible for enrollment. 
Objectives and Endpoints: The primary and secondary objectives and endpoints for this study are shown in the table 
below. 
 
Objectives 
Endpoints 
Primary 
• 
Part 1A, 1B, 2A, and 2B: To characterize the safety, 
tolerability, DLTs, and MTD/RP2D of BMS 986207 
administered as monotherapy and in combination with 
nivolumab in participants with advanced solid tumors. 
• 
Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs 
leading to discontinuation, and death; 
Incidence of laboratory abnormalities. 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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Objectives 
Endpoints 
• 
Part 1C: To characterize the safety, tolerability, and DLTs of 
BMS-986207 in combination with nivolumab and ipilimumab 
in participants with advanced solid tumors. 
• 
Incidence of AEs, SAEs, AEs meeting. 
protocol-defined DLT criteria, AEs 
leading to discontinuation, and death; 
Incidence of laboratory abnormalities. 
• 
Part 2C: To evaluate the preliminary efficacy and safety of 
BMS-986207 in combination with nivolumab and ipilimumab 
in previously untreated participants with NSCLC whose 
tumors express ≥ 1% PD-L1 based on PD-L1 IHC results from 
central testing. 
• 
ORR, mDOR, and PFSR at 24 weeks 
by RECIST v1.1 by investigator; 
Incidence of AEs, SAEs, AEs leading 
to discontinuation, and death. 
Secondary 
• 
To assess the preliminary efficacy of BMS-986207 alone and 
in combination with nivolumab in advanced solid tumors 
(Parts 1A, 2A, 1B, and 2B) and in combination with 
nivolumab and ipilimumab in advanced solid tumors (Part 1C). 
• 
To characterize the PK and immunogenicity of BMS-986207 
when administered alone, in combination with nivolumab or in 
combination with nivolumab and ipilimumab. 
• 
ORR, mDOR, and PFSR at 24 weeks 
by RECIST v1.1 
• 
Summary measures of PK parameters 
of BMS-986207 and incidence of 
ADA to BMS-986207 
Abbreviations: 
ADA, 
anti-drug 
antibody 
AE, 
adverse 
event; 
DLT, 
dose 
limiting 
toxicity; 
IHC, 
immunohistochemistry; mDOR, median duration of response; MTD, maximum tolerated dose; NSCLC, non-small 
cell lung cancer; ORR, objective response rate; PD-L1, programmed death ligand 1; PFSR, progression-free survival 
rate; PK, pharmacokinetic; RECIST, Response Evaluation Criteria in Solid Tumors; RP2D, recommended Phase 2 
dose; SAE, serious adverse event. 
 
OVERALL DESIGN 
This is a Phase 1/2a, open-label study of BMS-986207 administered as a single agent, in combination with nivolumab, 
and in combination with both nivolumab and ipilimumab in participants with advanced solid tumors. The duration of 
the study will be approximately 6 years. 
The study comprises 2 parts. Part 1 includes dose escalation of BMS-986207 alone (Part 1A) and in combination with 
nivolumab (Part 1B) to determine the MTD/RP2D, as well as a select dose level of BMS-986207 in combination with 
nivolumab and ipilimumab (Part 1C) to evaluate safety and preliminary 
activity of the triplet combination. 
Part 1B includes a substudy conducted at a single site under site-specific Amendments 6, 7, and 8 to evaluate the 
safety and preliminary efficacy of BMS-986207 in combination with nivolumab in PD-1 naive and relapsed/refractory 
participants with melanoma. Part 2 includes expansion cohorts to gather additional preliminary 
activity, as 
well as additional safety, tolerability, PK, 
information for BMS-986207 alone (Part 2A), in 
combination with nivolumab (Part 2B), and in combination with nivolumab and ipilimumab in NSCLC (Part 2C). 
Participants in each study phase will complete up to 4 periods in the study: screening, treatment, safety follow-up, and 
response/survival follow-up. The overall study design is illustrated in Figure 1 and the treatment cohorts are presented 
in Figure 2. 
Screening: The screening period will last for up to 28 days, and will begin by establishing the participant’s initial 
eligibility and signing of the informed consent form. Participants will be enrolled using an Interactive Response 
Technology (IRT). 
Preliminary Safety Cohort: The Preliminary Safety Cohort precedes participant enrollment in Monotherapy-Dose 
Escalation (Part 1A) of the study. The first participant enrolled into monotherapy escalation will receive BMS-986207 
starting at the 2-mg dose level, followed 2 weeks later with intra-participant dose escalation to the 6-mg dose level, 
and followed 2 weeks after that with intra-participant dose escalation to the 20-mg dose level. This first participant 
will be subject to a 5-day safety observation period after receiving the first 20-mg dose. If no dose-limiting toxicities 
(DLTs) or other safety concerns are observed, an additional 2 participants will be enrolled in the 20-mg dose cohort. 
Treatment: Participants in Parts 1A, 1B, 2A, and 2B will be treated for up to 24 weeks (3 cycles) with monotherapy 
(Parts 1A and 2A) or combination therapy (Parts 1B and 2B). The treatment period will consist of up to 3 treatment 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
15 
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930104927 7.0 
 
 
cycles of 8 weeks. Following each treatment cycle, the decision to treat a participant with additional cycles of study 
therapy (up to a maximum of 6 cycles), will be based on tumor assessment at the end of each cycle. In Parts 1C and 
2C, nivolumab and BMS-986207 will be administered every 3 weeks and ipilimumab will be administered every 
6 weeks until progression, unacceptable toxicity, or other reasons specified in the protocol for up to 2 years. 
Each monotherapy treatment cycle will comprise 4 doses of BMS-986207 administered every 2 weeks (q2w) or 
2 doses of BMS-986207 every 4 weeks (q4w) in Part 1A and 2A. BMS-986207 infusions will take place over 
60 minutes and will require a 60 minute observation period after all infusions in Cycle 1 for each participant. For 
participants < 42 kg on the 1600 mg dose, the infusion time will be longer than 1 hour. In Parts 1B and 2B, each 
combination treatment cycle will comprise 4 doses of BMS-986207 administered q2w or 2 doses of BMS-986207 
when administered q4w, each dose administered with nivolumab. In Part 1B and 2B, when both study drugs are given 
in combination, nivolumab will be given first, over a 30-minute infusion period, followed by BMS-986207 over a 
60-minute infusion period, with a 60-minute observation period after all infusions in Cycle 1 for each participant, and 
at least 30 minutes after completion of the infusion of nivolumab. Tumor progression and response will be assessed 
using RECIST v1.1 criteria for solid tumors. The study design is shown in Figure 2. 
The approximate number of evaluable participants will be 241. Approximately 100 of these participants will be treated 
with monotherapy and combination dose escalation (Part 1A and Part 1B, respectively). Approximately 36 participants 
will be treated (6 initial participants for safety evaluation followed by evaluation of approximately 12 additional 
participants per dose level) with BMS-986207, nivolumab, and ipilimumab in the Triplet Cohort (Part 1C). The 
remaining (up to 105) participants will be treated as part of dose expansion with up to 24 participants in Part 2A and 
41 participants in Part 2B, and 40 participants with NSCLC 
pre-existing 
or prior PD-L1 IHC results from testing of tumor tissue) considered to be response-evaluable, in Part 2C. 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
16 
Approved v 71.0 
930104927 7.0 
 
 
Study Design 
Figure 1: 
Overall Study Design 
 
 
Abbreviations: CR, complete response; EOT, end of treatment; IP, investigational product; PD, progressive disease; 
PR, partial response; SD, stable disease; 
Figure 2: 
Treatment Cohorts in CA020002 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
 
 
Abbreviations: 1L NSCLC, first-line non-small cell lung cancer; BMS, Bristol-Myers Squibb; CRC, colorectal cancer; 
HCC, hepatocellular carcinoma; IO, immuno-oncology; MTD, maximum tolerated dose; q2w, every 2 weeks. q3w, 
every 3 weeks; q4w, every 4 weeks, q6w, every 6 weeks; RP2D, recommended phase 2 dose. 
a Planned dose levels and dose schedules of BMS-986207 and/or nivolumab may be modified, and intermediate dose 
levels of BMS-986207 added, based upon the BLRM analysis and sponsor discretion and discussion with 
investigators. Once the safety (during the DLT evaluation) of a dose level has been established (Part 1A and/or Part 
1B), additional participants (up to 15) may be added at that dose, to better characterize the safety, dose schedule, 
PK,  profile 
assessments. 
b Participants were enrolled at a single site under site-specific Amendments 6, 7, and 8. This substudy has been closed 
for enrollment. 
c The safety profile of BMS-986207 1200 mg Q3W combined with nivolumab 360 mg Q3W and ipilimumab 1 mg/kg 
Q6W has been evaluated in 6 subjects. Of these subjects, 4 were DLT evaluable, and 2 developed DLTs. Per BOIN 
design, for all the remaining and future subjects, BMS-986207 was de-escalated to 600 mg Q3W (for details, see 
Section 3.2.1.4) Planned dose levels for BMS-986207 may be further modified based on generated data and 
additional doses, including 360 mg Q3W, may be assessed per BOIN design and for dose optimization analysis at 
Sponsor discretion and based upon discussion and agreement with investigators. 
d Part 2C will enroll a minimum of 20 participants per dose level of BMS-986207. One or two doses are planned to 
be evaluated and selected from the range of doses assessed as tolerable and not exceeding the maximum tolerated 
dose in Part 1C. If two doses will be tested at the Sponsor’s discretion, participants will be randomized in a 1:2 
ratio schema between the highest dose selected in Part 1C and the next lower dose, after at least 10 participants will 
have been tested at the dose found safe in Part 1C. 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
18 
Approved v 71.0 
930104927 7.0 
 
 
TREATMENT 
Preliminary Safety Cohort: The Preliminary Safety Cohort precedes participant enrollment in Monotherapy - Dose 
Escalation (Part 1A) of the study. The first participant enrolled into monotherapy escalation will receive BMS-986207 
starting at the 2 mg dose level, followed 2 weeks later with intra-participant dose escalation to the 6 mg dose level, 
followed 2 weeks after that with intra-participant dose escalation to the 20 mg dose level. This first participant will be 
subject to a 5-day safety observation period after receiving the first 20 mg dose. If there are no DLTs or other safety 
concerns observed, an additional 2 participants will be enrolled in the 20 mg dose cohort. 
 
 
Dose Escalation (Part 1A and Part 1B): Approximately 35 participants are expected to be treated during each dose 
escalation part of the study guided by Bayesian Logistic Regression Model (BLRM). Each participant will be 
administered intravenous (IV) doses of BMS-986207 per the cohort assignment as described below. 
In Part 1A (monotherapy dose escalation), the planned flat dose levels for BMS-986207 are 20, 80, 240, 800, and 
1600 mg (assuming an 80 kg participant) q2w, in 8-week cycles, for up to 3 cycles of study therapy (24 weeks). In 
addition, a q4wk schedule of BMS-986207 will be evaluated at flat doses of 480 mg and 1600 mg (assuming an 80 kg 
participant). Enrollment of the first q4w cohort will be guided by the safety, PK, 
analysis from the 
q2wk cohorts. Following each treatment cycle, the decision to treat a participant with additional cycles of study therapy 
(up to a maximum of 6 cycles), will be based on tumor assessment at the end of each cycle. 
In Part 1B, (combination therapy dose escalation), BMS-986207 and nivolumab will be administered at flat doses of 
80 and 240 mg BMS-986207 q2w and 240 mg nivolumab q2w. In addition, BMS-986207 will be administered at flat 
doses of 480, and 1600 mg q4w in combination with nivolumab administered at 480 mg q4w. Study drugs will be 
administered in 8-week cycles, for up to 3 cycles of study therapy (24 weeks). Following each treatment cycle, the 
decision to treat a participant with additional cycles of study therapy (up to a maximum of 6 cycles), will be based on 
tumor assessment at the end of each cycle. 
Planned dose levels may be modified, or intermediate dose levels added, based upon the BLRM analysis. Part 1B, 
combination dose escalation, will be initiated after at least 3 dose levels (ie, 20, 80, and 240 mg dose cohorts), have 
been found to be tolerable in Part 1A, monotherapy dose escalation. The starting dose of BMS-986207 in Part 1B will 
be at least 1 dose level below a dose that was demonstrated to be tolerated in Part 1A. At no time will the dose for 
BMS-986207 in Part 1B exceed the highest tolerated dose in Part 1A. BLRM may indicate evaluation of intermediate 
dose levels that fall in-between the planned dose levels. Any dose level increment will be limited to approximately a 
3-fold increase. Subsequently, escalation in Parts 1A and 1B may be done in parallel. 
Participants with biopsy eligible solid tumors will be enrolled in Parts 1A and 1B. Specifically participants with tumor 
types where the microbiome has been implicated, in preclinical or clinical data, to mediate TIGIT inhibition, such as 
but not limited to, CRC and squamous cell carcinoma of the head and neck (SCCHN), will be enrolled in Part 1A. 
Once the safety (during the dose limiting toxicity [DLT] evaluation) of a dose level has been established (Part 1A 
and/or Part 1B), additional participants (up to a total of 15) may be added at that dose level, to better characterize the 
safety, PK, 
 profile. 
Sentinel Participant: For all dose escalation cohorts, a sentinel participant approach will be used with a 5-day interval 
between the treatment initiation of the first participant and the treatment of subsequent participants in that dose level. 
The first participant in both Part 1A, starting at the 20-mg dose level, and Part 1B will receive Cycle 1 Day 1 dose of 
study drug(s), and be observed for 5 days before additional participants receive study drugs. The first participants to 
be dosed in all subsequent dose-level cohorts will also be subject to a 5-day sentinel period. Initially, 3 participants 
will be enrolled at the start of each dose-escalation cohort, in accordance with the sentinel participant approach above. 
However, to allow for any unforeseen discontinuations (such as disease progression) before the 4-week DLT period 
is completed, an extra participant may be enrolled at each dose-escalation cohort. Therefore, there will be a total of 
4 participants (3+1) at the start of each dose-escalation cohort, providing the fourth participant is able to start the first 
day of dosing within approximately 1 week of the third participant in the same dose-escalation cohort. 
Triplet Cohort (Part 1C): Approximately 36 participants will be treated (6 initial participants for safety evaluation 
followed by evaluation of approximately 12 additional participants for each dose level tested) with BMS-986207, 
nivolumab, and ipilimumab in the Triplet Cohort (Part 1C). BMS-986207 will be administered at 600 mg q3w and/or 
360 mg q3w and nivolumab will be administered at 360 mg q3w. Ipilimumab, at a dose of 1 mg/kg, will be given 
q6w. A dose of 1200 mg BMS-986207 administered every 3 weeks has been tested per Amendment 03 but due to the 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
DLTs observed no additional participants will be tested at this dose (see Section 3.2.1.4). Study drugs will be 
administered in 6-week cycles until disease progression, unacceptable toxicity, or other reasons as specified in the 
protocol for up to 2 years. Treatment beyond initial investigator-assessed RECIST v1.1 defined progression is 
permitted if the subject has investigator-assessed clinical benefit and is tolerating the treatment. 
The DLT period in Part 1C will be 42 days (6 weeks). The DLT safety monitoring during the dose evaluation phase, 
including the potential decision to de-escalate to a lower dose, will be based on the Bayesian optimal interval (BOIN) 
design framework with a dose-limiting toxicity (DLT) rate of 30% (24%, 36%). 
Subjects who do not complete the DLT observation period for reasons other than DLTs may be replaced. De-escalation 
may be considered if the safety and tolerability profiles for the selected BMS-986207 dose are deemed unacceptable, 
after discussion between the investigator (s) and the Sponsor/Medical Monitor. 
Cohort Expansion (Part 2A, 2B, and 2C): In the cohort expansion part of the study, additional safety, tolerability, 
preliminary efficacy, PK, 
information, regarding BMS-986207 alone and in combination with nivolumab, will 
be sought. Continuous evaluation of toxicity events will be performed throughout enrollment in the expansion cohorts. 
If, at any time, the aggregate rate of treatment-related toxicities meeting DLT criteria exceeds 33% across all 
participants treated in cohort expansions, reassessment of enrollment will take place. Depending on the nature and 
grade of the toxicity and after assessing the risk/benefit ratio, a new dose(s) for all cohorts may be initiated at a 
previously tested lower dose level or at a dose level intermediate to previously tested lower dose levels. 
In Part 2A, only CRC will be evaluated in cohort expansion with BMS-986207 as monotherapy. In Part 2B, the 
3 disease-restricted populations, ovarian cancer, CRC and HCC, will be investigated in cohort expansions with 
BMS-986207 in combination with nivolumab. A Fleming 2-stage design framework will be used as a guide in cohort 
expansion. 
During the expansion phase, participants with CRC who have disease progression on BMS-986207 monotherapy will 
be able to cross over to combination treatment (BMS-986207 + nivolumab), once the CRC expansion arms are 
enrolling. This cross-over option is not applicable during the escalation phases. CRC participants with disease 
progression who cross over to combination treatment will undergo the same efficacy and safety assessments as the 
main cohort. 
The purpose of Part 2C is to gather preliminary efficacy information regarding BMS-986207 in combination with 
nivolumab and ipilimumab in participants with advanced, treatment-naive NSCLC whose tumors express 
to assess optimal dose selection for RP2D. These subjects will be treated with BMS-986207 q3w at a dose not to 
exceed the dose declared tolerable in Part 1C, nivolumab 360 mg q3w, and ipilimumab 1 mg/kg q6w. Additional doses 
lower than the dose declared tolerable might be tested for dose optimization in Part 2C. 
Part 2C may begin once there is sufficient safety data from a minimum of 6 participants in Part 1C. 
Continuous evaluation of toxicity events will also be performed in this part of the study If, at any time, the aggregate 
rate of treatment-related toxicities meeting DLT criteria exceeds 33%, the findings will be discussed and further 
enrollment may be interrupted. Depending on the nature and grade of the toxicity, and after assessing the risk/benefit 
ratio, a new dose for all participants may be initiated at a lower dose level. 
Participants with an outcome of unconfirmed progressive disease, 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 either: 1) completion of the maximum number of 
cycles, 2) confirmed PD, 3) clinical deterioration suggesting that no further benefit from treatment is likely, 
4) intolerability to therapy, or 5) the participant meets criteria for discontinuation of study therapy. 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 in settings where benefit/risk 
justify discontinuation of study therapy. 
Dose Limiting Toxicities: For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, 
intensity, and duration of adverse events (AEs) for which no clear alternative cause is identified. DLT period will be 
28 days (4 weeks) in Part 1A and Part 1B and 42 days (6 weeks) in Part 1C. 
For the purpose of participant management, any AE that meets DLT criteria, regardless of the cycle in which it occurs, 
will lead to discontinuation of study drug unless the investigator determines that 1 of the agents must be discontinued 
due to toxicity attributed to that agent alone. Participants experiencing a DLT will not be retreated with study drug, 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
and will enter the safety follow-up period of the study. Following the last treatment with investigational product (IP), 
participants who withdraw from the study during the DLT evaluation interval for reasons other than a DLT may be 
replaced with a new participant at the same dose level. 
Treatment with Additional Cycles beyond 24 Weeks: Participants in Parts 1A, 1B, 2A, or 2B with ongoing disease 
control (CR, PR, SD) or unconfirmed progressive disease, and completing approximately 24 weeks of treatment, may 
be eligible for an additional 3 cycles of study therapy in both the monotherapy (Parts 1A and 2A) and combination 
therapy (Parts 1B and 2B) parts beyond the initial 24 weeks, at discretion of the Investigator and BMS Medical 
Monitor. Upon completion of 3 cycles of study therapy (or up to a maximum of 6 cycles if applicable), all participants 
will enter the safety follow-up period. 
The cohort expansion phase of the study is shown in the figure below. 
Schematic of Dose Escalation and Cohort Expansion Phases of the Study 
Prior to initiating Part 1A (Monotherapy -Dose Escalation), a preliminary safety cohort will be tested in which a single 
participant will undergo an intra-participant dose escalation to establish safety over the 2- to 20-mg dose range of 
BMS-986207. Thereafter, standard dose escalation panels as monotherapy and combination therapy with nivolumab 
will proceed as described below. 
 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
 
 
Abbreviations: CRC, colorectal cancer; HCC, hepatocellular carcinoma; PSC, preliminary safety cohort; RP2D, 
recommended Phase 2 dose, q2w, every 2 weeks; q4w, every 4 weeks; SCCHN, squamous cell carcinoma of the head 
and neck. 
 
FOLLOW-UP PERIODS 
Safety Follow-up: After the end-of-treatment (EOT) visit, all participants will be evaluated for any new AEs for at 
least 100 days after the last dose of therapy. Follow-up visits will occur at Day 30, 60, and 100 (± 7 days) after the 
last dose or date of discontinuation. 
Survival Follow-up: In parallel with the safety follow-up period, participants in Parts 1A, 1B, 2A and 2B will enter 
the survival follow-up period. Participants will be followed by telephone every 12 weeks from discontinuation of 
study drug/EOT visit for a period of 2 years, or until death, lost to follow-up, withdrawal of consent, or conclusion of 
the study, whichever comes first. Both the response and survival follow-up periods will occur simultaneously during 
the 2 year follow-up period. Radiological tumor assessments for participants who have ongoing clinical benefit may 
continue to be collected after participants complete the survival phase of the study. In Parts 1C and 2C, the survival 
follow-up period will continue for 2 years following the last dose of study drug or until death, lost to follow-up, 
withdrawal of consent, or conclusion of the study, whichever comes first. Survival follow-up visits will occur every 
12 weeks (±7 days) until 2 years after the last dose of study drug. 
Response Follow-up: Participants with SD, PR, or CR at the time of study drug discontinuation will continue to have 
radiologic and clinical tumor assessments every 12 weeks for the first year after discontinuation of study drug/EOT 
visit. Subsequently, they will continue to receive tumor assessment scans per standard-of-care guidelines, or, at a 
minimum, every 6 months up to 2 years following the last dose of study drug, or until disease progression or 
withdrawal of study consent. 
Retreatment: Retreatment may be allowed for participants in Parts 1A, 1B, 2A, or 2B with disease progression during 
response follow-up. Participants completing approximately 3 cycles of study therapy (or up to a maximum of 6 cycles, 
if applicable), and entering the response follow-up with ongoing disease control (CR, PR, or SD), may be eligible for 
retreatment. 


Clinical Protocol 
BMS-986207 
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Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
TREATMENTS ADMINISTERED 
The description and storage information of the drugs used in this open-label study are shown in the table below. 
 
Product Description 
Class and Dose Form 
Potency 
Blinding 
Packaging 
Appearance 
Storage Conditions 
(per label) 
BMS-986207 for 
injection 
160 mg/vial 
(20 mg/ml) 
None 
Vial 
2 to 8°C. Protect 
from light and 
freezing. 
Nivolumab 
(BMS-936558) solution 
for injection 
100 mg/vial 
(10 mg/ml) 
None 
Vial 
2 to 8°C. Protect 
from light and 
freezing. 
Ipilimumab 
(BMS-734016) solution 
for injection 
200 mg 
(5 mg/ml) 
None 
Vial 
2 to 8°C. Protect 
from light and 
freezing. 
In Parts 1A, 1B, 2A, and 2B, the initial treatment period is up to 24 weeks (3 cycles) of dosing and the number of 8- 
week cycles will depend on tumor assessment at each cycle. Following each treatment cycle, the decision to treat a 
participant with the next cycle of study therapy, up to a maximum of 48 weeks (6 cycles) of treatment, will be based 
on safety/benefit and tumor assessment. For Parts 1C and 2C, the treatment period is up to a maximum of 2 years in 
the absence of disease progression or unacceptable toxicity. Upon completion of these treatment, participants will 
enter a safety follow-up period. 
Details of the dose escalation and cohort expansion phase in this study are given in the study design section and the 
schematic above. For Parts 1A, 1B, 2A and 2B intra-participant dose escalation/reduction of BMS-986207, nivolumab, 
or ipilimumab is not permitted in this study in order to allow better evaluation of the extended safety and efficacy at 
individual dose levels and schedules. For intra-participant dose reduction of BMS-986207 in Part 1C and 2C see 
Section 5.1.2.6 and Section 5.1.2.7, respectively. 
Study treatment will be dispensed at the study visits. For participants on combination treatment, a 30-minute infusion 
of nivolumab will be followed by a 30-minute observation period, followed by a 60-minute infusion of BMS-986207, 
with a 60-minute observation period after all infusions in Cycle 1 for each participant. For participants < 42 kg 
receiving the 1600-mg dose of BMS-986207 or <38 kg receiving the 1200-mg dose of BMS-986207, the infusion time 
will be longer than 1 hour. For participants in Part 1C or Part 2C, a 30-minute infusion of nivolumab will be followed 
by a 30-minute observation period; followed by a 30-minute infusion of ipilimumab, a 30-minute observation period, 
and by a 60-minute infusion of BMS-986207. 
Treatment Assignment: In this open-label study, no blinding will be required. Enrolled participants will be assigned 
sequential participant numbers via IRT starting with 
(eg, 
). Enrolled participants 
meeting the inclusion criteria will be eligible to be dosed. In the expansion phase only, participants with CRC will be 
randomized in a 1:1 manner to either BMS-986207 monotherapy or combination therapy with BMS-986207 and 
nivolumab to eliminate the possibility of enrollment bias. 
 
STUDY ASSESSMENTS AND ANALYSES: 
Safety Assessments: Safety assessments will be based on reported AEs and the measurement results of vital signs, 
ECGs, physical examinations, and clinical laboratory tests. AEs will be coded using the most current version of the 
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 the last dose of BMS-986207 in the case of monotherapy, and the last dose of BMS-986207 and 
nivolumab, and the last dose of BMS-986207, nivolumab, and ipilimumab for combination therapy. A central/local 
laboratory will perform the clinical laboratory tests and will provide reference ranges for these tests. Both AEs and 
laboratory tests will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events 
v4.03. 


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PK Assessments: Pharmacokinetics of BMS-986207 will be derived from serum concentration versus time data. The 
pharmacokinetic parameters that will be assessed, following the intensive PK collection, are: maximum observed 
serum concentration (Cmax), time of maximum observed serum concentration (Tmax), area under the plasma 
concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration (AUC[0-T]), AUC 
in 1 dosing interval (AUC[tau]), observed concentration at the end of a dosing interval (Ctau), total body clearance 
(CLT), average concentration over a dosing interval (Css-avg), accumulation index (AI), effective elimination half- 
life that explains the degree of accumulation observed for a specific exposure measure (T-HALFeff), 
. Individual participant PK parameter values will be 
derived by noncompartmental methods by a validated PK analysis program. Actual times will be used for the analyses. 
Immunogenicity Assessments: Serum samples for BMS-986207, 
anti-drug antibody 
(ADA) will be collected from all participants at specified time points. 
Efficacy Assessments: Efficacy assessments for the 
 activity of BMS-986207, alone, in combination with 
nivolumab, or in combination with nivolumab and ipilimumab will be based on tumor measurements, using RECIST 
v1.1, with computer tomography and/or magnetic resonance imaging, as appropriate, at baseline, every 8 weeks 
(± 1 week) for Parts 1A, 1B, 2A, and 2B or every 6 weeks for Part 1C and Part 2C during the treatment period, and 
every 12 weeks thereafter during the response follow-up period. 


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2. 
SCHEDULE OF ACTIVITIES 
Study assessments and procedures are shown in Table 2-1, Table 2-2, Table 2-3, Table 2-4, Table 
2-5, and Table 2-6. 
Abbreviations used in the protocol are shown in Appendix 1. 
In limited instances, the scheduled events (including those other than safety assessments) can occur 
outside of indicated timeframes, but the Sponsor should always be notified first. 
If a subject has a delay in study drug administration for any reason, then assessments and 
laboratory tests (with the exception of any tests needed to ensure subject safety) should be 
correspondingly delayed with the exception of tumor assessments (see Table 2-2, Table 2-3, and 
Table 2-4) regardless of dosing delays). 


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Table 2-1: 
Screening - Schedule of Activities 
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Procedure 
Screening Visit 
(Day -28 to -1) 
Notes 
Eligibility Assessments 
Informed Consent 
X 
A participant is considered enrolled only when a protocol-specific informed consent is signed. 
IRT Participant Assignment 
X 
Following obtainment of consent, sites will use IRT for participant number assignment. Subsequent 
visits will be registered into IRT system for drug supply. See Section 5.1.1 
Inclusion/Exclusion Criteria 
X 
See Sections 6.1 and 6.2 
Medical History 
X 
Include any toxicities or allergy related to previous treatments 
Prior Cancer Therapies 
X 
Concomitant Medications 
X 
ECOG Performance Status 
X 
Safety Assessments 
PE 
X 
If the screening PE is performed within 72 hours prior to dose administration 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 
ECGs 
X 
ECGs should be recorded after the participant has been supine for at least 5 minutes, and prior to 
blood draws. Screening ECG to be collected as a single reading (Section 9.4.3) 
Laboratory Testsa 
X 
See Clinical Laboratory Assessments in Section 9.4.4 and Table 9.4.4-1 
Urinalysis 
X 
Screening only; microscopic urine reflex only for urinalysis positive for blood/protein/leukocyte 
Serology 
X 
Includes hepatitis C antibody, reflex HCV RNA viral load, hepatitis B surface antigen. HIV-1 and 
HIV-2 antibody should be tested if mandated by local requirement. 
For HCC participants: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core 
antibody, hepatitis B DNA PCR, hepatitis C antibody and hepatitis C RNA PCR, and hepatitis D 
antibody testing for those with concurrent hepatitis B infection. See Section 9.4.4 and Table 9.4.4-1. 


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Table 2-1: 
Screening - Schedule of Activities 
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Procedure 
Screening Visit 
(Day -28 to -1) 
Notes 
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 taken within 24 hours of dosing (C1D1), a further pregnancy 
test is not required. 
FSH 
X 
Women only, as needed to document postmenopausal status. 
Adverse Event Reporting 
Assessment of Signs/Symptoms/ 
Clinical Complaints 
X 
All AEs (SAEs or non-serious AEs) associated with SARS-CoV-2 infection collected from time of 
onset. 
Monitor for Serious Adverse Events 
X 
All SAEs must be collected from the date of participant’s written consent until 100 days after 
discontinuation of dosing. 
Tumor Assessments 
CT/MRI 
X 
Refer to Imaging Assessment details in Section 9.4.5 
MRI Brain 
MRI scan of the brain required at screening only if participant is symptomatic or has history of brain 
metastasis 
Bone Scan 
May be used to evaluate presence of metastatic lesions; should not be used as modality for 
assessment of measurable disease 
Dispense Study Drug 
X 
Study drugs (BMS-986207, nivolumab, and ipilimumab [Parts 1C and 2C only]) to be supplied by 
BMS, and in assigned vials per IRT 


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Screening - Schedule of Activities 
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Procedure 
Screening Visit 
(Day -28 to -1) 
Notes 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; 
BMS, Bristol-Myers Squibb; C, cycle; CLIA, Clinical Laboratory Improvements 
Amendments; CT, computed tomography; D, day; DNA, deoxyribonucleic acid; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; 
FSH, follicle stimulating hormone; HCV, hepatitis C virus; HCC, hepatocellular 
carcinoma; HIV, human immunodeficiency virus; IgG, immunoglobulin G; 
IRT, Interactive Response Technology, MRI, magnetic 
resonance imaging; 
PCR, polymerase chain reaction; PE, physical examination; RNA, ribonucleic acid; SAE, serious adverse 
events; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WOCBP, women of childbearing potential, 
a There will be a 72 hour window at screening prior to C1D1 for the collection of laboratory tests, 
 


Clinical Protocol 
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Table 2-2: 
On Treatment - Schedule of Activities - q2w and q4w Dosing - Cycles 1 to 3 (Parts 1A, 1B, 2A, and 2B) 
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Procedure 
Cycle 1 
Cycles 2 to 3 
EOTa, b 
D1 
D2 
D5 
D8 
D15 
D22 
D29 
D43 
D1 
D2 
D5 
D8 
D15 
D29 
D43 
Safety Assessments 
ECOG Performance 
Status 
X 
PE 
X 
X 
X 
Symptom Directed PE 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
Vital Signsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Oxygen Saturationc 
X 
X 
ECGsd 
X 
X 
X 
X 
X 
Laboratory Testse 
X 
X 
X k 
X 
X 
X k 
X 
X k 
X 
X k 
Urinalysis 
As clinically indicated; microscopic urine reflex only for urinalysis positive for blood/protein/leukocyte esterase 
Pregnancy Test 
(WOCBP only)f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Reporting 
Monitor for Non- 
Serious Adverse 
Events 
(Appendices 3 and 4) 
X 
Non-Serious AEs will be collected starting with the first dose of study medication and through 100 days following last dose 
of study drug. 
Monitor for Serious 
Adverse Events 
(Appendices 3 and 4) 
X 
All SAEs must be collected from the date of the participant’s written consent until 100 days following the last dose of study 
drug. 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetic (PK) Assessments 
Serial Serum PK and 
Immunogenicity 
Sampling 
See Table 9.5-2 and Table 9.5-3 of pharmacokinetic and immunogenicity sampling schedule and Section 9.5. 


Clinical Protocol 
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Table 2-2: 
On Treatment - Schedule of Activities - q2w and q4w Dosing - Cycles 1 to 3 (Parts 1A, 1B, 2A, and 2B) 
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D43 
D29 
D22 
D15 
D8 
D5 
D2 
D1 
 
 
 
 
 
CT/MRIg 
Tumor imaging assessment to be performed q8w from baseline/screening ± 1 weeka 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: AE, adverse event; 
BMS, Bristol Myers Squibb; C, cycle; D, day; 
ECG; electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EOI, end of infusion; EOT, end of treatment; HCG, human 
chorionic gonadotrophin; IRT, Interactive Response Technology; IU, international units; MRI, magnetic resonance imaging; PE, physical examination; 
PK, pharmacokinetic; q2w, every 2 weeks; q4w, every 4 weeks, q8w, every 8 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; SAE, serious adverse 
event, WOCBP, women of childbearing potential. 
a End of treatment (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. 
Procedure 
Cycle 1 
Imaging Assessments 
D43 
D29 
D15 
D8 
D5 
D2 
D1 
EOTa, b 
Cycles 2 to 3 


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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, Cycle 
3 Day 43) and the start of the safety follow-up period. For participants that 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), does not need to be repeated and will be considered the start of the safety follow-up period. 
c For BMS-986207, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of all infusions in 
Cycle 1; oxygen saturation to also be performed in conjunction with vital signs monitoring on these days. For nivolumab, vital signs will be obtained before the 
infusion and then every 30 minutes (± 10 minutes) until the start of BMS-986207 infusion or per institution guidelines for administration of nivolumab. The 30- 
minute post nivolumab infusion vital signs may correspond to the pre-infusion BMS-986207 vital signs. In the event BMS-986207 administration is delayed, 
nivolumab vital signs will be obtained until 60 minutes after completion of the 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. Obtainment of vital signs surrounding study drug 
administration(s) from Cycle 2 on as per institutional practice/Investigator discretion. For participants < 42 kg on the 1600 mg dose, the infusion time will be 90 
minutes. Details of study drug preparation are found in the Pharmacy Manual, a document that will be provided separately to the site. 
d 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 PK sampling, at predose, EOI, and 4-hr post dose, on day 1 of both C1 and C2 for dose escalation phase only (see Table 9.5-2). Single safety ECGs to be 
done on Day 1 and Day 29 of all treatment cycles where ECG not performed in conjunction with PK sampling. 
e There will be a 72-hour window for collection of all laboratory tests. See Section 9.4.4 and Table 9.4.4-1. 
f 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 drug (urine pregnancy test: 
minimum sensitivity 25 IU/L or equivalent units of hCG). 
g Same imaging modality to be used for all assessments, per RECIST v1.1 (Appendix 5). Tumor assessment to be performed prior to initiating next cycle of 
treatment. Unconfirmed PR/CR must be confirmed at least 4 weeks after initial assessment finding (Section 9.4.5) 
 
 
 
 
 
 
 
k Pregnancy testing on D15 and D43 time points only for q2w dosing. 


Clinical Protocol 
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Table 2-3: 
On Treatment - Schedule of Activities - q2w and q4w Dosing - Cycles 4-6 (Parts 1A, 1B, 2A, and 2B) 
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Procedure 
Cycles 4, 5 and 6 
EOTa, b 
D1 
D8 
D15 
D29 
D43 
Safety Assessments 
PE 
X 
X 
Symptom Directed PE 
X 
X 
X 
Weight 
X 
X 
Vital Signsc 
X 
X 
X 
X 
ECGsd 
X 
X 
X 
Laboratory Testse 
X 
X 
X 
X 
Urinalysis 
As clinically indicated; microscopic urine reflex only for urinalysis positive for blood/protein/leukocyte esterase 
Pregnancy Test 
(WOCBP only)f 
X 
X i 
X 
X i 
X 
Adverse Event Reporting 
Monitor for Non- 
Serious Adverse 
Events 
(Appendices 3 and 4) 
Non-Serious AEs will be collected starting with the first dose of study medication and through 100 days following last dose of study 
drug. 
Monitor for Serious 
Adverse Events 
(Appendices 3 and 4) 
All SAEs must be collected from the date of the participant’s written consent until 100 days following the last dose of study drug. 
Concomitant 
Medications 
X 
X 
X 
X 
Pharmacokinetic (PK) Assessments 
Serial Serum PK and 
Immunogenicity 
Sampling 
See Table 9.5-2 and Table 9.5-3 of pharmacokinetic and immunogenicity sampling schedule and Section 9.5. 


Clinical Protocol 
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Table 2-3: 
On Treatment - Schedule of Activities - q2w and q4w Dosing - Cycles 4-6 (Parts 1A, 1B, 2A, and 2B) 
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Procedure 
Cycles 4, 5 and 6 
EOTa, b 
D1 
D8 
D15 
D29 
D43 
Imaging Assessments 
CT/MRIg 
Tumor imaging assessment to be performed q8w from baseline/screening ± 1 weekb 
Clinical Drug Supplies 
BMS-986207 and 
Nivolumab Infusion 
h 
X 
X 
X 
X 
BMS-986207 and 
Nivolumab Infusion 
h 
X 
X 
Abbreviations: AE, adverse event; BMS, Bristol Myers Squibb; CR, complete response; CT, computed tomography; D, day; ECG; electrocardiogram; EOT, end 
of treatment; HCG, human chorionic gonadotropin; IRT, Interactive Response Technology; IU, international unit; MRI, magnetic resonance imaging; PE, physical 
examination; PK, pharmacokinetic; PR, partial response; q2w, every 2 weeks; q4w, every 4 weeks; q8w, every 8 weeks; RECIST, Response Evaluation Criteria in 
Solid Tumors; SAE, serious adverse event; WOCBP, women of childbearing potential. 
a End of treatment (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, Cycle 
3 Day 43) and the start of the safety follow-up period. For participants that 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), does not need to be repeated and will be considered the start of the safety follow-up period. 
c Obtainment of vital signs surrounding study drug administration(s) from Cycle 2 on as per institutional practice/Investigator discretion. 
d ECGs should be recorded after the participant has been supine for at least 5 minutes, and prior to blood draws. Single safety ECGs to be done on Day 1 and Day 
29 of all treatment cycles where ECG not performed in conjunction with PK sampling. 
e There will be a 72-hour window for collection of all laboratory tests. See Section 9.4.4 and Table 9.4.4-1. 
f 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 drug (urine pregnancy test: 
minimum sensitivity 25 IU/L or equivalent units of hCG). 
g Same imaging modality to be used for all assessments, per RECIST v1.1 (Appendix 5). Tumor assessment to be performed prior to initiating next cycle of 
treatment. Unconfirmed PR/CR must be confirmed at least 4 weeks after initial assessment finding (Section 9.4.5) 


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h Study drugs, BMS-986207 and nivolumab, to be supplied by BMS; vials assigned by IRT should be used. In limited instances, scheduled drug administration 
can occur outside of the indicated timeframes but the Sponsor should always be notified first. 
i Pregnancy testing on D15 and D43 time points only for q2w dosing. 
 


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Table 2-4: 
On Treatment- Schedule of Activities -Triplet Cohort (Part 1C) and Triplet NSCLC Expansion (Part 
2C) 
 
Procedure 
Cycle 1 
Visit Window = -3 Days for C1D1, ± 3 
Days for All Others 
Each Subsequent 
Cycle 
D1 
D8 
D15 
D22 
D29 
D36 
D1 
(± 3 
Days) 
D22 
(± 3 
Days) 
EOT 
Notes 
1 Cycle = 6 weeks 
Safety Assessments 
PE 
X 
X 
X 
Physical Measurements 
X 
X 
X 
X 
See Appendix 8: For C1D21 and each 
subsequent cycle D1 and D21 weight only 
Symptom-directed PE 
X 
X 
X 
X 
To include signs and symptoms 
Vital Signs and Oxygen 
Saturation 
X 
X 
X 
X 
X 
X 
X 
X 
ECGs 
X 
X 
X 
ECGs should be recorded after the 
participant has been supine for at least 5 
minutes, and prior to blood draws. Single 
safety ECGs to be done on Day 1 of all 
treatment cycles. 
Adverse Event Assessments 
Continuously during the study 
All SAEs must be collected from the date 
of the participant’s written consent until 
100 days following the last dose of study 
drug. 
All AEs (including SAEs and non-serious 
AEs), including those associated with 
SARS-CoV-2 infection, must be collected 
continuously during the treatment period. 
Review of Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Table 2-4: 
On Treatment- Schedule of Activities -Triplet Cohort (Part 1C) and Triplet NSCLC Expansion (Part 
2C) 
 
Procedure 
Cycle 1 
Visit Window = -3 Days for C1D1, ± 3 
Days for All Others 
Each Subsequent 
Cycle 
D1 
D8 
D15 
D22 
D29 
D36 
D1 
(± 3 
Days) 
D22 
(± 3 
Days) 
EOT 
Notes 
1 Cycle = 6 weeks 
Pregnancy Test (WOCBP only) 
X 
X 
X 
X 
X 
For WOCBP; serum/urine pregnancy test 
to be performed (urine pregnancy test: 
minimum sensitivity 25 IU/L or equivalent 
units of hCG), see Section 9.2.5. 
ECOG Performance Status 
X 
X 
Confirm status prior to randomization and 
on C1D1 
Laboratory Assessments 
Chemistry and hematology tests 
X 
X 
X 
X 
Within 72 hrs prior to dosing. See 9.4.4 
and Table 9.4.4-1. 


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Table 2-4: 
On Treatment- Schedule of Activities -Triplet Cohort (Part 1C) and Triplet NSCLC Expansion (Part 
2C) 
 
Procedure 
Cycle 1 
Visit Window = -3 Days for C1D1, ± 3 
Days for All Others 
Each Subsequent 
Cycle 
D1 
D8 
D15 
D22 
D29 
D36 
D1 
(± 3 
Days) 
D22 
(± 3 
Days) 
EOT 
Notes 
1 Cycle = 6 weeks 
Efficacy Assessments 
Body Imaging 
Contrast enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all other known and/or suspected sites of disease 
should occur every 6 weeks starting from date of first dose (± 7 days) for the first 12 months (week 48), then every 
12 weeks (± 7 days) until the end of year 2, then every 12 weeks (± 14 days) thereafter until disease progression or 
treatment discontinuation, whichever occurs later. See Section 9.1 and Section 5.1.4 for further details. 
Brain Imaging 
Participants with a history of brain metastasis or symptoms should have a surveillance MRI study per standard of care 
(approximately every 12 weeks), or sooner if clinically indicated. CT of the brain without and with contrast can be 
performed if MRI is contraindicated. See Section 9.1 for further details. 
Pharmacokinetic (PK) and Immunogenicity Assessments 
PK and Immunogenicity 
Samples 
See Section 9.5 and Table 9.5-4. 
Clinical Drug Supplies 
IWRS Vial Assignment 
X 
X 
X 
Within 1 day prior to dosing 
Study Drug Treatments 
BMS-986207 
X 
X 
X 
X 
BMS-986207 to be administered q3W. 
For participants < 38 kg on the 1200 mg 
dose, the infusion time will be longer than 
1 hour (approximately 90 minutes). For 
participants with a bodyweight of > 250 kg 
the dosing of BMS-986207 will occur the 


Clinical Protocol 
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Table 2-4: 
On Treatment- Schedule of Activities -Triplet Cohort (Part 1C) and Triplet NSCLC Expansion (Part 
2C) 
 
Procedure 
Cycle 1 
Visit Window = -3 Days for C1D1, ± 3 
Days for All Others 
Each Subsequent 
Cycle 
D1 
D8 
D15 
D22 
D29 
D36 
D1 
(± 3 
Days) 
D22 
(± 3 
Days) 
EOT 
Notes 
1 Cycle = 6 weeks 
day after dosing of nivolumab and 
ipilimumab when these drugs are 
administered on the same day (ie, D2 and 
D22 of each cycle).Details of study drug 
preparation are found in the Pharmacy 
Manual. 
Nivolumab 
X 
X 
X 
X 
Nivolumab to be administered q3W 
Ipilimumab 
X 
X 
Ipilimumab to be administered q6W 
Abbreviations: AE, adverse event; BMS, Bristol-Myers Squibb; C, cycle; CT, computed tomography; D, day; ECG, electrocardiogram; ECOG, Eastern Cooperative 
Oncology Group; eCRF, electronic case report form; EOT, end of treatment; hCG, human chorionic gonadotropin; 
IU, international units; 
IWRS, Interactive Web Response System, MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PE, physical exam; PK, pharmacokinetics; 
q3w, every 3 weeks; q6w, every 6 weeks; SAE, serious adverse events; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; WOCBP, women of 
childbearing potential 
 
NOTES: 
1) If a dose is delayed, the procedures scheduled for that same time point should be delayed to coincide with when the time point’s dosing actually occur (except 
radiographic tumor assessments). 
2) Some of the assessments referred to in this section may not be captured as data in the eCRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Table 2-5: 
Follow-up Procedural Outline (All Participants) 
Protocol Amendment No: 04 
Date:06-Jan-2022 
38 
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Safety Follow-up 
Survival Follow-up 
Response 
Follow-upa 
Commences 
All Participants - 
with Start of 
Commence with 
Safety 
Procedure 
Follow-up 1 
30 Daysb 
(± 7 days) 
Follow-up 2 
60 Days 
(± 7 days) 
Follow-up 3 
100 Days 
(± 7 days) 
Start of Safety 
Follow-up: 
Follow-up Every 
12 Weeks until 2 
Follow-up: 
Follow-up Done 
Every 
12 Weeks for 1 
Notes 
Years After LAST 
Year After 
Dose of Study Drug 
LAST Dose of 
Study Drug 
Safety Assessments 
Physical 
Examination 
X 
X 
X 
Vital Signs 
X 
X 
X 
Includes body temperature, 
seated/supine blood pressure, and 
heart rate. 
Laboratory Testsc 
X 
X 
X 
Lab tests also as clinically indicated; 
See laboratory assessments in Section 
9.4.4 and Table 9.4.4-1 
Urinalysis 
As clinically indicated. See Section 9.4.4 
Pregnancy Test 
X 
X 
X 
For WOCBP; serum/urine pregnancy 
test to be performed (urine pregnancy 
test: minimum sensitivity 25 IU/L or 
equivalent units of hCG), (Section 
9.2.5. 
Adverse Event Reporting and Concomitant Medication Assessments 
Monitor for Non- 
Serious Adverse 
Events 
X 
X 
X 
Non-Serious AEs will be collected 
starting with the first dose of study 
medication and through 100 days 
after discontinuation of dosing 
(Appendices 3 and 4). 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Table 2-5: 
Follow-up Procedural Outline (All Participants) 
Protocol Amendment No: 04 
Date:06-Jan-2022 
39 
Approved v71.0 
930104927 7.0 
 
 
 
 
Procedure 
Safety Follow-up 
Survival Follow-up 
Response 
Follow-upa 
Follow-up 1 
30 Daysb 
(± 7 days) 
Follow-up 2 
60 Days 
(± 7 days) 
Follow-up 3 
100 Days 
(± 7 days) 
All Participants - 
Commence with 
Start of Safety 
Follow-up: 
Follow-up Every 
12 Weeks until 2 
Years After LAST 
Dose of Study Drug 
Commences 
with Start of 
Safety 
Follow-up: 
Follow-up Done 
Every 
12 Weeks for 1 
Year After 
LAST Dose of 
Study Drug 
Notes 
Monitor for Serious 
Adverse Events 
X 
X 
X 
All SAEs must be collected from the 
date of the participant’s written 
consent until 100 days post 
discontinuation of dosing. 
Participants will be followed for all 
SAEs and all AEs (SAEs and non- 
serious AEs) associated with 
confirmed or suspected SARS-CoV-2 
infection until resolution, the 
condition stabilizes, the event is 
otherwise explained, the event is 
deemed irreversible, the participant is 
lost to follow-up (as defined in 
Section 8.3), or for suspected cases, 
until SARS-CoV-2 infection is ruled- 
out. 
Concomitant 
Medication 
Assessments 
X 
X 
X 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Table 2-5: 
Follow-up Procedural Outline (All Participants) 
Protocol Amendment No: 04 
Date:06-Jan-2022 
40 
Approved v71.0 
930104927 7.0 
 
 
 
 
Procedure 
Safety Follow-up 
Survival Follow-up 
Response 
Follow-upa 
Follow-up 1 
30 Daysb 
(± 7 days) 
Follow-up 2 
60 Days 
(± 7 days) 
Follow-up 3 
100 Days 
(± 7 days) 
All Participants - 
Commence with 
Start of Safety 
Follow-up: 
Follow-up Every 
12 Weeks until 2 
Years After LAST 
Dose of Study Drug 
Commences 
with Start of 
Safety 
Follow-up: 
Follow-up Done 
Every 
12 Weeks for 1 
Year After 
LAST Dose of 
Study Drug 
Notes 
Pharmacokinetic (PK) Assessments 
Serial Serum PK and 
Immunogenicity 
Sampling 
See Table 9.5-2 and Table 9.5-3 for pharmacokinetic and immunogenicity sampling schedule and Section 9.5. 
Efficacy 
Assessments 
Tumor/Response 
Assessments 
X 
X 
Contrast enhanced CT of the chest, 
CT/MRI of the abdomen, pelvis, and 
all other known and/or suspected 
sites of disease should occur every 
8 weeks (6 weeks for Parts 1C and 
2C) starting from date of first dose 
(± 7 days) for the first 12 months 
(week 48), then every 12 weeks (± 7 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Table 2-5: 
Follow-up Procedural Outline (All Participants) 
Protocol Amendment No: 04 
Date:06-Jan-2022 
41 
Approved v71.0 
930104927 7.0 
 
 
 
 
Procedure 
Safety Follow-up 
Survival Follow-up 
Response 
Follow-upa 
Follow-up 1 
30 Daysb 
(± 7 days) 
Follow-up 2 
60 Days 
(± 7 days) 
Follow-up 3 
100 Days 
(± 7 days) 
All Participants - 
Commence with 
Start of Safety 
Follow-up: 
Follow-up Every 
12 Weeks until 2 
Years After LAST 
Dose of Study Drug 
Commences 
with Start of 
Safety 
Follow-up: 
Follow-up Done 
Every 
12 Weeks for 1 
Year After 
LAST Dose of 
Study Drug 
Notes 
days) until the end of year 2, then 
every 12 weeks (± 14 days) thereafter 
until disease progression or treatment 
discontinuation, whichever occurs 
later. See Section 9.1 for further 
details. 
Brain Imaging 
X 
As clinically indicated 
Bone Scan 
X 
As clinically indicated 
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. 
Abbreviations: AE, adverse event; CR, complete response; CT, computed tomography; EOT, end of treatment; hCG, human chorionic gonadotropin; 
IU, international units; MRI, magnetic resonance imaging; PK, pharmacokinetic; PR, partial response;; SAE, serious adverse event; SARS- 
CoV 2, severe acute respiratory syndrome coronavirus-2; SD, stable disease; WOCBP, women of childbearing potential. 
a Only participants with SD, PR, or CR at EOT visit. After first year of response follow-up, participants will continue to receive tumor assessment scans as per 
standard-of-care guidelines, or at a minimum of every 6 months for a total of 2 years response follow-up after the last dose of study drug. 
b Follow-up visits at Days 30, 60 (± 7days), and 100 (± 10days) should occur relative to the last dose of study drug or date of discontinuation. 
c For details of laboratory tests, see Section 9.4.4 and Table 9.4.4-1. 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Table 2-6: 
Retreatment Day 0 Procedural Outline (Parts 1A, 1B, 2A, 2B only) 
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Date:06-Jan-2022 
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Procedure 
Day 0a,b 
Notes 
Eligibility Assessments 
X 
Participants must meet eligibility criteria and discussion with BMS Medical Monitor should occur. 
Safety Assessments 
Physical Examination 
X 
If the screening physical examination is performed within 72 hours of dosing on re-treatment Cycle 1/ 
Day 1, then a single examination may count as both the screening and predose evaluations. 
ECOG Performance Status 
X 
Physical Measurements 
X 
Weight only 
Vital Signs and Pulse Oximetry 
 
X 
Includes body temperature, respiratory rate, seated/supine blood pressure, and heart rate. Blood 
pressure, respiratory rate, and heart rate should be measured after the participant has been seated quietly 
for at least 5 minutes. 
Laboratory Testsc 
X 
Laboratory tests must be completed within 2 weeks of retreatment Cycle 1/Day 1 unless otherwise 
noted. For laboratory assessments, see Section 9.4.4 and Table 9.4.4-1 
Urinalysis 
X 
See Section 9.4.4 
Serology Tests 
 
 
X 
Repeat the following if > 6 months since last treatment: serum for hepatitis C antibody, hepatitis B 
surface antigen, HIV-1 and HIV-2 antibody (screening, and as mandated by local requirement), and 
hepatitis C RNA (reflex). 
For HCC participants: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core 
antibody, hepatitis B deoxyribonucleic acid (DNA) polymerase chain reaction (PCR), hepatitis C 
antibody, and hepatitis C ribonucleic acid (RNA) PCR and hepatitis D antibody testing for those with 
concurrent hepatitis B infection. 
Thyroid Function Tests 
X 
TSH with free T3 and free T4 (reflex only) 
Serial Serum PK Sampling 
PK/ADA sampling to be done at predose on Day 1 of all cycles; @ EOT and 30 and 60 day followup 
visits. PK sampling to be performed w/SAEs, with addition of ADA if suspected hypersensitivity 
reaction. No dose delay PK sampling to be done in Retreatment. 
Serum Pregnancy Test 
 
X 
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 retreatment provided results are available prior to starting study 
therapy. If pregnancy test taken within 24 hours of dosing (retreatment C1D1), a further pregnancy test 
is not required. 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Table 2-6: 
Retreatment Day 0 Procedural Outline (Parts 1A, 1B, 2A, 2B only) 
Protocol Amendment No: 04 
Date:06-Jan-2022 
43 
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Procedure 
Day 0a,b 
Notes 
FSH 
X 
Women only, as needed to document postmenopausal status 
Efficacy Assessments 
Tumor Assessments 
X 
CT with contrast is the preferred modality (MRI if CT is not feasible). Previous CT scan within 28 days 
can be used for this timepoint. 
Brain Imaging 
X 
Brain imaging (CT/MRI) for participants with history or symptoms of brain metastases and who have 
not had brain imaging within 30 days of anticipated first retreatment dose. 
Bone Scan 
X 
As clinically indicated (eg, participants with history or symptoms of bone metastases), but bone scans 
will not be considered a modality for the assessment for measurable disease. 
Clinical Drug Supplies 
Participant Registration for 
Retreatment via IRT 
X 
Ensure participant continues to meet eligibility for protocol treatment. 
Abbreviations:; ADA, antidrug antibody; BMS, Bristol Myers Squibb; C1D1, Cycle 1 Day 1; CT, computed tomography DNA, deoxyribonucleic acid; 
ECOG, Eastern Cooperative Oncology Group; EOT, end of treatment; FSH, follicle stimulating hormone; HCC, hepatocellular carcinoma; HIV, human 
immunodeficiency virus; IRT, Interactive Response Technology; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PK, pharmacokinetic; 
RNA, ribonucleic acid; SAE, serious adverse event;TSH, thyroid stimulating hormone; T3, triiodothyronine; T4, thyroxine; WOCBP, women of child bearing 
potential. 
a All procedures for retreatment eligibility will be performed within 28 days prior to retreatment Cycle 1/Day 1 dosing. 
b All participants entering retreatment will follow the same time and events table as previously assigned. Limited PK/
 samples will be collected. 
c For details of laboratory tests, see Section 9.4.4 and Table 9.4.4-1. 


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CA020002 
Anti-TIGIT mAb 
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Date:06-Jan-2022 
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3. 
INTRODUCTION 
This is a Phase 1/2a, first-in-human (FIH), dose escalation study of BMS-986207, an anti-T cell 
immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) 
monoclonal antibody (mAb), alone, in combination with nivolumab (anti-programmed cell death 
1 [PD-1]), and in combination with nivolumab and ipilimumab (anti-cytotoxic T-lymphocyte 
associated protein 4 [CTLA-4] antibody) in humans with advanced solid tumors. 
3.1 
Study Rationale 
Antibody-based therapy for cancer is well established and constitutes an important strategy for the 
treatment of patients with hematological malignancies and solid tumors. 1 In addition to the 
targeting of antigens involved in cancer cell proliferation and survival, antibodies can function 
either to activate or antagonize immunological pathways involved in cancer immune surveillance. 
The anti-cancer, antigen-specific immune response is the result of a complex dynamic interplay 
between antigen-presenting cells, T-lymphocyte cells, and the target cancer cells.2 The critical 
balance of T cell activity that dictates whether endogenous anti-cancer immune responses will be 
effective is thought to be controlled by antigen-specific stimuli sensed by the T cell receptor and 
by the combined activity of both positive (co-stimulatory) and negative (co-inhibitory) T cell 
surface molecules.3 Within the past decade, antibodies against these key receptors have been 
designed and evaluated in the clinic with encouraging results, heralding the onset of 
immunotherapy as a key pillar of anti-cancer therapy.4 
Tumors modulate and evade the host immune response through a number of mechanisms, 
including down regulation of tumor-specific antigen expression and presentation, secretion of 
anti-inflammatory cytokines, and upregulation of inhibitory ligands. Immunotherapeutic 
approaches such as checkpoint pathway blockade have demonstrated clinical efficacy in several 
cancers, including melanoma, renal cell, lung, and hormone-refractory prostate cancers. 5 
Following the success of CTLA-4 and anti-PD-1 pathway-targeted agents in several cancers, the 
field of tumor immunotherapy is rapidly expanding, recognizing the potential value of combination 
therapies.6 
TIGIT is a 26-kDa type I transmembrane immunoglobulin superfamily member with a single 
extracellular IgV domain, an intracellular domain containing immunoglobulin tail tyrosine motif 
and ITIM, and a growth factor receptor-bound protein binding site. In healthy individuals, TIGIT 
is expressed on a subset of memory CD4+ and CD8+ T cells and on the majority of regulatory T 
cells (Tregs) and NK cells. In the settings of chronic viral infections and cancer, TIGIT is strongly 
upregulated on CD8+ T cells and has been associated with other 
 of T cell exhaustion, 
including PD-1, CTLA-4, lymphocyte-activation gene 3 (LAG-3), and T cell immunoglobulin and 
mucin domain-containing-3 (TIM-3).7,8 In human tumors, TIGIT is expressed on the majority of 
tumor-infiltrating Tregs and CD8+ T cells, and to a lesser extent on CD4+ T effectors.8 
TIGIT ligands poliovirus receptor (PVR) and Nectin-2 are highly expressed on many tumors and 
tumor-infiltrating myeloid cells, and likely contribute to the immunosuppressive tumor 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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microenvironment. Upon ligand engagement, TIGIT can partially suppress T cell and natural killer 
(NK) cell activation. 9 Furthermore, TIGIT agonism leads to Treg stabilization and increased 
interleukin 10 production by Tregs.10,11 TIGIT competes for ligand binding with costimulatory 
receptor DNAX accessory molecule 1 (DNAM-1, also CD226), which has been shown to be 
involved in tumor immune surveillance, and TIGIT co-expression on the cell surface has been 
linked to decreased DNAM-1 signaling.8,12 
In ex vivo experiments using peripheral blood mononuclear cells (PBMC) from melanoma 
patients, antibody blockade of TIGIT/PVR interaction on tumor antigen-stimulated CD8+ T cells 
resulted in increased proliferation and cytokine production. This activity was further enhanced 
when combined with PD-1 blockade.13Comparable studies were conducted using PBMC from 
human immunodeficiency virus (HIV) positive patients with similar results.14 Studies at BMS 
have shown that TIGIT blockade on NK cells results in increased activation and lysis of 
PVR-expressing tumor cells in a DNAM-1 expression dependent manner. BMS-986207, a fully 
human anti-TIGIT mAb, was designed with an inert isotype (termed IgG1.1) to eliminate fragment 
crystallizable region (Fc) effector function, which is intended to increase anti-tumor immune 
response by decreasing inhibitory signals and allowing increased DNAM-1 co-stimulation on 
intra-tumoral CD8+ T cells. Based on preclinical models, blockade of PD1/programmed death- 
ligand 1 (PD-L1) pathway is expected to enhance or synergize with TIGIT blockade. 
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of 
intravenous (IV) doses of BMS-986207, administered as monotherapy, in combination with 
nivolumab, and as of Protocol Amendment 03, in combination with nivolumab and ipilimumab, 
in participants with advanced solid tumors. This study will also determine the maximum tolerated 
dose (MTD)/recommended Phase 2 dose (RP2D) of BMS-986207 to be used in future 
monotherapy and combination studies. Further details on the scientific rationale for the study 
design are presented in Section 5.4. 
 
BMS-986207 was well tolerated as monotherapy and in combination with nivolumab.19 
Preliminary data from the CA020002 study have, thus far, shown some clinical benefit in 
participants with melanoma (2 participants with partial response [PR]) and prostate cancer (1 
participant with PR) when BMS-986207 was combined with nivolumab. No clinical benefit was 
observed in any participants who received BMS-986207 monotherapy (unpublished results). 


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CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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Other tumor types in this study included colorectal cancer (CRC), ovarian, breast, gastric, and 
urothelial cancer. 
Recently, reports in the literature have shown comparable efficacy results with anti-TIGIT agents 
in combination with anti-PD-(L)1 agents, pembrolizumab and atezolizumab, in most tumor 
types.15,16 Best responses, however, were observed in those studies in 1L and previously treated 
NSCLC participants whose tumors expressed PD-L1. A randomized Phase 2 study comparing the 
anti-TIGIT agent tiragolumab plus atezolizumab versus placebo plus atezolizumab in PD-L1- 
positive 1L Stage IV NSCLC patients demonstrated improvement in the overall response rate 
(ORR; 37% vs. 21% with atezolizumab alone). The treatment regimen was well tolerated, with 
safety similar to that seen in the placebo plus atezolizumab treatment (see Section 5.4.4 for more 
details).16 In addition, recent data presented from a Phase 1 study (NCT02964013) of the anti- 
TIGIT antibody vibostolimab plus pembrolizumab in participants with anti-PD-(L)1-naive 
NSCLC demonstrated anti-tumor activity (ORR 29% and 46% in patients with PDL1-positive 
disease ).17 These data suggest that combining anti-TIGIT with anti-PD-(L)1 can be safe, tolerable, 
and have clinical benefits in PD-L1-positive 1L NSCLC patients.17 
As of 20-Oct-2021, the safety profile of BMS-986207 1200 mg Q3W in combination with 
nivolumab 360 mg Q3W and ipilimumab 1 mg/kg Q6W has been evaluated in 6 subjects with 
multiple metastatic solid tumors in CA020002 Part 1C. Of the 4 dose-limiting toxicity (DLT)- 
evaluable participants, 2 participants reported DLTs (Grade 3 encephalitis and Grade 3 bullous 
dermatitis [n = 1 each]). Per Bayesian optimal interval (BOIN) design, in all the remaining and 
future subjects, BMS-986207 was de-escalated to a lower dose (600 mg Q3W). For details, see 
Section 3.2.1.4. 
The combination of nivolumab +/- ipilimumab is approved in 17 countries as 1L treatment for 
patients with metastatic non-small cell lung cancer (NSCLC) expressing PD-L1 ≥ 1% (eg, United 
States, Canada, etc.) or both PD-L1 ≥ 1% and < 1% (e.g. Japan, Argentina). This regimen is also 
recommended by the European Society for Medical Oncology and National Comprehensive 
Cancer Network Clinical Practice Guidelines in Oncology as a 1L treatment option for metastatic 
NSCLC regardless of PD-L1 expression.18 Data from BMS CheckMate 227, a randomized, open- 
label Phase 3 study in participants with treatment-naive NSCLC, demonstrated that the 
combination of nivolumab plus ipilimumab was safe and tolerable and improved overall survival 
(OS) compared to chemotherapy alone (PD-L1 ≥ 1% overall survival [OS] 29% vs. 18%, hazard 
ratio [HR] 0.76; 95% confidence interval [CI]: 0.65 to 0.90).33 Thus, the nivolumab and 
ipilimumab combination is an appropriate backbone for exploring the effects of BMS-986207 in 
PDL1-positive 1L NSCLC. Using this triplet combination in NSCLC participants allows the 
combination of a checkpoint inhibitor-responsive patient population (NSCLC) with a checkpoint 
inhibitor combination (nivolumab + ipilimumab) that has been demonstrated to work as an 
appropriate therapy for this patient population. 
In the present study, to further evaluate whether TIGIT inhibition together with cancer 
immunotherapies can enhance 
immune activity, the safety of this triplet combination 
will be tested in a small group of participants across all tumor types. Once safety is established, 


Clinical Protocol 
BMS-986207 
CA020002 
Anti-TIGIT mAb 
Protocol Amendment No: 04 
Date:06-Jan-2022 
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930104927 7.0 
 
 
1L NSCLC participants whose tumor cells express ≥ 1% PD-L1 will be treated with BMS-986207 
plus nivolumab and ipilimumab. 
It is anticipated that anti-TIGIT antibody (BMS-986207), administered as a single agent, in 
combination with anti-PD1 antibody (nivolumab), or in combination with nivolumab and anti- 
CTLA-4 antibody (ipilimumab) will demonstrate adequate safety and tolerability, as well as a 
favorable risk/benefit profile, to support further clinical testing. No prospective hypotheses are 
being formally evaluated. 
3.2 
Background 
3.2.1 
BMS-986207 
BMS-986207 is a fully human immunoglobulin G1 (IgG1) mAb that binds with high affinity to 
TIGIT (T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based 
inhibitory motif domain), a negative regulatory molecule that suppresses activation and functional 
responses in T cells and NK cells. The antibody is engineered to negate Fc gamma receptor (FcγR) 
binding by the introduction of 5 specific amino acid mutations. TIGIT upregulation has been 
observed in cancer patients, in particular on T cells and is co-expressed with 
 of T cell 
exhaustion. Binding of PVR and Nectin-2 (TIGIT ligands) to TIGIT results in suppression of T 
cell and NK cell function. Blockade of TIGIT therefore may increase the immune anti-tumor 
response both by removing the suppressive signal emanating from TIGIT as well as by freeing its 
ligands to bind to the stimulatory receptor CD226 (DNAM-1), which shares these ligands. BMS- 
986207 blocks interaction of TIGIT with its ligands and thereby may induce or enhance anti-tumor 
immune responses. 
3.2.1.1 
Nonclinical Pharmacology 
BMS-986207 binds recombinant TIGIT with an equilibrium dissociation constant (KD) of 
and to cell surface TIGIT on activated CD8+ T cells with a half-maximal effective concentration 
(EC50) of 
 . The antibody binds to recombinant cynomolgus monkey TIGIT with and 
EC50 of 
and to activated cynomolgus monkey CD8+ T with an EC50 of 
BMS-986207 inhibits the binding of PVR and Nectin-2 to TIGIT in a dose-dependent manner with 
an EC50 of 
. BMS-986207 blocked the inhibitory activity of TIGIT/PVR interaction in a 
Jurkat cell line reporter assay, a T cell peptide stimulation assay, and an NK cell redirected lysis 
assay. In the Jurkat and NK cell assays, TIGIT blockade alone resulted in increased nuclear factor- 
kappa-B (NF-κB) luciferase signals and increased lysis of target cells, respectively. In the T cell 
peptide stimulation assay, the effect of TIGIT blockade was strongest when combined with PD-1 
blockade, and resulted in increased interferon gamma (IFNγ) secretion and an elevated percentage 
of IFNγ−producing T cells. 
Due to its engineered inert Fc region, as expected, BMS-986207 does not induce antibody- 
dependent cellular cytotoxicity (ADCC)- or antibody-dependent cellular phagocytosis (ADCP)- 
mediated killing of TIGIT-expressing target cells. In addition, BMS-986207 does not bind 
complement 1q (C1q). Based on these findings, BMS-986207-induced depletion of TIGIT- 
expressing cells is not expected. BMS-986207 showed no unexpected binding in 8 cynomolgus 


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CA020002 
Anti-TIGIT mAb 
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Date:06-Jan-2022 
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tissue types tested. Additionally, BMS-986207 did not mediate spontaneous cytokine secretion at 
detectable levels in fresh whole blood samples from 8 normal human donors. These data suggest 
that BMS-986207 treatment does not lead to cytokine release syndrome (CRS) in whole blood. 
A number of mouse studies were undertaken to examine the role of TIGIT blockade in tumor 
settings. An MC38 colon adenocarcinoma murine tumor study in PD-1/TIGIT double knockout 
(KO) mice suggested dual blockade of TIGIT and PD-1 may be beneficial in the treatment of 
cancer through enhanced antitumor immunity. PD-1/TIGIT double KO mice showed superior 
tumor rejection as compared to the other groups. There were no tumor-free mice in the groups of 
TIGIT KO mice or wild-type mice. In the CT26 colon murine tumor model and the A20 B cell 
lymphoma murine model, TIGIT blockade with a surrogate antibody in combination with PD-1 
blockade or CTLA-4 by surrogate antibodies resulted in anti-tumor responses. In these models, 
the combination of PD-1 blockade or CTLA-4 blockade with TIGIT blockade resulted in a greater 
number of tumor-free mice than either agent alone. 
The in vitro and in vivo data indicating that TIGIT blockade can enhance T cell and NK cell 
activation, and that TIGIT blockade (together with PD-1 or CTLA-4 blockade) enhances anti- 
tumor immune activity, support the development of BMS-986207 for the treatment of cancer. 
3.2.1.2 
Nonclinical Pharmacokinetics 
The pharmacokinetics (PK) of BMS-986207 were evaluated in cynomolgus monkeys in 2 studies 
Following a single IV dose of 1, 10, and 100 mg/kg 
or 0.5 and 3 mg/kg 
BMS-986207 serum concentrations exhibited biexponential 
decline, dose-proportional increase in systemic exposure, low total body serum clearance ( 
), low volume of distribution at steady-state 
and long 
apparent half-life 
The Vss is similar to the reported plasma volume in 
monkeys, indicating limited extravascular distribution. The presence of anti-drug antibodies 
(ADAs) was observed in all except 1 monkeys. Anti-drug-antibodies were detected as early as 
Day 7 and their appearance appeared to correlate with an accelerated decline in BMS-986207 
serum concentrations. 
In mice, a dose dependent tumor efficacy was observed with a combination of 10A7-mIgG1 
D265A (anti-mouse TIGIT with a D265A mutated inert mIgG1 isotype; the surrogate antibody for 
BMS-986207) and 4H2-mIgG1 D265A (mAb to mouse PD-1 Clone 4H2, isotype mouse IgG1- 
D265A); either antibody had little or no tumor efficacy. Therefore, PK of 10A7-mIgG1 D265A in 
combination with 4H2-mIgG1 D265A were evaluated in mice. After multiple intraperitoneal (IP) 
doses of 10A7-mIgG1 D265 (10 mg/kg) alone or in combination with anti-mPD-1-mIgG1 D265A 
(7.5 mg/kg) at 0.3, 1, and 3 mg/kg to female BALB/c mice bearing CT26 tumors, 10A7-mIgG1 
D265A exhibited a dose-proportional increase in exposure. Fitting the exposures to a 
1-compartment PK model with an absorption compartment yielded an estimated apparent CLTs 
. 
3.2.1.3 
Nonclinical Toxicology 
The nonclinical safety of BMS-986207 was evaluated in vitro in a human tissue cross-reactivity 
study and cytokine release and lymphocyte activation assays with human cells, and in an in vivo 


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Anti-TIGIT mAb 
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Date:06-Jan-2022 
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1-month intermittent repeat-dose IV toxicity study in cynomolgus monkeys. The cynomolgus 
monkey was selected as the toxicology species because BMS-986207 binds to TIGIT expressed 
on activated cynomolgus monkey T cells with a similar affinity as TIGIT expressed on activated 
human T cells 
and is pharmacologically 
active in monkeys; it does not bind rodent TIGIT. 
In a Good Laboratory Practice (GLP)-compliant tissue cross-reactivity study in normal human 
tissues fluoresceinated BMS-986207 produced membrane and cytoplasmic staining of 
mononuclear cells in human lymphoid tissues and select non-lymphoid tissues. This staining was 
expected based on TIGIT expression by mononuclear cell types, such as T cells and NK cells. No 
unexpected tissue cross-reactivity was observed. BMS-986207 did not induce cytokine release or 
increase the expression of activation 
 on human T, B, or NK cells in an in vitro human 
peripheral blood mononuclear cell cytokine release and cell activation assay, suggesting a low risk 
of BMS-986207-induced CRS in humans. 
In a 1-month pivotal toxicity study in monkeys, BMS-986207 was administered IV as a slow bolus 
at doses of 0, 10, 30, or 100 mg/kg (once weekly [qw]× 5 doses). BMS-986207 was clinically well 
tolerated by all monkeys at 30 and 100 mg/kg doses while 3 out of 10 monkeys in the 10 mg/kg 
dose group exhibited signs of ADA mediated hypersensitivity reactions immediately after dosing 
on study days 22 and/or 29 (fourth and/or fifth dose). The clinical signs were transient, 
accompanied by increases in serum cytokine levels and complement activation, and no treatment 
was required for the affected monkeys. The timing, type of clinical observations, correlative 
complement activation are consistent with the formation of treatment-emergent ADA, a common 
response by monkeys to a foreign protein. This immunogenicity is not considered to be predictive 
for ADA responses in humans (International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use [ICH] S6). 
 responses were 
observed at all doses and included NK cell activation and CD8+ T cell activation and proliferation, 
and were generally dose-independent. Based on the lack of directly BMS-986207-related adverse 
findings, the no-observed-adverse-effect level (NOAEL) was considered to be 
 
. In addition, for determination of the maximum 
recommended human starting dose, 
was also considered the highest non-severely toxic 
dose (HNSTD). The HNSTD/NOAEL of 
 
than the proposed 
starting dose in humans (1 mg/kg) with a corresponding plasma 
 
of the 
projected human AUC (0-336),ss at 1 mg/kg 
 
Overall, the nonclinical toxicology assessment of BMS-986207 has demonstrated an acceptable 
safety profile, supporting clinical use in oncology patients. 
3.2.1.4 
Preliminary Clinical Safety Profile 
Overall, based on preliminary data as of 21-Jan-2021, the safety profile of BMS-986207 as 
monotherapy (n = 42) or in combination with nivolumab (n = 30) is manageable at the doses 
tested. 19 
no new serious adverse events (SAEs) or 
treatment-related adverse events (AEs) had been reported for BMS-986207 monotherapy or in 


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combination with nivolumab. BMS-986207 was evaluated as a monotherapy at doses ranging from 
20 mg to 1600 mg q2w (20 mg: n = 3; 80 mg: n = 3; 240 mg: n = 4; 800 mg: n = 28; 1600 mg: n 
= 4.). A single participant was dosed using an intra-participant dose escalation approach at 2, 6, 
and 20 mg. Escalation in this participant occurred 2 weeks after each dose with continued treatment 
at 20 mg q2w. There was no relationship between the incidence, severity, or causality of AEs and 
BMS-986207 dose level. A majority of treatment-related AEs were of Grade 1 to Grade 2, with 5 
treatment-related Grade 3 to Grade 4 AEs (Grade 3 elevated aspartate aminotransferase, n = 1; 
Grade 3 hypertension, n = 1; Grade 3 hyponatremia, n = 2; Grade 3 hyperglycemia, n = 1). 
Infusion-related AEs were reported in 1 participant, which were managed based on the updated 
protocol guidelines. There were no drug-related SAEs with monotherapy. A total of 26 deaths were 
reported in participants treated with BMS-986207 monotherapy. All deaths were due to 
complications from disease progression except for 1 death attributed to aspiration pneumonia. All 
were considered by the Investigator to be not related to study drugs. 
The safety profile of BMS-986207 in combination with nivolumab was evaluated at the following 
doses: 80 mg BMS-986207 + 240 mg nivolumab q2w (n = 4), 240 mg BMS-986207 + 240 mg 
nivolumab q2w (n = 4), 480 mg BMS-986207 + 480 mg nivolumab q4w (n = 18), and 1600 mg 
BMS-986207 + 480 mg nivolumab q4w (n = 4). There was no relationship between the incidence, 
severity, or causality of AEs and the combination regimen dose levels. Most AEs were of Grade 1 
and Grade 2. With combination therapy, treatment-related AEs were similar to those expected 
from nivolumab alone.19 A total of 13 deaths occurred in participants treated with combination 
therapy. All deaths were due to complications from disease progression and all were considered 
by the Investigator to be not related to study drug. 
As of 20-Oct-2021, the safety profile of BMS-986207 1200 mg Q3W in combination with 
nivolumab 360 mg Q3W and ipilimumab 1 mg/kg Q6W was assessed in 6 participants. Of the 6 
treated participants (the first participant was a sentinel participant), 4 participants were DLT 
evaluable. Based on preliminary data, 2 out of the 4 DLT-evaluable participants reported 
experiencing DLTs. One participant was a 79-year-old female with second-line (2L) pancreatic 
cancer who was reported to have Grade 3 encephalitis. The patient received the triplet combination 
once on Day 1. On Day 22, treatment was held for Grade 2 pneumonitis, which began on Day 12. 
On Day 40, treatment was discontinued due to disease progression. On Day 41, Grade 3 
encephalitis, a DLT, was reported, treated with corticosteroids and mycophenolate mofetil, and 
had improved to Grade 2 on Day 53. The participant died on Day 118 due to disease progression. 
The Grade 2 pneumonitis and Grade 2 encephalitis did not resolve. The second participant was a 
73-year-old female with fourth-line (4L) melanoma who received the triplet once on Day 1 and 
developed Grade 3 bullous dermatitis, a DLT, on Day 21. Treatment with corticosteroids and 
mycophenolate mofetil was consequently initiated, and dermatitis resolved on Day 49. A total of 
2 deaths were reported, and both were attributed to disease progression and not related to study 
intervention. Based on the BOIN design, ongoing participants in the first cohort, as well as future 
participants in the next cohort, in the dose evaluation for Study CA020002 will dose de-escalate 
to BMS986207 600 mg Q3W in combination with nivolumab 360 mg Q3W + ipilimumab 1 mg/kg 
Q6W. 


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3.2.2 
Nivolumab 
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human monoclonal 
antibody (immunoglobulin G4 [IgG4]-S228P) that targets the programmed death-1 (PD-1) cluster 
of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a negative regulatory 
molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, 
programmed death–ligands 1 (PD-L1) and 2 (PD-L2), results in the down-regulation of 
lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes 
immune responses and antigen-specific T cell responses to both foreign antigens as well as self- 
antigens. Nivolumab is expressed in Chinese hamster ovary (CHO) cells and is produced using 
standard mammalian cell cultivation and chromatographic purification technologies. The clinical 
study product is a sterile solution for parenteral administration. 
Nivolumab is approved for the treatment of several types of cancer in multiple regions including 
the United States (US, Dec-2014), the European Union (EU, Jun-2015), and Japan (Jul-2014). 
Nivolumab has demonstrated durable responses exceeding 6 months as monotherapy in several 
tumor types, including NSCLC, melanoma, renal cell carcinoma (RCC), Classical Hodgkin 
Lymphoma (cHL), small-cell lung cancer (SCLC), gastric cancer, squamous cell carcinoma of the 
head and neck (SCCHN), urothelial cancer, hepatocellular carcinoma (HCC), and CRC. In 
confirmatory trials, nivolumab as monotherapy demonstrated a statistically significant 
improvement in OS as compared with the current standard of care in patients with advanced or 
metastatic NSCLC, unresectable or metastatic melanoma, advanced RCC, or recurrent or 
metastatic SCCHN. Details of the clinical activity in these various malignancies are provided in 
the US prescribing information (USPI) and Summary of Product Characteristics (SmPC).34,20 
For nivolumab monotherapy, the safety profile is similar across tumor types. The only exception 
is pulmonary inflammation adverse events (AEs), which may be numerically greater in participants 
with NSCLC. In NSCLC patients, it can be difficult to distinguish between nivolumab-related and 
unrelated causes of pulmonary symptoms and radiographic changes. There is no relationship 
between the incidence, severity, or causality of AEs and the nivolumab dose level. Additional 
details on the safety profile of nivolumab, including results from other clinical studies, are 
summarized in the nivolumab Investigators Brochure. 
3.2.3 
Ipilimumab 
Ipilimumab (BMS-734016, MDX010, MDX-CTLA4) is a fully human monoclonal 
immunoglobulin (Ig) G1 kappa specific for human cytotoxic T-lymphocyte antigen 4 (CTLA-4, 
cluster of differentiation [CD] 152), which is expressed on a subset of activated T cells. CTLA-4 
is a negative regulator of T cell activity. Ipilimumab is a monoclonal antibody (mAb) that binds to 
CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA- 
4 has been shown to augment T cell activation and proliferation, including the activation and 
proliferation of tumor-infiltrating T effector cells. Inhibition of CTLA-4 signaling can also reduce 
T-regulatory cell (Treg) function, which may contribute to a general increase in T cell 
responsiveness, including the anti-tumor response. 


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3.2.4 
Nivolumab Combined with Ipilimumab Clinical Activity 
Multiple clinical studies have evaluated nivolumab combined with ipilimumab 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 RCC, previously untreated metastatic NSCLC expressing 
 and 
microsatellite instability-high or mismatch repair deficient colorectal cancer. Details of the clinical 
activity in these various malignancies are provided in the USPI and SmPC.34.20 
3.3 
Benefit/Risk Assessment 
Through the CA020002 study, some initial evidence of clinical benefit has been observed in 
patients with advanced cancer especially when used in combination with PD-1 inhibition. Recent 
reports with other anti-TIGIT antibodies have shown similar clinical benefit when used in 
combination with PD-1/PD-L1 inhibitors.15,16 Prior to these studies, the evaluation of risk was 
based on information from nonclinical studies with BMS-986207 in monkeys (Section 5.5.1.3) 
and potential effects based on the proposed mechanism of action. The nonclinical toxicology 
assessment of BMS-986207 has demonstrated an acceptable safety profile, supporting clinical use 
in oncology patients. Because BMS-986207 blocks interaction of TIGIT with nectin-2 or PVR, it 
has the potential to remove an inhibitory signal to T cells and NK cells. TIGIT expression is limited 
to lymphoid cells, so the principal effects are anticipated to be related to the effects of 
inflammatory cells in specific tissues. Similar to other Immuno-Oncology (I-O) drugs, a general 
principle is to monitor for immune-mediated adverse reactions in various organ systems. 
Noninflammatory etiologies should be considered and discussions with the BMS Medical Monitor 
should be used to guide treatment. Consultation with a medical or surgical specialist, especially 
prior to an invasive diagnostic or therapeutic procedure, is recommended. 
In vitro treatment of human mononuclear cells with BMS-986207 did not induce 
 of 
lymphocyte activation or cytokine release. Moreover, there was no evidence for CRS in 
cynomolgus monkeys treated with BMS-986207. To assess for unanticipated potential effects of 
lymphocyte activation, a sentinel participant will be monitored for 5 days at each dose level for 
Parts 1A and 1B. 
Novel monoclonal antibodies such as BMS-986207 have the potential to induce anti-idiotype 
antibodies that can be neutralizing or non-neutralizing. BMS-986207 is a fully human antibody 
and the clinical experience with other human mAb I-O agents is that infusion-related reactions or 
hypersensitivity reactions occur at a frequency of < 10% and are generally low grade. Severe 
infusion-related reactions or anaphylaxis are rare and occur at a frequency of approximately 0.1%. 
For the proposed clinical study of BMS-986207, the administration will start with a single 
participant enrolled into monotherapy escalation, receiving BMS-986207 starting at the 2 mg dose 
level, followed 2 weeks later with intra-participant dose escalation to the 6 mg dose level, followed 
2 weeks after that with intra-participant dose escalation to the 20 mg dose level. This first 
participant was subject to a 5-day safety observation period after receiving the first 20 mg dose. 
This study design was intended to thoroughly assess the risk of any immediate hypersensitivity 


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reactions. As of 21-Jan-2021, 1 participant out of 42 treated participants in monotherapy (2.4%) 
was noted to have an infusion-related reaction (Grade 1) with BMS-986207 treatment.19 
All BMS-986207 infusions 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 will undergo observation and assessment for signs of infusion 
reaction for 60 minutes post infusion after all infusions of BMS-986207 in Cycle 1. 
In combination therapy, BMS-986207 may potentiate immune-mediated adverse reactions caused 
by nivolumab and ipilimumab. The safety profile of nivolumab monotherapy is well defined and 
is based on experience with greater than 23,500 patients evaluated in clinical trials. 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 (BMS-986558) IB.21 
Management algorithms for nivolumab-induced AEs involving gastrointestinal, renal, pulmonary, 
hepatic, endocrinopathy, skin, neurologic systems, and myocarditis are included in the protocol. 
As of 23-Mar-2021, more than 30,000 participants have been enrolled in ipilimumab monotherapy 
and combination therapy studies, including compassionate use programs, in several cancer types, 
allowing the safety profile to be well defined. 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 ipilimumab (BMS-734016, MDX-010) IB. 22 Management 
algorithms for ipilimumab- induced AEs are included in the protocol. 
The safety profile of nivolumab and nivolumab plus ipilimumab is characterized by immune- 
related toxicities, such as diarrhea, rash, pneumonitis, liver toxicity, and endocrinopathies. The 
frequencies and intensities of these events are variable and depend on the specific doses and 
schedule used. In the dosing schedules selected, these events were mostly low grade and 
manageable with the use of corticosteroids. Nivolumab and ipilimumab combination therapy has 
shown improved efficacy over either agent alone in melanoma. 
Overall, the safety profiles of nivolumab monotherapy, ipilimumab monotherapy, and the 
combination of the two are manageable and generally consistent across completed and ongoing 
clinical trials. There was no MTD reached at any dose of nivolumab tested up to 10 mg/kg. Most 
AEs were low-grade (Grade 1 to 2) with relatively few related high-grade (Grade 3 to 4) AEs. 
There was no pattern in the incidence, severity, or causality of AEs with respect to nivolumab dose 
level. 
A pattern of immune-related AEs has been defined, for which management algorithms have been 
developed; these are provided in Appendix 6. Most high-grade events were manageable with the 
use of corticosteroids or hormone replacement therapy (endocrinopathies) as instructed in these 
algorithms. 
Participants with newly diagnosed metastatic or recurrent NSCLC represent a great unmet need. 
Recent studies from other agencies using anti-TIGIT antibodies in combination with PD-1/PD-L1 
inhibition have shown some clinical benefit in PD-L1 positive 1L NSCLC.15,16 These anti-TIGIT 


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antibodies, have differed from BMS-986207 as they have wild type Fc regions while BMS-986207 
has an inert Fc region. This inert Fc region may provide less toxicity in participants when used as 
monotherapy or in combination with PD-1/PD-L1 or CTLA-4 inhibitors. 
The potential benefit of combination immunotherapy of BMS-986207 plus nivolumab plus 
ipilimumab in first line treatment of NSCLC is not yet known. The safety profile of nivolumab 
and ipilimumab plus BMS-986207 is expected to have no new categories of AEs compared to 
BMS-986207 monotherapy, nivolumab monotherapy, ipilimumab monotherapy, or nivolumab 
plus ipilimumab combination therapy. The frequencies and intensities of these AEs in the 
nivolumab and ipilimumab plus BMS-986207 combination may be higher. Preliminary data of 
CA020002 Part 1C, as per 20-Oct-2021, revealed that 2 out of 4 DLT-evaluable participants 
experienced DLTs with the combination of BMS-986207 1200 mg Q3W, nivolumab 360 mg 
Q3W, and ipilimumab 1 mg/kg Q6W (Grade 3 encephalitis and Grade 3 bullous dermatitis, see 
Section 3.2.1.4 for more details).19 Per BOIN design, BMS-986207 dose of 1200 mg Q3W was 
reduced to 600 mg due to the reported DLTs. If needed, BMS-986207 dosing will be further 
reduced in the setting of SAEs or worsening AE profiles. When BMS-986207 was combined with 
nivolumab, participants with melanoma (1 participant with a complete response [CR], 2 
participants with partial response [PR]), and prostate cancer (1 participant with PR) experienced 
clinical benefit (unpublished results). When 1200 mg BMS-986207 was combined with nivolumab 
and ipilimumab (n = 6 treated participants), PR was observed in one participant with CRC and 
stable disease (SD) with NSCLC (post PD-1 therapy). No clinical benefit was observed in any 
participants who received BMS-986207 monotherapy (unpublished results). Other tumor types in 
this study included pancreatic, ovarian, breast, gastric, and urothelial cancer. In efforts to reduce 
toxicity associated with ipilimumab, a lower dose of 1 mg/kg at a 6-week dosing interval will be 
used. This dose of ipilimumab is currently approved for the treatment of 1L NSCLC in 
combination with nivolumab or with nivolumab and 2 cycles of chemotherapy. 
Patients who develop immune-related AEs may require prolonged treatment with high dose 
corticosteroids and other immunosuppressive agents. This could increase the risk of opportunistic 
infections. Immune-related AE management algorithms in the protocol recommend antibiotic 
prophylaxis against opportunistic infections in such situations. 
The clinical studies of BMS-986207 have been designed to minimize the overall risk to 
participants. Complete blood counts and chemistry (including liver enzyme) tests will be carried 
out prior to administration of study therapy and on a weekly basis during the first 4 weeks of 
treatment. 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 4 weeks of treatment. 
Due to the potential risk of exaggerated inflammatory response, participants with auto-immune 
disorders, who are at risk for flare of auto-immunity, will be excluded. 
 


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Continuous safety assessments will be utilized by the Investigators and Sponsor to determine 
whether dose modification, additional safety measures, or termination of the study is required at 
any time. In addition, AEs and SAEs will be reviewed on an ongoing basis by the BMS Medical 
Monitor and World Wide Patient Safety (WWPS) representatives to monitor for any safety signals 
or trends. As BMS-986207 is an experimental agent, it is possible that unforeseen, unknown, or 
unanticipated reactions may occur. However, based on the nonclinical safety profile of 
BMS-986207, and with a 91-fold exposure margin built into the planned starting dose of 1 mg/kg 
(or 80 mg based an average body weight of 80 kg in cancer patients), the potential safety risks are 
expected to be minimized. 
 
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. If a participant has a confirmed SARS-CoV-2 infection while on study 
treatment, dose delay or interruption of study treatment is required as described in Section 8.1. 
 
 
4. 
OBJECTIVES AND ENDPOINTS 
The objective and endpoints for this study are shown in Table 4-1. 
Table 4-1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• 
Part 1A, 1B, 2A, and 2B: To characterize the safety, 
tolerability, DLTs, and MTD/RP2D of BMS-986207 
administered as monotherapy and in combination with 
nivolumab in participants with advanced solid tumors. 
• 
Part 1C: To characterize the safety, tolerability, and DLTs of 
BMS-986207 in combination with nivolumab and ipilimumab 
in participants with advanced solid tumors. 
• 
Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs 
leading to discontinuation, and death; 
Incidence of laboratory abnormalities. 
• 
Incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, AEs 
leading to discontinuation, and death; 
Incidence of laboratory abnormalities. 
• 
Part 2C: To evaluate the preliminary efficacy and safety of 
BMS-986207 in combination with nivolumab and ipilimumab 
in previously untreated participants with NSCLC whose 
tumors express ≥ 1% PD-L1 based on PD-L1 IHC results from 
central testing. 
• 
ORR, mDOR, and PFSR at 24 weeks 
by RECIST v1.1 by Investigator; 
Incidence of AEs, SAEs, AEs leading 
to discontinuation, and death. 


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Table 4-1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Secondary 
• 
To assess the preliminary efficacy of BMS-986207 alone and 
in combination with nivolumab, in advanced solid tumors 
(Parts 1A, 2A, 1B, and 2B) and in combination with 
nivolumab and ipilimumab in advanced solid tumors (Part 1C). 
• 
To characterize the PK and immunogenicity of BMS-986207 
when administered alone, in combination with nivolumab or in 
combination with nivolumab and ipilimumab. 
• 
ORR, mDOR, and PFSR at 24 weeks 
by RECIST v1.1 
• 
Summary measures of PK parameters 
of BMS-986207 and incidence of 
ADA to BMS-986207 
Abbreviations: 
ADA, 
anti-drug 
antibody 
AE, 
adverse 
event; 
DLT, 
dose 
limiting 
toxicity; 
IHC, 
immunohistochemistry; mDOR, median duration of response; MTD, maximum tolerated dose; NSCLC, non-small 
cell lung cancer; ORR, objective response rate; 
PD-L1, programmed 
death ligand 1; PFSR, progression-free survival rate; PK, pharmacokinetic; RECIST, Response Evaluation Criteria in 
Solid Tumors; 
RP2D, recommended Phase 2 dose; 
SAE, serious adverse event; 
. 


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AEs and laboratory values will be graded according to National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) v4.03. 
5. 
STUDY DESIGN 
5.1 
Overall Design 
This is a Phase 1/2a, open-label study of BMS-986207, administered as a single agent, in 
combination with nivolumab, and in combination with both nivolumab and ipilimumab in 
participants with advanced solid tumors. The duration of the study will be approximately 6 years. 
The study comprises 2 parts. Part 1 includes dose escalation of BMS-986207 alone (Part 1A) and 
in combination with nivolumab (Part 1B) to determine the MTD/RP2D, as well as a select dose 
level of BMS-986207 in combination with nivolumab and ipilimumab (Part 1C) to evaluate safety 
and preliminary 
 activity of the triplet combination. Part 1B includes a substudy 
conducted at a single site under site-specific Amendments 6, 7, and 8 to evaluate the safety and 
preliminary efficacy of BMS-986207 in combination with nivolumab in PD-1 naive and 
relapsed/refractory participants with melanoma. Part 2 includes expansion cohorts to gather 
additional preliminary 
 activity, as well as additional safety, tolerability, PK, 
 
information for BMS-986207 alone (Part 2A), in combination with nivolumab 
(Part 2B), and in combination with nivolumab and ipilimumab in NSCLC (Part 2C). Participants 
in each study phase will complete up to 4 periods in the study: screening, treatment, safety follow- 
up, and response/survival follow-up. The overall study design is shown in Figure 5.1.2.2-1. 
5.1.1 
Screening Period 
The screening period for all parts of the study will be up to 28 days, and begins by establishing the 
participant’s initial eligibility and signing of the informed consent form (ICF). See Appendix 2 for 
details of the informed consent process and other study governance considerations. Participants 
will be enrolled using an Interactive Response Technology (IRT), and the screening assessments 
are shown in Table 2-1. 
If a participant exceeds the 28-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. 
5.1.2 
Treatment Period 
Treatment cohorts are illustrated in Figure 5.1.2.2-2. 
5.1.2.1 
Treatment in Parts 1A, 1B, 2A, and 2B 
Participants will be treated for up to 24 weeks (3 cycles) with monotherapy as will participants 
treated with combination therapy (Parts 1B and 2B). The treatment period will consist of up to 
3 treatment cycles of 8 weeks. Following each treatment cycle, the decision to treat a participant 
with additional cycles of study therapy (up to a maximum of 6 cycles), will be based on tumor 
assessment at the end of each cycle. Weekly study visits will be performed for the first 4 weeks 
following the first dose of study drug, followed by study visits q2w thereafter. 


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Following a preliminary, within-patient dose escalation, safety cohort, each monotherapy 
treatment cycle will comprise 4 doses of BMS-986207 administered q2w or 2 doses of 
BMS-986207 administered q4w. BMS-986207 infusions will take place over 60 minutes and will 
require a 60 minute observation period following the completion of the infusion for the first four 
doses of Cycle 1 for each participant. A 60-minute post infusion safety observation period is 
considered appropriate given BMS-986207 is a fully human monoclonal antibody that is an 
antagonist (not an agonist) and has a low likelihood of resulting in infusion reactions. For 
participants < 42 kg on the 1600 mg dose, the infusion time will be longer than 1 hour 
(approximately 90 minutes; see Pharmacy Manual for more detail). In Parts 1B and 2B, each 
combination treatment cycle will comprise 4 doses of BMS-986207 administered q2w or 2 doses 
of BMS-986207 when administered q4w, each dose administered in combination with nivolumab. 
Nivolumab will be given first, over a 30-minute infusion period, followed by BMS-986207 over a 
60-minute infusion period, beginning at least 30 minutes after completion of the infusion of 
nivolumab. 
Additional infusion details are given in the Pharmacy Manual. Tumor progression and response 
endpoints will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 
criteria for solid tumors (Appendix 5). 
5.1.2.2 
Treatment in Part 1C and Part 2C 
In Part 1C (Triplet cohort) and Part 2C (Triplet NSCLC Expansion), each treatment cycle is equal 
to 6 weeks. Nivolumab (360 mg) will be administered every 3 weeks and ipilimumab (1 mg/kg) 
will be administered every 6 weeks at least 30 minutes after completion of the nivolumab infusion. 
BMS-986207 will be administered every 3 weeks at 600 mg and/or 360 mg and will be tested in 
Part 1C per BOIN design and for dose optimization. A dose not to exceed the dose declared 
tolerable in Part 1C will be used in Part 2C. Additional doses lower than the dose declared tolerable 
in Part 1C might be tested for dose optimization in Part 2C. A dose of 1200 mg BMS-986207 
administered every 3 weeks has been tested per Amendment 03 but due to the DLTs observed no 
additional participants will be tested at this dose (see Section 3.2.1.4). 
Treatment will occur until disease progression, unacceptable toxicity, or other reasons as specified 
in Section 8.1 for up to 2 years. Treatment beyond initial investigator-assessed RECIST v1.1 
defined progression is permitted if the participant has investigator-assessed clinical benefit and is 
tolerating the treatment, as specified in Section 5.1.4. 


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Figure 5.1.2.2-1: 
Overall Study Design Schematic 
 
Abbreviations: CR, complete response; EOT, end of treatment; IP, investigational product; PD, progressive disease; 
PR, partial response; SD, stable disease. 
a Details of the response and survival follow-up periods are given in Sections 5.1.3.2 and 5.1.3.3, respectively. 


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Figure 5.1.2.2-2:   Treatment Cohorts in CA020002 
 
Abbreviations: 1L NSCLC, first-line non-small cell lung cancer; BMS, Bristol-Myers Squibb; CRC, colorectal cancer; 
HCC, hepatocellular carcinoma; IO, immuno-oncology; IP, investigational product; MTD, maximum tolerated dose; 
q2w, every 2 weeks. q3w, every 3 weeks; q4w, every 4 weeks, RP2D, recommended phase 2 dose. 
 
a Planned dose levels and dose schedules of BMS-986207 and/or nivolumab may be modified, and intermediate dose 
levels of BMS-986207 added, based upon the BLRM analysis and sponsor discretion and discussion with 
Investigators. Once the safety (during the DLT evaluation) of a dose level has been established (Part 1A and/or Part 
1B), additional participants (up to 15) may be added at that dose, to better characterize the safety, dose schedule, 
PK,  profile 
assessments. 
b Participants were enrolled at a single site under site-specific Amendments 6, 7, and 8. This substudy has been closed 
for enrollment. 
c The safety profile of BMS-986207 1200 mg Q3W combined with nivolumab 360 mg Q3W and ipilimumab 1 mg/kg 
Q6W has been evaluated in 6 subjects. Of these subjects, 4 were DLT evaluable, and 2 developed DLTs. Per BOIN 
design, in all the remaining and future subjects in Part 1C, BMS-986207 was de-escalated to 600 mg Q3W (for 
details, see Section 3.2.1.4). Planned dose levels for BMS-986207 may be further modified based on generated data 
and additional doses, including 360 mg Q3W, may be assessed per BOIN design and for dose optimization analysis 
at sponsor discretion and based upon discussion and agreement with investigators. 
d Part 2C will enroll a minimum of 20 participants per dose level of BMS-986207. One or two doses are planned to 
be evaluated and selected from the range of doses assessed as tolerable and not exceeding the maximum tolerated 
dose in Part 1C. If two doses will be tested at the sponsor's discretion, participants will be randomized in a 1:2 ratio 
schema between the highest dose selected in Part 1C and the next lower dose, after at least 10 participants will have 
been tested at the dose found safe in Part 1C. 


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5.1.2.3 
Preliminary Safety Cohort & Dose Escalation (Part 1A and 1B) 
Approximately 35 participants are expected to be treated during each dose escalation part of the 
study guided by Bayesian Logistic Regression Model (BLRM). Each participant will be 
administered IV doses of BMS-986207 per the cohort assignment as follows: 
• The Preliminary Safety Cohort precedes participant enrollment in Monotherapy - Dose 
Escalation (Part 1A) of the study. The first participant enrolled into monotherapy escalation 
will receive BMS-986207 starting at the 2 mg dose level, followed 2 weeks later with intra- 
participant dose escalation to the 6 mg dose level, followed 2 weeks after that with intra- 
participant dose escalation to the 20 mg dose level, This first participant will be subject to a 5- 
day safety observation period after receiving the first 20 mg dose. No other intra-participant 
dose escalation is planned for this study. If there are no DLTs or other safety concerns 
observed, an additional 2 participants will be enrolled in the 20 mg dose cohort. Please refer 
to Appendix 13 for complete details of the Preliminary Safety Cohort 
• In Part 1A (monotherapy dose escalation), the planned flat dose levels for BMS-986207 are 
20, 80, 240, 800 and 1600 mg (assuming an 80kg participant) q2w, in 8-week cycles, for up to 
3 cycles of study therapy (24 weeks). In addition, a q4w schedule of BMS-986207 will be 
evaluated at flat doses of 480 mg and 1600 mg (assuming an 80kg participant). Enrollment of 
the first q4w cohort will be guided by the safety, PK, 
analysis from the q2w 
cohorts. Following each treatment cycle, the decision to treat a participant with additional 
cycles of study therapy (up to a maximum of 6 cycles), will be based on tumor assessment at 
the end of each cycle. 
• In Part 1B, (combination therapy dose escalation), BMS-986207 and nivolumab will be 
administered at flat doses of 80 and 240 mg BMS-986207 q2w with 240 mg nivolumab q2w. 
In addition, BMS-986207 will be administered at flat doses of 480 and 1600 mg q4w in 
combination with nivolumab administered at 480 mg q4w. Study drugs will be administered 
in 8-week cycles, for up to 3 cycles of study therapy (24 weeks). Following each treatment 
cycle, the decision to treat a participant with additional cycles of study therapy (up to a 
maximum of 6 cycles), will be based on tumor assessment at the end of each cycle. 
 
Planned dose levels and dose schedules of BMS-986207 and/or nivolumab may be modified, and 
intermediate dose levels of BMS-986207 added, based upon the BLRM analysis and/or sponsor 
discretion and discussion with the Investigators. Once the safety (during the DLT evaluation) of a 
dose level has been established (Part 1A and/or Part 1B), additional participants (up to 15) may be 
added at that dose, to better characterize the safety, dose schedule, PK, 
 profile 
assessments. Part 1B combination dose escalation will be initiated after at least 3 dose 
levels have been found to be tolerable in Part 1A monotherapy dose escalation. The starting dose 
of BMS-986207 in Part 1B will be at least 1 dose level below a dose that was demonstrated to be 
tolerated in Part 1A. At no time will the dose for BMS-986207 in Part 1B exceed the highest 
tolerated dose in Part 1A. Escalation within Parts 1A and 1B, within the constraints cited above, 
may be done in parallel. 


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Sentinel Participant 
During the dose escalation phase, a staggered dosing (sentinel participant) approach will be used. 
The first participant in both Parts 1A and 1B will receive Cycle 1 Day1 dose of study drug(s), and 
be observed for 5 days, before additional participants (ie, Participant 2 onward in that cohort) 
receive study drugs. The first participants to be dosed in all subsequent dose level cohorts will also 
be subject to a 5-day sentinel period. 
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 4-week dose-limiting toxicity (DLT) period is completed, an extra 
participant may be enrolled in each dose escalation cohort. Therefore, there will be a total of 
4 participants (3 + 1) at the start of each cohort, provided that the fourth participant is able to start 
the first day of dosing within approximately 1 week of the third participant in the same dose 
escalation cohort. 
Figure 5.1.2.3-1 illustrates the dose escalation phase of the study. 
Figure 5.1.2.3-1: 
Schematic of the Dose Escalation and Cohort Expansion Phases of the 
Study 
 


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Abbreviations: CRC, colorectal cancer; HCC, hepatocellular carcinoma; PSC, preliminary safety cohort; RP2D, 
recommended Phase 2 dose; SCCHN, squamous cell carcinoma of the head and neck 
5.1.2.4 
Dose Escalation Decisions for Monotherapy and Combination (Parts 1A 
and 1B) 
The dose escalation phase of the study will evaluate the safety and tolerability of BMS-986207, 
given alone or in combination with nivolumab, based on DLTs, using a BLRM model (for 
BMS-986207 as monotherapy) and a BLRM-copula model (for BMS-986207 in combination with 
nivolumab). 
Combination dose escalation (Part 1B) will not begin until 3 dose cohorts (i.e., 20 mg, 80 mg and 
240 mg) have been determined to be safe in monotherapy dose escalation (Part 1A) During the 
dose escalation phase, a set of approximately 3 participants will be treated at each specified dose 
level. Cohort tolerability assessment and subsequent dose recommendation will occur when at 
least 2 evaluable participants within a cohort have completed a 4-week DLT period. Any toxicities 
that occur beyond the 4-week DLT period will be accounted for in making dose level decisions 
and/or dose level modifications. 
If the potential DLT occurring in the third evaluable participant regarding the specific dose level 
does not influence the dose recommendation by BLRM or the BLRM-Copula model, the next dose 
level may proceed without waiting for the third participant to complete the corresponding DLT 
observation period, after discussion and agreement between the Sponsor and Investigators. 
Continuous re-assessment of dose recommendation, by BLRM in the escalation phase and BLRM- 
Copula in the combination phase, will be carried out for each dose level. Planned dose levels for 
dose escalation are provided in Table 5.1.2.4-1. Planned dose levels may be modified, or 
intermediate dose levels added, based upon the BLRM analysis. 


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Table 5.1.2.4-1:    Planned Doses During Part 1B (Combination Dose Escalation) 
 
Dose Level/Cohort 
BMS-986207 
Nivolumab 
Dose Schedule 
1 
80 mg 
240 mg 
q2w 
2 
240 mg 
240 mg 
q2w 
3 
480 mg 
480 mg 
q4w 
4 
1600 mg 
480 mg 
q4w 
 
 
The RP2D dose of BMS-986207, alone and in combination with nivolumab, selected for cohort 
expansion will be based on evaluating the recommendation from BLRM and an overall assessment 
of all available safety, PK/
 and efficacy data. 
Once the safety (during DLT evaluation) of a dose level has been established (Part 1A and/or Part 
1B), additional participants (up to a total of 15) may be added to that dose level, to better 
characterize the PK, safety 
 profiles 
assessments. 
5.1.2.5 
Dose Limiting Toxicities in Dose Escalation Phases (Parts 1A and 1B) 
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, intensity, 
and duration of AEs for which no clear alternative cause is identified. The DLT period will be 28 
days (4 weeks) in Part 1A and 28 days (4 weeks) in Part 1B. Any toxicities that occur beyond the 
4-week DLT period will be accounted for in making dose level decisions. 
For the purpose of participant management, any AE that meets DLT criteria, regardless of the 
cycle in which it occurs, will lead to discontinuation of study drug. Participants who withdraw 
from the study during the DLT evaluation period for reasons other than a DLT may be replaced 
with a new participant at the same dose level. The incidence of DLT(s) during the DLT evaluation 
period will be used in dose escalation decisions and to define the MTD. AEs occurring after the 
4-week DLT evaluation period will be considered for the purposes of defining the RP2D upon 
agreement between the Sponsor, Medical Monitor, and Investigators, if the AEs are determined to 
have no clear alternative cause and are not related to disease progression. 
Participants experiencing a DLT will not be retreated with study drug and will enter the safety 
follow-up period of the study. AEs will be graded according to the NCI CTCAE v4.03. 
5.1.2.6 
Safety Evaluation Phase of Part 1C 
Up to 18 participants per dose level tested will be treated in the Triplet Cohort. BMS-986207 will 
be administered at 600 mg and/or 360 mg q3w and nivolumab will be administered at 360 mg q3w. 
Ipilimumab, at a dose of 1 mg/kg, will be given q6w. The DLT period in Part 1C will be 42 days 
(6 weeks). 
A dose of 1200 mg BMS-986207 administered every 3 weeks has been tested per Amendment 03 
but due to the DLTs observed no additional participants will be tested at this dose (see 
Section 3.2.1.4). 


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The DLT safety monitoring during the dose evaluation phase, including the potential decision to 
de-escalate to a lower dose, will be based on the BOIN design framework with target toxicity 
(DLT) rate of 30% (24%, 36%), as presented in Table 5.1.2.6-1.23,24 The BOIN design takes a 
very simple form, rendering it easy to implement in practice. It is more straightforward and 
transparent than other model-based and model-assisted methods. The decisions on dose tolerability 
guided by the design are based on comparing the observed DLT rate at the current dose with a pair 
of fixed dose escalation and de-escalation boundaries. This allows generation of a decision table 
that guides DLT assessment depending on the number of participants treated and observed DLTs. 
The performance of the design based on the operating characteristics is shown in Appendix 12. 
As a dose escalation is not planned in Part 1C, a design recommendation to declare a dose as 
tolerable is based on meeting the same criteria needed to escalate. A minimum of 6 DLT evaluable 
participants will be required in Part 1C to declare a dose tolerable for initiation of Part 2C. In 
addition, to better estimate tolerability of the dose level in combination with nivolumab and 
ipilimumab, more participants will be treated even if a dose is declared tolerable with n=6, for up 
to a total of 18 treated. In contrast, a design recommendation “Stay” indicates that this dose level 
needs to be evaluated further for safety to declare this dose tolerable. In that case, additional 
cohorts of 3-4 or more participants (depending on the number of observed DLTs) will be treated 
up to a total of 18. If dose-de-escalation is recommended by the design based on the number of 
participants with DLTs observed during this dose evaluation phase (Table 5.1.2.6-1), then the next 
lower dose level will be used (360 mg BMS-986207 q3w) for the remaining participants as well 
as for those currently on treatment. In addition, other lower doses of BMS-986207 (200 mg q3w) 
than that seen as safe and tolerable may also be tested. 
Initially, the first 3 to 4 participants treated in the Triplet Cohort will be evaluated for DLTs. If 0 
or 1 DLT is observed during the 6-week DLT period, an additional 3-4 participants will be treated 
at the same BMS-986207 dose level. If ≤1 DLTs are observed out of the first 6 DLT-evaluable 
participants, the dose will be considered safe. If 2 DLTs are observed out of 6 DLT-evaluable 
participants, an additional 3-4 participants will be enrolled. If ≤3 DLTs are observed out of 9 DLT- 
evaluable participants, an additional 3 participants will be enrolled. If 2 DLTs are observed out of 
12 DLT evaluable participants, the dose level will be considered safe. 
If 3 or 4 DLTs are observed out of 12 DLT evaluable participants as shown in Table 5.1.2.6-1, the 
design recommends to stay at the same dose level, indicating that more participants may need to 
be evaluated to determine whether the dose level is safe. After considering additional information 
such as provided in Table 5.1.2.6-2 and the totality of available data including safety, 
PK/pharmacodynamics from all treated participants, a lower dose may be considered for 
evaluation, (eg, if 4 /12 DLTs) or the dose may be considered safe (eg, with 3/12 DLTs) based on 
discussion between the Investigator and Sponsor/Medical Monitor, and based on posterior 
probability of the DLT rate exceeding the target. Once a dose is declared safe based on at least 
6 participants, an additional 6-12 participants may be treated up to a total of 18 to continue to 
confirm the safety of the selected dose. At the same time, enrollment in Part 2C may begin. In 
addition, another cohort up to 18 participants may be treated at the next lower dose of BMS-986207 
to optimize dose selection. Participants who do not complete the DLT observation period for 


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reasons other than DLTs may be replaced. De-escalation may be considered if the safety and 
tolerability profile for the selected BMS-986207 dose is evaluated as not acceptable, after 
discussion between the Investigator (s) and the Sponsor/Medical Monitor. 
Table 5.1.2.6-1: 
Triplet Safety Evaluation Guidance for DLT-Related Decisions by 
BOIN Design Framework 
 
Actions based on 
number of DLT’s 
The number of DLT-evaluable participants treated at the current dose 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Declare dose 
tolerable if # of 
DLT ≤a 
0/NA 
0/NA 
1/NA 
1 
 
1 
1 
2 
2 
2 
2 
Stay if # of DLT= 
1 
1 
NA 
2 
2 
2 
3 
3 
3 
3,4 
De-escalate if # of 
DLT ≥ 
2 
2 
2 
3 
3 
3 
4 
4 
4 
5 
Eliminate if # of 
DLT ≥ 
3 
3 
4 
4 
5 
5 
5 
6 
6 
7 
Abbreviations: BOIN, Bayesian optimal interval; DLT, dose-limiting toxicity 
a The decision meets the same requirements as needed to “escalate” in standard design. NA indicates that decisions 
to declare a dose tolerable will not be made with fewer than 6 participants 
 
In addition to the above guidance, the following posterior probability may be considered to guide 
the DLT tolerability decision. Assuming a 33% acceptable DLT rate in triplet, which corresponds 
to a Beta (1, 2) distribution, Table 5.1.2.6-2 shows the chance of confirming a BMS-986207 dose 
level as safe based on the observed DLTs and expressed as a posterior of DLT probability given 
the number of DLTs observed in the first 6, 9, or 12 participants during the triplet evaluation phase. 
Table 5.1.2.6-2: 
Posterior Probability of DLT in Triplet Cohort Assuming Observed 
Data 
 
Number of 
Participants at a 
Dose level 
Number of Participants 
with an Observed DLT 
Probability of 
DLT Rate>30% 
Probability of 
DLT Rate>33% 
Probability of 
DLT 
Rate>40.0% 
6 
1 
0.26 
0.2 
0.11 
6 
2 
0.55 
0.47 
0.32 
9 
2 
0.31 
0.24 
0.12 
9 
3 
0.57 
0.48 
0.30 
12 
2 
0.16 
0.11 
0.04 
12 
3 
0.36 
0.27 
0.12 
12 
4 
0.58 
0.48 
0.28 
Abbreviations: DLT, dose-limiting toxicity. 


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5.1.2.7 
Cohort Expansion (Parts 2A, 2B, and 2C) 
The purpose of cohort expansion is to gather additional safety, tolerability, preliminary efficacy, 
PK, 
 information regarding BMS-986207 alone and in combination with nivolumab. 
Continuous evaluation of toxicity events in the cohort expansions will be performed throughout 
enrollment in the expansion cohorts. If, at any time, the aggregate rate of treatment-related 
toxicities meeting DLT criteria exceeds 33% across all participants treated in cohort expansions 
2A or 2B, the findings will be discussed and further enrollment will be interrupted. Depending on 
the nature and grade of the toxicity, and after assessing the risk/benefit ratio, a new dose for all 
cohorts may be initiated at a previously tested lower dose level or at a dose level intermediate to 
previously tested, lower dose levels. 
In Part 2A, only CRC will be evaluated in cohort expansion with BMS-986207 as monotherapy. 
In Part 2B, the 3 disease-restricted populations, ovarian cancer, colorectal cancer (CRC) and HCC 
will be investigated in cohort expansions with BMS-986207 in combination with nivolumab. A 
Fleming 2-stage design framework will be used as a guide in cohort expansion. 
During the cohort expansion phase, participants with CRC who have disease progression on 
BMS-986207 monotherapy will be able to cross over to combination treatment (BMS-986207 + 
nivolumab), once the CRC expansion arms (ie, monotherapy and combination therapy) are both 
enrolling. This cross-over option, for CRC participants only, is not applicable during the escalation 
phases. 
The purpose of Part 2C is to gather preliminary efficacy information regarding BMS-986207 in 
combination with nivolumab and ipilimumab. Participants with advanced, treatment-naive 
NSCLC whose tumors express PD-L1 will be treated with BMS-986207 in combination with 
nivolumab and ipilimumab. BMS-986207 will be administered at 600 mg q3w (or tolerable dose 
as determined in Part 1C) and nivolumab will be administered at 360 mg q3w. Ipilimumab, at a 
dose of 1 mg/kg, will be given q6w. 
Part 2C may begin once there is sufficient safety data from a minimum of 6 participants in Part 
1C. 
Part 2C will enroll a minimum of 20 participants per dose level of BMS-986207. One or two doses 
are planned to be evaluated and selected from the range of doses assessed as tolerable and not 
exceeding the maximum tolerated dose in Part 1C. If two doses will be tested at the Sponsor’s 
discretion, participants will be randomized in a 1:2 ratio schema between the highest dose selected 
in Part 1C and the next lower dose, after at least 10 participants will have been tested at the dose 
found safe in Part 1C. 
Continuous evaluation of toxicity events will also be performed in this part of the study. If, at any 
time, the aggregate rate of treatment-related toxicities meeting DLT criteria exceeds 33% in Parts 
2A or 2B, the findings will be discussed and further enrollment may be interrupted. In addition, a 
more guided continuous safety monitoring will be implemented in Part 2C, 1L NSCLC expansion, 
using a Bayesian framework and specific criteria based on a posterior probability of a DLT rate 
exceeding 33% implemented starting with n=6 (Table 10.3.8-1). Depending on the nature and 


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grade of the toxicity, and after assessing the risk/benefit ratio, a new BMS-986207 dose for all 
participants, including those currently on treatment, may be initiated at a lower dose level. 
Participants with an outcome of unconfirmed progressive disease, 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 number of cycles 
• Confirmed PD (see 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 
 
5.1.2.8 
Treatment with Additional Cycles Beyond 24 Weeks (Parts 1A, 1B, 2A, 
and 2B) 
All participants will be treated for up to 24 weeks (3 cycles) with monotherapy (Parts 1A and 2A) 
or combination therapy (Parts 1B and 2B), unless treatment discontinuation criteria are met earlier 
(Section 8.1). Participants with ongoing disease control (CR, PR or SD) or unconfirmed 
progressive disease, after completing approximately the initial 24 weeks of treatment, may be 
eligible for an additional 3 cycles of study therapy in both the monotherapy (Parts 1A and 2A) 
and combination therapy (Parts 1B and 2B). These participants will be selected on a case by case 
basis, after careful evaluation and discussion with the BMS Medical Monitor, to determine whether 
the risk/benefit ratio supports administration of further study therapy. Upon completion of 3 cycles 
of study therapy (or up to a maximum of 6 cycles if applicable), all participants will enter the safety 
follow-up period. 
Individual participants with confirmed CR will be given the option to discontinue study treatment, 
on a case by case basis, after specific consultation and agreement between the Investigator and 
BMS Medical Monitor in settings where benefit/risk justify discontinuation of study therapy. 
5.1.3 
Follow-up 
5.1.3.1 
Safety Follow-up Period 
For participants in Parts 1A, 1B, 2A and 2B, upon completion of 3 cycles of study therapy (or up 
to a maximum of 6 cycles if applicable), and once the decision is made to discontinue the 
participant from treatment, ie, at end of treatment (EOT), all participants will enter a safety follow- 
up period. 
In Parts 1C and 2C, participants can receive study treatments up to a maximum of 2 years in the 
absence of disease progression or unacceptable toxicity. Once a decision is made to discontinue 
treatment, the participant will enter a safety follow-up period. 
For participants who complete all scheduled cycles of therapy, the EOT visit will be the same visit 
as the last scheduled and completed on-treatment visit, and will be the start of the safety follow- 


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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), and will not 
need to be repeated. Accordingly, for these participants, this visit will be considered the start of 
the safety follow-up period. 
After the EOT visit, all participants will be evaluated for any new AEs for at least 100 days after 
the last dose of therapy. Follow-up visits should occur at Day 30, 60 and 100 (± 7 days) after the 
last dose, or the date of discontinuation (± 7 days). All participants will be required to complete 
the 3 clinical safety follow-up visits, regardless of whether new anti-cancer therapy is started, 
except those participants who withdraw consent for study participation. 
5.1.3.2 
Response Follow-up Period (Parts 1A, 1B, 1C, 2A, 2B, and 2C) 
Participants, with SD, PR, or CR, at the time of the EOT visit or at the time of study drug 
discontinuation, will continue to have radiologic and clinical tumor assessments every 12 weeks 
for the first year after discontinuation of study drug/EOT visit. Subsequently, they will continue 
to receive tumor assessment scans as per standard of care guidelines, or at a minimum of every 
6 months up to 2 years following the last dose of study drug, or until disease 
progression/withdrawal of study consent. 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 following an initial 
course of study therapy will not be evaluated for response 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, participants in Parts 1A, 1B, 2A and 2B will start the 
survival follow-up period. Participants will be followed-up by telephone every 12 weeks (from 
EOT) for 2 years until death, loss to follow-up, withdrawal of consent, or conclusion of the study, 
whichever comes first. Participants with SD, PR or CR will have both the response follow-up 
period and survival follow-up period occur simultaneously during the 2-year follow-up period. 
The duration of this follow-up is up to 2 years following the last dose of study drug, although a 
longer follow-up period could be considered in selected cases if an efficacy signal is apparent. 
Tumor assessment scans, for participants who have ongoing clinical benefit beyond the 2 year 
period following last dose of study drug, may continue to be collected as part of standard-of-care 
treatment. 
In Parts 1C and 2C, the survival follow-up period will continue for 2 years following the last dose 
of study drug or until death, lost to follow-up, withdrawal of consent, or conclusion of the study, 
whichever comes first. Survival follow-up visits will occur every 12 weeks (±7 days) until 2 years 
after the last dose of study drug. Study assessments are to be collected as outlined in Table 2-5. 
5.1.3.4 
Retreatment During Follow-up Periods (Parts 1A, 1B, 2A, and 2B) 
Retreatment may be allowed for participants with disease progression during the safety, response 
or survival follow-up period. Participants completing approximately 3 cycles of study therapy (or 
up to a maximum of 6 cycles, if applicable), and entering the survival follow-up period with 


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ongoing disease control (CR, PR or SD), may be eligible for retreatment upon disease progression. 
Eligibility will be dependent upon participants having confirmed disease progression within 
12 months after the last dose of study drug, and will considered on a case by case basis, after 
careful evaluation and discussion with the BMS Medical Monitor, to determine whether the 
risk/benefit ratio supports administration of further study therapy. Participants meeting criteria for 
retreatment will have to provide written consent prior to receiving any additional retreatments, by 
signing an ICF which describes any reasonably foreseeable risks or discomforts, or other 
alternative treatment options. Participants meeting criteria for, and consenting to, retreatment, will 
be treated with the originally assigned monotherapy or combination therapy regimen (eg, same 
dose and dose schedule as administered during the first 24 weeks), unless that dose and its schedule 
were subsequently found to exceed the MTD. In that case, the participant will be treated at the next 
lower or alternate dose and schedule. Alternatively, if the MTD has been determined at the time 
point when the participant is being retreated, that participant can be retreated at the MTD. 
Participants entering retreatment will follow the same Time and Events schedule as outlined in 
Section 2. Samples for PK will be collected less frequently (only at predose of each treatment 
 
5.1.4 
Treatment Beyond Progression 
Treatment beyond progression may be allowed for a maximum treatment duration of up to 2 years 
in selected participants with initial RECIST v1.1 progressive disease, following discussion and 
agreement with the BMS Medical Monitor that the benefit-risk assessment favors continued 
administration of study treatment (eg, participants are continuing to experience clinical benefit, as 
assessed by the Investigator, tolerating treatment, and meeting other criteria). 
A described in Section 5.4.6, accumulating evidence indicates a minority of participants treated 
with immunotherapy may derive clinical benefit despite initial evidence of progressive disease. 
Participants will be permitted to continue on study drug for treatment beyond initial RECIST v1.1- 
defined progressive disease as long as they meet the following criteria: 
• Investigator-assessed clinical benefit and no rapid disease progression 
• Participant is tolerating study treatment 
• Stable performance status 
• Treatment beyond progression will not delay an imminent intervention to prevent serious 
• complications of disease progression (eg, CNS metastases) 
• Participant provides written informed consent prior to receiving additional BMS-986207, 
nivolumab, and ipilimumab treatment, using an ICF describing any reasonably foreseeable 
risks or discomforts, or other alternative treatment options. 
The decision to continue treatment beyond initial Investigator-assessed progression should be 
discussed with the BMS Medical Monitor and documented in the study records. A follow-up scan 
should be performed within 4 to 6 weeks of original progressive disease to determine whether 
there has been a decrease in the tumor size or continued progression of disease. Subsequent scans 
should be performed every 12 weeks until further progression is determined. If the Investigator 
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feels that the participant continues to achieve clinical benefit by continuing treatment, the 
participant should remain on the trial and continue to receive monitoring according to the Schedule 
of Activities in Section 2. For participants who continue study therapy beyond progression, further 
progression is defined as an additional 10% increase in tumor burden from time of initial 
progressive disease. This includes an increase in the sum of diameters of all target lesions and/or 
the diameters of new measurable lesions compared to the time of initial progressive disease. 
Nivolumab, ipilimumab, and BMS-986207 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. 
5.1.5 
Data Monitoring Committee and Other External Committees 
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 
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 accumulated safety data. Within BMS, an SMT is 
established for investigational therapies under clinical development, and a member of WWPS 
chairs this team. In addition, safety signal detection is performed at least monthly and ad hoc 
throughout the study by the SMT composed, at a minimum, of the WPS medical safety assessment 
physician (Chair of the SMT) and WWPS single-case review physician, the study Medical 
Monitor, the study biostatistician, and epidemiologist, all of whom evaluate the safety data 
regularly. Furthermore, the SMT routinely monitors for actual or potential issues related to 
participant safety that could result in a change in the medical benefit-risk balance associated with 
the use of study treatment(s). For Part 2C, continuous safety monitoring based on a Bayesian 
framework is also planned in the NSCLC cohort for ongoing evaluation of the tolerability of the 
selected dose. 
5.2 
Number of Participants 
The approximate number of evaluable participants will be approximately 241. Approximately 100 
of these participants will be treated with monotherapy and combination therapy dose escalation 
(35 participants each for Part 1A and Part 1B and additional 30 participants for the substudy of 


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Part 1B), and approximately 36 participants treated (6 initial participants for safety evaluation 
followed by evaluation of approximately 12 additional participants per dose level) with BMS- 
986207, nivolumab, and ipilimumab in the Triplet Cohort (Part 1C). The remaining participants 
(up to 105) will be treated as part of dose expansion, with up to 24 participants in Part 2A and 41 
participants in Part 2B, and 40 participants with NSCLC and 
(pre-existing or prior PD-L1 IHC results from testing of tumor tissue) considered to 
be response-evaluable, in Part 2C. In the event more than 25% of the participants in Part 2C are 
found to have a PD-L1 tumor cell score of < 1%, based on central lab testing, additional 
participants may be enrolled in order to have at least 30 participants with a PD-L1 tumor cell score 
≥ 1%. 
5.3 
End of Study Definition 
The start of the study is defined as the first visit for the first participant screened. Similarly, the 
end of the study is defined as the last visit or scheduled procedure shown in the Time and Events 
schedule for the last participant. Primary study completion is defined as the final date on which 
data for the primary endpoint was or is expected to be collected. 
5.4 
Scientific Rationale for Study Design 
BMS-986207 is being investigated in humans with advanced solid tumors; either as monotherapy 
and in combination with nivolumab and ipilimumab. The study design for Parts 1A, 1B, 2A, and 
2B includes the following: 
• 28-day screening period 
• 24-week (3 cycles) treatment period, with the option of an additional 24 weeks (3 cycles) of 
treatment (granted on a case by case basis) 
− Dose escalation phase 
− Cohort expansion phase 
• Safety follow-up period 
• Response/Survival follow-up period, with the possibility for retreatment 
The study design for Parts 1C and 2C, aligned with concurrent use of nivolumab and ipilimumab, 
includes the following: 
• 28-day screening period 
• Treatment period – up to a maximum of 2 years in the absence of disease progression or 
unacceptable toxicity 
• Safety follow-up period (30, 60, and 100 days (± 7 days) after last dose or date of 
discontinuation) 
• Survival follow-up period – 2 years following the last dose of study drug or until death, lost to 
follow-up, withdrawal of consent, or conclusion of the study, whichever comes first 
The rationale for the individual elements of the study design are given below. 


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5.4.1 
Rationale for BMS-986207 Monotherapy in Colorectal Cancer Cancer 
and Other Cancers Associated with Fusobacterium Nucleatum 
In CRC, bacteria such as Fusobacterium nucleatum (F. nucleatum) are abundant in the tumor 
microenvironment. The amount of F. nucleatum DNA in CRC tissue is associated with shorter 
survival, and may potentially serve as a prognostic 
 F. nucleatum is thought to facilitate 
a tumor’s ability to evade immune cell attack through inhibition of the function of T lymphocytes 
and NK cells.25 Tumor-infiltrating lymphocytes usually express TIGIT, thus T cell activities can 
be inhibited by F. nucleatum via Fap2, a protein unique to F. nucleatum. Given localization of 
Fap2 in the colon, it is anticipated that BMS-986207 monotherapy will be therapeutically effective 
for CRC. F. nucleatum may play a role in mediating tumor immune escape through interaction 
with TIGIT in other indications, such as SCCHN, in which the bacterium may be isolated from 
saliva samples.26 In these other tumors, similarly to CRC, F. nucleatum activates lymphocyte 
apoptosis by Fap2 and RadD,27 supporting the rationale for testing anti-TIGIT therapy in SCCHN 
and other tumor types associated with F. nucleatum infection. 
In addition, microbiome data will be collected in other tumor types in expansion (HCC and ovarian 
cancer) to explore the hypothesis that the gut microbiome may condition the response to 
immunotherapy.28 
5.4.2 
Rationale for the Combination of BMS-986207 and Nivolumab 
Therapeutic antibodies with the ability to block immune checkpoint receptors, or activate 
immunostimulatory receptors, have the potential to be effective for the treatment of cancer by 
modulating the participant’s immune system. It has become apparent that tumors co-opt some 
specific immune-checkpoint pathways to engender immune resistance, particularly against T cells 
that are specific for tumor antigens.29 Co-engagement of multiple immune receptors on activated 
T cells (combination immunotherapy) may result in better outcomes as compared to engagement 
of a single immune receptor. Nonclinical data, evaluating the combination of BMS-986207 and 
nivolumab in the CT26 mouse, support this hypothesis (Section 3.2.1.1). Combining the anti- 
TIGIT mAb, BMS-986207, with the anti-PD1 antibody, nivolumab, is an opportunity to evaluate 
the activity of therapeutic drugs targeting PD1 and TIGIT, given in combination, in humans. 
5.4.3 
Rationale for the Combination of BMS-986207, Nivolumab, and 
Ipilimumab 
As discussed in Section 3.2.4, nivolumab and ipilimumab have demonstrated beneficial effects in 
multiple tumor types in multiple clinical trials. Several studies have shown benefit of combining 
TIGIT and PD-L1 inhibitors, particularly in NSCLC patient populations.15,16 There are no studies, 
to date, which have examined the effects of both anti-TIGIT and anti-CTLA-4 in tumors in 
humans. TIGIT and CTLA-4 are members of the same family of immunoglobulin-related receptors 
that are responsible for various aspects of T cell immune regulation. Like PD-1 these receptors 
have inhibitory roles in T cell function. In BMS study BDX-1482-105, anti-mouse TIGIT 
combined with anti-mouse CTLA-4 showed superior antitumor activity and prolonged survival 
compared with antibodies administered as single agents in a CT26 mouse model.30 In the present 


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CA020002 study, to evaluate whether a differentiated approach of using TIGIT inhibition and 
cancer immunotherapies can further enhance 
 immune activity, BMS-986207 in 
combination with nivolumab and ipilimumab will first be evaluated for safety and proper doses of 
each drug in participants with various solid tumors (Part 1C). This safety evaluation will then be 
followed by evaluation of the safety and efficacy of this triplet combination in 1L NSCLC patients 
with tumors having PD-L1 expression ≥1%. 
The above data, together with the recent data shown for TIGIT inhibition and PD-L1 inhibitors in 
this tumor type, as well as that only limited participants (n=2) with NSCLC have been treated in 
the present CA020002 study 
, indicate that further 
evaluation is warranted for BMS-986207 in combination with nivolumab and ipilimumab in 1L 
NSCLC participants whose tumors have ≥ 1% PD-L1 expression.31,32 
5.4.4 
Rationale for the Combination of BMS-986207, Nivolumab and 
Ipilimumab in NSCLC 
Recent reports in the literature have shown comparable efficacy with anti-TIGIT agents, 
vibostolimab or tiragolumab in combination with anti-PD-L1 agents, pembrolizumab and 
atezolizumab, respectively. Modest or no anti-tumor activity was seen when the anti-TIGIT agents 
were given as monotherapy in NSCLC, HNSCC, triple-negative breast cancer, or esophageal 
cancer populations. Best clinical responses were observed in these studies in 1L and previously 
treated NSCLC participants whose tumors expressed PD-L1.15,16,17,31 
A randomized Phase 2 study comparing the anti-TIGIT agent tiragolumab plus atezolizumab 
versus placebo plus atezolizumab in PD-L1-positive 1L Stage IV NSCLC patients demonstrated 
improvement in the overall response rate (ORR; 37% vs. 21% with atezolizumab alone). The 
treatment regimen was well tolerated, with safety similar to that seen in the placebo plus 
atezolizumab treatment. In addition, recent data presented from a Phase 1 study (NCT02964013) 
of the anti-TIGIT  antibody vibostolimab  plus pembrolizumab  in participants with 
anti-PD-(L)1-naive NSCLC demonstrated anti-tumor activity (ORR 29% in all patients and 46% 
in patients with PD-L1 ≥ 1% expression).16,17 These data suggest that combining TIGIT blockade 
with anti-PD-(L)1 can be safe, tolerable, and have clinical benefits in PD-L1-positive 1L 
NSCLC.16,32 
In the present CA020002 study, heterogeneous, refractory solid tumor participant populations 
primarily with tumors that are not anti-PD-1 responsive (eg, CRC, ovarian, post-PD-1 melanoma) 
have been enrolled and treated either with BMS-986207 monotherapy or BMS-986207 in 
combination with nivolumab. There was no opportunity to evaluate BMS-986207 in NSCLC 
patients in Cohorts 1A, 1B, 2A, and 2B. The first two participants with NSCLC were enrolled in 
Part 1C. 
Data from BMS CheckMate 227, a randomized, open-label, phase 3 study in participants with 
treatment-naive PD-L1-positive NSCLC demonstrated that, among the patients with a PD-L1 
tumor cell expression level of 1% or more, the combination of nivolumab plus ipilimumab was 
safe and tolerable and improved overall survival (OS) compared to chemotherapy alone (median 


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OS=17.1 versus 14.9 months, HR=0.79, 95% CI: 0.65-0.96).33 The combination of nivolumab and 
ipilimumab without chemotherapy is approved, per the USPI, for adults with metastatic NSCLC 
expressing PD-L1 ≥ 1%.34,35 
Based on these data and specific indications, the nivolumab and ipilimumab combination is an 
appropriate backbone therapy in PD-L1 positive 1L NSCLC for the addition of a novel anti-TIGIT 
agent BMS-986207. Using this triplet combination enables the use of a checkpoint inhibitors 
combination of proven efficacy (nivolumab + ipilimumab), along with the potential advantage of 
adding anti-TIGIT (BMS-986207) to a NSCLC population that appears to benefit from TIGIT 
inhibition based on recent studies.16,17 Inclusion of 1L NSCLC patients with PD-L1 expression 
≥ 1% will capture the potential benefit of an anti-TIGIT antibody in a larger population and 
promote enrollment. Recently published data support the use of anti-TIGIT antibodies in this 
population and, if proved to be effective, will fulfill the unmet need of treatment options that do 
not include chemotherapy. 
5.4.5 
Rationale for Treatment Duration 
Despite recent advances in immunotherapies for the treatment of cancer, the ideal treatment 
duration to achieve and perpetuate good durable response is still an area of ongoing investigation. 
Current clinical data on the time to response suggest that, most patients who show a response, do 
so within the first 24 weeks on therapy. At the time of this study’s initiation, treatment with BMS- 
986207, alone or in combination with nivolumab, was limited to 24 weeks (3 cycles), with an 
option of an additional 24 weeks (3 cycles) based on evaluation of individual risk/benefit on a case 
by case basis. 
Accumulating evidence from different clinical trials in which participants with different tumor 
types were treated with nivolumab or nivolumab combined with ipilimumab indicates that most 
responses generally occur early, with a median time to response of 2 to 4 months including 
responses observed in patients with NSCLC. 36,37, 38 A recent analysis in a melanoma study 
suggests the majority of patients who discontinue nivolumab and/or ipilimumab for toxicity 
maintain disease control in the absence of further treatment. 39 For these reasons, treatments in 
Parts 1C and 2C will be given for up to 2 years in the absence of disease progression or 
unacceptable toxicity. 
5.4.6 
Rationale for Treatment Beyond Progression 
Immunotherapeutic agents produce atypical clinical response patterns that are not usually observed 
with conventional chemotherapy. Accumulating clinical evidence indicates that some participants 
treated with immune system stimulating agents may develop disease progression by the 
conventional response criteria before demonstrating clinical objective responses and/or SD. 
Two distinct nonconventional patterns have been reported: 1) a reduction in target tumor burden 
despite the appearance of new lesion(s), and 2) a transient increase in target tumor burden in an 
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These phenomena were observed in the Phase 2 study (CA209003) of nivolumab in solid tumor 
patients. Two hypotheses potentially explain these phenomena. First, enhanced inflammation 
within tumors could lead to an increase in tumor size, which would appear as enlarged index 
lesions and as newly visible small non-index lesions. Over time, both the malignant and 
inflammatory portions of the mass may then decrease, leading to overt signs of clinical 
improvement. Alternatively, in some individuals, the kinetics of tumor growth may initially 
outpace anti-tumor immune activity. With sufficient time, the anti-tumor activity will dominate 
and become clinically apparent. Therefore, it is important to avoid premature discontinuation of 
the study drug that might induce a nonconventional response pattern in some patients. 
The decision to continue treatment beyond investigator-assessed progression should be discussed 
with the BMS Medical Monitor and documented in the study records. The assessment of clinical 
benefit should take into account whether the participant is clinically deteriorating and unlikely to 
receive further benefit from continued treatment. 
5.4.7 
Rationale for Tumor Selection 
TIGIT is expressed by activated T cells, Tregs, and NK cells, and binds the adhesion molecules 
PVR (CD155) and Nectin-2 (CD112) with higher and lower affinity, respectively.13 PVR and 
Nectin-2 also bind to TIGIT’s co-stimulatory counterpart, DNAM-1 (CD226). DNAM-1 is an 
activating receptor expressed on NK cells, CD8+ T cells, and other immune cells. 40 Upon 
recognizing its ligands PVR and Nectin-2, DNAM-1 promotes NK cell–mediated elimination of 
damaged cells. 
One can hypothesize that the tumors most likely to respond to anti-TIGIT therapy are those with 
the highest PVR/Nectin-2 expression, and those with moderate-to-high immune cell infiltration. 
Accordingly, the selected tumor types of HCC, CRC, ovarian cancer, and NSCLC and their 
respective rationale for selection, are given in Table 5.4.7-1. 
 
Table 5.4.7-1: 
Rationale for Tumor Selection 
 
 
Rationale 
Tumor 
Selection 
Comments 
1 
• High ligand expression but low TILs 
• Aim to increase TILs and trigger 
anti-tumor activity 
• Potential for anti-TIGIT and nivolumab 
combination 
2 
PD1 nonresponsive tumors with mechanistic 
rationale 
HCC 
 
 
 
 
 
CRC 
TIGIT-mediated immune escape via 
microbiome. CRC, and other 
indications in which F nucleatum may 
play a role in the immune escape, will 
be evaluated in TIGIT monotherapy 
and TIGIT + nivolumab. 
 
 


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Table 5.4.7-1: 
Rationale for Tumor Selection 
 
 
Rationale 
Tumor 
Selection 
Comments 
3 
Nectin-centric tumor to differentiate role of 
nectin-2 and PVR 
 
4 
• High ligand expression correlates with PD- 
L1 expression especially in TILs 
• Potential for anti-TIGIT and anti-PD- 
L1/PD-1 antibodies combination in PD-L1- 
positive NSCLC. 
Ovarian 
cancer 
 
NSCLC 
Nectin-2 in ovarian cancer is the key 
driver of TIGIT-mediated immune 
suppression. 
 
 
Abbreviations: CRC, colorectal cancer; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; PD- 
(L)1, anti-programmed cell death (ligand) 1; PVR, poliovirus receptor TIGIT, T cell Ig and ITIM domain; TIL, tumor 
infiltrating lymphocyte. 
 
 
5.4.8 
Rationale for Dose Escalation Phase Design 
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 preclinical 
studies as well as historical clinical trials. The Escalation with Overdose Control (EWOC) 
principle limits the risk of exposing participants in the next cohort to an unsafe 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 with 
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. After completing the monotherapy phases (Parts 
1A and 1B), the drug-associated dose-toxicity profiles are characterized and incorporated as prior 
knowledge into the drug combination phase of the study (Parts 2A and 2B) or used in future 
studies. 
For Part 1C where a single select dose level of BMS-986207 will be evaluated with potential for a 
lower dose (de-escalation), a simpler mode-assisted design framework will be used, the BOIN 
design, to evaluate tolerability based on incidence of DLTs.23,24 Additional lower doses may be 
tested for dose optimization at the Sponsor’s discretion. 
5.5 
Justification for Planned Dose Selection 
5.5.1 
The current study is a FIH study. 
There is no previous clinical experience with BMS-986207. 
5.5.1.1 
Introduction 
The FIH starting dose of BMS-986207 as an immune-mediated anti-cancer agent was determined 
using both toxicology- and pharmacology- (anti-tumor efficacy)-based approaches to ensure 


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participant safety while limiting the number of participants receiving nonpharmacologically active 
doses. The toxicology-based approach utilized the HNSTD determined from a 1-month repeat- 
dose toxicity study in cynomolgus monkeys. The pharmacology-based approach leveraged the 
pharmacology data (ie, anti-tumor efficacy) obtained from mouse surrogates to project the human 
effective dose, from which the FIH starting dose was selected. The starting doses determined from 
both approaches were integrated, and the lower dose (1 mg/kg or 80 mg assuming an average body 
weight of 80 kg in cancer patients) derived from the pharmacology data is recommended as the 
FIH starting dose for BMS-986207. 
To further ensure a sufficient safety margin for the monotherapy starting dose, given the absence 
of previous clinical experience with BMS-986207, a Preliminary Safety Cohort (PSC) was added 
to the study. In the PSC, a single participant will receive BMS-986207 monotherapy starting at 
the 2 mg dose, with intra-participant dose escalation to 6 mg, and then to 20 mg. Following a 
5-day safety observation period for this participant following the initial administration of the 20 
mg dose, two additional participants will begin the study at the 20 mg BMS-986207 dose level. 
See Appendix 13 for complete detail on the Preliminary Safety Cohort. 
5.5.1.2 
Nonclinical Pharmacokinetics and Efficacy 
Human starting dose selection is based on preclinical pharmacological activity. The anti-tumor 
efficacy of an anti-mouse TIGIT antibody surrogate (10A7-mIgG1 D265A, abbreviated as 10A7) 
was studied in a mouse CT26 colon adenocarcinoma model as a single agent and in combination 
with an anti-mouse PD-1 antibody (4H2-mIgG1 D265A, abbreviated as 4H2). In the study, 10A7 
did not have single agent activities. When combined with 4H2, 10A7 exhibited dose-dependent 
anti-tumor efficacies, and with the dose increased from 0 to 0.3, 1, 3, and 10 mg/kg, the median 
tumor growth inhibition (TGI) increased from 
respectively. 
Consistently, the number of tumor-free mice in each dose group 
 
also 
increased in a dose-dependent manner. The effective dose of 10A7 in combination with 4H2 in the 
mouse CT26 model is considered to be 
 to achieve close to maximal efficacy (    TGI). 
At the effective dose level, the Cave.14d and Cmin.14d of 10A7 are estimated to be 
μM, respectively. Because 10A7 and BMS-986207 exhibited similar binding affinities on the 
respective activated mouse and human CD8+ T cells 
respectively), the human effective dose of BMS-986207 is projected to target the steady-state Cave 
and Cmin of 
 , respectively. 
To project the human effective dose, the human clearance 
 was allometrically scaled 
from the cynomolgus monkey data with a power exponent of  , and the human volume of 
distribution (
 was assumed to be equal to that in cynomolgus monkeys (Please refer to 
Table 5.5.1.2-1). Additionally, the following assumptions were made: 1) 2-compartment PK 
model; 2) dose-proportional PK; and 3) minimal impact of ADAs on PK. By achieving the same 
Cave and Cmin in humans at the steady state as the effective Cave.14d and Cmin.14d in mice, the 
human effective dose of BMS-986218, administered q2w, was projected to be 4 mg/kg (or 320 mg 
for a body weight of 80 kg). At the equivalent exposure of the clinical starting dose, the projected 
anti-tumor efficacy of its mouse surrogate 10A7 in combination with 4H2 is approximately 
TGI in the CT26 tumor model. 


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a Based on BMS-986207 exposure 
dosing in 
Cmax 4110 µg/mL) following repeat IV qw 
). 
at the NOAEL/HNSTD ( 
Table 5.5.1.2-1: 
Exposure Multiples from Monkey GLP Toxicity Studies versus 
Proposed FIH Starting Dose of 1 mg/kg and Other Planned Clinical 
Doses 
 
 
 
BMS-986207 Dose, 
mg/kg (Flat Dose) 
Projected Human 
AUC(0-336h),ss 
(µg•h/mL) 
 
Projected Human 
Cmax (µg/mL) 
Safety 
Multiplesa 
Based on 
AUCτ,ss 
Safety 
Multiplesa 
Based on 
Cmax,ss 
 
 
Abbreviations: AUC, area under the concentration-time curve; BMS, Bristol-Myers Squibb; FIH, first-in-human 
 
5.5.1.3 
Nonclinical Toxicity Data 
The nonclinical safety of BMS-986207 was evaluated in vitro in a human tissue cross-reactivity 
study and cytokine release and lymphocyte activation assays with human cells, as well as in an 
in vivo 1-month intermittent repeat-dose IV toxicity study in cynomolgus monkeys. The 
cynomolgus monkey was selected as the toxicology species because BMS-986207 binds to TIGIT 
expressed on activated cynomolgus monkey T cells with a similar affinity as TIGIT expressed on 
activated human T cells 
and is 
pharmacologically active in monkeys. BMS-986207 does not bind rodent TIGIT. 
In a Good Laboratory Practice-compliant tissue cross-reactivity study in normal human tissues, 
fluoresceinated BMS-986207 produced membrane and cytoplasmic staining of mononuclear cells 
in human lymphoid tissues and select nonlymphoid tissues. This staining was expected based on 
TIGIT expression by mononuclear cell types, such as T cells and NK cells. No unexpected tissue 
cross-reactivity was observed. BMS-986207 did not induce cytokine release or increase the 
expression of activation 
 on human T, B, or NK cells in an in vitro human peripheral blood 
mononuclear cell cytokine release and cell activation assay, suggesting a low risk of 
BMS-986207-induced cytokine release syndrome. 
In a 1-month pivotal toxicity study in monkeys, BMS-986207 was administered IV as a slow bolus 
at doses of 0, 10, 30, or 100 mg/kg (5 doses/week). BMS-986207 was clinically well tolerated by 
all monkeys at 30 and 100 mg/kg doses, while 3 out of 10 monkeys in the 10 mg/kg dose group 
exhibited signs of ADA mediated hypersensitivity reactions immediately after dosing. The clinical 
signs were transient, accompanied by increases in serum cytokine levels and complement 
activation, and no treatment was required for the affected monkeys. The timing, type of clinical 
observations, and correlative complement activation are consistent with the formation of 


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treatment-emergent ADAs, a common response by monkeys to a foreign protein. This 
immunogenicity is not considered to be predictive for ADA responses in humans (ICH S6). 
responses in terms of NK cell activation, CD8+ T cell activation and 
proliferation, were observed at all doses, and were generally dose-independent. Based on the lack 
of directly BMS-986207-related adverse findings, the no-observed-adverse-effect level (NOAEL) 
 
Overall, the nonclinical toxicology assessment of BMS-986207 has demonstrated an acceptable 
safety profile, supporting clinical use in oncology patients. 
5.5.1.4 
Rationale for Starting Dose in Humans 
The selection of the BMS-986207 starting dose is based on the nonclinical CT26 mouse syngeneic 
tumor model (TGM1607), for combined BMS-986207 and nivolumab, and the pivotal repeat-dose 
IV toxicology study in monkeys. 
In the pivotal repeat-dose (5 doses/week) IV toxicity study, the dose of 
) was established as the HNSTD and NOAEL dose. Using a safety factor of 6, 
the maximum recommended starting dose (MRSD) of
 was derived. This toxicity-based 
dose of 
 was considered an inappropriate starting dose given that dose level’s 
relationship to the projected human effective dose. 
Therefore, the projected human effective dose derived from CT26 mouse tumor model was used 
to determine the selection of the FIH starting dose. At the dose of 1 mg/kg for BMS-986207 
(IV q2w), its TGI was projected as approximately 
 
Additionally, the dose of 1 mg/kg was 
projected with AUC (0-336h),ss of 
which has an approximate 
fold safety 
margin relative to the AUC[0-168h],ss of HNSTD and NOAEL dose 
from the weekly, repeat-dose monkey study, after normalization of the dosing interval. 
Based on the projected 
 TGI and the corresponding 
-fold safety margin, 1 mg/kg was 
selected as the FIH starting dose for BMS-986207 monotherapy, administered q2w. The 
recommended starting human dose of 1 mg/kg was converted to a flat dose of 80 mg by multiplying 
by a standard body weight assumption of 80 kg. 
5.5.2 
Rationale for Dosing Schedule 
5.5.2.1 
BMS-986207 
In this study, the BMS-986207 dosing schedule of q2w was based on the projected human half- 
life, derived from a monkey single dose study 
. The PK profiles of BMS-986207 in 
monkeys following a single IV dose of 1, 10, and 100 mg/kg were used to project the human PK 
was considered to be 
human starting dose, 
a corresponding plasma 
In addition, for determination of the maximum recommended 
was also considered the HNSTD. The HNSTD/NOAEL of 
than the proposed starting dose in humans (1 mg/kg) with 
the projected human AUC (0-336),ss at 1 mg/kg 


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parameters. The projected half-life in humans is 
, which approximates 14 days (q2w), the 
selected dosing schedule. 
The human effective dose of BMS-986207 administered in combination with nivolumab in cancer 
patients, was projected to target steady-state average plasma concentration (Cave) and minimum 
plasma concentration (Cmin) of 
 
, respectively, equivalent to 10A7-mIgG1 
D265A Cave_14d and Cmin_14d at the efficacious dose in CT26 mouse tumor model. Based on 
the projected human PK of BMS-986207, the human effective is projected to be 4 mg/kg IV 
administered once every 2 weeks (q2w). A flat dose of BMS-986207 (mg) will be used in this 
study, given similar exposure variability of flat-dose as compared to body weight-based dosing for 
many therapeutic antibodies and practical advantages. 41 
The current protocol evaluates the q2w dosing regimen. A dosing regimen of q4w is being 
considered for the single-agent of BMS-986207, as well as with in combination with nivolumab. 
The q4w option will benefit the patients with less frequent visits and reduce the medical burden 
from the care givers and the cancer treatment institutions. The projected human PK profile of 
BMS-986207 is linear, and the dose for q4w dosing schedule will be based on q2w with linear 
extrapolation. The exposure, efficacy and safety, of BMS-986207 as a single agent and in 
combination with nivolumab, will be evaluated and compared with the q2w dosing schedule. 
Based on the totality of clinical data, the sponsor will consider to revise the dosing regimen, if 
appropriate. 
BMS-986207 PK was evaluated in participants with advanced solid tumors receiving q2w (20, 80, 
240, 800, or 1600 mg) and q4w (480 or 1600 mg) doses in Part 1A, 1B and 2A of CA020002. 
Preliminary PK results of BMS 986207 suggest the increase in exposure is proportional across the 
dose range evaluated, which is in agreement with preclinical predictions. The CLT appears 
consistent across doses. For participants who received combination treatment with nivolumab in 
Part 1B, the PK of BMS-986207 appears to be consistent with that reported for monotherapy in 
Part 1A and 2A.19 
In the Triplet Cohort (Part 1C), the initial proposed BMS-986207 dose was 1200 mg q3w based 
on lower Cmax, similar Cavg and 
 as compared to 1600 mg q4w, a safe and tolerable dose 
evaluated in combination with nivolumab in Part 1B and the projected saturation of intratumoral 
TIGIT receptor occupancy at 
 level to provide optimal clinical benefit. Preliminary data as 
per 20-Oct-2021, revealed that 2 out of 4 DLT-evaluable participants experienced DLTs with the 
combination of BMS-986207 1200 mg Q3W, nivolumab 360 mg Q3W, and ipilimumab 1 mg/kg 
Q6W (see Section 3.2.1.4 for more details). BMS-986207 dose of 1200 mg Q3W was reduced to 
600 mg per BOIN design. BMS-986207 dose of 600 mg Q3W is expected to provide half of the 
exposure as compared to 1200 mg Q3W, and a relatively high intratumoral TIGIT receptor 
occupancy at the 
 level. In addition, BMS-986207 dose of 360 mg Q3W may be explored 
to aid in RP2D dose selection and per BOIN design if de-escalation is needed. 
The selection of an every-3-weeks regimen allows for aligning the schedule of BMS-986207 with 
combination of nivolumab q3w and ipilimumab q6w in 1L NSCLC (See Section 5.5.2.2 and 


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Section 5.5.2.3), since the primary efficacy evaluation in Part 2C will be in participants with 1L 
NSCLC. 
5.5.2.2 
Nivolumab 
Nivolumab monotherapy has been extensively studied in multiple tumor types, including 
melanoma, NSCLC, RCC, cHL, SCCHN, and urothelial carcinoma, and has been safely 
administered at doses up to 10 mg/kg q2w. Nivolumab is currently approved for the treatment of 
various tumor types with monotherapy regimen of 480 mg q4w, 240 mg q2w, or 3 mg/kg q2w. 
When used in combination with ipilimumab and chemotherapy, nivolumab 360 mg q3w is 
approved for the treatment of 1L NSCLC. 
Based on the clinical experience and quantitative clinical pharmacology understanding, nivolumab 
480 mg q4w, 360 mg q3w, or 240 mg q2w infused over approximately 30 minutes were selected 
in this study as these doses are expected to provide similar nivolumab exposures (Cavg and 
Ctrough), and to allow the flexibility of aligning doses of nivolumab at the same dosing frequency 
of BMS-986207 for the combination treatment. 
Specifically, in the Triplet Cohort (Part 1C) and Triplet NSCLC Expansion (Part 2C), participants 
will receive 360 mg q3w nivolumab in combination with ipilimumab 1 mg/kg q6w and BMS- 
986207 600 mg q3w. 
5.5.2.3 
Ipilimumab 
Ipilimumab is approved as monotherapy for the treatment of advanced melanoma and adjuvant 
melanoma with 3 mg/kg q3w for 4 doses and 10 mg/kg q3w for 4 doses followed by maintenance 
dose, respectively. Ipilimumab is also approved in combination with nivolumab for the treatment 
of various cancers, including melanoma, RCC, CRC, and HCC with a dosing regimen of 1 mg/kg 
q3w or 3 mg/kg q3w for 4 doses, depending on tumor type.22 
In addition, a less frequent but continuous ipilimumab regimen (1 mg/kg q6w) is being evaluated 
in combination with nivolumab or nivolumab plus chemotherapy in a number of pivotal studies, 
including 1L NSCLC studies CA209227 and CA2099LA, 1L SCCHN study CA209651, and 1L 
mesothelioma study CA209743. For instance, study CA2099LA, evaluating nivolumab 360 mg 
q3w plus ipilimumab 1 mg/kg q6w given concomitantly with 2 cycles of chemotherapy, 
demonstrated superior survival benefit to patients with 1L NSCLC as compared to SOC 
chemotherapy. The safety profile of this triple combination regimen was reflective of the known 
safety profiles of the immunotherapy and chemotherapy. Ipilimumab 1 mg/kg q6w is currently 
approved for the treatment of 1L NSCLC, in combination with nivolumab or with nivolumab and 
2 cycles of chemotherapy, and is also approved for the treatment of 1L mesothelioma, in 
combination with nivolumab.34 
Based on the clinical experience, low-dose ipilimumab 1 mg/kg q6w infused over approximately 
30 minutes will be examined in combination with nivolumab and BMS-986207 in the Triplet 
Cohort (Part 1C) and Triplet NSCLC Expansion (Part 2C) of this study. 


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5.5.2.4 
Rationale for Infusion Times 
Long infusion times (greater than or equal to 60 minutes), especially when multiple agents are 
administered sequentially to an individual, place a burden on participants and treatment centers. 
Establishing that investigational agents, such as BMS-986207, can be safely administered using 
an infusion time of 60 minutes will diminish the burden, provided there is no change in the safety 
profile. 
In addition, a 60-minute post infusion safety observation period is considered appropriate given 
BMS-986207 is a fully human monoclonal antibody that is an antagonist (not an agonist) and has 
a low likelihood of resulting in infusion reactions. For participants < 42 kg on the 1600 mg dose, 
the infusion time will be 90 minutes. Details of drug preparation are found in Pharmacy Manual, 
a document that will be provided separately to the site. 
In Parts 1B and 2B, when both study drugs are given in combination, nivolumab will be given 
first, over a 30 minute infusion period, followed by BMS-986207 over a 60-minute infusion period, 
beginning at least 30 minutes after completion of the infusion of nivolumab. 
Nivolumab has been administered safely over 60 minutes at doses ranging up to 10 mg/kg over 
long treatment duration. In Study CA209010 (a Phase 2, randomized, double-blinded, 
dose-ranging study of nivolumab in participants with advanced/metastatic clear cell RCC), a dose 
association was observed for infusion site reactions and hypersensitivity reactions (1.7% at 
0.3 mg/kg, 3.7% at 2 mg/kg, and 18.5% at 10 mg/kg). All the events were Grade 1 to 2 and were 
manageable. An infusion duration of 30 minutes for 3 mg/kg nivolumab (30% of the dose provided 
at 10 mg/kg) is not expected to present any safety concerns compared to the prior experience at 
10 mg/kg nivolumab dose infused over a 60 minute duration. 
Similarly, ipilimumab, which will be given in Part 1C and Part 2C, was safely administered over 
90 minutes at 10 mg/kg. In the CA184022 study, where ipilimumab was administered up to a dose 
of 10 mg/kg, on-study drug related hypersensitivity events (Grade 1-2) were reported in 1 (1.4%) 
participant in the 0.3 mg/kg group and in 2 (2.8%) participants in the 10 mg/kg group. There were 
no drug-related hypersensitivity events reported in the 3 mg/kg group. Across the 3 treatment 
groups, no Grade 3-4 drug-related hypersensitivity events were reported and there were no reports 
of infusion reactions. Ipilimumab 10 mg/kg monotherapy has also been safely administered as a 
90 minute infusion in large phase 3 studies in prostate cancer (CA184043) and as adjuvant therapy 
for stage 3 melanoma (CA184029), with infusion reactions occurring in participants. 
Administering 1 mg/kg of ipilimumab represents one-tenth of the 10 mg/kg dose and will be 
administered over one-third the time, for a lower infusion rate. 
Of note, CA209153, a Phase 3b/4 safety study of nivolumab in participants with metastatic 
NSCLC who have progressed during or after at least 1 prior systemic regimen, used a 30 minute 
infusion in a cohort of participants with no safety issues. 
Overall, infusion reactions, including high-grade hypersensitivity reactions, have been uncommon 
with nivolumab or ipilimumab administration or the combination of nivolumab and ipilimumab. 
Overall, a change in safety profile is not anticipated with a 30-minute infusion of nivolumab or 
ipilimumab, infusion times that are consistent with the current USPIs for each drug. 


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For participants with a bodyweight of > 250 kg the dosing of BMS-986207 will occur the day after 
dosing of nivolumab and ipilimumab when these drugs are administered on the same day. Details 
of study drug preparation are found in the Pharmacy Manual, a document that will be provided 
separately to the site. 
6. 
STUDY POPULATION 
For entry into the study, the following criteria MUST be met prior to dosing on Day 1. No 
exceptions will be granted. This study permits the re-enrollment of a participant that has 
discontinued the study as a pretreatment failure. If re-enrolled, the participant must be re-consented 
and meet all inclusion/exclusion criteria. 
6.1 
Inclusion Criteria 
1) Signed Written Informed Consent 
a) The participant must sign the ICF prior to the performance of any study-related procedures 
that are not considered part of standard of care. 
b) The participant must sign the consent for pretreatment and on treatment 
(See 
 for details). 
2) Target Population 
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). 
b) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 8) 
c) All solid tumor histologies will be permitted in Parts 1A, 1B, and 1C 
d) Parts 1A, 1B, and 1C, participants must have received, and then progressed or been 
intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting, if 
such a therapy exists. 
e) Part 1A, participants with tumor types where the microbiome has been hypothesized, based 
on preclinical or clinical data, to mediate TIGIT inhibition (such as, but not limited to, CRC 
and SCCHN), will be prioritized for enrollment 
f) Part 1B, participants with tumor types where PD1/PD-L1 inhibitors are indicated as front 
line treatment can be enrolled to this study treatment naïve 
g) Part 2 A, only participants with CRC 
h) Part 2 B, only participants with CRC, HCC and ovarian cancer, 
i) Participants with CRC must have received, and then progressed on 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). 
j) Participants with CRC, microsatellite instability (MSI), mismatch repair (MMR), V-Ki- 
ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), and B-Raf proto-oncogene 
(BRAF) status, if known, should be documented. If unknown, participants must consent to 
allow their submitted archived tumor tissue sample (block or unstained slides) to be tested. 


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k) For Part 2B Participants with HCC must have advanced HCC not amenable to curative 
resection, ablation or liver transplant. 
l) For participants with HCC who progressed after locoregional therapy, then locorgegional 
therapy must be completed at least 4 weeks prior to the baseline scan. All acute toxic 
effects of any prior local treatment must have resolved to NCI CTCAE v4.03 Grade ≤ 1 or 
been deemed irreversible 
m) Participants with radiological diagnosis of HCC may be enrolled for screening in the study 
but histological confirmation of HCC is mandatory prior to initiation of study therapy. 
n) For participants with HCC, previous progressive disease, or been intolerant to, at least 1 
line of therapy or refused treatment with sorafenib 
o) For participants with HCC A Child-Pugh Class A (6 points or less) (Appendix 11) 
p) For participants with HCC Must have results of testing for hepatitis B surface antigen, 
hepatitis B surface antibody, hepatitis B core antibody, hepatitis B DNA polymerase chain 
reaction (PCR), hepatitis C antibody and hepatitis C ribonucleic acid (RNA) PCR. 
q) For HCC participants with hepatitis B infection, a hepatitis B DNA viral load < 100 IU/mL 
is required and the participant must be on anti-viral therapy per institutional guidelines 
r) For participants with hepatitis B infection, there must be no co-infection with hepatitis C 
or hepatitis D (must obtain hepatitis D antibody testing) 
s) For participants with hepatitis C infection (HCV), active HCV infection, as defined by any 
detectable HCV RNA and positive antibody, can be enrolled providing they are on anti- 
viral therapy. Resolved HCV infection, as evidenced by undetectable HCV RNA and 
positive antibody, can be enrolled. Participants on antiviral therapy for HCV are permitted 
to enroll in the study and should continue treatment during the study. Participants with 
active HCV who are not on antiviral therapy at screening cannot be enrolled in the study 
t) For participants with ovarian cancer in Part 2B, histologically or cytologically documented 
epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer 
u) For participants with ovarian cancer in Part 2B completed at least one platinum based 
therapy (PBT) regimen (carboplatin, cisplatin, or another organoplatinum compound) 
v) For participants with ovarian cancer in Part 2B, with platinum refractory, resistant, 
sensitive, intolerance to PBT (inability to receive PBT due to hypersensitivity reactions to 
platinum) are eligible 
w) Part 2C, only participants with NSCLC who are treatment naive with baseline tumor PD- 
L1 expression ≥1% are eligible 
i) Participants with NSCLC in Part 2C must have histologically confirmed NSCLC per 
the 8th International Association for the Study of Lung Cancer classification (IASLC) 
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(including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase 
(ALK)/ROS1 inhibitors) given as primary therapy for advanced or metastatic disease. 
ii) Prior definitive chemoradiation for locally advanced disease is permitted as long as 
the last administration of chemotherapy or radiotherapy (which ever was given last) 
occurred at least 6 months prior to enrollment. 
iii) Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last 
administration of the prior regimen occurred at least 6 months prior to enrollment. 
iv) Measurable disease by CT or MRI per RECIST v1.1 criteria (Appendix 5); 
radiographic tumor assessment performed within 28 days before randomization 
v) Target lesions may be located in a previously irradiated field if there is documented 
(radiographic) disease progression in that site after the completion of radiation 
therapy. 
vi) A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (preferred) or a 
minimum of 20 unstained slides of tumor tissue from core biopsy, excisional or 
incisional biopsy obtained during screening or prior to enrollment (within 3 months of 
enrollment and with no intervening systemic anti-cancer treatment between time of 
acquisition and enrollment) must be sent to the central laboratory. Fine needle 
aspirates or other cytology samples are not acceptable. Biopsies of bone lesions that 
do not have a soft tissue component or decalcified bone tumor samples are also not 
acceptable. 
vii) Participants must have pre-existing or prior PD-L1 immunohistochemistry (IHC) 
results within 3 months of enrollment from testing of tumor tissue. PD-L1 expression 
must be tumor cell positive ≥ 1% for a participant to be eligible for enrollment. 
viii) 
Prior palliative radiotherapy to non-CNS lesions must have been completed at 
least 2 weeks prior to randomization. Participants with symptomatic tumor lesions at 
baseline that may require palliative radiotherapy within 4 weeks of randomization are 
strongly encouraged to receive palliative radiotherapy prior to treatment assignment. 
3) Physical and Laboratory Test Findings 
a) Adequate hematologic function for participants as defined by the following: 
i) Neutrophils ≥ 1500/µL 
ii) Platelets ≥ 100 × 103/µL (transfusion to achieve this level is not permitted within 
2 weeks of first study drug administration) 
iii) Hemoglobin ≥ 9 g/dL (transfusion to achieve this level is not permitted within 2 weeks 
of first study drug administration) 
iv) WBC > 2000/μL 
b) Adequate hepatic function (except for HCC) 
i) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper 
limit of normal (ULN) 


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ii) Total bilirubin ≤ 1.5 × ULN (except participants with Gilbert’s Syndrome who must 
have normal direct bilirubin) 
iii) Specifically for participants with HCC: 
(1) Prothrombin time-international normalized ratio (PT/INR) ≤ 2.3 or PT ≤ 6 seconds 
above control 
(2) Adequate hepatic function as documented by: 
(a) Serum albumin ≥ 2.8 g/dL 
(b) Total bilirubin ≤ 3 mg/dL 
(c) AST and ALT ≤ 5 x the institutional ULN 
c) Clinically stable thyroid function 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 PD sample collection and required study follow- 
up periods 
4) Age and Reproductive Status 
a) Males and females, aged at least 18 years old or local age of majority. 
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity of 25 IU/L or equivalent units of human chorionic 
gonadotrophin) within 24 hours prior to the first dose of study drug. 
i) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the participant must be excluded from 
participation if the serum pregnancy result is positive. 
ii) Additional requirements for pregnancy testing during and after study intervention are 
located in Section 2, Schedule of Activities. 
iii) The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
c) Women must not be breastfeeding 
d) WOCBP must agree to follow instructions for method(s) of contraception defined in 
Appendix 4 and as described below (g) and included in the ICF. 


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e) WOCBP who are continuously not heterosexually active are also exempt from 
contraceptive requirements, but should still undergo pregnancy testing as described in this 
section. 
f) Male participants should maintain their usual practice with regard to contraception (if any); 
however, no specific contraceptive measures are required. 
g) Please see Appendix 4 for further information on contraception methods. 
h) WOCBP are permitted to use hormonal contraception methods (as described in 
Appendix 4) 
i) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least 1 of the following conditions applies: 
(1) Is not a WOCBP 
OR 
(2) Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of < 1% per year), preferably, with low user dependency, as described 
in Appendix 4 during the intervention period and for at least 5 months and agrees 
not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time 
period 
i) Female participants must have documented proof that they are not of childbearing 
potential. 
j) Women who are not of childbearing potential are exempt from contraceptive requirements. 
 
Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
6.2 
Exclusion Criteria 
1) Target Disease Exclusions 
a) Participants with primary CNS disease, or tumors with CNS metastases as the only site of 
disease, will be excluded. Participants with controlled brain metastases, however, will be 
allowed to enroll. Controlled brain metastases are defined as no radiographic progression 
for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation 
if no intervention is clinically indicated), and no longer taking steroids for at least 2 weeks 
prior to first dose of study drug, and with no new or progressive neurological signs and 
symptoms. 
b) Participants in Part 2C with known EGFR mutations which are sensitive to available 
targeted inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 
[L858R] substitution mutations) are excluded. All participants with non-squamous 
histology must have been tested for EGFR mutation status; use of an FDA-approved test 


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is strongly encouraged. Participants with non-squamous histology and unknown or 
indeterminate EGFR status are excluded. 
c) 
Participants in Part 2C with known ALK translocations which are sensitive to available 
targeted inhibitor therapy are excluded. If tested, use of an FDA-approved test is strongly 
encouraged. 
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 Sponsor/Medical Monitor is 
mandatory 
c) Prior immune therapy 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 
d) Prior participation in an anti-TIGIT clinical study 
3) Prior anti-cancer treatments such as chemotherapy, radiotherapy, hormonal, or immunotherapy 
(including anti-PD1/PD-L1) are permitted (except for NSCLC participants in Part 2C). 
4) Medical History and Concurrent Diseases 
a) Participants with concomitant second malignancies (except adequately treated 
nonmelanomatous skin cancers or in situ bladder, breast, or cervical cancers) are excluded 
unless a complete remission was achieved at least 2 years prior to study entry, and no 
additional therapy is required or anticipated to be required during the study period 
b) Participants with other active malignancy requiring concurrent intervention 
c) Prior organ allograft 
d) Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless 
the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible 
i) Any active neuropathy > Grade 2 (NCI CTCAE v4.03) 
e) Participants with the following: 
i) Active, known, or suspected autoimmune disease 
− Participants with well controlled asthma and/or mild allergic rhinitis (seasonal 
allergies) are eligible 
− Participants with the following disease conditions are also eligible: 
• Vitiligo 
• Type 1 diabetes mellitus 
• Residual hypothyroidism due to autoimmune condition only requiring 
hormone replacement 
• Euthyroid participants with a history of Grave’s disease (participants with 
suspected autoimmune thyroid disorders must be negative for thyroglobulin 


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and thyroid peroxidase antibodies and thyroid stimulating Ig prior to the first 
dose of study drug) 
• 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 (eg, anti-CTLA-4 
or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting 
T cell co-stimulation or immune checkpoint pathways) except those that are unlikely 
to re-occur with standard countermeasures (eg, hormone replacement after adrenal 
crisis). 
iii) Conditions requiring systemic treatment with either corticosteroids > 10 mg daily 
prednisone equivalents or other immunosuppressive medications within 14 days of 
study drug administration, except for adrenal replacement steroid doses ≤ 10 mg daily 
prednisone equivalent in the absence of active autoimmune disease. 
− 
Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating 
study drug is permitted 
iv) Uncontrolled or significant cardiovascular disease including, but not limited, to any 
of the following: 
• Myocardial infarction or stroke/transient ischemic attack within the past 6 months 
• Uncontrolled angina within the past 3 months 
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, 
ventricular fibrillation, or torsades de pointes) 
• History of other clinically significant heart disease (eg, cardiomyopathy, congestive 
heart failure with New York Heart Association functional classification III to IV 
[Appendix 9] pericarditis or significant pericardial effusion) 
• Cardiovascular disease-related requirement for daily supplemental oxygen therapy 
• QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation 
> 480 msec, except for right bundle branch block 
• History of myocarditis, regardless of etiology 
v) History of chronic hepatitis (except for HCC) as evidenced by the following: 
• Positive test for hepatitis B surface antigen 
• Positive test for qualitative hepatitis C viral load by PCR 
− 
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. 
− 
Additional testing or substitute testing per institutional guidelines to rule out 
infection is permitted. 
• 
Specific exclusions for participants with HCC: 
− 
Active coinfection with both hepatitis B and C 


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− 
Hepatitis D infection in participants with hepatitis B 
− 
Clinically significant ascites or clinically significant variceal bleeding 
vi) Evidence of active infection that requires systemic antibacterial, antiviral, or 
antifungal therapy ≤ 7 days prior to the first dose of study drug (except for viral 
infections that are presumed to be associated with the underlying tumor type required 
for study entry) 
vii) Known history of testing positive for HIV or known acquired immunodeficiency 
syndrome 
Note: Testing for HIV must be performed at sites where mandated by local 
requirements. 
viii) Any major surgery within 4 weeks of the first dose of study drug. Participants must 
have recovered from the effects of major surgery or significant traumatic injury at 
least 14 days before the first dose of study drug. 
ix) Receipt of nononcology vaccines containing live virus for prevention of infectious 
diseases within 4 weeks prior to first dose of study drug 
(1) The use of inactivated seasonal influenza vaccines, eg, Fluzone®, will be permitted 
on study without restriction. 
(2) Previous SARS-CoV-2 vaccine within 14 days of C1D1 is not permitted. 
x) Receipt of packed red blood cells or platelet transfusion within 2 weeks of the first 
dose of study drug unless agreed by the medical monitor. 
xi) Any known or underlying medical, psychiatric condition and/or social reason that, in 
the opinion of the Investigator or Sponsor, could make the administration of study 
drug hazardous to the participants or could adversely affect the ability of the 
participant to comply with or tolerate the study. 
xii) 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 
xiii) Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections 
or 20 days for severe/critical illness prior to C1D1. 
(3) 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. 
f) WOCBP who are pregnant or breastfeeding 
5) Allergies and Adverse Drug Reaction 
a) History of allergy to study drug components 
b) History of severe hypersensitivity reaction to any mAb 


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6) Other Exclusion Criteria 
a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to continue 
as a participant. Strict conditions apply and Sponsor approval is required. 
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness 
 
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria. 
6.3 
Lifestyle Restrictions 
There are no lifestyle restrictions applicable for this study given that the participants will receive 
the study investigational products (IPs) IV. 
6.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomized/entered in the study. 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 (Appendix 10), and to 
respond to queries from regulatory authorities. Minimal information includes date of consent, 
demography, screen failure details, eligibility criteria, and any SAEs. 
6.4.1 
Retesting During Screening or Lead-In Period 
This study allows for the re-enrollment of a participant that has discontinued the study as a 
pretreatment failure. Retesting of laboratory parameters and/or other assessments during the 
extended screening period will be allowed. 
The most current result prior to enrollment is the value by which study inclusion will be assessed, 
as it represents the participant’s most current, clinical state. 
Testing for asymptomatic SARS-CoV-2 infection by RT-PCR or viral antigen is not required. 
However, some participants may develop suspected or confirmed symptomatic SARS-CoV-2 
infection, or be discovered to have asymptomatic SARS-CoV-2 infection during the screening 
period. In such cases, 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 (e.g. 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 


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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 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. 
TREATMENT 
7.1 
Treatments Administered 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo or 
medical device intended to be administered to a study participant according to the study 
randomization or treatment allocation. 
An IP, also known as investigational medicinal product in some regions, is defined as a 
pharmaceutical form of an active substance or placebo being tested or used as a reference in a 
clinical study, including products already with a marketing authorization but used or assembled 
(formulated or packaged) differently than the authorized form, or used for an unauthorized 
indication, or when used to gain further information about the authorized form. 
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as 
noninvestigational products. 
All drugs used in this open-label study qualify as IPs, as per previous text, and their description 
and storage information are described in Table 7.1-1. 
Table 7.1-1: 
Study Drugs 
 
Product Description 
Class and Dose Form 
Potency 
Blinding 
Packaging 
Appearance 
Storage Conditions 
(per Label) 
BMS-986207 for 
injectiona 
160 mg/vial 
(20 mg/mL) 
None 
Vial 
2 to 8°C. Protect 
from light and 
freezing. 
Nivolumab 
(BMS-936558) solution 
for injectiona 
100 mg/vial 
(10 mg/mL) 
None 
Vial 
2 to 8°C. Protect 
from light and 
freezing. 
Ipilimumab 
(BMS-734016) solution 
for injectiona 
200 mg 
(5 mg/mL) 
None 
Vial 
2 to 8°C. Protect 
from light and 
freezing. 
Abbreviation: BMS = Bristol-Myers Squibb; C = Celsius; IP = investigational product 
a All study drugs are considered IPs 
 
 
For Parts 1A, 1B, 2A and 2B, the initial treatment period is up to 24 weeks (3 cycles) of dosing. 
Following each treatment cycle, the decision to treat a participant with the next cycle of study 
therapy, up to a maximum of 48 weeks (6 cycles) of treatment, will be based on risk/benefit 


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analysis and tumor assessment. For Parts 1C and 2C, the treatment period is up to a maximum of 
2 years in the absence of disease progression or unacceptable toxicity. 
Upon completion of treatment, participants will enter a safety follow-up period. Details of the dose 
escalation and cohort expansion phases in this study are given as part of the study design in Section 
5. The selection and timing of dose for each participant are as shown in Table 7.1-2. 
Table 7.1-2: 
Selection and Timing of Dose 
 
Study Treatment 
 
Participant 
Weight 
Dosage formulation 
Frequency of 
Administration 
 
Route of 
Administration 
 
Infusion Time 
(min) 
BMS-986207a 
80 mg 
Any 
Infusion q2w 
IV 
60 
200 mg 
Any 
Infusion q3w 
IV 
60 
240 mg 
Any 
Infusion q2w 
IV 
60 
360 mg 
Any 
Infusion q3w 
IV 
60 
480 mg 
Any 
Infusion q4w 
IV 
60 
600 mg 
Any 
Infusion q3w 
IV 
60 
600 mg 
Any 
Infusion q4w 
IV 
60 
800 mg 
Any 
Infusion q2w 
IV 
60 
1200 mg 
< 38 kg 
Infusion q3w 
IV 
90 
1200 mg 
≥ 38 kg 
Infusion q3w 
IV 
60 
1600 mg 
< 42 kg 
Infusion q2w and q4w 
IV 
90 
1600 mg 
≥ 42 kg 
Infusion q2w and q4w 
IV 
60 
Nivolumab 
240 mg 
Any 
Infusion q2w 
IV 
30 
360 mg 
Any 
Infusion q3w 
IV 
30 
480 mg 
Any 
Infusion q4w 
IV 
30 
Ipilimumab 
1 mg/kg 
Any 
Infusion q6w 
IV 
30 
Abbreviations: IV, intravenous; q2w, every 2 weeks, q3w, every 3 weeks; q4w, every 4 weeks; q6w, every 6 weeks. 
 
a If dose-de-escalation is recommended by the design based on the number of participants with DLTs observed during 
this dose evaluation phase (Table 5.1.2.6-1), then the next lower dose level will be used (360 mg BMS-986207 
q3w) for the remaining participants. In addition, other lower doses of BMS-986207 (200 mg q3w) than that seen 
as safe and tolerable may also be tested. 
 
For participants < 42 kg on the 1600 mg dose, the infusion time will be 90 minutes. Details of 
study drug preparation are found in the Pharmacy Manual, a document that will be provided 
separately to the site. 
For participants on combination treatment, a 30-minute infusion of nivolumab will be followed by 
a 30-minute observation period, followed by a 60-minute infusion of BMS-986207 and a 
60-minute observation period after all infusions in Cycle 1 for each participant. A 60-minute post- 
infusion safety observation period is considered appropriate given BMS-986207 is fully human 


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antibody that is an antagonist antibody (not an agonist antibody) and has a low likelihood of 
resulting in infusion reactions. For participants in the Triplet Cohort (Part 1C) and Triplet NSCLC 
Expansion (Part 2C), a 30-minute infusion of nivolumab will be followed by a 30-minute 
observation period, followed by a 30-minute infusion of ipilimumab, a 30-minute observation 
period, followed by a 60-minute infusion of BMS-986207. 
For participants < 38 kg on the 1200 mg dose, the infusion time will be 90 minutes. For participants 
with a bodyweight of > 250 kg the dosing of BMS-986207 will occur the day after dosing of 
nivolumab and ipilimumab when these drugs are administered on the same day. Details of study 
drug preparation are found in the Pharmacy Manual. 
 
7.2 
Method of Treatment Assignment 
In this open-label study, enrolled participants, including those not dosed, will be assigned via IRT 
sequential participant numbers starting with 
 (eg, 
). Those 
enrolled participants meeting the inclusion criteria, and none of the exclusion criteria, will be 
eligible to be dosed. Sequential numbering may restart at 
 for each participating site as the 
distinct participant identification number will ultimately comprise of the site number and 
participant number, (eg, 
 ). In the expansion phase only, participants with CRC will be 
randomized in a 1:1 manner to either BMS-986207 monotherapy, or combination therapy with 
BMS-986207 and nivolumab, to eliminate the possibility of enrollment bias. 
Participants in Part 2C with 1L NSCLC and tumor cell PD-L1 expression of > 1% based on 
pre-existing lab results will be enrolled to receive combination therapy with BMS-986207, 
nivolumab, and ipilimumab. If more than 25% of the participants have a PD-L1 score < 1% as 
determined by the central lab, additional participants may be enrolled in order to have at least 30 
participants with a tumor cell score of ≥ 1%. 
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. If a participant is replaced after dosing, 
then the replacement participant will be assigned the original participant’s number plus 
 The 
replacement participant will receive the same treatment as the participant being replaced but a new 
participant number will be assigned to him or her. For example, Participant 
by Participant 
would be replaced 
Study treatment will be dispensed at the study visits as listed in Schedule of Activities (Section 2). 
7.3 
Blinding 
This is a non-randomized, open-label study and blinding procedures are not applicable. 
7.4 
Dosage Modification 
For Parts 1A, 1B, 2A, and 2B intra-participant dose escalation/reduction of BMS-986207, 
nivolumab, or ipilimumab is not permitted in this study in order to allow better evaluation of the 
safety and efficacy at individual dose levels and schedules except as described for the Preliminary 


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Safety Cohort (see Section 5.1.2.3). For intra-participant dose reduction of BMS-986207 in Part 
1C and 2C, see Section 5.1.2.6 and Section 5.1.2.7, respectively. 
7.4.1 
Dose Limiting Toxicities 
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, intensity, 
and duration of AEs for which no clear alternative cause is identified. The DLT period will be 
28 days (4 weeks) in Parts 1A and 1B. The DLT period for Part 1C will be 42 days (6 weeks). 
For the purpose of participant management, any AE that meets DLT criteria, regardless of the 
cycle in which it occurs, will lead to discontinuation of study drug unless the Investigator 
determines that only 1 of the agents must be discontinued due to toxicity attributed to that agent 
alone. Participants who withdraw from the study during the 4-week DLT evaluation period (6- 
week DLT evaluation period for Parts 1C and 2C) for reasons other than a DLT may be replaced 
with a new participant at the same dose level. The incidence of DLTs during the 4-week DLT 
evaluation period (6-week DLT evaluation period for Parts 1C and 2C) will be used in dose 
escalation decisions and to define the MTD. AEs occurring after the 4-week DLT period (6-week 
DLT evaluation period for Parts 1C and 2C) will be considered for the purposes of defining the 
RP2D upon agreement between the Sponsor, Medical Monitor, and Investigators. 
Participants experiencing a DLT will not be retreated with study drug, and will enter the safety 
follow-up period of the study. DLTs occurring after the 4-week (or 6-week period for Parts 1C and 
2C) DLT observation period will be accounted for in determining the RP2D for expansion. 
AEs will be graded according to the NCI CTCAE v4.03. 
7.4.1.1 
Hepatic Dose-Limiting Toxicity 
Any one of the following study drug-related events will be considered a hepatic DLT (except for 
HCC participants): 
• Grade 4 elevations in serum transaminases (AST, ALT), alkaline phosphatase (ALP) or total 
bilirubin 
• Grade 3 elevations in serum transaminases (AST, ALT) or alkaline phosphatase (ALP) that 
last longer than 5 days, or is associated with clinical symptoms, or bilirubin > 2 x ULN in the 
absence of cholestasis 
• Grade 2 elevations in AST or ALT with symptomatic liver inflammation (eg, right upper 
quadrant tenderness, jaundice, pruritus) 
• AST or ALT > 3 x ULN and concurrent total bilirubin > 2 x ULN without initial findings of 
cholestasis (elevated ALP, eg, findings consistent with Hy’s law or FDA definition of potential 
drug-induced liver injury [pDILI]). Note that this specific category of DLT uses ULN rather 
than CTCAE grade for definition. 
 
Hepatic DLT for HCC participants 
− AST or ALT > 10 × ULN for > 2 weeks 
− AST or ALT > 15 × ULN, irrespective of duration 


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− Total bilirubin > 8 × ULN, irrespective of duration for participants with elevated total 
bilirubin at study entry, or > 5 × ULN for those with normal total bilirubin at entry 
− Concurrent ALT ≥ 10 × ULN AND total bilirubin ≥ 2 × ULN or baseline value (if elevated 
bilirubin at study entry), AND no other immediately apparent possible causes of ALT 
elevation and hyperbilirubinemia. (For definition of p-DILI, see Section 9.2.7). 
 
7.4.1.2 
Hematologic Dose-Limiting Toxicity 
• Grade 4 neutropenia ≥ 7 days in duration 
• Grade 4 thrombocytopenia 
• Grade 3 thrombocytopenia with bleeding, or any requirement for platelet transfusion 
• Febrile neutropenia 
• Grade 3 hemolysis (ie, requiring transfusion or medical intervention such as steroids) 
• Grade 4 anemia not explained by underlying disease 
 
7.4.1.3 
Dermatologic Dose-Limiting Toxicity 
• Grade 4 rash 
• Grade 3 rash if no improvement (ie, resolution to ≤ Grade 1) after a 1 to 2 week infusion delay. 
 
7.4.1.4 
Other Dose-Limiting Toxicities 
Any of the following events will be considered a DLT: 
• Grade 2 drug-related uveitis, episcleritis, iritis eye pain or blurred vision that does not 
respond to topical therapy and does not improve to Grade 1 severity within the re-treatment 
period OR requires systemic treatment 
•  Grade 3 drug-related uveitis, episcleritis, iritis, pneumonitis, bronchospasm or neurologic 
toxicity 
• Grade ≥ 4 hypersensitivity reaction or Grade 3 that does not resolve to Grade 1 in < 6 hours 
• Other ≥ Grade 3 study drug-related toxicity will be considered a DLT. However, the following 
Grade 3 or 4 events will not be considered DLTs: 
o Grade 3 or Grade 4 electrolyte abnormalities that are not complicated by associated 
clinical adverse experiences, last less than 48 hours and either resolve 
spontaneously or respond to conventional medical intervention 
o Grade 3 nausea, vomiting, or diarrhea that lasts less than 48 hours, and either 
resolves spontaneously or responds to conventional medical intervention 
o Grade 3 or grade 4 elevation of amylase or lipase not associated with clinical or 
radiographic evidence of pancreatitis 
o Grade 3 fever not associated with hemodynamic compromise (eg, hypotension, 
clinical or laboratory evidence of impaired end-organ perfusion) 
− Grade 3 endocrinopathy that is well controlled by hormone replacement 


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− Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to sites of known or 
suspected tumor) 
− Grade 3 fatigue 
− Grade 3 infusion reaction that returns to Grade 1 in < 6 hours 
 
7.4.2 
Management Algorithms for Immuno-Oncology Agents 
Immuno-oncology agents are associated with immune-related AEs that can differ in severity and 
duration from AEs caused by other therapeutic classes. BMS-986207 and nivolumab are 
considered I-O agents in this protocol. Early recognition and management of immune-related AEs 
associated with I-O agents may mitigate severe toxicity. Management algorithms have been 
developed from extensive experience with nivolumab to assist Investigators in assessing and 
managing the following groups of immune-related AEs: 
• Gastrointestinal 
• Renal 
• Pulmonary 
• Hepatic 
• Endocrinopathies 
• Skin 
• Neurological 
• Myocarditis 
 
The clinical nature of AEs events noted with BMS-986207 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 immune-related AEs in this protocol are in Appendix 6. 
7.4.3 
Dose Delays Due To Toxicity 
Participants who experience the following must have all study drug(s) withheld: 
• Potential DLTs, until DLT relatedness is defined. 
• Select AEs and laboratory abnormalities: 
− ≥ Grade 1 pneumonitis 
− ≥ Grade 2 abnormality in AST, ALT or total bilirubin 
− ≥ Grade 2 creatinine 
− ≥ Grade 2 diarrhea or colitis 
− ≥ Grade 2 neurological AE 
− AE, laboratory abnormality, or concurrent illness that, in the judgment of the Investigator, 
warrants delaying study drug administration. 
• Confirmed SARS-CoV-2 infection. 


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Criteria for participants who are required to permanently discontinue both study drugs is listed in 
Section 8.2. Participants not meeting guidelines for permanent discontinuation will be permitted 
to resume therapy based on the criteria specified below in Section 7.4.3.3. Participants eligible to 
resume study therapy will resume study therapy at the nominal treatment visit following their last 
received study medication dose. 
The end of cycle tumor assessments, such as computed tomography (CT), magnetic resonance 
imaging (MRI), or positron emission tomography (PET), will continue on a q8w schedule relative 
to the participant’s first dose, regardless of any treatment delay incurred. 
7.4.3.1 
Criteria for Dose Delay Secondary to Changes in AST or ALT for 
Participants with HCC 
Participants with HCC who experience the following must have the study drug delayed: 
1) If a participant has a baseline AST or ALT that is within normal limits, delay dosing for drug- 
related ≥ Grade 2 toxicity (2 grade shift) 
2) If a participant has baseline AST or ALT within the Grade 1 toxicity range, delay dosing for 
drug-related ≥ Grade 3 toxicity (2 grade shift) 
3) If a participant has baseline AST or ALT within the Grade 2 toxicity range, delay dosing for a 
2-fold drug-related increase in AST or ALT or for AST or ALT values 8 × ULN (whichever 
is lower) 
4) Hepatic DLT as defined in Section 7.4.1.1 
 
 
It is recommended to monitor elevations in AST or ALT approximately every 3 days until levels 
peak and begin to decline. BMS-986207 dosing can be resumed where criteria to resume treatment 
are met (Section 7.4.3.3) 
7.4.3.2 
Protocol-Specific Recommendation for Management of Hepatic Events 
in HCC Participants 
The algorithms recommended for the management of immune-related AEs in this protocol are in 
Appendix 6. Protocol-specific recommendation for the management of hepatic events in HCC 
participants are as follows: 
• Dose delay criteria for hepatic events are outlined in Section 7.4.3.1. If AST or ALT levels do 
not improve with a dose delay of 3 to 5 days, or if the levels worsen, steroid therapy should be 
initiated at 0.5 to 2 mg/kg/day methylprednisolone or oral equivalent 
• For ALT or AST levels > 8 x ULN, steroid therapy should be initiated promptly at 
1 to 2 mg/kg/day methylprednisolone IV, intramuscularly, or oral equivalent 
• For all participants receiving steroid treatment for hepatic events, the BMS Medical Monitor 
should be consulted within 24 hours after initiation of steroids. Gastroenterology consult is 
recommended 
• If AST or ALT levels do not improve within 3 to 5 days after the start of steroid therapy, or 
the levels worsen after the start of steroid therapy, discussion with the BMS Medical Monitor 
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• Tapering of steroids can start once AST or ALT levels have declined by 1 CTCAE grade. 
Steroids should be tapered slowly, over no less than 1 month 
 
As outlined in Section 7.4.3.3, study therapy may resume when AST or ALT have returned to 
Grade 1 or baseline unless the AE meets the criteria for permanent discontinuation (Section 7.4.4). 
The BMS Medical Monitor must be consulted prior to resuming nivolumab for all participants 
who required steroid intervention. 
7.4.3.3 
Criteria to Resume Treatment 
Subsequent dosing with study therapy may resume once drug-related nonDLT AEs resolve to 
Grade 1 or baseline. 
Participants experiencing AEs not meeting criteria for permanent discontinuation as outlined in 
Section 7.4.4 may resume treatment with study medication under the following criteria: 
• Participants may resume treatment with study drug when the drug-related AE(s) resolve to 
Grade ≤ 1 or baseline value, with the following exceptions: 
− Participants may resume treatment in the presence of Grade 2 fatigue 
− Participants who have not experienced a Grade 3 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity 
− Participants with Grade 2 uveitis, episcleritis, iritis, eye pain or blurred vision not meeting 
DLT criteria (Section 8.2) must resolve to baseline prior to resuming study therapy 
• For participants with Grade 2 AST, ALT, or total bilirubin elevations, dosing may resume 
when laboratory values return to baseline, and management with corticosteroids (if needed), is 
complete 
• Participants with combined Grade 2 AST/ALT and total bilirubin values meeting DLT criteria 
(Section 7.4.1.1) should have treatment permanently discontinued 
• 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. 
 
• Criteria for HCC Participants: 
− Participants with baseline Grade 1 AST, ALT, or total bilirubin who require dose delays, 
for reasons other than a drug-related hepatic event, may resume treatment in the presence 
of Grade 2 AST, ALT, or total bilirubin increases. 


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− Participants who require dose delays for drug-related increased AST, ALT, or bilirubin 
may resume treatment when hepatic parameters are at baseline or Grade 1, and after 
discussion with the BMS Medical Monitor 
− Participants with AST, ALT or bilirubin values meeting permanent discontinuation 
parameters (Section 7.4.4) should have treatment permanently discontinued 
• Drug-related pulmonary toxicity, diarrhea, or colitis, must have resolved to baseline before 
treatment is resumed. Participants with persistent Grade 1 pneumonitis after completion of a 
steroid taper over at least 1 month, may be eligible for retreatment if discussed with, and 
approved by, the BMS Medical Monitor 
• Participants with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement, may resume treatment 
 
If the criteria to resume treatment are met, the participant should restart treatment at the next 
nominally scheduled timepoint per protocol. 
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, to determine the risks and benefits of continuing on therapy following resolution versus 
discontinuing therapy permanently. 
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 unless the Investigator determines that only 1 of the agents 
must be discontinued due to toxicity attributed to that agent alone, with the exception of the 
following: 
• Grade 3 diarrhea, nausea, vomiting, or abdominal pain that returns to Grade 1 or baseline 
within 3 days with medical intervention 
• Grade 3 pruritus or rash that returns to Grade 1 or baseline within 7 days with medical 
intervention 
• Isolated Grade 3 or 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 3 days of 
their onset 
• Grade 4 neutropenia < 7 days in duration 
• Grade 4 lymphopenia or leukopenia 
• Grade 3 or 4 increase in amylase or lipase that is not associated with clinical or radiographic 
evidence of pancreatitis 
• Grade 3 infusion reactions that return to Grade 1 in < 6 hours 
• Grade 3 fever not associated with hemodynamic compromise (eg, hypotension, clinical, or 
laboratory evidence of impaired end-organ perfusion) 


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• Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to sites of known or 
suspected tumor) 
• Grade 3 fatigue 
• Grade 3 or 4 drug-related endocrinopathy AEs, such as adrenal insufficiency, 
adrenocorticotropic hormone, hyper- or hypothyroidism, or glucose intolerance, which resolve 
or are adequately controlled with physiologic hormone replacement (corticosteroids, thyroid 
hormones) or glucose-controlling agents, respectively, may not require discontinuation after 
discussion with and approval from the BMS Medical Monitor 
• Any event that leads to delay in dosing, lasting > 6 weeks from the previous dose, requires 
discontinuation, with the exception of the following: 
− Dosing delays to allow for prolonged steroid tapers to manage drug-related AEs are 
allowed. Prior to re-initiating treatment in a participant with a dosing delay lasting 
> 6 weeks from the previous dose, the BMS Medical Monitor must be consulted. Tumor 
assessments should continue as per protocol even if dosing is delayed. Periodic study visits 
to assess safety and laboratory studies should also continue every 6 weeks, or more 
frequently if clinically indicated, during such dosing delays. 
− Dosing delays lasting > 6 weeks from the previous dose that occur for non drug-related 
reasons may not require discontinuation, if approved by the BMS Medical Monitor. Prior 
to re-initiating treatment in a participant with a dosing delay lasting > 6 weeks, the BMS 
Medical Monitor must be consulted. 
• Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
Investigator, presents a substantial clinical risk to the participant with continued nivolumab 
dosing. 
 
All participants who discontinue IP should comply with protocol specified follow-up procedures 
as outlined in Section 8.2. 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 (eg, imprisonment, involuntarily incarceration for the treatment of either a 
psychiatric or physical illness). 
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate case report form (CRF) page. 
7.4.5 
Management of Drug-related Infusion Reactions 
Since BMS-986207 and nivolumab contain only human Ig protein sequences, they are unlikely to 
be immunogenic and induce infusion or hypersensitivity reactions. However, if such a reaction 
were to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, arthralgia, 
hypotension, hypertension, bronchospasm, or other allergic-like reactions. All Grade 3 or 4 
infusion reactions should be reported within 24 hours to the BMS Medical Monitor and reported 
as an SAE. Infusion reactions should be graded according to NCI CTCAE v4.03 guidelines. 
Treatment recommendations for infusion reactions are provided below and may be modified based 
on local treatment standards and guidelines, as appropriate. 


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For Grade 1 symptoms (mild reaction; infusion interruption not indicated; intervention not 
indicated): 
• Remain at bedside and monitor participant until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg at least 30 minutes before 
study drug administrations. 
 
For Grade 2 symptoms (moderate reaction requiring therapy or infusion interruption but 
responding promptly to symptomatic treatment such as antihistamines, nonsteroidal 
anti-inflammatory drugs, narcotics, corticosteroids, bronchodilators, IV fluids, or prophylactic 
medications indicated for ≤ 24 hours): 
• Stop the study drug infusion, begin an IV infusion of normal saline, and treat the participant 
with diphenhydramine 50 mg IV (or equivalent) and/or acetaminophen/paracetamol 
325 to 1000 mg; remain at bedside and monitor participant until resolution of symptoms. 
Corticosteroid and/or bronchodilator therapy may also be administered as appropriate. If the 
infusion is interrupted, then restart the infusion at 50% of the original infusion rate when 
symptoms resolve; if no further complications ensue after 30 minutes, the rate may be 
increased to 100% of the original infusion rate. Monitor participant closely. If symptoms recur, 
then no further BMS-986207 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 1000 mg 
should be administered at least 30 minutes before study drug infusions. If necessary, 
corticosteroids (up to 25 mg of hydrocortisone or equivalent) may be used. 
 
For Grade 3 or 4 symptoms (severe reaction, Grade 3: prolonged [ie, not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following 
initial improvement; hospitalization indicated for other clinical sequelae [eg, renal impairment, 
pulmonary infiltrates]; Grade 4: Life-threatening; pressor or ventilatory support indicated): 
• Immediately discontinue infusion of study drug. Begin an IV infusion of normal saline and 
treat the participant as follows: recommend bronchodilators, epinephrine 0.2 to 1 mg of a 
1:1000 solution for subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution 
injected slowly for IV administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed. Participant should be monitored 
until the Investigator is comfortable that the symptoms will not recur. Study drug will be 
permanently discontinued except for a Grade 3 infusion reaction that returns to Grade 1 in less 
than 6 hours. Investigators should follow their institutional guidelines for the treatment of 
anaphylaxis. Remain at bedside and monitor participant until recovery of the symptoms. 
 
In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine or corticosteroids). 


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7.4.6 
Discontinuation Due to Hypersensitivity 
Any single grade 5 hypersensitivity related event, or two grade 4 hypersensitivity related events 
(according to the NCI CTCAE v4.03) will require permanent discontinuation of drug 
administration for these participants and further enrollment in the study will be halted until a full 
safety assessment can be completed. 
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. 
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets). 
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. 
Refer to the current version of the IB and/or Pharmacy Manual for complete storage, handling, and 
dispensing information. 
Further guidance and information for final disposition of unused study treatment are provided in 
Appendix 2 and the Pharmacy Manual. 
7.5.1 
Retained Samples for Bioavailability / Bioequivalence 
Not Applicable. 
7.6 
Treatment Compliance 
Study treatment compliance will be periodically monitored by Drug Accountability Concomitant 
Therapy. 
7.6.1 
Prohibited and/or Restricted Treatments 
Prohibited and/or restricted medications taken prior to the first dose of study drug in the study are 
described below. Medications taken within 4 weeks prior to the first dose of study drug must be 
recorded on the CRF. 
• Prior exposure to anti-TIGIT therapy 
• Exposure to any investigational drug within 4 weeks of the first dose of study drug 


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• Any live/attenuated vaccine (eg varicella, zoster, yellow fever, rotavirus, oral polio and 
measles, mumps, rubella) during treatment and until 100 days post-last dose 
• Administration of investigational SARS-CoV-2 vaccines is not allowed during the study. 
Participants may receive approved SARS-CoV-2 vaccines while continuing on study treatment 
at the discretion of the Investigator. Non-live SARS-CoV-2 vaccination is considered a simple 
concomitant medication within 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. 
The following medications are prohibited during the study (unless utilized to treat a drug related 
AE): 
• Immunosuppressive agents 
• Immunosuppressive doses of systemic corticosteroids (except as stated in Section 6.2) 
• Any concurrent anti-neoplastic therapy (ie, chemotherapy, hormonal therapy, immunotherapy, 
extensive, nonpalliative radiation therapy, or standard or investigational agents). 
 
7.7 
Treatment After the End of the Study 
At the conclusion of the study, participants who continue to demonstrate clinical benefit may be 
eligible to receive BMS-supplied study treatment. Study treatment may 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). 
7.7.1 
Permitted Therapy 
Participants are permitted the use of the following treatments: 
• Topical, ocular, intra-articular, intra-nasal, and inhalational corticosteroids 
• Adrenal replacement steroid doses ≥ 10 mg daily prednisone equivalent 
• A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) 
or for treatment of nonautoimmune conditions (eg, delayed-type hypersensitivity reaction 
caused by a contact allergen) 
 
8. 
DISCONTINUATION CRITERIA 
8.1 
Discontinuation from Study Treatment 
BMS reserves the right to terminate access to BMS supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns; b) the development of the BMS-986207 
is terminated for other reasons, including, but not limited, to lack of efficacy and/or not meeting 
the study objectives; c) the participant can obtain the study medications from a government 
sponsored or private health program. In all cases, BMS will follow local regulations. 


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• Participants MUST discontinue the IP (and nonIP at the discretion of the Investigator) 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 
• Protocol-defined reasons for permanent discontinuation (Section 7.4.4) 
• Any drug-related AE occurring at any time that meets DLT criteria as outlined in Section 7.4.1 
will require permanent discontinuation unless the Investigator determines that only 1 of the 
agents must be discontinued due to toxicity attributed to that agent alone. Exceptions to 
permanent discontinuation are listed in Section 7.4.4. 
• Participant requests to stop study treatment and/or participation in the study 
• Any clinical AE, laboratory abnormality or intercurrent illness, which, in the opinion of the 
Investigator, indicates that continued participation in the study is not in the best interest of the 
participant 
• Termination of the study by BMS 
• Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances, a participant who has been imprisoned may be permitted to continue 
as a participant. Strict conditions apply and BMS approval is required.) 
• 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 in settings where benefit/risk justifies 
discontinuation of study therapy. 
 
Discontinuation of the study treatment for abnormal liver tests should be considered by the 
Investigator when a participant meets one of the conditions outlined in Section 9.2.7 (p-DILI) or 
if the Investigator believes that it is in best interest of the participant. 
Refer to the Schedule of Activities for data to be collected at the time of treatment discontinuation 
and required 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. 


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All participants who discontinue study treatment should comply with protocol specified follow-up 
procedures as outlined in Section 2. The only exception to this requirement is when a participant 
withdraws consent for all study procedures, including post treatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness). 
If study treatment is discontinued prior to the participant’s completion of the study, the reason for 
the discontinuation must be documented in the participant’s medical records and entered on the 
appropriate CRF page. 
8.1.1 
Discontinuation Due to Further Progression (Confirmed Progression) 
A radiographic assessment should be performed at each scheduled tumor assessment, 4 to 6 weeks 
following initial disease progression, to determine whether there has been continued progressive 
disease or not. Participants should discontinue study therapy upon evidence of further progression, 
defined as an additional 10% or greater increase in tumor burden volume from time of initial 
progression (including all target lesions and new measurable lesions). 
The tumor burden volume from time of initial progression should be used as the reference baseline 
for comparison with the postprogression assessment. 
Any new lesion considered nonmeasurable at the time of initial progression may become 
measurable and, therefore, must be included in the tumor burden measurement according to the 
following: 
• For solid tumors: 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). 
 
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 progressive disease at the time of the initial progression 
event. 
8.1.2 
Assessment Schedule for Participants with Post-progression Treatment 
Participants should continue to receive monitoring according to the on-treatment assessments in 
Section 2. Radiographic assessment, by CT (preferred) or MRI described in Section 9.4.5, is 
required when participants continue post-progression treatment. For participants that discontinue 
post progression treatment with study therapy, no additional radiographic assessments will be 
required. 
8.1.3 
Post study Treatment Study Follow-up 
In this study, safety is a primary endpoint. Post study follow-up is of critical importance and is 
essential to preserving participant safety and the integrity of the study. Participants who 
discontinue study treatment must continue to be followed-up for collection of outcome and/or 
survival follow-up data as required and in line with Section 5.1.3.3. 


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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 
3 documented phone calls, faxes, or emails as well as lack of response by participant to 
1 registered mail letter. All attempts should be documented in the participant’s medical 
records. 
• If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death. 
• If Investigator’s use of a third-party representative to assist in the follow-up portion of the 
study has been included in the participant’s informed consent, then the Investigator may use a 
Sponsor retained third-party representative to assist site staff with obtaining participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 
• The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information. 
• If after all attempts, the participant remains lost to follow-up, then the last known alive date as 
determined by the Investigator should be reported and documented in the participant’s medical 
records. 


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9. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and timing are summarized in the Schedule of Activities. Protocol waivers 
or exemptions are not allowed. Adherence to the study design requirements, including those 
specified in the Schedule of Activities, is essential and required for study conduct. 
• Study governance considerations in terms of compliance and reporting of AEs are available in 
Appendices 2 and 3. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before enrollment. The Investigator will maintain a 
screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in the Schedule of Activities. 
• All immediate safety concerns must be discussed with BMS immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue treatment 
 
9.1 
Efficacy Assessments 
Efficacy assessments for the 
 activity of BMS-986207, alone, in combination with 
nivolumab, or in combination with nivolumab and ipilimumab will be based on tumor 
measurements, using RECIST v1.1, with CT and/or MRI, as appropriate. In Parts 1A, 1B, 2A, and 
2B, assessments will be performed at baseline, q8w (± 1 week) during the treatment period, and 
q12w for the first year after discontinuation of study drug/EOT visit. Subsequently, they will 
continue to receive tumor assessment scans as per standard of care guidelines, or at a minimum of 
every 6 months up to 2 years following the last dose of study drug, or until disease 
progression/withdrawal of study consent. In Parts 1C and 2C, contrast-enhanced CT of the chest, 
CT/MRI of the abdomen, pelvis, and all other known and/or suspected sites of disease should occur 
every 6 weeks starting from date of first dose (± 7 days) for the first 12 months (week 48), then 
every 12 weeks (± 7 days) until the end of year 2, then every 12 weeks (± 14 days) thereafter until 
disease progression or treatment discontinuation, whichever occurs later. The same imaging 
modality must be used for all assessments, per RECIST v1.1 (Appendix 5). Tumor assessment 
should be performed prior to initiating next cycle of treatment. Unconfirmed PR/CR must be 
confirmed at least 4 weeks after initial assessment finding. 
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. 
9.2 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 


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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 are specified in Appendix 3. 
9.2.1 
Time Period and Frequency for Collecting AE and SAE Information 
The collection of nonserious AE information should begin at initiation of study treatment until the 
follow-up contact, at the time points specified in the Schedule of Activities (Section 2). Nonserious 
AE information should also be collected from the start of an observational period intended to 
establish a baseline status for the participants. 
Sections 5.6.1 and 5.6.2 in the BMS-986207 IB represent the Reference Safety Information to 
determine expectedness of SAEs for expedited reporting.19 Following the participant’s written 
consent to participate in the study, all SAEs, whether related or not related to study drug, must be 
collected, including those thought to be associated with protocol-specified procedures. 
All SAEs must be collected that occur during the screening period and within 100 days of 
discontinuation of dosing. 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. Please 
note the following adverse event reporting requirements: 
• Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF section. 
• All SAEs will be recorded and reported to the Sponsor or Designee within 24 hours. 
• The Investigator will submit any updated SAE data to the Sponsor within 24 hours of this being 
available. 
 
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the Investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the Investigator must promptly notify the Sponsor. 
The method of evaluating, and assessing causality of AEs and SAEs and the procedures for 
completing and reporting/transmitting SAE reports are provided in Appendix 3. 
9.2.2 
Method of Detecting AEs and SAEs 
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a participant. In order to prevent reporting bias, participants should 
not be questioned regarding the specific occurrence of AEs. 


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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 (Section 9.2). 
• 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. 
• All SAEs and AEs (including non-serious 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 9.2.3) or for suspected cases, until SARS-CoV-2 infection is ruled-out. 
 
After the initial AE/SAE report, the Investigator is required to proactively follow-up each 
participant at subsequent visits/contacts. All SAEs, and nonserious AEs of special interest (as 
defined in Section 9.2) will be followed-up 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). 
9.2.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
product under clinical investigation are met. 
• An Investigator who receives an Investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the IB and will notify the Institutional Review Board/ Independent Ethics Committee, if 
appropriate according to local requirements. 
 
The 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 SUSAR (Suspected, Unexpected Serious 
Adverse Reaction) is a subset of SAEs that will be reported to the appropriate regulatory authorities 
and Investigators following local and global guidelines and requirements. 
9.2.5 
Pregnancy 
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 months after product administration, the Investigator must immediately notify the BMS Medical 
Monitor/designee of this event. The Investigator must also complete and forward a Pregnancy 
Surveillance Form to the BMS Designee within 24 hours of awareness of the event and in 
accordance with SAE reporting procedures described in Appendix 3. 
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 


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Surveillance Form. Protocol-required procedures for study discontinuation and follow-up must be 
performed on the participant. 
9.2.6 
Laboratory Test Result Abnormalities 
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE electronic Report Form, as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning. 
• Any laboratory test result that is clinically significant or meets the definition of an SAE 
• Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted 
• Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy 
 
It is expected that, wherever possible, the clinical rather than the laboratory term would be used 
by the reporting Investigator (eg, anemia versus low hemoglobin value). 
9.2.7 
Potential Drug-induced Liver Injury (p-DILI) 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a p-DILI event. All occurrences of p-DILIs meeting the defined 
criteria, must be reported as SAEs (see Section 9.2 for reporting details). 
Potential drug induced liver injury is defined as: 
• ALT or AST elevation > 3 x ULN 
AND 
• Total bilirubin > 2 x ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase), 
AND 
• No other immediately apparent possible causes of aminotransaminases elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic. 
 
Specifically for HCC: p-DILI is defined as: 
• Concurrent ALT ≥ 10 × ULN AND total bilirubin ≥ 2 × ULN or baseline value (if elevated 
bilirubin at study entry), AND 
• No other immediately apparent possible causes of ALT elevation and hyperbilirubinemia, 
including, but not limited to, tumor progression, acute viral hepatitis, cholestasis, pre-existing 
hepatic disease or the administration of other drug(s), herbal medications and substances 
known to be hepatotoxic. 


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This is the standard drug-induced liver injury definition across the BMS HCC program. 
The key responsibilities for investigators during p-DILI assessment include: (i) Early detection, 
medical evaluation (including the exclusion of other potential causes) and rapid laboratory 
confirmation of liver-related abnormalities, and (ii) BMS notification of p-DILI cases via SAE 
forms. Following the gathering and assessment of relevant clinical information, BMS is 
responsible for: (iii) Timely evaluation and triaging of p-DILI cases, (iv) Expedited reporting of 
p-DILI cases and (v) Expanded review of p-DILI cases including a detailed assessment of all 
available clinical information, investigations and biochemical data. 
Investigators are expected to monitor ongoing routine and ad hoc hepatic laboratory test results to 
rapidly determine whether a participant meets p-DILI criteria. They are expected to promptly 
notify BMS of all p-DILI cases. p-DILI cases may be identified by abnormal liver biochemistry 
values, whether or not they are accompanied by liver-related signs and/or symptoms. In both cases, 
expedited confirmation with repeat laboratory testing should occur within 3 business days using a 
Hepatic Laboratory Panel (ALT, AST, total bilirubin, ALP). Any participant with an abnormal 
Hepatic Laboratory Panel that meets p-DILI criteria is a candidate for study drug 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, nonexhaustively and 
by way of example only: infectious diseases (such as active hepatitis A, B and C), congenital 
diseases (such as Gilbert’s syndrome), neoplastic diseases (such as HCC), 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. 
9.2.8 
Other Safety Considerations 
Any significant worsening noted during interim or final physical examinations, including 
electrocardiogram (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 
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. 
For this study, any dose of BMS-986207 greater than the assigned dose, and considered excessive 
and medically important by the Investigator, will be considered an overdose. 
All intentional overdose taken with possible suicidal/self-harming intent must be reported as SAEs 
(see Section 9.2). 


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In the event of an overdose the Investigator or treating physician should: 
• Contact the Medical Monitor immediately 
• Closely monitor the participant for AEs/SAEs and laboratory abnormalities until BMS-986207 
can no longer be detected systemically 
• Obtain a plasma sample for PK if requested by the Medical Monitor (determined on a case by 
case basis) 
• Document the quantity of the excess dose as well as the duration of the overdosing in the CRF 
 
Decisions regarding dose interruptions or modifications secondary to an overdose will be made by 
the Investigator in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
9.4 
Safety 
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 for timing of assessments in Table 2-1, Table 2-2, Table 2-3, Table 
2-4, Table 2-5, and Table 2-6. 
9.4.2 
Vital Signs 
Refer to Schedule of Activities for timing of assessments in Table 2-1, Table 2-2, Table 2-3, Table 
2-4, Table 2-5, and Table 2-6. 
9.4.3 
Electrocardiograms 
Refer to Schedule of Activities for timing of assessments in Table 2-1, and Table 2-2. 
The effect of BMS-986207 on the 
 will be evaluated by a central reader using ECG 
data collected in triplicates and conducted during the monotherapy and combination dose 
escalation only (Part 1A and Part 1B) (eg, 1 ECG test equals 3 consecutive individual 12-lead 
ECGs performed 5 minutes apart). For the purposes of monitoring participant safety, the 
Investigators will review the 12-lead ECGs using their site’s standard ECG machines throughout 
the study. The 
will be applied to each ECG reading. 
9.4.4 
Clinical Safety Laboratory Assessments 
Investigators must document their review of each laboratory safety report. 
A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests performed on Day -1 must be available prior to dosing. 
The laboratory tests that will be performed for study participants are shown in Table 9.4.4-1. 
Results of all laboratory tests required by this protocol must be provided to the Sponsor, recorded 
either on the laboratory pages of the CRF or by another mechanism as agreed upon between the 
Investigator and BMS (eg, provided electronically). If the units of a test result differ from those 
printed on the CRF, the recorded laboratory values must specify the correct units. Any abnormal 


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laboratory test result considered clinically significant by the Investigator must be recorded on the 
appropriate AE page of the CRF. 
Table 9.4.4-1: 
Clinical Laboratory Assessments 
 
Hematology 
Hemoglobin and hematocrit 
Total leukocyte count, including differential 
Platelet count 
Prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR) (at 
screening and D0 for Retreatment eligible participants only) 
Serum Chemistry 
Aspartate aminotransferase 
Alanine aminotransferase 
Total bilirubin 
Direct bilirubin (reflex only if total bilirubin is 
elevated) 
Alkaline phosphatase 
Lactate dehydrogenase 
Creatinine 
Blood urea nitrogen 
Uric acid 
Glucose 
Lipase 
Amylase 
Gamma glutamyl transferase (reflex only when AST, 
ALT are outside of normal range) 
Thyroid stimulating hormone 
Free T3 and T4 (screening and reflex only when TSH 
is outside of normal range) 
Total protein 
Albumin 
Sodium 
Potassium 
Chloride 
Calcium 
Phosphorus 
Magnesium 
Creatinine clearance (Cockcroft-Gault method) 
(screening only D0 for Retreatment eligible 
participants) 
Urinalysis screening and D0 for Retreatment eligible participants only, unless clinically indicated 
Protein 
Glucose 
Blood 
Leukocyte esterase 
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 (screening, and as 
mandated by local requirement), and hepatitis C RNA (reflex only for positive serology results) 
For HCC participants: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, 
hepatitis B DNA PCR, hepatitis C antibody and hepatitis C RNA PCR, and hepatitis D antibody testing for those 
with concurrent hepatitis B infection 
Other Analyses 
Pregnancy test (WOCBP only: screening, predose, discharge). 
Follicle stimulating hormone (FSH) (screening only and women only) 
Abbreviations: DNA, deoxyribonucleic acid FSH, follicle stimulating hormone; HCC, hepatocellular carcinoma; HIV, 
human immunodeficiency virus; PCR, polymerase chain reaction; PT, prothrombin time; RNA, ribonucleic acid; 
WOCBP, Women of childbearing potential 


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9.4.5 
Imaging Assessment for the Study 
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. 
Central assessments are not planned for this study, however copies of all scans will be stored for 
possible future central analysis, if determined to be necessary by BMS. At the Sponsor’s discretion, 
scans may be collected centrally to be reviewed by independent radiologists. 
Computer Tomography/Magnetic Resonance Imaging 
Contrast-enhanced CT scans acquired on dedicated CT equipment is preferred for this study. CT 
with contrast of the chest, abdomen, and pelvis are to be performed for tumor assessments. CT 
scans should be acquired with 5 mm slices with no intervening gap (contiguous). 
Should a participant have a contraindication for CT IV contrast, a noncontrast CT of the chest and 
a contrast enhanced MRI of the abdomen and pelvis may be obtained. MRIs should be acquired 
with slice thickness of < 5 mm with no gap (contiguous). 
Every attempt should be made to image each participant using an identical acquisition protocol on 
the same scanner for all imaging timepoints. 
Use of CT component of a PET/CT scanner: 
Combined modality scanning such as with fluorodeoxyglucose (FDG)-PET/CT is increasingly 
used in clinical care, and is a modality/technology that is in rapid evolution; therefore, the 
recommendations outlined here may change rather quickly with time. At present, low dose or 
attenuation correction CT portions of a combined FDG-PET/CT are of limited use in anatomically 
based efficacy assessments and it is therefore suggested that they should not be substituted for 
dedicated diagnostic contrast enhanced CT scans for anatomically based RECIST measurements. 
However, if a site can document that the CT performed as part of a FDG-PET/CT is of identical 
diagnostic quality to a diagnostic CT (with IV and oral contrast) then the CT portion of the FDG- 
PET/CT can be used for RECIST 1.1 measurements. Note, however, that the FDG-PET portion of 
the CT introduces additional data which may bias an Investigator if it is not routinely or serially 
performed. 
MRI Brain 
A MRI of the brain is required at screening if a participant is symptomatic or has a history of brain 
metastasis. Participants with a history of brain metastasis should have surveillance MRI 
approximately every 12 weeks, or sooner if clinically indicated. 
MRI brain scans during on-study treatment and follow-up periods are required only if there is a 
prior history of lesions present at screening, or as clinically indicated for new signs and symptoms 
that suggest CNS involvement. 


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Bone Scan 
Bone scans can be used to evaluate the presence of metastatic disease, and should not be used as 
modality for assessment of measurable metastatic disease. 
9.5 
Pharmacokinetics and Immunogenicity 
The PK of BMS-986207 will be derived from serum concentration versus time data when 
appropriate. The PK parameters that will be assessed, following the intensive PK collection, are 
shown in Table 9.5-1. 
Table 9.5-1: 
Pharmacokinetic Parameters 
 
Parameters 
Definition 
 
Cmax 
Maximum observed serum concentration 
Tmax 
Time of maximum observed serum concentration 
AUC(0-T) 
Area under the serum concentration-time curve from time zero to time of last quantifiable 
concentration 
AUC(TAU) 
Area under the concentration-time curve in one dosing interval 
Parameters that may potentially be assessed following the dose administration in Cycle 2 Day 1 
Ctau 
Observed concentration at the end of a dosing interval 
CLT 
Total body clearance 
Css-avg 
Average concentration over a dosing interval (AUC[TAU]/tau) 
AI_TAU 
Ratio of an exposure measure at steady state to that after the first dose (exposure measure 
includes AUC[TAU]) 
T-HALFeff 
Effective elimination half-life that explains the degree of accumulation observed for a 
specific exposure measure (exposure measure includes AUC[TAU]) 
Parameter to be reported separately 
 
 
Individual participant PK parameter values will be derived by noncompartmental methods by a 
validated PK analysis program. Actual times will be used for the analyses. 
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 and immunogenicity. Further details of blood collection and processing will be 
provided to the site in the Laboratory Manual. 
All predose samples should preferably be taken within 30 minutes before the start of any dose 
infusion. In Part 1C and 2C, as shown in Table 9.5-4 end-of-infusion (EOI) PK samples for BMS- 
986207, nivolumab, and ipilimumab should be taken immediately following the last drug infusion 
(preferably within 5 minutes after end of the infusion) on the contralateral arm (ie, the arm not 
used for the infusion). Since the EOI PK sample is drawn with the intent of accurately estimating 
the maximum concentration (Cmax) of the drug, draw the EOI-PK after all the study drug has been 


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infused. If the site infuses drug without a flush, then collect the EOI-PK sample within 
approximately 5 minutes after end of infusion. If a flush is administered to clear the IV lines of the 
drug and to ensure delivery of the entire drug dose, then draw the EOI-PK sample within 
approximately 5 minutes after the end of the flush. If the end of infusion is delayed to beyond the 
nominal infusion duration, the collection of this sample should also be delayed accordingly. On- 
treatment PK samples are intended to be drawn relative to actual dosing days. For Part 1A, 1B, 
2A, and 2B, EOI PK samples for BMS-986207 or nivolumab should be taken following the 
instructions noted in Table 9.5-2 and Table 9.5-3. 
If a dose occurs on a different day within the cycle due to delays or minor schedule adjustments, 
PK and ADA 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, an additional predose sample 
should be collected. ‘Event Kit - Dose Delay’ should be used in the event that a predose PK sample 
was obtained and the participant is not dosed on that same day. Following consensus of the 
Investigator and the BMS Medical Monitor, an additional PK and/or ADA sample may be taken 
following a SAE or important medical event using an ‘Event Kit - AE’. Further details of sample 
collection, processing, and shipment will be provided in the Laboratory Manual. 


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Table 9.5-2: 
Pharmacokinetic and Immunogenicity Sampling Schedule for BMS-986207 
in q2w 
Dose Panels in Part 1A, 1B, 2A, and 2B 
 
Study Day of 
Sample Collection 
(1 cycle = 8 weeks) 
Event 
Time (Relative to 
Start of Infusion) 
Hour: Min 
BMS-986207 
Blood Sample 
(All Participants) 
BMS-986207 
ADA Samples 
(All participants) 
C1D1 
Predose 
00.00 
X 
X 
EOIb 
30 to 60 min 
X 
4:00 
X 
C1D2 
24:00 
X 
C1D5c 
96:00 
X 
C1D8d 
168:00 
X 
C1D15 
Predosea 
00: 00 
X 
X 
EOIb 
30 to 60 min 
X 
4:00 
X 
C1D29 
Predosea 
00: 00 
X 
X 
EOIb 
30 to 60 min 
X 
C2D1 
Predosea 
00: 00 
X 
EOIb 
30 to 60 min 
X 
4:00 
X 
C2D2 
24:00 
X 
C2D5c 
96:00 
X 
C2D8d 
168:00 
X 
C2D15 
Predosea 
00: 00 
X 
C2D29 
Predosea 
00: 00 
X 
X 


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Table 9.5-2: 
Pharmacokinetic and Immunogenicity Sampling Schedule for BMS-986207 
in q2w 
Dose Panels in Part 1A, 1B, 2A, and 2B 
 
Study Day of 
Sample Collection 
(1 cycle = 8 weeks) 
Event 
Time (Relative to 
Start of Infusion) 
Hour: Min 
BMS-986207 
Blood Sample 
(All Participants) 
BMS-986207 
ADA Samples 
(All participants) 
C3D1 
Predosea 
00: 00 
X 
X 
C3D29 
Predosea 
00: 00 
X 
C4D1 
Predosea 
00: 00 
X 
X 
C5D1 
Predosea 
00: 00 
X 
X 
EOT 
X 
X 
30-day follow-up 
X 
X 
60-day follow-up 
X 
X 
PK SAE event 
‘PK EVENT Kit - AE’ should be used when PK and/or ADA sample is taken following a SAE or important medical 
PK dose delay 
‘PK DELAY Kit - Dose Delay’ should be used to collect an additional predose sample if a predose sample was already collected for the 
same visit but the dose was subsequently delayed 
Retreatment 
PK/ADA sampling to be done predose on Day 1 of all cycles; @ EOT and 30 and 60 day followup visits. 
No dose delay PK sampling to be done in Retreatment 
Abbreviations: ADA, anti-drug antibody, BMS, Bristol-Myers Squibb; EOI, end of infusion, EOT, end of treatment 
a Predose: All predose samples for 
 BMS-986207 should be taken prior to the start of the 
 infusion. If the predose sample has been taken, 
however, the unscheduled, missing, or delayed dose occurs, an additional predose sample shall be taken. 
b EOI samples for both
 BMS-986207 should be collected immediately following the infusion (preferably within 2 minutes of stopping the infusion). 
If the end of infusion is delayed to beyond the nominal infusion duration, the collection of this sample should also be delayed accordingly. 
c The 96:00 hour sample may be taken between 72:00 and 120:00 hours post dose 
d The 168:00 hour sample may be taken between 144:00 and 192:00 hours post dose 


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Table 9.5-3: 
Pharmacokinetic and Immunogenicity Sampling Schedule for BMS-986207 
in q4w 
Dose Panels in Parts 1A, 1B, 2A, and 2B 
 
Study Day of 
Sample Collection 
(1 cycle = 8 weeks) 
Event 
Time (Relative to 
Start of Infusion) 
Hour: Min 
BMS-986207 
Blood Sample 
(All Participants) 
BMS-986207 
ADA Samples 
(All participants) 
C1D1 
Predose 
00.00 
X 
X 
EOIb 
30 to 60 min 
X 
4:00 
X 
C1D2 
24:00 
X 
C1D5 c 
96:00 
X 
C1D8 d 
168:00 
X 
C1D15 
336.00 
X 
C1D22 
504.00 
X 
C1D29 
Predosea 
00: 00 
X 
EOIb 
30 to 60 min 
X 
C2D1 
Predosea 
00: 00 
X 
X 
EOIb 
30 to 60 min 
X 
C2D29 
Predosea 
00:00 
X 
EOI 
30 to 60 min 
X 
C3D1 
Predosea 
00: 00 
X 
X 
EOIb 
30 to 60 min 
X 
4:00 
X 
C3D2 
24:00 
X 
C3D5 c 
96:00 
X 


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Table 9.5-3: 
Pharmacokinetic and Immunogenicity Sampling Schedule for BMS-986207 
in q4w 
Dose Panels in Parts 1A, 1B, 2A, and 2B 
 
Study Day of 
Sample Collection 
(1 cycle = 8 weeks) 
Event 
Time (Relative to 
Start of Infusion) 
Hour: Min 
BMS-986207 
Blood Sample 
(All Participants) 
 
 
 
 
 
BMS-986207 
ADA Samples 
(All participants) 
C3D8 d 
168:00 
X 
C3D15 
336: 00 
X 
C3D22 
504: 00 
X 
C3D29 
Predosea 
00: 00 
X 
C4D1 
Predosea 
00: 00 
X 
X 
C5D1 
Predosea 
00: 00 
X 
X 
EOT 
X 
X 
30-day follow-up 
X 
X 
60-day follow-up 
X 
X 
PK SAE Event 
‘PK EVENT Kit - AE’ should be used when PK and/or ADA sample is taken following a SAE or important medical 
PK Dose Delay 
‘PK DELAY Kit - Dose Delay’ should be used to collect an additional predose sample if a predose sample was already collected for 
the same visit but the dose was subsequently delayed 
Retreatment 
PK/ADA sampling to be done predose on Day 1 of all cycles; @ EOT and 30 and 60 day followup visits. No dose delay PK sampling 
to be done in Retreatment 
Abbreviations: ADA, anti-drug antibody, BMS, Bristol-Myers Squibb; EOI, end of infusion, EOT, end of treatment 
a Predose: All predose samples for 
 BMS-986207 should be taken prior to the start of the 
 infusion. If the predose sample has been taken, 
however, the unscheduled, missing, or delayed dose occurs, an additional predose sample shall be taken. 
b EOI samples for both
 BMS-986207 should be collected immediately following the infusion (preferably within 2 minutes of stopping the infusion). 
If the end of infusion is delayed to beyond the nominal infusion duration, the collection of this sample should also be delayed accordingly. 
c The 96:00 hour sample may be taken between 72:00 and 120:00 hours post dose 
d The 168:00 hour sample may be taken between 144:00 and 192:00 hours post dose 


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Table 9.5-4: 
Pharmacokinetic and Immunogenicity Sampling Schedule for BMS-986207, 
in Parts 1C and 2C 
 
Study Day of 
Sample Collection 
(1 cycle = 6 weeks) 
Event 
Time Relative to 
Dose 
Hour: Min 
BMS-986207 
PK Serum 
Sample 
BMS-986207 
(ADA) Serum 
Samples 
C1D1 
Predosea 
00.00 
X 
X 
EOIb 
X 
4:00 
X 
C1D2 
24:00 
X 
C1D5 c 
96:00 
X 
C1D8 d 
168:00 
X 
C1D15 
336.00 
X 
C1D22 
Predosea 
00: 00 
X 
C1D29e 
168:00 
X 
C2D1 
Predosea 
00: 00 
X 
X 
C2D22 
Predosea 
00:00 
X 
C3D1 
Predosea 
00: 00 
X 
X 
EOIb 
X 
4:00 
X 
C3D2 
24:00 
X 
C3D5 
96:00 
X 
C3D8 
168:00 
X 
C3D15 
336: 00 
X 


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Table 9.5-4: 
Pharmacokinetic and Immunogenicity Sampling Schedule for BMS-986207, 
in Parts 1C and 2C 
 
Study Day of 
Sample Collection 
(1 cycle = 6 weeks) 
Event 
Time Relative to 
Dose 
Hour: Min 
BMS-986207 
PK Serum 
Sample 
BMS-986207 
(ADA) Serum 
Samples 
C3D22 
Predosea 
00: 00 
X 
C4D1 
Predosea 
00: 00 
X 
X 
Every 4 cycles 
starting at Cycle 5 
Day 1 until Cycle 
17 (C5D1; C9D1; 
C13D1; C17D1) 
Predosea 
00: 00 
X 
X 
Abbreviations: ADA, anti-drug antibody, BMS, Bristol-Myers Squibb; C, cycle; D, day; EOI, end of infusion; PK, pharmacokinetics. 
a Predose: All predose samples for 
BMS-986207 should be taken prior to the start of the 
 infusion. If the predose sample 
has been taken, however, the unscheduled, missing, or delayed dose occurs, no additional predose sample shall be taken. 
b EOI samples for 
BMS-986207 should be collected immediately following the last drug infusion (preferably within 5 minutes of 
after end of infusion) on the contralateral arm (i.e. the arm not for the infusion). Since the EOI PK sample is drawn with the intent of accurately estimating the 
maximum concentration (Cmax) of the drug, draw the EOI-PK when all the study drug has been infused. If the site infuses drug without a flush, then collect the 
EOI-PK sample within approximately 5 minutes after end of infusion. If a flush is administered to clear the IV lines of the drug and to ensure delivery of the 
entire drug dose, then draw the EOI-PK sample within approximately 5 minutes after end of the flush. If the end of infusion is delayed to beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly. 
c The 96:00 hour sample may be taken between 72:00 and 120:00 hours post dose 
d The 168:00 hour sample may be taken between 144:00 and 192:00 hours post dose 
e PK sample collection for C1D29 is strongly recommended to be synchronized (collected on the day) with biopsy collection for C1D29. 


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The serum samples will be analyzed for BMS-986207 
ADA (anti-BMS-986207 
antibodies 
). 
9.5.1 
Pharmacokinetic Sample Analyses 
Validated immunoassays will be used to measure concentrations of BMS-986207, 
in serum. 
9.5.2 
Immunogenicity Sample Analysis 
Validated immunoassays will be used to assay samples for the presence of, and measure titers of 
 
 
 
 
 
 
 
 
 
 
 
9.7 
Pharmacogenomics 
Circulation tumor DNA (ctDNA) and T cell Repertoire analysis may be performed to assess the 
association of these tumor-specific genetic features with clinical outcome. More details about these 
assays are described 
9.7.1 
ADME Sampling 
A whole blood sample will be drawn at baseline (Day 1) for potential analysis of DNA variants in 
absorption, distribution, metabolism and excretion (ADME)-related genes (Table 2-2, Appendix 
7). Paxgene sampling will be performed in accordance with the Laboratory Manual. Further details 
of blood collection and processing will also be provided to the site in the Laboratory Manual. 
anti-BMS-986207, 
antibodies in serum. 


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10. 
STATISTICAL CONSIDERATIONS 
10.1 
Sample Size Determination 
10.1.1 
Dose Escalation 
During the dose escalation phase, an adaptive dose escalation scheme (BLRM for monotherapy 
and BLRM-copula for combination therapy) employing the escalation with overdose control 
(EWOC) principle will be used. The 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. 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 unsafe dose by ensuring the posterior probability of the DLT rate 
exceeding 33% at any dose is capped at 30%. 
The maximum number of participants treated will be 35 for each dose escalation part 
(BMS-986207 monotherapy [Part 1A], BMS-986207 in combination with nivolumab [Part 1B]). 
However, simulation studies with various scenarios show that the expected number of 
DLT-evaluable participants is no more than approximately 20. (Appendix 12). 
Approximately 3 participants will be treated at the starting dose levels of BMS-986207 or 
BMS-986207 in combination with nivolumab. While the BLRM/BLRM-copula will use DLT 
information from the DLT period only, clinical assessment will take into consideration of the 
totality of available data including PK/
 from all treated participants encompassing monotherapy 
and combination therapy, in assigning a dose level for the next cohort of 3 participants. At least 


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6 DLT-evaluable participants will be treated at the MTD. At most 12 DLT-evaluable participants 
will be treated at each dose level. Additional participants (up to a total of 15) may be treated at or 
any dose level below the estimated MTD for further evaluation of safety, PK, 
parameters as 
required. 
The model-recommended MTD is the dose that satisfies the following three conditions: 
1) The empirical posterior probability that the “DLT rate of 16% - <33%” is greater than a 
pre-specified value (i.e., 50%); 
2) This probability needs to be the largest amongst the dose levels that satisfy the EWOC 
condition (i.e., the probability that the “DLT rate > 33%” must be less than 30%); 
3) Minimum number of participants (i.e., 6) were treated at this dose level. 
 
The final recommended MTD/RP2D will be based on the recommendation from the 
BLRM/BLRM-copula and overall clinical assessment of all available safety, PK, 
 and efficacy 
data. Lower doses of BMS-986207 may be tested if none of the planned doses are found to be 
tolerable as monotherapy or in combination with nivolumab. Such decisions will be made after 
discussion and agreement between the Investigators and the BMS Medical Monitor. 
10.1.2 
Safety Evaluation Phase (Part 1C) 
The safety of triplet therapy will be evaluated across the tumor types in up to approximately 18 
treated participants per dose level who receive triplet therapy based on the number of DLTs 
observed. Assuming a DLT target of 30% (24%, 36%) the BOIN design framework will be used 
to guide decisions in this setting, including potential de-escalation to a lower dose of BMS-986207 
in combination with both nivolumab and ipilimumab, if warranted by the observed results (see 
Table 5.1.2.6-1). In addition, calculations related to the risk of a BMS-986207 dose level selected 
as tolerable are shown expressed as a posterior probability of toxicity in Section 5.1.2.2 (Table 
5.1.2.6-2). 
10.1.3 
Cohort Expansion 
The purpose of cohort expansion is to gather additional safety, tolerability, preliminary efficacy, 
PK, 
 information regarding BMS-986207 alone or in combination with nivolumab. 
However, the sample size is strictly based on efficacy, specifically on the target ORR relative to 
historic response rate. 
10.1.3.1 
Cohort Expansion in Part 2A and Part 2B 
Part 2A will be an expansion phase of the BMS-986207 monotherapy in participants with CRC at 
1 dose level. Part 2B will be an expansion phase for BMS-986207 in combination with nivolumab 
in participants with CRC, HCC, and ovarian cancer. Each disease cohort expansion will be handled 
independently and there will be no multiplicity adjustment. 
The Fleming 2-stage design framework will be used as a guide for the expansion cohorts in 
Parts 2A and 2B.42,43 The total sample size for each expansion cohort will be calculated to provide 
a reasonable false-positive rate (FPR) <10% and false-negative rate (FNR) < 10% based on 


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assumptions of true (target) and historic ORR for each indication. The assumed historic and target 
response rates may change over time and may need to be adjusted by the time when the response 
data from this study are available. The sample size and operational characteristics of using a 
2-stage design, as an example, are provided in Table 10.1.3.1-1, although this is not used for 
statistical hypothesis testing. Using a 2-stage design provides an option to stop early for futility, 
as well as a signal of preliminary 
 activity for strong-go, early on. Enrollment may 
continue into Stage 2, while the planned number of participants for Stage 1 are followed for 
efficacy evaluable tumor assessments. There will be no stopping of a disease cohort for efficacy, 
although an early plan for the next stage of clinical development may be initiated. Sample sizes 
may need to be increased in order to explore differential responses between 
expressed 
and nonexpressed groups. 
Guided by Table 10.1.3.1-1, approximately 11 CRC participants will be treated with BMS-986207 
monotherapy in Stage 1. Assuming the true response rate is 20% in this population when treated 
with BMS-986207 monotherapy, if there are 2 or more responses in 11 participants, it may trigger 
an expansion of the clinical development plan after careful evaluation of all available data 
including duration of response and safety profile. The probability to observe such a favorable 
response is approximately 68% if in fact the treatment is efficacious. If there is no response in 
11 treated participants, the cohort may be stopped for futility. The probability of early stopping for 
futility is approximately 80% if in fact the treatment is inefficacious, eg, 2%. If there is 1 response, 
an additional 13 participants may be treated to collect more data. At the end of Stage 2, if there is 
1 or no response, further clinical development may not be warranted. If there are 2 or more 
responses, it may show evidence of treatment efficacy. 
Table 10.1.3.1-1:   Example of a 2-stage Design Characteristics 
 
 
Treatment 
Indication 
Historic/ 
Target 
Rate 
Stage 
 Cum 
Sample 
Size 
Conclude 
Inefficacy 
if Ra 
Conclude 
Efficacy 
if Ra 
PETbfor 
Futility 
(%) 
PEEc 
for 
Efficacy 
 
 
 
 
 
 
 
 
 
 
Abbreviations: BMS = Bristol-Myers Squibb, CRC, colorectal cancer; FNR, false-negative rate; FPR, false-positive 
rate; HCC, hepatocellular carcinoma; nonMSI-H, nonmicrosatellite instability-high; PEE, probability of early 
efficacy; PET, probability of early termination 
a R is the cumulative number of responses at the end of stage; all FPRs and FNRs < 10% 
b Probability of early termination if the historic rate is true 
c Probability of early efficacy signal if the target rate is true 
(%) 
(%) 
BMS-986207 
CRC 
2/20 
1 
11 
0 
≥ 2 
80 
68 
(nonMSI-H) 
2 
24 
≤ 1 
≥ 2 
BMS-986207 
HCC, 
10/30 
1 
15 
≤ 1 
≥ 4 
and nivolumab 
ovarian 
cancer 
2 
26 
≤ 5 
≥ 6 
55 
70 
CRC 
2/30 
1 
7 
0 
≥ 2 
87 
67 
(nonMSI-H) 
2 
15 
≤ 1 
≥ 2 


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10.1.3.2 
Cohort Expansion in Part 2C 
Part 2C will be an expansion phase of the BMS-986207 in combination with nivolumab and 
ipilimumab in participants with advanced treatment-naive NSCLC whose tumor cells express 
≥ 1% PD-L1. 
The sample size for Part 2C is based on assessing an initial 
 activity signal as estimated 
by the ORR following treatment in the triplet combination arm and to provide additional 
information for the safety profile in the 1L NSCLC population. 
One or two doses are planned to be evaluated in Part 2C and a minimum of 20 participants are 
enrolled per dose level of BMS-986207. So approximately 40 evaluable participants in total with 
1L NSCLC with tumor cell PD-L1 expression of ≥ 1% will be treated with BMS-986207 in 
combination with nivolumab and ipilimumab. 
In the event pre-existing PD-L1 results are not confirmed by the central lab test, additional 
participants (up to 20%) will be enrolled to achieve a sample size of 40 evaluable participants. 
The following Bayesian posterior probability (PP) criteria will be used to assess signal of anti- 
tumor activity with benchmark of 36% as unfavorable ORR and 56% as desirable ORR:44,45 
• An 
activity signal is based on ORR satisfying the dual criteria: PP (ORR ≥ 0.56 ) 
≥ 40% and PP (ORR ≥ 0.36) ≥ 80% 
• A lack of activity signal is based on ORR meeting the criterion: PP (ORR ≥ 0.36) < 20% 
A beta prior distribution beta (1, 1) for ORR and Binomial Bin (n, ORR) likelihood for number of 
responders were used. 
Based on the above criteria, for each dose level a total of 20 evaluable participants in Part 2C will 
provide approximately 6.5% chance to show 
 activity when a true ORR is 36%, and at 
least 63% chance of showing activity signal if the true ORR is 56% or more (see Table 10.1.3.2- 
1) 
The ORR thresholds for efficacy signal (responders ≥ 11/20) and lack of efficacy (≤ 6/20) and the 
operating characteristics of the posterior probability criteria are shown in Table 10.1.3.2-1. 


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Table 10.1.3.2-1: 
Operating characteristics of criteria for antitumor activity by ORR 
 
Sample Size 
ORR 
PP (Activity) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ORR, objective response rate; PP: posterior probability 
 
 
In addition, to the above, Table 10.1.3.2-2 summarizes the 80% exact CI for various ORRs for 
combination therapy with sample sizes of 20, 22, 24, and 26. For example, 11 responders will need 
to be observed in 20 evaluable participants respectively, (an observed ORR ≥ 55%) for the lower 
bound of the 80% CI to exclude a 36% ORR. 
True 
PP (No Activity) 
PP(Inconclusive) 
Responder Cutoff 
Activity/ No 
Activity 
20 
0.3 
0.017 
0.416 
0.566 
11/6 
20 
0.36 
0.065 
0.217 
0.718 
11/6 
20 
0.5 
0.412 
0.021 
0.567 
11/6 
20 
0.56 
0.626 
0.005 
0.369 
11/6 
20 
0.6 
0.755 
0.002 
0.243 
11/6 
22 
0.3 
0.014 
0.313 
0.673 
12/6 
22 
0.36 
0.058 
0.14 
0.801 
12/6 
22 
0.5 
0.416 
0.008 
0.576 
12/6 
22 
0.56 
0.64 
0.002 
0.358 
12/6 
22 
0.6 
0.772 
0 
0.228 
12/6 
24 
0.3 
0.012 
0.389 
0.6 
13/7 
24 
0.36 
0.053 
0.182 
0.765 
13/7 
24 
0.5 
0.419 
0.011 
0.569 
13/7 
24 
0.56 
0.653 
0.002 
0.345 
13/7 
24 
0.6 
0.787 
0.001 
0.212 
13/7 
26 
0.3 
0.009 
0.46 
0.53 
14/8/ 
26 
0.36 
0.048 
0.226 
0.726 
14/8 
26 
0.5 
0.423 
0.014 
0.563 
14/8 
26 
0.56 
0.664 
0.003 
0.333 
14/8 
26 
0.6 
0.801 
0.001 
0.199 
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Table 10.1.3.2-2: 
Potential ORR in 1L NSCLC ( ≥ 1% PD-L1) and Exact 80% CI 
Sample size 
Number of Responders 
ORR 
80% Exact CI 
20 
10 
0.5 
[0.34, 0.66] 
11 
0.55 
[0.38, 0.71] 
13 
0.65 
[0.48, 0.79] 
14 
0.7 
[0.53, 0.83] 
22 
11 
0.5 
[0.35, 0.65] 
12 
0.55 
[0.39, 0.70] 
14 
0.64 
[0.48, 0.78] 
16 
0.73 
[0.57, 0.85] 
24 
12 
0.5 
[0.35, 0.65] 
13 
0.54 
[0.39, 0.69] 
15 
0.63 
[0.47, 0.75] 
17 
0.71 
[0.56, 0.83] 
26 
13 
0.5 
[0.36, 0.64] 
14 
0.54 
[0.40, 0.68] 
16 
0.62 
[0.47, 0.75] 
18 
0.69 
[0.55, 0.81] 
Abbreviations: 1L NSCLC, first-line non-small cell lung cancer; CI, confidence interval; ORR, objective response 
rate; PD-L1, programmed cell death ligand 1. 
 
10.2 
Populations for Analyses 
For purposes of analysis, the populations in are defined in Table 10.2-1. 
Table 10.2-1: 
Population for Analyses 
 
Population 
Description 
 
Enrolled 
All participants who sign informed consent and are registered into the IRT 
NSCLC efficacy 
All treated participants in Part 2C with PD-L1 ≥ 1% by central lab 
Treated 
All participants who take at least 1 dose of study treatment. 
All treated participants with measurable disease at baseline and one of the 
Response-evaluable 
following: (a) at least 1 post baseline tumor assessment, (b) clinical progression, 
(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 
 
Abbreviations: IRT, Interactive Response Technology. 


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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. 
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 response-evaluable 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, 
will be described in the Statistical Analysis Plan. 


 
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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 per RECIST v1.1 
BOR for a participant will be assessed per RECIST v1.1 by Investigator 
Estimate of ORR and corresponding 2-sided exact 95% CI using the 
Clopper-Pearson method by treatment for each tumor type (Parts 2A and 
2B). 
Estimate of ORR and corresponding 2-sided exact 80% CI using the 
Clopper-Pearson method by treatment for 1L NSCLC with PD-L1 
expression ≥ 1% by central lab (Part 2C). 
Median DOR 
DOR for a participant with a BOR of CR or PR is defined as the time between the 
date of first response and the date of the first objectively documented tumor 
progression per RECIST v1.1 or death, whichever occurs first. 
Median duration of response using 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 and treatment (Parts 1A, 2B, and 2C) 
PFSR at 24 weeks 
PFS for a participant is defined as the time from the first dosing date (Part 1, Part 
2A, and Part 2B)/randomization date (Part 2C) 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 95% CI will be 
derived based on Greenwood formula by treatment for each tumor type. 
Abbreviations: BOR, best overall response; CI, confidence interval; CR, complete response; DOR, duration of response; ORR, overall response rate; PFS, 
progression free survival; PFSR, progression free survival rate; PR partial response; RECIST, Response Evaluation Criteria In Solid Tumors 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.3.2 
Safety Analyses 
All safety analyses will be performed on the treated population. 
 
Endpoint 
Statistical Analysis Methods 
Incidence of DLTs, AEs, SAEs, AEs leading to 
discontinuation, and death 
AEs will be graded according to CTCAE v4.03 
 
 
 
Laboratory abnormalities 
Laboratory values will be graded according to 
CTCAE v4.03. 
DLT rate by dose level, frequency distribution of treated 
participants with AE using the worst CTC grade. Participants 
will only be counted (1) once at the PT level, (2) once at the 
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 shift table using the worst CTC grade on treatment 
per participant 
 
 
Abbreviations: AE, adverse event; CTC, common terminology criteria; CTCAE, common terminology criteria for 
adverse events; DLTs, dose-limiting toxicities; PT, preferred term; SAE, serious adverse event. 
In addition, continuous safety monitoring for toxicity will be conducted in the NSCLC Expansion 
Phase 2C as described in Section 10.3.8. 
10.3.3 
Pharmacokinetic Analyses for BMS-986207, Nivolumab, and Ipilimumab 
 
Endpoint 
Statistical Analysis Methods 
 
BMS-986207 
 
Cmax, AUC(0-T), AUC(TAU), Ctau, CLT, Css-avg, AI_AUC, 
Summary statistics: geometric means and 
and T-HALFeff_AUC 
coefficients of variation 
 
Cmax, AUC(0-T), AUC 
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 
 
Nivolumab and Ipilimumab 
 
Abbreviations: AI_AUC, accumulation index ratio of AUC at steady state to that after the first dose; 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; CI, confidence interval; CLT, total body clearance; Cmax, 
maximum observed concentration; Css-avg, average concentration over a dosing interval (AUC(TAU)/tau); 
Ctau, observed concentration at the end of a dosing interval; 
T-HALFeff, effective elimination half-life that explains the degree of accumulation observed for a specific exposure 
measure; Tmax, time of maximum observed concentration. 


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PK time-concentration data may be pooled with data from other studies for population PK analysis, 
which will be presented in a separate report. 
10.3.4 
Immunogenicity 
 
Endpoint 
Statistical Analysis Methods 
Incidence of ADA to BMS-986207, 
 
Baseline ADA-positive participant is defined as a participant 
who has an ADA-detected sample at baselinea ADA-positive 
participant is a participant with at least 1 ADA-positive sample 
relative to baseline after initiation of the treatment 
Abbreviations: ADA, anti-drug antibody. 
Frequency distribution of baseline ADA- 
positive participants and ADA-positive 
participants after initiation of the treatment for 
each of BMS-986207, 
. 
a Baseline sample is the last sample before initiation of the treatment. 
 
 
 
 
 
 
 
 
 
 
 
 
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 (Part 1A). The details of ECG data analysis will be provided in the 
SAP. 
10.3.7 
Other Analyses 
analyses will be described in detail in the statistical analysis plan 
finalized before database lock. 
 at 1 year will be analyzed similarly to PFSR. The population 
PK 
 analysis may be presented separately from the main clinical study report. 
10.3.8 
Interim Analyses for Parts 2A, 2B, and 2C 
The expansion phase of this study (Part 2A and Part 2B) employs a 2-stage design framework. 
Therefore, there will be an interim analysis as planned when an adequate number of participants 
have response-evaluable data. Additional interim analyses may also be performed for 
administrative purposes or publications. No formal inferences requiring any adjustment to 
statistical significance level will be performed. 
For Part 2C, interim analyses may also be performed for administrative purposes or publications 
prior to the final database lock. No formal inferences requiring any adjustment to statistical 
significance level will be performed. Continuous safety monitoring will be implemented in Part 


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2C to further evaluate the safety of the triplet combination in the NSCLC population, in addition 
to that in Part 1C, as described below. 
A Bayesian framework will be utilized for continuous monitoring of toxicity in Part 2C based on 
AEs meeting DLT criteria.46 Observed incidence rates of treatment-related toxicities meeting DLT 
criteria (defined in Section 7.4.1) will be evaluated relative to a boundary (number of DLTs) 
associated with higher chance of the true DLT rate exceeding 33%. 
Bayesian safety monitoring boundaries are established using a non-informative 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 2C 
participants and n is the subset of these m participants who experience treatment-related toxicities 
meeting DLT criteria. All treated Part 2C participants are considered evaluable. The criterion for 
excess toxicity is based on a posterior probability (PP) of treated Part 2C participants with 
toxicities meeting DLT criteria > 33% | cumulative data exceeding 80%. If the criterion is met 
during continuous monitoring in Part 2C, there is greater than 80% PP that the DLT rate exceeds 
33%; based on the observed data, the dose level may be re-evaluated and, based on the totality of 
data, a lower dose may be administered to the remaining participants. The cutoff number of 
participants with DLT needed to meet the criterion depends on the number of evaluable 
participants, with a final boundary of 14 participants with a DLT out of 37 or more. 
Table 10.3.8-1: 
Safety Monitoring Boundaries for AEs Meeting DLT Criteria in 
Part 2C 
 
Number of evaluable participants 
Minimum Number of participants with AE meting DLT criteria 
4 -6 
3 
7-8 
4 
9-11 
5 
12-14 
6 
15-17 
7 
18-19 
8 
20-23 
9 
24-26 
10 
27-29 
11 
30-32 
12 
33-36 
13 
37-39 
14 
Abbreviations: AE = adverse event; DLT, dose limiting toxicity. 


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32 Ahn M, Niu J, Kim J, et al. Vibostolimab, an anti-TIGIT antibody, as monotherapy and in 
combination with pembrolizumab in anti-PD-1/PD-L-1-refractory NSCLC. Annals of 
Oncology 31 (Suppl 4): S754-S840. 2020 (ESMO Sept 2020) 
33 Hellmann M, Ramalingam S, Reck M, et al. An open label randomized Phase III trial of 
nivolumab or nivolumab plus ipilimumab vs platinum doublet chemotherapy (PT-DC) in 
patients with chemotherapy-naïve stage IV or recurrent non-small cell lung cancer (NSCLC) 
(CheckMate 227). J Immunother Cancer 2015;3(Suppl 2):P154. 
34  Opdivo US Prescribing Information. Bristol-Myers Squibb Company; 2021. 
35  Yervoy US Prescribing Information. Bristol-Myers Squibb Company; 2021. 
36 Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous- 
cell non–small-cell lung cancer. N Engl J Med 2015; 373:123-35. 
37 Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced Nonsquamous 
non–small-cell lung cancer. N Engl J Med 2015; 373:1627-39. 
38 Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, et al. Nivolumab plus ipilimumab first 
line in advanced non-small-cell lung cancer: results of an open-label, phase 1, multicohort 
study (CheckMate 012). Lancet Oncol Manuscript submitted for publication. 
39 Schadendorf D. Efficacy and quality of life outcomes in patients with advanced melanoma 
(MEL) who discontinued treatment with nivolumab (NIVO) plus ipilimumab (IPI) due to 
toxicity in a phase III trial (CheckMate 067). 2016 Annual Meeting of the European 
Association of Dermato-Oncology; August 31-September 3, 2016; Vienna, Austria. 
40 Zhang Z, Wu N, Lu Y, et al. DNAM-1 controls NK cell activation via an ITT-like motif. J Exp 
Med 2015;212(12):2165-2182. 
41 Bai S, Jorga K, Xin Y, et al. A guide to rational dosing of monoclonal antibodies. Clin 
Pharmacokinet 2012;51:119-135. 
42 Fleming TR. One sample multiple testing procedure for phase II clinical trials. Biometrics 
1982;38:143-151. 
43 Kramar A, Potvin D, Hill C.. Multistage design for phase II clinical trials: statistical issues in 
cancer research. Br J Cancer 1996:74:1317-1320. 


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44 Fisch R, Jones I, Jones J, et al. Bayesian design of proof-of-concept trials. Ther Innov Regul 
Sci 2015;49:155-162. 
45 Frewer P, Mitchell P, Watkins C, et al. Decision-making in early clinical drug development. 
Pharm Stat 2016;15(3): 255-63 
46 Thall PF, Simon R. Practical Bayesian guidelines for phase IIB clinical trials. Biometrics 
1994;50:337-49. 


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12 
APPENDICES 


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APPENDIX 1 
ABBREVIATIONS AND TRADEMARKS 
 
Term 
Definition 
1L 
first-line 
AD-NSCLC 
nonsmall cell lung adenocarcinoma 
ADA 
anti-drug antibody 
ADME 
absorption, distribution, metabolism and excretion 
AE 
adverse event 
AI 
accumulation index 
AI_AUC 
AUC accumulation index 
AI_Cmax 
Cmax accumulation index 
AI_Ctau 
Ctau accumulation index 
ALK 
anaplastic lymphoma kinase 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
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 
BLRM 
Bayesian Logistic Regression Model 
BMS 
Bristol-Myers Squibb 
BOIN 
Bayesian optimal interval 
BRAF 
B-Raf proto-oncogene 
C 
celsius 
C1D1 
cycle 1 day 1 
Cave 
steady-state average plasma concentration 
CD155 
adhesion molecules PVR 
cHL 
Classical Hodgkin Lymphoma 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CLcr 
creatinine clearance 
CLR 
renal clearance 


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Term 
Definition 
CLT 
total body clearance 
CLT/F 
apparent total body clearance 
CLT/F/fu or CLT/fu 
apparent clearance of free drug or clearance of free if (if IV) 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration 
CNS 
central nervous system 
CONSORT 
consolidated standards of reporting trials 
CR 
complete response 
CRC 
colorectal cancer 
CrCl 
creatinine clearance 
CRF 
case report form, paper or electronic 
CRO 
contract research organization 
CRS 
cytokine release syndrome 
Css-avg 
average concentration over a dosing interval (AUC(TAU)/tau) 
CT 
computed tomography 
CTAg 
Clinical Trial Agreement 
Ctau 
concentration in a dosing interval (eg, concentration at 24 hours, 
concentration at 12 hours, etc.) 
CTC 
common terminology criteria 
CTCAE 
common terminology criteria for adverse events 
CTDNA 
circulation tumor DNA 
CTLA 
cytotoxic T lymphocyte-associated protein 
Ctrough 
trough observed plasma concentration 
DLT 
dose limiting toxicity 
DNA 
deoxyribonucleic acid 
DNAM-1 
DNAX accessory molecule 1, also called CD226 
DOR 
duration of response 
EC 
Ethics Committee 
EC50 
half-maximal effective concentration 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 


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Term 
Definition 
eCRF 
electronic case report form 
eg 
exempli gratia (for example) 
EGFR 
epidermal growth factor receptor 
EMA 
European Medicines Agency 
EOI 
end-of-infusion 
EOT 
end of treatment 
EU 
endotoxin unit 
EWOC 
Escalation with Overdose Control 
Fc 
fragment crystallizable 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
FIH 
first-in-human 
FNR 
false-negative rate 
FPR 
false-positive rate 
FSH 
follicle stimulating hormone 
fu 
fraction of unbound drug 
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practice 
GPVE 
Global Pharmacovigilance and Epidemiology 
h 
hour 
HBsAg 
hepatitis B surface antigen 
HCC 
hepatocellular carcinoma 
hCG 
human chorionic gonadotropin 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HNSTD 
highest non-severely toxic dose 
HR 
hazard ratio 
IB 
investigator brochure 
ICF 
informed consent form 


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Term 
Definition 
ICH 
International Council on Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
ie 
id est (that is) 
Ig 
immunoglobulin 
IgG4 
kappa 
IHC 
immunohistochemistry 
IMP 
investigational medicinal products 
IND 
investigational new drug 
INR 
international normalized ratio 
I-O 
immuno-oncology 
IP 
investigational product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITIM 
immunoreceptor tyrosine-based inhibitory motif 
IV 
intravenous 
kg 
kilogram 
KO 
knockout 
KRAS 
V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 
L 
liter 
LAG-3 
lymphocyte-activation gene 3 
LDH 
lactate dehydrogenase 
LFT 
liver function test 
mAb 
monoclonal antibody 
MRSD 
maximum recommended starting dose 
MAD 
maximum administered dose 
mDOR 
median duration of response 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
milliliter 
MMR 
mismatch repair 


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Term 
Definition 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NK 
natural killer 
NOAEL 
no-observed-adverse-effect level 
Non-MSI-H 
nonmicrosatellite instability-high 
NSCLC 
nonsmall cell lung cancer 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cells 
PBT 
platinum based therapy 
PCR 
polymerase chain reaction 
PD1 
programmed cell death 1 
PD-L1 
programmed death-ligand 1 
pDILI 
potential drug-induced liver injury 
PE 
physical examination 
PET 
positron emission tomography 
PFS 
progression free survival 
PFSR 
progression free survival rate 
PI 
product information 
PK 
pharmacokinetics 
PP 
posterior probability 
PR 
partial response 
PSC 
preliminary safety cohort 
PT 
prothrombin time 
PVR-2 
poliovirus receptor-2 
qd 
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Term 
Definition 
qw 
once weekly 
q2w 
every 2 weeks 
q3w 
every 3 weeks 
q4w 
every 4 weeks 
q8w 
every 8 weeks 
QTcf 
QT correction method, Fridericia’s 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RO 
receptor occupancy 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SCCHN 
squamous cell carcinoma of the head and neck 
SCLC 
small-cell lung cancer 
SD 
stable disease 
SmPC 
Summary of Product Characteristics 
SMT 
Safety Management Team 
SOC 
standard of care 
SQ-NSCLC 
squamous nonsmall cell lung carcinoma 
SUSAR 
suspected, unexpected serious adverse reaction 
TFT 
thyroid function test 
TGI 
tumor growth inhibition 
TIL 
tumor infiltrating lymphocyte 
T-HALF 
half life 
T-HALFeff_AUC 
effective elimination half-life that explains the degree of AUC 
accumulation observed 
T-HALFeff_Cmax 
effective elimination half-life that explains the degree of Cmax 
accumulation observed) 
TIGIT 
T cell immunoglobin and ITIM domain 
Tmax 
time of maximum observed concentration 


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Term 
Definition 
Tregs 
regulatory T cells 
TSH 
thyroid stimulating hormone 
ULN 
upper limit of normal 
USPI 
US Prescribing Information 
Vss 
apparent volume of distribution at steady state 
WOCBP 
women of childbearing potential 
WWPS 
Worldwide Patient Safety 


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APPENDIX 2 
STUDY GOVERANCE CONSIDERATIONS 
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the 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 Guidelines Good Clinical Practice (GCP) 
• As defined by the International Council on Harmonisation (ICH) 
• In accordance with the ethical principles underlying European Union Directive 2001/20/EC 
• United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
• Applicable local requirements. 
 
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study. 
All potential serious breaches must be reported to Sponsor or designee immediately. A serious 
breach is a breach of the conditions and principles of GCP (occurring in any country) in connection 
with the study or the protocol, which is likely to affect, to a significant degree, the safety or 
physical or mental integrity of 1 or more subjects of the study or the scientific value of the study. 
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 (e.g., 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 (e.g., 
advertisements), and any other written information to be provided to subjects. The investigator or 
BMS should also provide the IRB/IEC with a copy of the Investigator Brochure or product labeling 
information to be provided to subjects and any updates. 
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (e.g., expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures. 


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COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS 
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local health authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as 
soon as possible to: 
• IRB/IEC for 
• Regulatory Authority(ies), if applicable by local regulations (per national requirements) 
 
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local health authority must be sent to BMS. 
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment. 
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s). 
FINANCIAL DISCLOSURE 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate health authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 
INFORMED CONSENT PROCESS 
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives (as 
per country guidelines) are clearly and fully informed about the purpose, potential risks, and other 
critical issues regarding clinical studies in which the participant volunteers to participate. 
Sponsor or designee will provide the investigator with an appropriate (i.e., 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. 


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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, prior to the beginning of the study, 
and after any revisions are completed for new information. 
 
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant. 
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF and, in the 
US, the subjects’ signed HIPAA Authorization. 
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society. 
SOURCE DOCUMENTS 
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are 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). 


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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. 
If 
Then 
Supplied by BMS (or 
its vendors): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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) 
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, if applicable 
• dates and initials of person responsible for Investigational Product 
dispensing/accountability, as per the Delegation of Authority 
Form. 
The investigator or designee accepts responsibility for documenting 
traceability and study drug integrity in accordance with requirements 
applicable under law and the SOPs/standards of the sourcing 
pharmacy. 
These records should include: 
• label identification number or batch number 
• amount dispensed to and returned by each participant, including 
unique participant identifiers 
• dates and initials of person responsible for Investigational Product 
dispensing/accountability, as per the Delegation of Authority 
Form. 
 
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements. 


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CASE REPORT FORMS 
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study. 
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and Pregnancy Surveillance form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used. 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 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 
Sponsor or designee representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. 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. 


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The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee. 
RECORDS RETENTION 
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study. 
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed. 
If the investigator withdraws from the study (e.g., relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (e.g., 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 
 
 
 
 
 
 
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) 
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 (e.g., 
cytotoxics or biologics). 
If study treatments will be returned, the return will be 
arranged by the responsible Study Monitor. 
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. 


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• Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request. 
• Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, i.e., incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor must be documented. 
• Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period. 
 
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers. 
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non- study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee. 
CLINICAL STUDY REPORT AND PUBLICATIONS 
A Signatory Investigator must be selected to sign the clinical study report. 
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria: 
• Study Steering Committee chair or their designee 
 
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing Investigator participation in the study. These 
requirements include, but are not limited to, submitting proposed publications to Sponsor or 
designee at the earliest practicable time prior to submission or presentation and otherwise within 
the time period set forth in the CTA. 


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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 drug, 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).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 (eg, 
routine colonoscopy) 
• medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases 
• admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (e.g., lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason) 
• admission for administration of anticancer therapy in the absence of any other SAEs (applies 
to oncology protocols) 
Results in persistent or significant disability/incapacity 
 
Is a congenital anomaly/birth defect 
Is an important medical event (defined as a medical event(s) that may not be immediately life- 
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 9.2.7 for the definition of potential DILI.) 


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• SAEs, whether related or not related to study drug, 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. 
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). 
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 drug or if new 
information becomes available, the SAE report must be updated and submitted within 24 
hours to BMS (or designee) using the same procedure used for transmitting the initial SAE 
report. 
All SAEs must be followed to resolution or stabilization. 
 
REPORTING OF SAES TO SPONSOR OR DESIGNEE 
 


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− The required method for SAE data reporting collection 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 
Appendix 4 provides general information and definitions related to Woman of Childbearing 
Potential and methods of contraception that can be applied to most clinical trials. For information 
specific to this study regarding acceptable contraception requirements for female and male 
participants, refer to Section 6.1 of the protocol. Only the contraception methods as described in 
Section 6.1 are acceptable for this study. 
DEFINITIONS 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
Women in the following categories are not considered WOCBP: 
• Premenarchal 
• Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
• Postmenopausal female 
− A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle-stimulating hormone (FSH) level 
> 40 mIU/mL to confirm menopause. 
 
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. Suggested 
guidelines for the duration of the washout periods for HRT types are presented below. Investigators 
should use their judgement in checking serum FSH levels. 
• 1-week minimum for vaginal hormonal products (rings, creams, gels) 
• 4-week minimum for transdermal products 
• 8-week minimum for oral products 


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Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal. 
End of Relevant Systemic Exposure 
End of relevant systemic exposure is the timepoint where the Investigational Medicinal Product 
(IMP) or any active major metabolites have decreased to a concentration that is no longer 
considered to be relevant for human teratogenicity or fetotoxicity. This should be evaluated in 
context of safety margins from the no-observed-adverse-effect level or the time required for 5 half- 
lives of the IMP to pass. 
METHODS OF CONTRACEPTION 
Local laws and regulations may require use of alternative and/or additional contraception methods. 
 
Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of < 1% per year when used consistently and correctly.a 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation. (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol.)b 
− Oral (birth control pills) 
− Intravaginal (rings) 
− Transdermal 
• Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy. 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation. (This 
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol.)b 
− Oral 
− Injectable 
• Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy. 
Highly Effective Methods That Are User Independent 
• Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation. (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol.)b 
• Intrauterine device. 


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• Intrauterine hormone-releasing system (IUS). (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol.)b,c 
• Bilateral tubal occlusion. 
• Vasectomized partner 
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
A vasectomy is a highly effective contraception method provided that the participant is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used. 
• Sexual abstinence. 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
• Continuous abstinence must begin at least 30 days prior to initiation of study therapy. 
• It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
• WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 
• Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participant chooses to forego complete abstinence. 
• 
Periodic abstinence (including, but not limited to, calendar, symptothermal, postovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea 
method (LAM) are not acceptable methods of contraception for this study. 
NOTES: 
a Typical use failure rates may differ from failure rates when contraceptive methods are used consistently and 
correctly. Use should be consistent with local regulations regarding the use of contraceptive methods for 
participants in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous. In this case, alternative 
methods of contraception should be utilized. For information specific to this study regarding permissibility of 
hormonal contraception, refer to Sections 6.1 INCLUSION CRITERIA and 7.6.1 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 


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study regarding permissibility of hormonal contraception, refer to Sections 6.1 INCLUSION CRITERIA and 
7.6.1 PROHIBITED AND/OR RESTRICTED TREATMENTS of the protocol. 
 
Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of > 1% per year when used consistently and correctly. 
• Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously. 
• Diaphragm with spermicide. 
• Cervical cap with spermicide. 
• Vaginal sponge with spermicide. 
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action. (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited.) 
Unacceptable Methods of Contraception 
• Periodic abstinence (calendar, symptothermal, postovulation methods). 
• Withdrawal (coitus interruptus). 
• Spermicide only. 
• LAM. 
 
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS 
Male participants should maintain their usual practice with regard to contraception (if any); 
however, no specific contraceptive measures are required. 
 
COLLECTION OF PREGNANCY INFORMATION 
Guidance for collection of pregnancy information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and Appendix 3. 


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APPENDIX 5 
RECIST 1.1 CRITERIA 
1 
ASSESSMENT OF OVERALL TUMOR BURDEN AND MEASURABLE 
DISEASE 
To assess objective response or future progression, it is necessary to estimate the overall tumor 
burden at baseline and use this as a comparator for subsequent measurements. Measurable disease 
is defined by the presence of at least 1 measurable tumor lesion. When computed tomographic 
(CT) scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion 
should be twice the slice thickness. 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows: 
1.1 
Measurable Lesions 
Measurable lesions must be accurately measured in at least 1 dimension (longest diameter in the 
plane of the measurement to be recorded) with a minimum size of: 
• 10 mm by CT/magnetic resonance imaging (MRI) scan (CT/MRI scan slice thickness no 
greater than 5 mm) 
• 10-mm caliper measurement by clinical examination (lesions that cannot be accurately 
measured with calipers should be recorded as non-measurable) 
• 20 mm by chest X-ray 
• Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be □ 15 mm in the short axis when assessed by CT scan (CT scan slice thickness is 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis 
will be measured and followed. 
 
1.2 
Non-Measurable Lesions 
• All other lesions, including small lesions (longest diameter < 10 mm or pathological lymph 
nodes with □ 10 to < 15 mm short axis), as well as truly non-measurable lesions 
• Lesions considered truly non-measurable include the following: leptomeningeal disease, 
ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement 
of the skin or lung, and abdominal masses/abdominal organomegaly identified by physical 
examination that are not measurable by reproducible imaging techniques 
 
1.3 
Special Considerations Regarding Lesion Measurability 
1.3.1 
Bone Lesions 
• Bone scan, positron emission tomography (PET) scan or 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 


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as measurable lesions if the soft tissue component meets the definition of measurability 
described above. 
• Blastic bone lesions are non-measurable. 
1.3.2 
Cystic Lesions 
• Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
• ‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions 
if they meet the definition of measurability described above. However, if non-cystic lesions 
are present in the same subject, these are preferred for selection as target lesions. 
 
1.3.3 
Lesions with Prior Local Treatment 
Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional 
therapy, are usually not considered measurable unless there has been demonstrated progression in 
the lesion. 
1.4 
Specifications by Methods of Measurements 
1.4.1 
Measurement of Lesions 
All measurements should be recorded in metric notation (mm). All baseline evaluations should be 
performed as close as possible to the treatment start and never more than 30 days before the 
beginning of the treatment. 
1.4.2 
Method of Assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation should 
always be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical examination. 
1.4.2.1 
CT/MRI Scan 
CT/MRI is the best currently available and reproducible method to measure lesions selected for 
response assessment. Measurability of lesions on CT/MRI scan is based on the assumption that 
CT/MRI slice thickness is 5 mm or less. When CT scans have slice thickness greater than 5 mm, 
the minimum size for a measurable lesion should be twice the slice thickness. 
1.4.2.2 
Chest X-ray 
Chest CT is preferred over chest X-ray, particularly when progression is an important endpoint, 
since CT is more sensitive than X-ray, particularly in identifying new lesions. However, lesions 
on chest X-ray may be considered measurable if they are clearly defined and surrounded by aerated 
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1.4.2.3 
Clinical Lesions 
Clinical lesions will only be considered measurable when they are superficial and ≥ 10 mm 
diameter as assessed using calipers. For the case of skin lesions, documentation by color 
photography including a ruler to estimate the size of the lesion is suggested. As previously noted, 
when lesions can be evaluated by both clinical examination and imaging, imaging evaluation 
should be undertaken since it is more objective and may also be reviewed at the end of the study. 
1.4.2.4 
Ultrasound 
Ultrasound is not useful in assessment of lesion size and should not be used as a method of 
measurement. If new lesions are identified by ultrasound in the course of the study, confirmation 
by CT or MRI is advised. 
1.4.2.5 
Endoscopy, Laparoscopy 
The utilization of these techniques for objective tumor evaluation is not advised. 
2 
BASELINE DOCUMENTATION OF ‘TARGET’ AND ‘NON-TARGET’ 
LESIONS 
2.1 
Target Lesions 
When more than 1 measurable lesion is present at baseline all lesions up to a maximum of 5 lesions 
total (and a maximum of 2 lesions per organ) representative of all involved organs should be 
identified as target lesions and will be recorded and measured at baseline. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), 
should be representative of all involved organs, and should lend themselves to reproducible 
repeated measurements. 
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 below, 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. 
2.1.1 
Lymph Nodes 
Lymph nodes merit special mention since they are normal anatomical structures that may be 
visible by imaging even if not involved by tumor. Pathological nodes that are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. 
Nodes that have a short axis < 10 mm are considered non-pathological and should not be recorded 
or followed. 
2.2 
Non-Target Lesions 
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 


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progression’. 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’). 
3 
TUMOR RESPONSE EVALUATION 
3.1 
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 1 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. 
3.1.1 
Special Notes on the Assessment of Target Lesions 
3.1.1.1 
Lymph Nodes 
Lymph nodes merit special mention since they are normal anatomical structures that may be visible 
by imaging even if not involved by tumor. Pathological nodes that are defined as measurable and 
may be identified as target lesions must meet the criterion of a short axis of ≥ 15 mm by CT scan. 
Only the short axis of these nodes will contribute to the baseline sum. Nodes that have a short axis 
< 10 mm are considered non-pathological and should not be recorded or followed. 
3.1.1.2 
Target Lesions That Become ‘Too Small to Measure’ 
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). If the radiologist is able 
to provide an actual measurement, that should be recorded, even if it is below 5 mm. 
However, when such a lesion becomes difficult to assign an exact measure to then: 
• 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 (note: in case of a lymph node believed to be present and 
faintly seen but too 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). 


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3.1.1.3 
Target 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. 
• 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’. 
 
3.2 
Evaluation 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 timepoints specified in the protocol. 
Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be non- 
pathological in size (< 10 mm short axis). 
Non-CR/Non-PD: Persistence of 1 or more non-target lesion(s) above the normal limits. 
Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: The 
appearance of 1 or more new lesions is also considered progression.) 
3.2.1 
Special Notes on Assessment of Non-Target Lesions 
The concept of progression of non-target disease requires additional explanation as follows: 
3.2.1.1 
When the Subject Also Has Measurable Disease 
• 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 the 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 1 or more non-target lesions is usually not sufficient to 
quality for unequivocal progression status. 
 
3.2.1.2 
When the Subject Has Only Non-Measurable Disease 
• To achieve ‘unequivocal progression’ on the basis of the non-target disease, there must be an 
overall level of substantial worsening such that the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy. 
• A modest ‘increase’ in the size of 1 or more non-target lesions is usually not sufficient to 
qualify for unequivocal progression status. 
• Because worsening in non-target disease cannot be easily quantified (by definition: if all 
lesions are non-measurable), a useful test that can be applied when assessing subjects 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: that is, 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 a pleural effusion from ‘trace’ to ‘large’ 


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or an increase in lymphangitic disease from localized to widespread or may be described in 
protocols as ‘sufficient to require a change in therapy’. 
• If ‘unequivocal progression’ is seen, the subject should be considered to have had overall PD 
at that point. 
 
3.3 
New Lesions 
The appearance of new malignant lesions denotes disease progression. The finding of a new lesion 
should be unequivocal: that is, not attributable to differences in scanning technique, change in 
imaging modality or findings thought to represent something other than tumor (eg, some ‘new’ 
bone lesions may be simply healing or flare of preexisting lesions). This is particularly important 
when the subject’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. 
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 subject 
who has visceral disease at baseline and while on study has a CT or MRI brain scan ordered that 
reveals metastases. The subject’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and 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. 
3.3.1 
FDG-PET Evaluation 
While [18F] fluorodeoxyglucose (FDG)-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of the qualitative assessment of FDG-PET scanning 
to complement CT scanning in assessment of progression (particularly possible ‘new’ disease). 
New lesions on the basis of FDG-PET imaging can be identified according to the following 
algorithm: 
• Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion. 
• 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 positive FDG-PET 
scan). 


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− If the positive FDG-PET at follow-up corresponds to a preexisting site of disease on CT 
that is not progressing on the basis of the anatomic images, this is not PD. 
 
4 
RESPONSE CRITERIA 
4.1 
Timepoint Response 
A response assessment should occur at each timepoint specified in the protocol. 
For subjects who have measurable disease at baseline Table 4.1-1 provides a summary of the 
overall response status calculation at each timepoint. 
 
Table 4.1-1: 
Timepoint Response: Subjects 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 
 
Abbreviations: CR = complete response; NE =not evaluable; PD = progressive disease; PR = partial response; 
SD = stable disease. 
 
 
Missing Assessments and Not Evaluable Designation 
When no imaging/measurement is done at all at a particular timepoint, the subject is not evaluable 
(NE) at that timepoint. If only a subset of lesion measurements are made at an assessment, the case 
is also considered NE at that timepoint, unless a convincing argument can be made that the 
contribution of the individual missing lesion(s) would not have changed the assigned timepoint 
response. 


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4.1.1 
Confirmation Scans 
• Verification of Response: Confirmation of PR and CR is required at least 4 weeks following 
initial assessment to ensure responses identified are not the result of measurement error. 
 
4.2 
Best Overall Response: All Timepoints 
The best overall response is determined once all the data for the subject are known. It is the best 
response recorded from the start of the study treatment until the date of objectively documented 
progression based on RECIST v1.1, taking into account any requirement for confirmation, or the 
date of subsequent anti-cancer therapy, whichever occurs first in the study. The subject’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. 
Best response is defined as the best response across all timepoints with subsequent confirmation. 
Complete or partial responses may be claimed only if the criteria for each are met at a subsequent 
timepoint as specified in the protocol (generally 4 weeks later). 
In this circumstance, the best overall response can be interpreted as specified in Table 4.2-1. When 
SD is believed to be best response, it must meet the protocol specified minimum time from 
baseline. Measurements must have met the SD criteria at least once after study entry at a minimum 
interval (in general, not less than 6 to 8 weeks) that is defined in the study protocol. 
 
Table 4.2-1: 
Best Overall Response When Confirmation of CR and PR Is 
Required 
 
Overall Response 
First Timepoint 
Overall Response 
Subsequent Timepoint 
Best Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PRa 
 
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, 
PD 
 
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, 
PD 
CR 
NE 
SD provided minimum criteria for SD duration met, otherwise NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 


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Table 4.2-1: 
Best Overall Response When Confirmation of CR and PR Is 
Required 
Overall Response  
Overall Response 
Best Overall Response 
First Timepoint 
Subsequent Timepoint 
 
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 
 
Abbreviations: CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response; 
SD = stable disease. 
a If a CR is truly met at first timepoint, then any disease seen at a subsequent timepoint, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since the disease must have reappeared after CR). 
The 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 subject had PR, not 
CR at the first timepoint. Under these circumstances, the original CR should be changed to PR and the best response 
is PR. 
 
4.3 
Duration of Response 
4.3.1 
Duration of Overall Response 
The duration of overall response is measured from the time measurement criteria are first met for 
CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded on study). 
The duration of overall complete response is measured from the time measurement criteria are first 
met for CR until the first date that recurrent disease is objectively documented. 
4.3.2 
Duration of Stable Disease 
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum on 
study (if the baseline sum is the smallest, this is the reference for calculation of PD). 


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APPENDIX 6 
MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS 
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens. 
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated. 
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The oral 
equivalent of the recommended IV doses may be considered for ambulatory patients with low- 
grade toxicity. The lower bioavailability of oral corticosteroids should be taken into account when 
switching to the equivalent dose of oral corticosteroids. 
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended. 
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used. 


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APPENDIX 7 
ADME RELATED GENES 
http://pharmaadme.org 
Core ADME Gene List 
 
Gene 
Symbol 
Full Gene Name 
Class 
ABCB1 
ATP-binding cassette, sub-family B (MDR/TAP), member 1 
Transporter 
ABCC2 
ATP-binding cassette, sub-family C (CFTR/MRP), member 2 
Transporter 
ABCG2 
ATP-binding cassette, sub-family G (WHITE), member 2 
Transporter 
CYP1A1 
cytochrome P450, family 1, subfamily A, polypeptide 1 
Phase I 
CYP1A2 
cytochrome P450, family 1, subfamily A, polypeptide 2 
Phase I 
CYP2A6 
cytochrome P450, family 2, subfamily A, polypeptide 6 
Phase I 
CYP2B6 
cytochrome P450, family 2, subfamily B, polypeptide 6 
Phase I 
CYP2C19 
cytochrome P450, family 2, subfamily C, polypeptide 19 
Phase I 
CYP2C8 
cytochrome P450, family 2, subfamily C, polypeptide 8 
Phase I 
CYP2C9 
cytochrome P450, family 2, subfamily C, polypeptide 9 
Phase I 
CYP2D6 
cytochrome P450, family 2, subfamily D, polypeptide 6 
Phase I 
CYP2E1 
cytochrome P450, family 2, subfamily E, polypeptide 1 
Phase I 
CYP3A4 
cytochrome P450, family 3, subfamily A, polypeptide 4 
Phase I 
CYP3A5 
cytochrome P450, family 3, subfamily A, polypeptide 5 
Phase I 
DPYD 
dihydropyrimidine dehydrogenase 
Phase I 
GSTM1 
glutathione S-transferase M1 
Phase II 
GSTP1 
glutathione S-transferase pi 
Phase II 
GSTT1 
glutathione S-transferase theta 1 
Phase II 
NAT1 
N-acetyltransferase 1 (arylamine N-acetyltransferase) 
Phase II 
NAT2 
N-acetyltransferase 2 (arylamine N-acetyltransferase) 
Phase II 
SLC15A2 
solute carrier family 15 (H+/peptide transporter), member 2 
Transporter 
SLC22A1 
solute carrier family 22 (organic cation transporter), member 1 
Transporter 
SLC22A2 
solute carrier family 22 (organic cation transporter), member 2 
Transporter 
SLC22A6 
solute carrier family 22 (organic anion transporter), member 6 
Transporter 
SLCO1B1 
solute carrier organic anion transporter family, member 1B1 
Transporter 
SLCO1B3 
solute carrier organic anion transporter family, member 1B3 
Transporter 
SULT1A1 
sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1 
Phase II 
TPMT 
thiopurine S-methyltransferase, 
Phase II 
UGT1A1 
UDP glucuronosyltransferase 1 family, polypeptide A1 
Phase II 
UGT2B15 
UDP glucuronosyltransferase 2 family, polypeptide B15 
Phase II 
UGT2B17 
UDP glucuronosyltransferase 2 family, polypeptide B17 
Phase II 


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Gene 
Symbol 
Full Gene Name 
Class 
UGT2B7 
UDP glucuronosyltransferase 2 family, polypeptide B7 
Phase II 
 
Extended ADME Gene List 
Rank 
Gene Symbol 
Full Gene Name 
Class 
7 
ABCB8 
ATP-binding cassette, sub-family B (MDR/TAP), member 8 
Transporter 
7 
ABCC12 
ATP-binding cassette, sub-family C (CFTR/MRP), member 12 
Transporter 
7 
ABCC3 
ATP-binding cassette, sub-family C (CFTR/MRP), member 3 
Transporter 
7 
ABCC4 
ATP-binding cassette, sub-family C (CFTR/MRP), member 4 
Transporter 
7 
AHR 
aryl hydrocarbon receptor 
Modifier 
7 
ALDH4A1 
aldehyde dehydrogenase 4 family, member A1 
Phase I 
7 
ALDH5A1 
aldehyde dehydrogenase 5 family, member A1 
Phase I 
7 
ALDH6A1 
aldehyde dehydrogenase 6 family, member A1 
Phase I 
7 
CES1 
carboxylesterase 1 (monocyte/macrophage serine esterase 1) 
Phase I 
7 
CES2 
carboxylesterase 2 (intestine, liver) 
Phase I 
7 
CYP7A1 
cytochrome P450, family 7, subfamily A, polypeptide 1 
Phase I 
7 
EPHX1 
epoxide hydrolase 1, microsomal (xenobiotic) 
Phase I 
7 
FMO3 
flavin containing monooxygenase 3 
Phase I 
7 
GSTA1 
glutathione S-transferase A1 
Phase II 
7 
GSTA2 
glutathione S-transferase A2 
Phase II 
7 
GSTA3 
glutathione S-transferase A3 
Phase II 
7 
GSTA4 
glutathione S-transferase A4 
Phase II 
7 
GSTA5 
glutathione S-transferase A5 
Phase II 
7 
GSTM2 
glutathione S-transferase M2 (muscle),glutathione S-transferase M4 
Phase II 
7 
GSTM3 
glutathione S-transferase M3 (brain) 
Phase II 
7 
GSTM4 
glutathione S-transferase M4 
Phase II 
7 
GSTO1 
glutathione S-transferase omega 1,glutathione S-transferase omega 2 
Phase II 
7 
GSTO2 
glutathione S-transferase omega 2 
Phase II 
7 
GSTT2 
 
glutathione S-transferase theta 2 
Phase II 
solute carrier family 10 (sodium/bile acid cotransporter family), member 
7 
SLC10A1 
1 
Transporter 
7 
SLC15A1 
solute carrier family 15 (oligopeptide transporter), member 1 
Transporter 
7 
SLC22A11 
solute carrier family 22 (organic anion/cation transporter), member 11 
Transporter 
7 
SLC22A8 
 
solute carrier family 22 (organic anion transporter), member 8 
Transporter 
solute carrier family 7 (cationic amino acid transporter, y+ system), 
7 
SLC7A5 
member 5 
Transporter 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
7 
SLCO1A2 
solute carrier organic anion transporter family, member 1A2 
Transporter 
7 
SLCO2B1 
solute carrier organic anion transporter family, member 2B1 
Transporter 
7 
SULT1A2 
sulfotransferase family, cytosolic, 1A, phenol-preferring, member 2 
Phase II 
7 
SULT1A3 
sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3 
Phase II 
7 
SULT1B1 
sulfotransferase family, cytosolic, 1B, member 1 
Phase II 
7 
UGT1A3 
UDP glucuronosyltransferase 1 family, polypeptide A3 
Phase II 
7 
UGT1A6 
UDP glucuronosyltransferase 1 family, polypeptide A6 
Phase II 
7 
UGT1A7 
UDP glucuronosyltransferase 1 family, polypeptide A7 
Phase II 
7 
UGT1A8 
UDP glucuronosyltransferase 1 family, polypeptide A8 
Phase II 
7 
UGT1A9 
UDP glucuronosyltransferase 1 family, polypeptide A9 
Phase II 
7 
UGT2A1 
UDP glucuronosyltransferase 2 family, polypeptide A1 
Phase II 
7 
UGT2B11 
UDP glucuronosyltransferase 2 family, polypeptide B11 
Phase II 
7 
UGT2B28 
UDP glucuronosyltransferase 2 family, polypeptide B28 
Phase II 
7 
UGT2B4 
UDP glucuronosyltransferase 2 family, polypeptide B4 
Phase II 
6 
ABCA1 
ATP-binding cassette, sub-family A (ABC1), member 1 
Transporter 
6 
ABCA4 
ATP-binding cassette, sub-family A (ABC1), member 4 
Transporter 
6 
ABCB11 
ATP-binding cassette, sub-family B (MDR/TAP), member 11 
Transporter 
6 
ABCB4 
ATP-binding cassette, sub-family B (MDR/TAP), member 4 
Transporter 
6 
ABCB5 
ATP-binding cassette, sub-family B (MDR/TAP), member 5 
Transporter 
6 
ABCB6 
ATP-binding cassette, sub-family B (MDR/TAP), member 6 
Transporter 
6 
ABCB7 
ATP-binding cassette, sub-family B (MDR/TAP), member 7 
Transporter 
6 
ABCC1 
ATP-binding cassette, sub-family C (CFTR/MRP), member 1 
Transporter 
6 
ABCC10 
ATP-binding cassette, sub-family C (CFTR/MRP), member 10 
Transporter 
6 
ABCC11 
ATP-binding cassette, sub-family C (CFTR/MRP), member 11 
Transporter 
6 
ABCC5 
ATP-binding cassette, sub-family C (CFTR/MRP), member 5 
Transporter 
6 
ABCC6 
ATP-binding cassette, sub-family C (CFTR/MRP), member 6 
Transporter 
6 
ABCC8 
ATP-binding cassette, sub-family C (CFTR/MRP), member 8 
Transporter 
6 
ABCC9 
ATP-binding cassette, sub-family C (CFTR/MRP), member 9 
Transporter 
6 
ABCG1 
ATP-binding cassette, sub-family G (WHITE), member 1 
Transporter 
6 
ADH1A 
alcohol dehydrogenase 1A (class I), alpha polypeptide 
Phase I 
6 
ADH1B 
alcohol dehydrogenase IB (class I), beta polypeptide 
Phase I 
6 
ADH1C 
alcohol dehydrogenase 1C (class I), gamma polypeptide 
Phase I 
6 
ADH4 
alcohol dehydrogenase 4 (class II), pi polypeptide 
Phase I 
6 
ADH5 
alcohol dehydrogenase 5 (class III), chi polypeptide,methionyl 
aminopeptidase 1 
Phase I 
6 
ADH6 
alcohol dehydrogenase 6 (class V) 
Phase I 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
6 
ADH7 
alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide 
Phase I 
6 
ALDH1A1 
aldehyde dehydrogenase 1 family, member A1 
Phase I 
6 
ALDH1A2 
aldehyde dehydrogenase 1 family, member A2 
Phase I 
6 
ALDH1A3 
aldehyde dehydrogenase 1 family, member A3 
Phase I 
6 
ALDH1B1 
aldehyde dehydrogenase 1 family, member B1 
Phase I 
6 
ALDH2 
aldehyde dehydrogenase 2 family (mitochondrial) 
Phase I 
6 
ALDH3A1 
aldehyde dehydrogenase 3 family, memberA1 
Phase I 
6 
ALDH3A2 
aldehyde dehydrogenase 3 family, member A2 
Phase I 
6 
ALDH3B1 
aldehyde dehydrogenase 3 family, member B1 
Phase I 
6 
ALDH3B2 
aldehyde dehydrogenase 3 family, member B2 
Phase I 
6 
ALDH7A1 
aldehyde dehydrogenase 7 family, member A1 
Phase I 
6 
ALDH8A1 
aldehyde dehydrogenase 8 family, member A1 
Phase I 
6 
ALDH9A1 
aldehyde dehydrogenase 9 family, member A1 
Phase I 
6 
AOX1 
aldehyde oxidase 1 
Phase I 
6 
ARNT 
aryl hydrocarbon receptor nuclear translocator 
Modifier 
6 
CBR1 
carbonyl reductase 1 
Phase I 
6 
CBR3 
carbonyl reductase 3 
Phase I 
6 
CDA 
cytidine deaminase 
Modifier 
6 
CYB5R3 
cytochrome b5 reductase 3 
Phase I 
6 
CYP11A1 
cytochrome P450, family 11, subfamily A, polypeptide 1 
Phase I 
6 
CYP11B1 
cytochrome P450, family 11, subfamily B, polypeptide 1 
Phase I 
6 
CYP11B2 
cytochrome P450, family 11, subfamily B, polypeptide 2 
Phase I 
6 
CYP17A1 
cytochrome P450, family 17, subfamily A, polypeptide 1 
Phase I 
6 
CYP1B1 
cytochrome P450, family 1, subfamily B, polypeptide 1 
Phase I 
6 
CYP20A1 
cytochrome P450, family 20, subfamily A, polypeptide 1 
Phase I 
6 
CYP20A1 
cytochrome P450, family 20, subfamily A, polypeptide 1 
Phase I 
6 
CYP21A2 
cytochrome P450, family 21, subfamily A, polypeptide 2 
Phase I 
6 
CYP24A1 
cytochrome P450, family 24, subfamily A, polypeptide 1 
Phase I 
6 
CYP26A1 
cytochrome P450, family 26, subfamily A, polypeptide 1 
Phase I 
6 
CYP27A1 
cytochrome P450, family 27, subfamily A, polypeptide 1 
Phase I 
6 
CYP2A13 
cytochrome P450, family 2, subfamily A, polypeptide 13 
Phase I 
6 
CYP2A7 
cytochrome P450, family 2, subfamily A, polypeptide 7 
Phase I 
6 
CYP2C18 
cytochrome P450, family 2, subfamily C, polypeptide 18 
Phase I 
6 
CYP2F1 
cytochrome P450, family 2, subfamily F, polypeptide 1 
Phase I 
6 
CYP2J2 
cytochrome P450, family 2, subfamily J, polypeptide 2 
Phase I 
6 
CYP39A1 
cytochrome P450, family 39, subfamily A, polypeptide 1 
Phase I 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
6 
CYP3A43 
cytochrome P450, family 3, subfamily A, polypeptide 43 
Phase I 
6 
CYP3A7 
cytochrome P450, family 3, subfamily A, polypeptide 7 
Phase I 
6 
CYP4B1 
cytochrome P450, family 4, subfamily B, polypeptide 1 
Phase I 
6 
CYP4F11 
cytochrome P450, family 4, subfamily F, polypeptide 11 
Phase I 
6 
CYP51A1 
cytochrome P450, family 51, subfamily A, polypeptide 1 
Phase I 
6 
EPHX2 
epoxide hydrolase 2, cytoplasmic 
Phase I 
6 
FMO1 
flavin containing monooxygenase 1 
Phase I 
6 
FMO2 
flavin containing monooxygenase 2 
Phase I 
6 
FMO4 
flavin containing monooxygenase 4 
Phase I 
6 
FMO5 
flavin containing monooxygenase 5 
Phase I 
6 
GPX2 
glutathione peroxidase 2 (gastrointestinal) 
Phase I 
6 
GPX3 
glutathione peroxidase 3 (plasma) 
Phase I 
6 
GPX7 
glutathione peroxidase 7 
Phase I 
6 
GSR 
glutathione reductase 
Phase I 
6 
GSTK1 
glutathione S-transferase kappa 1 
Phase II 
6 
GSTM5 
glutathione S-transferase M5 
Phase II 
6 
GSTZ1 
glutathione transferase zeta 1 (maleylacetoacetate isomerase) 
Phase II 
6 
NNMT 
nicotinamide N-methyltransferase 
Phase II 
6 
NR1I2 
nuclear receptor subfamily 1, group I, member 2 
Modifier 
6 
NR1I3 
nuclear receptor subfamily 1, group I, member 3 
Modifier 
6 
PNMT 
phenylethanolamine N-methyltransferase 
Phase II 
6 
PON1 
paraoxonase 1 
Phase I 
6 
PON2 
paraoxonase 2 
Phase I 
6 
PON3 
paraoxonase 3 
Phase I 
6 
POR 
P450 (cytochrome) oxidoreductase 
Modifier 
6 
PPARD 
peroxisome proliferative activated receptor, delta 
Modifier 
6 
PPARG 
peroxisome proliferative activated receptor, gamma 
Modifier 
6 
RXRA 
 
retinoid X receptor, alpha 
Modifier 
solute carrier family 10 (sodium/bile acid cotransporter family), member 
6 
SLC10A2 
2 
Transporter 
6 
SLC13A1 
 
solute carrier family 13 (sodium/sulfate symporters), member 1 
Transporter 
solute carrier family 13 (sodium-dependent dicarboxylate transporter), 
6 
SLC13A2 
 
6 
SLC13A3 
member 2 
Transporter 
solute carrier family 13 (sodium-dependent dicarboxylate transporter), 
member 3 
Transporter 
6 
SLC16A1 
solute carrier family 16 (monocarboxylic acid Transporter), member 1 
Transporter 
6 
SLC19A1 
solute carrier family 19 (folate transporter), member 1 
Transporter 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
6 
SLC22A10 
solute carrier family 22 (organic anion/cation transporter), member 10 
Transporter 
6 
SLC22A12 
solute carrier family 22 (organic anion/cation transporter), member 12 
Transporter 
6 
SLC22A13 
solute carrier family 22 (organic cation transporter), member 13 
Transporter 
6 
SLC22A14 
solute carrier family 22 (organic cation transporter), member 14 
Transporter 
6 
SLC22A15 
solute carrier family 22 (organic cation transporter), member 15 
Transporter 
6 
SLC22A16 
solute carrier family 22 (organic cation transporter), member 16 
Transporter 
6 
SLC22A17 
solute carrier family 22 (organic cation transporter), member 17 
Transporter 
6 
SLC22A18 
solute carrier family 22 (organic cation transporter), member 18 
Transporter 
solute carrier family 22 (organic cation transporter), member 18 
6 
SLC22A18AS 
 
6 
SLC22A3 
antisense 
Transporter 
solute carrier family 22 (extraneuronal monoamine transporter), member 
3 
Transporter 
6 
SLC22A4 
solute carrier family 22 (organic cation transporter), member 4 
Transporter 
6 
SLC22A5 
solute carrier family 22 (organic cation transporter), member 5 
Transporter 
6 
SLC22A7 
solute carrier family 22 (organic anion transporter), member 7 
Transporter 
6 
SLC22A9 
solute carrier family 22 (organic anion/cation transporter), member 9 
Transporter 
6 
SLC27A1 
 
solute carrier family 27 (fatty acid transporter), member 1 
Transporter 
solute carrier family 28 (sodium-coupled nucleoside transporter), 
6 
SLC28A1 
 
6 
SLC28A2 
 
6 
SLC28A3 
member 1 
Transporter 
solute carrier family 28 (sodium-coupled nucleoside transporter), 
member 2 
Transporter 
solute carrier family 28 (sodium-coupled nucleoside transporter), 
member 3 
Transporter 
6 
SLC29A1 
solute carrier family 29 (nucleoside Transporter), member 1 
Transporter 
6 
SLC29A2 
solute carrier family 29 (nucleoside Transporter), member 2 
Transporter 
6 
SLC2A4 
 
solute carrier family 2 (facilitated glucose transporter), member 4 
Transporter 
solute carrier family 2 (facilitated glucose/fructose transporter), member 
6 
SLC2A5 
5 
Transporter 
6 
SLC5A6 
solute carrier family 5 (sodium-dependent vitamin transporter) 
Transporter 
6 
SLC6A6 
solute carrier family 6 (neurotransmitter transporter, taurine), member 6 
Transporter 
solute carrier family 7 (cationic amino acid transporter, y+ system), 
6 
SLC7A8 
member 8 
Transporter 
6 
SLCO1C1 
solute carrier organic anion transporter family, member 1C1 
Transporter 
6 
SLCO2A1 
solute carrier organic anion transporter family, member 2A1 
Transporter 
6 
SLCO3A1 
solute carrier organic anion transporter family, member 3A1 
Transporter 
6 
SLCO4A1 
solute carrier organic anion transporter family, member 4A1 
Transporter 
6 
SLCO4C1 
solute carrier organic anion transporter family, member 4C1 
Transporter 
6 
SLCO5A1 
solute carrier organic anion transporter family, member 5A1 
Transporter 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
6 
SLCO6A1 
solute carrier organic anion transporter family, member 6A1 
Transporter 
6 
SULT1C1 
sulfotransferase family, cytosolic, 1C, member 1 
Phase II 
6 
SULT1C2 
sulfotransferase family, cytosolic, 1C, member 2 
Phase II 
6 
SULT1E1 
sulfotransferase family 1E, estrogen-preferring, member 1 
Phase II 
6 
SULT2A1 
sulfotransferase family, cytosolic, 2A, DHEA preferring, member 1 
Phase II 
6 
SULT2B1 
sulfotransferase family, cytosolic, 2B, member 1 
Phase II 
6 
TAP1 
transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 
Transporter 
6 
UGT1A10 
UDP glucuronosyltransferase 1 family, polypeptide A10 
Phase II 
6 
UGT1A4 
UDP glucuronosyltransferase 1 family, polypeptide A4 
Phase II 
6 
UGT1A5 
UDP glucuronosyltransferase 1 family, polypeptide A5 
Phase II 
6 
UGT2B10 
UDP glucuronosyltransferase 2 family, polypeptide B10 
Phase II 
5 
ABCC13 
ATP-binding cassette, sub-family C (CFTR/MRP), member 13 
Transporter 
5 
ARSA 
arylsulfatase A 
Modifier 
5 
CAT 
catalase 
Modifier 
5 
CHST8 
carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 8 
Phase II 
5 
CYP19A1 
cytochrome P450, family 19, subfamily A, polypeptide 1 
Phase I 
5 
CYP26C1 
cytochrome P450, family 26, subfamily C, polypeptide 1 
Phase I 
5 
CYP27B1 
cytochrome P450, family 27, subfamily B, polypeptide 1 
Phase I 
5 
CYP2R1 
cytochrome P450, family 2, subfamily R, polypeptide 1 
Phase I 
5 
CYP2S1 
cytochrome P450, family 2, subfamily S, polypeptide 1 
Phase I 
5 
CYP46A1 
cytochrome P450, family 46, subfamily A, polypeptide 1 
Phase I 
5 
CYP4A11 
cytochrome P450, family 4, subfamily A, polypeptide 11 
Phase I 
5 
CYP4F12 
cytochrome P450, family 4, subfamily F, polypeptide 12 
Phase I 
5 
CYP4F2 
cytochrome P450, family 4, subfamily F, polypeptide 2 
Phase I 
5 
CYP4F3 
cytochrome P450, family 4, subfamily F, polypeptide 3 
Phase I 
5 
CYP4F8 
cytochrome P450, family 4, subfamily F, polypeptide 8 
Phase I 
5 
CYP4Z1 
cytochrome P450, family 4, subfamily Z, polypeptide 1 
Phase I 
5 
CYP7B1 
cytochrome P450, family 7, subfamily B, polypeptide 1 
Phase I 
5 
CYP8B1 
cytochrome P450, family 8, subfamily B, polypeptide 1 
Phase I 
5 
DHRS13 
dehydrogenase/reductase (SDR family) member 13 
Phase I 
5 
DHRS2 
dehydrogenase/reductase (SDR family) member 2 
Phase I 
5 
GPX1 
glutathione peroxidase 1 
Phase I 
5 
GPX4 
glutathione peroxidase 4 (phospholipid hydroperoxidase) 
Phase I 
5 
GPX5 
glutathione peroxidase 5 (epididymal androgen-related protein) 
Phase I 
5 
GPX6 
glutathione peroxidase 6 (olfactory) 
Phase I 
5 
GSS 
glutathione synthetase 
Phase I 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
5 
GSTCD 
glutathione S-transferase, C-terminal domain containing 
Phase II 
5 
HNF4A 
hepatocyte nuclear factor 4, alpha 
Modifier 
5 
HNMT 
histamine N-methyltransferase 
Phase II 
5 
HSD11B1 
hydroxysteroid (17-beta) dehydrogenase 11 
Phase I 
5 
HSD17B11 
hydroxysteroid (17-beta) dehydrogenase 11 
Phase I 
5 
HSD17B14 
hydroxysteroid (17-beta) dehydrogenase 14 
Phase I 
5 
LOC731356 
similar to dehydrogenase/reductase (SDR family) member 4 like 2 
Phase I 
5 
MGST1 
microsomal glutathione S-transferase 1 
Phase II 
5 
MGST2 
microsomal glutathione S-transferase 2 
Phase II 
5 
MGST3 
microsomal glutathione S-transferase 3 
Phase II 
5 
MPO 
myeloperoxidase 
Modifier 
5 
NOS1 
nitric oxide synthase 1 (neuronal) 
Phase I 
5 
NOS2A 
nitric oxide synthase 2A (inducible, hepatocytes) 
Phase I 
5 
NOS3 
nitric oxide synthase 3 (endothelial cell) 
Phase I 
5 
PPARA 
 
peroxisome proliferator-activated receptor alpha 
Modifier 
serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), 
5 
SERPINA7 
 
5 
SLC7A7 
member 7 
Modifier 
solute carrier family 7 (cationic amino acid transporter, y+ system), 
member 7 
Transporter 
5 
SOD1 
superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) 
Modifier 
5 
SOD2 
superoxide dismutase 2, mitochondrial 
Modifier 
5 
SOD3 
superoxide dismutase 3, extracellular precursor 
Modifier 
5 
SULF1 
sulfatase 1 
Phase I 
5 
SULT4A1 
sulfotransferase family 4A, member 1 
Phase II 
5 
TAP2 
transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) 
Transporter 
UDP glycosyltransferase 8 (UDP-galactose ceramide 
5 
UGT8 
galactosyltransferase) 
Phase II 
5 
XDH 
xanthine dehydrogenase 
Phase I 
4 
ADHFE1 
alcohol dehydrogenase, iron containing, 1 
Phase I 
4 
CHST1 
carbohydrate (keratan sulfate Gal-6) sulfotransferase 1 
Phase II 
4 
CHST10 
carbohydrate sulfotransferase 10 
Phase II 
4 
CHST11 
carbohydrate (chondroitin 4) sulfotransferase 11 
Phase II 
4 
CHST12 
carbohydrate (chondroitin 4) sulfotransferase 12 
Phase II 
4 
CHST13 
carbohydrate (chondroitin 4) sulfotransferase 13 
Phase II 
4 
CHST2 
carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 2 
Phase II 
4 
CHST3 
carbohydrate (chondroitin 6) sulfotransferase 3 
Phase II 
4 
CHST4 
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 4 
Phase II 


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Rank 
Gene Symbol 
Full Gene Name 
Class 
4 
CHST5 
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 5 
Phase II 
4 
CHST6 
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 6 
Phase II 
4 
CHST7 
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 7 
Phase II 
4 
CHST9 
carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 9 
Phase II 
4 
CYP2D7P1 
cytochrome P450, family 2, subfamily D, polypeptide 7 pseudogene 1 
Phase I 
4 
DDO 
D-aspartate oxidase 
Phase I 
4 
DHRS1 
dehydrogenase/reductase (SDR family) member 1 
Phase I 
4 
DHRS12 
dehydrogenase/reductase (SDR family) member 12 
Phase I 
4 
DHRS3 
dehydrogenase/reductase (SDR family) member 3 
Phase I 
4 
DHRS4 
dehydrogenase/reductase (SDR family) member 4 
Phase I 
4 
DHRS4L1 
dehydrogenase/reductase (SDR family) member 4 like 1 
Phase I 
4 
DHRS4L2 
dehydrogenase/reductase (SDR family) member 4 like 2 
Phase I 
4 
DHRS7 
dehydrogenase/reductase (SDR family) member 7 
Phase I 
4 
DHRS7B 
dehydrogenase/reductase (SDR family) member 7B 
Phase I 
4 
DHRS7C 
dehydrogenase/reductase (SDR family) member 7C 
Phase I 
4 
DHRS9 
dehydrogenase/reductase (SDR family) member 9 
Phase I 
4 
DHRSX 
dehydrogenase/reductase (SDR family) X-linked 
Phase I 
4 
DPEP1 
dipeptidase 1 (renal) 
Phase I 
4 
FMO6P 
flavin containing monooxygenase 6 
Phase I 
4 
HAGH 
hydroxyacylglutathione hydrolase 
Phase I 
4 
IAPP 
islet amyloid polypeptide 
Modifier 
4 
KCNJ11 
potassium inwardly-rectifying channel, subfamily J, member 11 
Modifier 
4 
LOC728667 
similar to dehydrogenase/reductase (SDR family) member 2 isoform 1 
Phase I 
4 
LOC731931 
similar to dehydrogenase/reductase (SDR family) member 2 isoform 1 
Phase I 
4 
MAT1A 
methionine adenosyltransferase I, alpha 
Modifier 
4 
METAP1 
methionyl aminopeptidase 1 
Phase I 
4 
PDE3A 
phosphodiesterase 3A, cGMP-inhibited 
Phase I 
4 
PDE3B 
phosphodiesterase 3B, cGMP-inhibited 
Phase I 
4 
PLGLB1 
plasminogen-like B1 
Phase I 
3 
ATP7A 
ATPase, Cu++ transporting, alpha polypeptide (Menkes syndrome) 
Modifier 
3 
ATP7B 
ATPase, Cu++ transporting, beta polypeptide 
Modifier 
3 
CFTR 
cystic fibrosis transmembrane conductance regulator 
Modifier 


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APPENDIX 8 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS 
 


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APPENDIX 9 
NEW YORK HEART ASSOCIATION (NYHA) FUNCTIONAL 
CLASSIFICATION 
Heart failure is usually classified according to the severity of their symptoms. The table below 
describes the most commonly used classification system, the New York Heart Association 
(NYHA) Functional Classification. It places patients in one of four 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, dyspnea (shortness of breath). 
II 
Slight limitation of physical activity. Comfortable at rest. Ordinary physical 
activity results in fatigue, palpitation, 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 10    CONSORT PUBLISHING REQUIREMENTS 
The Consolidated Standards of Reporting Trials (CONSORT) encompasses various initiatives 
developed by the CONSORT Group to alleviate the problems arising from inadequate reporting 
of randomized controlled trials. 
The CONSORT Statement 
The main product of CONSORT is the CONSORT Statement, which is an evidence-based, 
minimum set of recommendations for reporting randomized trials. It offers a standard way for 
authors to prepare reports of trial findings, facilitating their complete and transparent reporting, 
and aiding their critical appraisal and interpretation. CONSORT 2010 is the current version of the 
statement and supersedes the 2001 and 1996 versions. 
The CONSORT Statement comprises a 25-item checklist and a flow diagram. The checklist items 
focus on reporting how the trial was designed, analyzed, and interpreted. The flow diagram 
displays the progress of all participants through the trial. The checklist and flow diagram are freely 
available for viewing and downloading at the CONSORT website (http://www.consort- 
statement.org/consort-2010). The CONSORT Statement is endorsed by general medical journals, 
specialty medical journals, and leading editorial organizations. CONSORT is part of a broader 
effort, to improve the reporting of different types of health research, and indeed, to improve the 
quality of research used in decision-making in healthcare. 
CONSORT 2010 Guideline 
The CONSORT (CONsolidated Standards of Reporting Trials) 2010 guideline is intended to 
improve the reporting of parallel-group randomized controlled trial (RCT), enabling readers to 
understand a trial's design, conduct, analysis and interpretation, and to assess the validity of its 
results. This can only be achieved through complete adherence and transparency by authors. 
CONSORT 2010 was developed through collaboration and consensus between clinical trial 
methodologists, guideline developers, knowledge translation specialists, and journal editors 
(see CONSORT group ). CONSORT 2010 is the current version of the guideline and supersedes 
the 2001 and 1996 versions. 
CONSORT “Explanation and Elaboration” Document 
The CONSORT “Explanation and Elaboration” document explains and illustrates the principles 
underlying the CONSORT Statement, and should preferably be used in conjunction with the 
CONSORT Statement. In addition, extensions of the CONSORT Statement have been developed 
to give additional guidance for RCTs with specific designs, data and interventions. The CONSORT 
website (http://www.consort-statement.org/consort-2010) contains the current definitive version 
of the CONSORT 2010 Statement and up-to-date information on extensions. 


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APPENDIX 11 
CHILD-PUGH CLASSIFICATION 
 


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1
APPENDIX 12 
STATISTICAL METHODOLOGY 
DETAILS FOR BAYESIAN LOGISTIC REGRESSION MODEL (BLRM AND BLRM- 
COPULA), PARTS 1A, 1B, AND BAYESIAN OPTIMAL INTERVAL (BOIN), PART 1C 
DESIGN 
1 
BLRM MODEL SETUP FOR BMS-986207 MONOTHERAPY 
1.1 
Monotherapy Methodology Description 
An adaptive 2-parameter Bayesian Logistic Regression Model (BLRM) guided by the escalation 
with overdose control (EWOC) principle1,2,3 will be used to guide the dose escalation of 
BMS-986207 monotherapy in the monotherapy phase, providing dose recommendation during 
dose escalation. 
The BLRM will be fitted on the dose-limiting toxicity (DLT) data during the first 4 weeks of 
treatment accumulated throughout the dose escalation to model the dose-toxicity relationship of 
BMS-986207 in the monotherapy dose escalation phase. 
The dose-toxicity relationships for BMS-986207 monotherapy is assumed to follow a logistic 
model: 
logit(pi) = log(a1) + {31log(d1ij ∗), 
1 
where pi is the probability of toxicity at dose level d1i. Note that the a1 and {31 parameters are 
assumed positive, and d∗ is the reference dose for BMS-986207 (please refer to the meaning of 
a1 and {31 in Section 1.2.1 for detailed implementation). 
1.2 
Prior Specification for BMS-986207 Monotherapy 
The Bayesian approach requires the specification of prior distributions for model parameters, 
which include parameters (a1, {31) for BMS-986207. The prior distributions for BMS-986207 
single agent activity were derived using a weakly informative prior, as well as discussion with the 
Bristol-Myers Squibb (BMS) clinical team. 
Derivation of prior distribution of these parameters is provided in the following subsections. 
1.2.1 
Prior Derivation for BMS-986207 Parameters (log (a1), log (P1)) 
A weakly informative prior will be used for parameters (a1, {31) for BMS-986207 to reflect the 
potential of the different toxicities of BMS-986207 and allow for considerable prior uncertainty. 
Further details are provided below. 
Weakly Informative Prior 
• The median DLT rate at the reference dose (BMS-986207 at 1600 mg qd) was assumed to be 
30%, that is, mean (log(a1)) = logit (0.3) = log(0.3/(1-0.3)) = -0.847. 
• A doubling in dose was assumed to double the odds of DLT, that is, mean(log({31)) = 0. 
• The standard deviation of log(a1) was set to 1.53 using the following steps: 


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• If the toxicity probability range was set to be [1%, 99%], then the toxicity interval would be 
logit (0.99)-logit (0.01) = 9.19. 
• To cover 99.7% of the variance, the toxicity interval will cover 6*sd (log(a1)), which gives us 
sd (log(a1)) = 9.19/6 = 1.53. 
 
Correspondingly, the standard deviation of log({31) was set to 1, which allows for considerably 
larger prior uncertainty for the dose toxicity. 
1) The correlation between log(a1) and log({31) was set to 0. 
2) log(a1) and log({31) follow a bivariate normal distribution. 
 
Table 1: 
Prior Distribution for Model Parameters for BMS-986207 
 
Parameter 
Means 
Standard Deviations 
Correlation 
log(a1), log(β1) 
(-0.847, 0) 
(1.53, 1) 
0 
 
2 
BLRM MODEL SETUP FOR BMS-986207 AND NIVOLUMAB 
COMBINATION 
2.1 
Methodology Description for Combination Therapy 
Toxicity profiles of both BMS-986207 monotherapy and nivolumab monotherapy will be 
incorporated to develop the combination model framework. A copula-type model will be used to 
cover all general combination cases, including additive and synergistic effects. The combination 
of the 2 treatments will be explored using a Bayesian hierarchical model by utilizing the toxicity 
profiles of the single agents as prior marginal profiles for the combination. The following copula- 
type model4 will be used to describe the probability pij of toxicity when dose level i of agent A 
and dose level j of agent B are administered in combination: 
m 
1/ 
n 
1/y yl 
pij = 1 − exp(− [{−log(1 − pi )} yl + {−log(1 − qj )} 
l]  ), 
where pi is the prespecified best guess toxicity probability for agent A, qj is the prespecified best 
guess toxicity probability for agent B, m and n characterize the individual drug effect, and 
y1 characterizes the drug-drug interactive effect. 
The joint toxicity framework models the toxicity rates of both agents as well as their interaction 
effects in a 7-parameter hierarchical model, where each monotherapy dose-toxicity relationship 
will be characterized by a 2-parameter BLRM model (see Section 1.1). There are 3 additional 
parameters for the copula-type model, 1 for each agent (m and n) as well as 1 for the interaction 
term (y1). A dose-toxicity surface will be characterized for different dose combinations of these 
2 agents. 
As there are currently no historical data or prior knowledge to indicate how much information is 
to be borrowed for each of the single agents, parameters m and n are both set to be 1, meaning 


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d
2
borrowing 100% of the information from the 2 agents. The above formula is then simplified into 
a 5-parameter model as follows: 
1/ 
1/y yl 
pij = 1 − exp(− [{− log(1 − pi)} yl + {− log(1 − qj)} 
l]  . 
 
 
Since only a fixed nivolumab dose (240 mg) will be used in the BMS-986207 and nivolumab 
combination, this surface will be simplified into a 2-dimensional dose-toxicity curve. Posteriors 
for the corresponding 5 parameters (2 logistic regression parameters [a1, {31] for BMS-986207 and 
2 logistic regression parameters [a2, {32] for nivolumab, as well as 1 interaction parameter for the 
copula-type model [y1, which will be discussed in detail in the following section]) will be fitted 
into the in-house developed model. It implements the above-described theoretical setup. 
2.2 
Prior Specification for Combination Therapy 
2.2.1 
Marginal Prior for BMS-986207 
Posterior information on log(α1) and log(β1) from the monotherapy part of the study will be used 
as marginal BMS-986207 prior for combination with nivolumab. This prior information is not 
prespecified and will be continuously updated when additional DLT information from the 
monotherapy is available. In the simulation (see Section 3, the prior of BMS-986207 as described 
in Section 1.2.1 (Table 1) is used for illustration purposes because no real-time DLT data are 
available at this time. 
2.2.2 
Marginal Prior Derivation for Nivolumab Parameters (log(α2), log(β2)) 
Similar to BMS-986207 monotherapy in the monotherapy phase, the logistic model for nivolumab 
is as follows: 
logit(qj) = log(a2) + {32log(d2jj ∗), 
2 
where qj is the probability of toxicity at dose level d2j. Note that the a2 and {32 parameters are 
assumed positive, and d∗ is the reference dose for nivolumab. 
The toxicity profile of nivolumab has been studied in several studies. A bivariate normal prior for 
the nivolumab model parameters (log(α2), log(β2)) was obtained by extracting a posterior of 
nivolumab using DLT and safety data from the Study CA209003, which is used later as the meta- 
analytical-predictive (MAP) prior for nivolumab. 
The MAP prior for the model parameters (log(α2), log(β2)) was obtained in the following steps. 
First, a prior distribution for nivolumab was developed: 
• The medianb DLT rate at the reference dose (3 mg/kg every 2 weeks) was assumed to be 10%, 
that is, mean (log(α2)) = logit(1/10) = log(1/9) = -2.197. 
• A doubling in dose was assumed to double odds of DLT, that is, mean(log(β2)) = 0. 
• The standard deviation of log(α2) was set to 2, and the standard deviation of log(β2) to 1, which 
allows for considerable prior uncertainty for the dose-toxicity profile. 


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• The correlation between log(α2) and log(β2) is assumed to be 0 (assuming independence of 
log(α2) and log(β2)). 
• In addition, heterogeneity between the historical study and current study was incorporated 
using a meta-analytic predictive approach by defining between-trial standard deviations τ1 and 
τ2 for log(α2) and log(β2), respectively. The between-trial variability is assumed to be 
moderate. Therefore, τ1 and τ2 were set to follow a log-normal distribution, with mean 
log(0.25) and log(0.125), respectively, with a common standard deviation log(2)/1.96. 
 
With this prior, the clinical trial data below (Table 2) were used to generate the posterior for 
nivolumab, which is then used as the MAP prior for this study (Table 3). 
Table 2: 
Data from Single-agent Nivolumab Study CA209003 
 
Every 2 Weeks 
Dose of Nivolumab (mg/kg) 
 
 
No. of DLTs/No. of Evaluable Patients in the Escalation Phase 
 
 
0.1 
0/3 
0.3 
0/3 
1 
0/3 
3 
0/3 
10 
1/6 
 
Abbreviation: DLT = dose limiting toxicity. 
 
 
Table 3: 
Marginal Prior Distribution for Model Parameters for Nivolumab 
(ie, Posterior from MAP Method) 
 
Parameter 
Means 
Standard Deviations 
Correlation 
log(α2), log(β2) 
(-3.269, -0.152) 
(1.186, 0.771) 
-0.369 
 
Note: Nivolumab prior information was based on a milligram-per-kilogram dosing instead of flat 
dosing. If real pharmacokinetic (PK) data from this study show difference from the milligram-per- 
kilogram assumption, the nivolumab prior will be revisited and modified accordingly. 
2.2.3 
Prior for Interaction Parameters for Joint Toxicity of BMS-986207 and 
Nivolumab Combination 
A gamma prior distribution for the interaction parameter γ1 is derived to reflect the current 
uncertainty about the toxicity profile of the combination of BMS-986207 and nivolumab. Although 
no PK drug-drug interaction is expected, the possibility of a significant positive interaction 
between BMS-986207 and nivolumab cannot be totally excluded. The interaction parameter γ1 
was chosen accordingly but with a degree of uncertainty to allow for the possibility that the 
interaction may be positive or negative. Therefore, the following assumptions are made for the 
interaction parameter: 


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• γ1 follows a gamma distribution and with a mean centered at 1.1, which means the combination 
of 2 agents is likely to have only a small synergistic effect. 
• The 97.5 percentile of γ1 is log(3), that is, a 3-fold increase in odds of DLT due to the 
interaction over independence at the starting dose of the combination. 
 
This model assigns the highest probability to there being small synergistic interaction and also 
allows for the potential of larger synergism of the toxic profiles. It also does not completely ignore 
the possibility of antagonism because there is a 40% prior probability that γ1 is less than 1. 
3 
BLRM DECISION RULE FOR DOSE ESCALATION AND SIMULATION 
Dose escalation recommendations for BMS-986207 monotherapy and in combination with 
nivolumab will be based on the inference from the Bayesian posterior and the probability that the 
true DLT rate for each dose lies in 1 of the following categories: 
• [0%, 16%) under-dosing 
• [16%, 33%) targeted toxicity 
• [33%, 100%] excessive toxicity 
 
These boundaries are similar to the toxicity boundaries 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. Following the principle of EWOC, dose recommendations for the next cohort will be based 
on the Bayesian model after DLT information becomes available during the DLT period, 
accounting for all of the available data from the administered doses, and the candidate doses are 
the ones fulfilling the overdose criterion that there is less than 30% chance of excessive toxicity. 
Only the candidate doses will be considered for the next cohort. While the Bayesian model will 
use DLT information from the DLT period only, clinical assessment will take into consideration 
of the totality of available data including PK/
 from all treated participants. 
Stopping Rules: 
The following is the general stopping rules of BLRM (-Copula) during Dose Escalation: 
• If all of 30 DLT evaluable participants are treated. 
• If all of the current pre-specified doses are considered intolerable according to the pre-specified 
cutoff (ie, EWOC criteria), then the model will recommend stopping the current dose level and 
a new dose level lower than the current lowest dose level will need to be identified. 
• The maximum number of participants in a dose level will be 12. This limit is set to avoid 
instances in which the model could recommend adding subjects indefinitely to a specific dose 
level due to uncertainty in the tolerability profile. 
• If, for a specific dose level, 6 subjects have been treated and the chance of determining that the 
dose level to be the “target” dose is > 50%, then the model will suggest to stop and declare the 
current dose level to be MTD. 
• Model-recommended MTD: 
• The MTD is the dose that satisfies the following 3 conditions: 


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• (1) The empirical posterior probability that the ‘DLT rate of 16% -< 33%’ is greater than 50%, 
• (2) This probability needs to be the largest among the dose levels that satisfy the EWOC 
condition (ie, the probability that ‘DLT rate ≥ 33%’ must be less than 30%); 
• (3) Minimum number of participants (ie, 6), were treated at this dose level. 
 
Final MTD/RP2D: 
The final recommended MTD/RP2D will be based on the recommendation from the 
BLRM/BLRM-copula and overall clinical assessment of all available safety, PK/
 and efficacy 
data. Lower doses of BMS-986207 may be tested if none of the planned doses are found to be 
tolerable as monotherapy or in combination with nivolumab. Such decisions will be made after 
discussion and agreement between the investigators and the BMS Medical Monitor. 
 
3.2 
Simulation Parameters 
One thousand trial simulations were used for each scenario. All simulations were run using EAST 
6.3.1® software for BLRM model for BMS-986207 monotherapy and in-house developed code via 
R and Openbugs for BLRM-copula method for BMS-986207 in combination with nivolumab. The 
number of subjects to be treated in each cohort in a specific dose level and the stopping rules used 
to declare MTD are defined as: 
• Fixed cohort size: 3 
• Probability of overdosing: < 30% 
• Probability of achieving the target toxicity: > 50% 
• Maximum number of participants treated: 30 
• Minimum number of participants treated at a given dose level in order to declare MTD: 6 
• Maximum number of participants at a dose:12 
 
The provisional dose levels for BMS-986207 monotherapy are 80-1600 mg. For the combination 
therapy, nivolumab is fixed at 240 mg flat dose for q2w. 
3.3 
Operating Characteristics 
Section 3.2.1 demonstrates operating characteristics of BLRM for monotherapy and Section 3.2.2 
demonstrates operating characteristics of BLRM-copula for combination therapy accounting for 
joint toxicity of the combination therapy. 
3.3.1 
Operating Characteristics of BLRM for Monotherapy 
Three scenarios were investigated by selecting (1) dose-DLT relationship derived by prior, (2) 
narrow safety window in order to explore how EWOC limits the risk of exposing participants from 
a toxic dose level, and (3) all doses above the target toxicity. 


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Table 4: 
Simulation Results of BLRM for Monotherapy 
 
BMS- 
MTD not 
Fitted
Toxicity 
Avg 
Scenario 
986207 
Dose 
80 
240 
800 
1600 
selected 
MTD 
Observed 
# Pts 
(%) 
 
 
(%) 
% DLT 
5 
10 
20a 
30a 
By prior 
% MTD 
0.9 
18.1 
51.7 
28.3 
1.0 
1384 
17.9 
19.9 
# Pts 
3.6 
4.8 
7.2 
4.3 
# DLTs 
0.2 
0.3 
1.4 
1.3 
% DLT 
5 
10 
20a 
80 
Narrow 
safety 
% MTD 
0.7 
26.2 
71 
0.3 
1.8 
1063 
21.5 
19.3 
window 
# Pts 
3.6 
5.4 
8.5 
1.8 
# DLTs 
0.2 
0.4 
1.7 
1.5 
All high 
% DLT 
50 
60 
75 
80 
% MTD 
5.7 
1.0 
0 
0 
93.3 
30 
62.0 
5.6 
# Pts 
4.7 
0.5 
0.4 
0.02 
# DLTs 
2.4 
0.3 
0.3 
0.02 
% DLT, true DLT rate; % MTD, proportion of the dose selected as the MTD; # Pts, average number of participants 
by assuming 3 participants for skipped dose level where the true toxicity rate is below the target rate; # DLTs, average 
number of DLTs by assuming no DLT for skipped dose level where the true toxicity rate is below the target rate; 
Fitted MTD: fitted MTD at 30% as the target toxicity rate; % toxicity observed, average proportion of DLTs given 
the doses were tried 
a Doses with true target toxicity within the target toxicity interval [16%, 33%) 
 
The average sample size was no more than 20 participants. The results for the scenarios of narrow 
safety window and all high show how the EWOC principle limits the risk of exposing participants 
from a toxic dose level. Overall, the scenarios illustrated above demonstrate that the model 
performs well in the hypothetical scenarios investigated by correctly identifying the MTD at least 
71% of the time while limiting participants from receiving excessive/unacceptable toxic dose 
levels. 
3.3.2 
Operating Characteristics of BLRM-copula for Combination Therapy 
Three hypothetical scenarios were investigated: (1) additive joint toxicity; (2) toxicity rates 25% 
higher than the additive scenario; (3) toxicity rates 50% higher than the additive scenario; 


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Table 5: 
Simulation Results of BLRM-copula for Various Doses of 
BMS-986207 in Combination with Nivolumab 240 mg q2w 
 
BMS- 
MTD not 
Fitted
Toxicity 
Avg 
Scenario 
986207 
Dose 
80 
240 
800 
1600 
selected 
MTD 
Observed 
# Pts 
(%) 
 
 
(%) 
% DLT 
10 
14 
25a 
40 
Additive 
% MTD 
3.9 
30.3 
51.4 
11.2 
3.2 
1335 
20.0 
19.9 
# Pts 
4.3 
5.0 
8.4 
2.2 
#DLT 
0.4 
0.7 
2.0 
0.9 
% DLT 
13 
18a 
32a 
50 
25% 
% MTD 
8.0 
39.8 
43.4 
2.6 
6.2 
1019 
30.0 
18.4 
higher 
# Pts 
4.8 
5.8 
6.7 
1.1 
#DLT 
0.6 
1.0 
2.0 
0.6 
50% 
higher 
% DLT 
15 
21a 
38 
60 
% MTD 
10.8 
49.8 
27.5 
0.5 
11.4 
788 
30.0 
17.2 
# Pts 
5.1 
6.2 
5.3 
0.6 
#DLT 
0.8 
1.3 
2.0 
0.3 
% DLT, true DLT rate; % MTD, proportion of the dose selected as the MTD; #DLT, average number of DLTs; MTD 
not selected: dose was below lowest dose or above highest dose; Fitted MTD: fitted MTD at 30% as the target toxicity 
rate and the dose range falls into the target toxicity range of [16%, 33%); Toxicity observed: Average proportion of 
DLTs out of all simulated trials; # Pts, average number of participants 
a Doses with true target toxicity within the target toxicity interval [16%, 33) 
 
The average sample size was no more than 20 participants. The results show how the EWOC 
principle limits the risk of exposing participants from unacceptable toxic dose levels, eg, 50% or 
above. Overall, the scenarios illustrated above demonstrate that the model performs well by 
correctly identifying the MTD ranging from 50% to 83% in the hypothetical scenarios investigated 
while limiting participants from receiving unacceptable toxic dose levels 
4 
BLRM INTERIM MONITORING CASE STUDY TO ILLUSTRATE 
PROVISION OF DOSE RECOMMENDATIONS DURING DOSE- 
ESCALATION 
In order to provide a comprehensive view of the dynamics of the models, different hypothetical 
scenarios exploring all possibilities are examined. For the simplicity of illustration purposes, a 
static cohort size of 3 subjects is applied for dose levels 80 mg, 240 mg, 800 mg and 1600 mg in 
the BMS-986207 monotherapy and for the dose level 80 mg in the combination setting. This cohort 
size could vary during the actual clinical trial, and the BLRM (-Copula) models are designed to fit 
various different cohort sizes, adaptively. In general, there are 4 possible scenarios for a specific 
dose level, which are 0 DLT observed in 3 total subjects in that cohort (denoted as 0/3), 1 DLT 


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observed in 3 subjects (1/3), 2 DLTs observed in 3 subjects (2/3), and 3 DLTs observed in 3 
subjects (3/3). 
During interim monitoring, posterior probabilities will be updated when there is new DLT 
information available. The following three visualization plots will be produced to reflect the real 
time dose-DLT relationship, to quantify benefit (in the form of target dosing) and risk (in the form 
of overdosing and underdosing) during model’s recommendation process, and to facilitate clinical 
team’s interpretation of the model recommendations for the final decision making: 
• Dose-DLT profile for the doses ranging between 0 mg and 1600 mg (Figure 1). 
• Stacking histograms displaying predictive probabilities on DLT rates classified into 3 different 
categories (Underdosing, Target dosing and Overdosing) (Figure 2). 
• Box plots summarizing the Markov Chain Monte Carlo (MCMC) samples of predicted DLT 
rates for the 5 pre-specified dose levels (Figure 3). 
 
Figure 1: 
Updated dose-DLT profile after incorporating prior information and 
all previous DLT information up to 80 mg (including all monotherapy 
DLT data for BMS-986207 up to 240 mg) 
 
 
 
Interpretation and usage of Figure 1: 
Figure 1 is a snapshot of an updated dose-DLT profile with DLT information available at dose 
level 80 mg for combination studies. The dose-DLT profile is captured with a continuous dose 
spectrum ranging from 0 mg to 1600 mg, which is a slice of the dose-DLT surface of the 
combination of two drugs with Nivolumab fixed at 240 mg. For each dose within the range, there 
is a corresponding distribution of the predicted DLT rates calculated from the posterior samples of 
the model parameters. This figure will be updated each time new DLT information becomes 


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available from the combination studies. Similar graphs will also be produced for the BMS-986207 
monotherapy. 
In Figure 1, there are 3 different quantiles (2.5%, 50%, and 97.5%) plotted to characterize the 
current trend of the toxicity profile (as shown by the 50% quantile), as well as the variation of the 
dose-DLT profile (as shown by the 2.5% percentile and the 97.5% percentile), according to the 
accumulation of DLT data from all previous and current dose levels. The toxicity boundaries 
(0.16 and 0.33) are illustrated in two dotted horizontal lines to benchmark the way in which the 
dose-DLT profile is trending. 
Intermediate dose levels can be identified using different boundary cutoffs. For example, using the 
50% percentile curve (green highlight), which represents the nearly average DLT distribution for 
each dose level, the 300 mg could be a potential intermediate dose level corresponding to the lower 
pre-specified DLT rate boundary of 0.16, and the 1600 mg could be a fitted MTD dose level 
associated with the upper boundary of 0.33. 
Moreover, if all of the current pre-specified doses are considered intolerable (overdosing 
probabilities > 0.3 for combination therapy, a case not shown on the current Figure 1), the model 
will recommend to stop the current dose level, and the clinical team can leverage the current 
updated dose-DLT curve to pinpoint a new dose, which is lower than pre-specified lowest dose 
(80 mg) by using the DLT rate boundaries. 
Figure 2: 
Updated stacking histogram after incorporating prior information 
and all previous DLT information up to 80 mg (including all 
monotherapy DLT data up to 240 mg for BMS-986207) to classify 
predicted DLT rates into 3 categories (Underdosing, Target Dosing 
and Overdosing) 
 


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Interpretation and usage of Figure 2: 
Figure 2 is a snapshot of stacking histogram with DLT information available at dose level 80 mg 
for the combination studies. This figure will be updated each time new DLT information becomes 
available in the combination setting. Similar graphs will also be produced for the BMS-986207 
monotherapy. 
When recommending the next dose level, the model will first exclude doses that are intolerable 
(with overdosing probabilities > 30%, the rate that has been specified for BMS-986207 in 
combination with nivolumab). Among those qualified candidate doses that are considered 
“tolerable”, the model will select the dose that maximizes the probability of being within the target 
toxicity range (DLT rate of 16% up to 33%). 
As illustrated in Figure 2, when there is 0 DLT observed out of 3 subjects for the dose level 80 mg 
and 1 DLT out of 3 subjects for the dose level 240 mg, the distribution of predicted DLT rates will 
be characterized into possibilities falling into 3 different categories. First, dose levels of 800 mg 
and 1600 mg for BMS-986207 are excluded according to the higher-than-cutoff (0.3 for 
combination therapy) overdosing probabilities (0.364 for 800mg and 0.503 for 1600mg). Among 
the remainder of tolerable dose levels (80 mg and 240 mg), the BLRM-Copula model recommends 
the dose that maximizes the probability of being within the target dosing interval. Therefore, the 
model’s recommendation would be to escalate to 240 mg, which is associated with the highest 
target dosing probability of 0.342 compared with that of 80 mg (0.231). 
Similarly (although not shown on Figure 2), according to the rules specified above, the model 
could possibly recommend to de-escalate to a lower dose level than current treated dose level, 
extend the current dose level, or even recommend to stop and identify a new dose level lower than 
80mg, the lowest pre-specified dose level. Please refer to description of Figure 1 for details on 
how to specify the new dose levels. 


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Figure 3: 
Updated box plot after incorporating prior information and all 
previous DLT information up to 80 mg in combination setting 
(including all monotherapy DLT data up to 240 mg for BMS-986207) 
for pre-specified dose levels 
 
Interpretation and usage of Figure 3: 
Figure 3 is a snapshot with DLT information available at dose level 80 mg for the combination 
setting. The dose-DLT distributions calculated from the posterior samples of the model parameters 
are characterized in the format of boxplots for the pre-specified dose levels. This figure will be 
updated each time there is new DLT information available. Similar graphs will also be produced 
for the BMS-986207 monotherapy. 
This plot supplements the information provided in Figure 1. It allows for a more in-depth and 
focused visualization of general trend of dose-DLT relationship, as well as the magnitude and 
variability in the DLT rates for each pre-specified dose level. 
4.1 
Example of the BLRM using BMS-986207 Monotherapy Dose Escalation 
According to safety consideration and clinical judgement, the dose level 80 mg is recommended 
as the starting dose for BMS-986207 monotherapy. With the current BMS-986207 prior specified 
in the Section 1.2.1 and all available DLT information up to 240 mg, a corresponding decision tree 
illustrating various models’ recommendations under all possible scenarios (for dose levels of 800 
mg and 1600 mg) is provided in Figure 4. 
Tracing a branch of the decision tree in Figure 4 illustrates the decision making process. Taking 
the left-most branch of the tree as an example, starting at 80 mg, there was 0 DLT observed at 
80 mg in the real clinical trial, the model recommended to escalate to 240 mg (The BLRM actually 
recommends escalating to dose level 800 mg but since this is a 10 fold increrase of dose and this 


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type of dose skipping is not allowed the dose level 240 mg is selected), one level above the current 
treated dose level according escalation rules per protocol (as detailed in Protocol Section 5.1). 
Additionally, there was 0 DLT observed at 240 mg in real data, the model recommended to escalate 
further one dose level to 800 mg. 
As illustrated in Figure 4, there are 6 potential decision paths for dose levels 800 mg and moving 
onwards up to 800 mg. During the actual clinical study, the tree would be narrowed or deepened 
based on actual DLT. The clinical team will be able to leverage this decision tree to preview 
decisions at each interim monitoring step and to plan proactively. 
 
Figure 4: 
The BLRM model hypothetical decision tree for BMS-986207 
monotherapy during dose escalation (up to 800 mg; E: escalation; S: 
stay; DE: de-escalation) 
 
5 
BOIN ESCALATION DESIGN SIMULATION WITH 2 DOSE LEVELS, PART 
1C 
The Bayesian optimal interval (BOIN) design framework will be used to guide the safety 
evaluation of BMS-986207 in combination with nivolumab and ipilimumab in Part 1C. The design 
is typically also used to determine maximum tolerated dose (MTD) selection in cases where more 
doses are evaluated.5,6 
As a single dose level of BMS-986207 will be evaluated in this triplet combination (with potential 
for a de-escalation if needed), the goal in this study part is to assess if the dose is tolerable. 
Therefore MTD reference below (as in typical multi-dose level design) represents a ‘tolerable 


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dose’ in Part 1C. As an escalation decision is not of interest in Part 1C, a design recommendation 
to declare a dose as tolerable is based on meeting the same criteria needed to escalate. 
The target toxicity rate for the MTD is ɸ = 0.3 and the maximum sample size is 12. Participants 
will be enrolled in cohorts of 3. The BOIN design framework uses the following rule optimized to 
minimize the probability of incorrect dose assignment, to guide dose escalation/de-escalation: 
• If the observed DLT rate at the current dose is ≤ 0.236, declare the dose tolerable; 
• If it is ≥ 0.359, de-escalate the dose to the next lower dose level; 
• Otherwise, stay at the current dose. 
 
The design MTD selection approach described next, is included for general information on the 
design; however, it is not used in this study. After the trial is completed, selection of the MTD is 
based on isotonic regression as specified in Liu and Yuan (2015).5 Specifically, the MTD is the 
dose for which the isotonic estimate of the DLT rate is closest to the target DLT rate. If there are 
ties, select the higher dose level when the isotonic estimate is lower than the target DLT rate and 
select the lower dose level when the isotonic estimate is greater than or equal to the target DLT 
rate. 
5.1 
Operating characteristics of BOIN design with 2 dose levels 
Table 6 shows the operating characteristics of the trial design based on 1000 simulations of the 
trial using the BOIN Design Desktop Program.7 The operating characteristics show that the design 
selects the true MTD (tolerable dose), if any, with high probability and allocates more patients to 
the dose levels with the DLT rate closest to the target of 0.3. 
 
Table 6: 
Operating Characteristics of the BOIN Design 
 
 
Dose Level 
Number of 
% Early 
 
1 
2 
Participants 
Stopping 
Scenario 1 
True DLT Rate 
0.30 
0.48 
Selection % 
60.8 
31.9 
7.3 
% Pts Treated 
40.8 
59.2 
11.8 
Scenario 2 
True DLT Rate 
0.16 
0.30 
Selection % 
22.1 
77.8 
0.1 
% Pts Treated 
16.3 
83.7 
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Scenario 3 
True DLT Rate 
0.20 
0.35 
Selection % 
33.7 
65.2 
1.1 
% Pts Treated 
22.9 
77.1 
12.0 
Abbreviations: BOIN, Bayesian optimal interval; DLT, dose limiting toxicity. Pts, participants. 
Note: “% Early Stopping” refers to early stopping due to excessive DLTs. 


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6 
REFERENCES 
 
1 Babb J, Rogatko A, Zacks S. Cancer Phase I clinical trials: efficient dose escalation with 
overdose control. Stat Med 1998;17:1103-20. 
2  Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to Phase 
I cancer trials. Stat Med 2008;27:2420-39. 
3  Neuenschwander B, Capkun-Niggli G, Branson M, et al. Summarizing historical information 
on controls in clinical trials. Clin Trials 2010;7:5-18. 
4 Yin G, Yuan Y. Bayesian dose finding in oncology for drug combinations by copula 
regression. J R Stat Soc Ser C Appl Stat 2009;58(2):211-24. 
5  Liu S. and Yuan Y. Bayesian Optimal Interval Designs for Phase I Clinical Trials, Journal of 
the Royal Statistical Society: Series C, 2015;64: 507-523. 
6 Yuan Y., Hess K.R., Hilsenbeck S.G. and Gilbert M.R. (2016) Bayesian Optimal Interval 
Design: A Simple and Well-performing Design for Phase I Oncology Trials, Clinical Cancer 
Research, 2016;22: 4291-4301. 
7 Venier J, Herrick R, Norris C et al. (2020). Bayesian Optimal Interval (BOIN) Phase I Design 
(PID-862): Version 1.0.8, Houston, Texas: The University of Texas MD Anderson Cancer 
Center. Available at: https://biostatistics.mdanderson.org/SoftwareDownload/. Accessed Sep 
2020. 


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APPENDIX 13    PRELIMINARY SAFETY COHORT 
1 
PRELIMINARY SAFETY COHORT FOR PHASE 1, PART 1A 
1.1 
Justification for the Preliminary Safety Cohort (PSC): 
The FIH starting dose of BMS-986207 monotherapy, as an immune-mediated anti-cancer agent, 
was determined using both toxicology- and pharmacology- (
 efficacy)-based 
approaches to ensure participant safety while limiting the number of participants receiving 
nonpharmacologically active doses. The toxicology-based approach utilized the HNSTD 
determined from a 1-month repeat-dose toxicity study in cynomolgus monkeys. The 
pharmacology-based approach leveraged the pharmacology data (ie, 
 efficacy) obtained 
from mouse surrogates to project the human effective dose, from which the FIH starting dose was 
selected. The starting doses determined from both approaches were integrated, and the lower dose 
of 1 mg/kg (or 80 mg flat dose, assuming an average body weight of 80 kg in cancer participants) 
was recommended as the starting monotherapy dose for BMS-986207. 
Subsequent to discussions with FDA, to further ensure a sufficient safety margin for the 
monotherapy starting dose, given the absence of previous clinical experience with BMS-986207, 
a Preliminary Safety Cohort (PSC) was added to the study. In the PSC, a single participant will 
receive BMS-986207 monotherapy starting at the 2-mg dose, with intra-participant dose escalation 
to 6 mg, and then to 20 mg. Following a 5-day safety observation period for this participant 
following the initial administration of the 20-mg dose, 2 additional participants will begin the study 
at the 20-mg BMS-986207 dose level. 
At the conclusion of the 4-week DLT period for these 3 participants in the PSC, which respectively 
begins with the first administration of the 20-mg dose for each of the 3 participants in the PSC, if 
no DLT is observed, the main study protocol will begin with participants receiving BMS-986207 
monotherapy at the 80 mg dose level. If a DLT is observed in the PSC, the BLRM will be initiated. 
A decision whether to treat additional patients at the same dose level, or escalate the dose, will be 
based on a recommendation from the BLRM and overall clinical assessment with all the safety, 
pharmacokinetic 
data.. 
1.2 
Study Design for PSC: 
In the PSC, the first cohort of 3 participants will be administered intravenous (IV) doses of BMS- 
986207 as follows: 
The starting dose of 2 mg of BMS-986207 will be assigned to the first participant, followed by 
intra-participant dose escalation after 2 weeks to 6 mg, and then 2 weeks later to 20 mg, if no DLTs 
are observed in any of the dose intervals. After the participant clears a 5-day safety observation 
period at the 20-mg dose level, 2 additional participants will be enrolled at the 20-mg dose level. 
The 4-week DLT period for all participants in the PSC begins with the first 20-mg dose 
administration. For these PSC participants, subsequently, flat dose levels of 20 mg will be given 
q2w, in 8-week cycles, for up to 3 cycles of study therapy. 
All the procedures for this PSC, in regard to the study design, study population, treatment, 
discontinuation criteria and study assessments/procedures, are the same as described in respective 


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Sections 5, 6, 7, 8 and 9 of the main protocol. The objectives, endpoints, and statistical 
considerations (Section 4 and Section 10) of the main protocol also apply to the PSC. The only 
exceptions to the provisions of the main protocol for the PSC are the Treatment Periods and the 
Pharmacokinetics, Immunogenicity 
 sampling schedules for the first participant 
undergoing intra-participant dose escalation. These exceptions to the main protocol are detailed 
below. 
1.2.1 
Treatment Periods 
The first participant will receive BMS-986207 as monotherapy at the starting dose of 2 mg. The 
infusion will take place over 5 minutes and will require a 60-minute observation period following 
the completion of the infusion. A 60-minute post infusion safety observation period is considered 
appropriate given BMS-986207 is a fully human monoclonal antibody that is an antagonist (not 
an agonist) and has a low likelihood of resulting in infusion reactions. The participant will follow 
the assessments and procedures described below and, after 2 weeks, if no DLT occurs in that 
2-week interval, the participant will proceed to the next dose infusion of BMS-986207 at 6 mg. 
This infusion will take place over 10 minutes and will require a 60-minute observation period 
following the completion of the infusion. After another 2-week observation period, if no DLT 
occurs in that 2-week interval, the participant will then escalate to the next dose level of 20 mg. At 
this dose level, a treatment cycle will be comprised of 4 doses of BMS-986207 administered q2w. 
At the 20-mg dose level, BMS-986207 infusions will take place over 60 minutes and will require 
a 60-minute observation period following the completion of the infusion for the first 4 doses of 
Cycle 1 for the participant, as described in Section 5.1.2 of the main protocol. After the first 
participant clears a sentinel period of 5 days with no safety issues observed, 2 new participants 
will be enrolled in the study to start treatment of BMS-986207 at the 20-mg dose level. These 
2 participants will follow all the same study procedures and evaluations as described in the main 
protocol. The PSC Treatment Scheme is summarized in Table 1.2.1-1 below. 
Vital signs and pulse oximetry monitoring, as outlined in Section 2, will be performed for all dose 
level administrations of BMS 986207. 
Table 1.2.1-1: 
Preliminary Safety Cohort Treatment Scheme 
 
Patient 
Treatment Time 
Dose (mg) 
Infusion Time, min 
Day 1 
2 
5 
Day 15 
6 
10 
Day 29 
20 
60 
> Day 34b 
20 
60 
> Day 34b 
20 
60 
b Patient 
 could be enrolled at 20 mg dose level after Patient has cleared a 5 day sentinel period after he 
received the first dose of 20 mg. These two participants will follow all the same study procedures and evaluations 
as described in the main protocol. 


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1.2.2 
Study assessments and procedures: 
The first participant enrolled in the PSC will follow the same study assessments and procedures 
for respective day number of the cycle as described in Section 9 and as outlined in Section 2 of the 
main protocol, including physical exams and safety laboratory assessment, with the exception of 
pharmacokinetic and immunogenicity sample collections, as detailed below in Table 1.2.2-1, and 
triplet ECGs which will be performed on both CAD1 and CBD1. 
Table 1.2.2-1: 
Pharmacokinetic and Immunogenicity Sampling Schedule for PSC - 
Intra-Participant Dose Escalation 
 
Study Cycle (C) and 
Day (D) of 
Sample Collection 
Days on 
Treatment 
Event 
Time (relative to dose 
administration) 
Hour: Min 
BMS-986207 
Blood Sample 
(all participants) 
BMS-986207 
ADA Samples 
(all participants) 
CAD1 (2 mg) 
1 
Predosea 
00.00 
X 
X 
EOIb 
60 to 90 min 
X 
4:00 
X 
CAD8c (2 mg) 
8 
168:00 
X 
CBD1 (6 mg) 
15 
Predosea 
00: 00 
X 
X 
EOI 
01:00 
X 
4:00 
X 
CBD8c (6 mg) 
22 
168:00 
X 
C1D1 (20 mg) 
29 
Predosea 
00: 00 
X 
X 
EOIb 
01:00 
X 
4:00 
C1D8 
36 
168: 00 
X 
C2D1 
85 
Predosea 
00: 00 
X 
EOIb 
60 to 90 min 
X 
C3D1 
141 
Predosea 
00: 00 
X 
X 
C4D1 
Predosea 
00: 00 
X 
X 
C5D1 
Predosea 
00: 00 
X 
X 
EOT 
X 
X 
30-day follow-up 
X 
X 
60-day follow-up 
X 
X 
Abbreviations: ADA, anti-drug antibody, BMS, Bristol-Myers Squibb; C, cycle; D, day; EOI, end of infusion, EOT, 
end of treatment; PSC, preliminary safety cohort. 


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a Predose: All predose samples for BMS-986207 should be taken prior to the start of the infusion. If the predose 
sample has been taken, however, and an unscheduled, missing, or delayed dose occurs, an additional predose sample 
shall be taken. 
b EOI samples for BMS-986207 should be collected immediately prior to stopping the infusion (preferably within 
2 minutes prior to the end of the infusion). If the end of infusion is delayed to beyond the nominal infusion duration, 
the collection of this sample should also be delayed accordingly. 
c Day 8 sample may be taken during Days 7-9 of a cycle. 


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APPENDIX 14    REVISED PROTOCOL SUMMARY OF CHANGE HISTORY 
Overall Rationale for the Protocol Amendment 03, 02-Jan-2021 
 
 
 
 
 
 
 
The study design has been updated to include 2 new cohorts, Part 1C, BMS 986207 + nivolumab 
+ ipilimumab in participants with advanced solid tumors and Part 2C, BMS 986207 + nivolumab 
+ ipilimumab in participants with 1L NSCLC with tumor cell PD-L1 expression ≥ 50%. Primary 
endpoints have been added that are specific to Parts 1C and 2C. A secondary objective related to 
has been changed 
because known downstream 
are not specific to TIGIT, but instead are measures of general increases 
in inflammation 
in the tumor. 
Other key changes include additional schedule of activities tables, pharmacokinetic sampling 
tables, 
for Parts 1C and 2C, and response to the SARS-Cov-2 
pandemic. Information within the appendices, including adverse events (AEs) and serious AEs 
(SAEs; Appendix 3), contraceptive methods (Appendix 4), and immune-mediated AE 
management algorithms (Appendix 6) have been updated to align with BMS standard language 
and the most recent safety information for investigational products used in this study. Minor 
editorial changes have been made throughout the protocol and the Synopsis has been amended to 
reflect the changes listed below. 
 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Title Page 
• Updated Medical Monitor contact information 
and added Clinical Scientist Contact 
information. 
• Updated Medical Monitor name and 
contact information supersedes 
Administrative Letter 05 
Title Page 
• Updated study title 
• To accurately describe the study 
given the addition of the BMS- 
986207 + nivolumab + ipilimumab 
treatment groups 
Section 2, Schedule 
of Activities 
• Table 2-1 Screening: Updated 
• These changes were made to clarify 
and align expectations and timing of 
scheduled activities with the study 
design. 
rows to add instructions for Parts 
1C and 2C, added 
row for 
participants in Part 2C, and serum collection 
of 
. 
• Added new Table 2-4:On Study Assessments 
Triplet Safety (Parts 1C and 2C) 
• Added information to Table 2-5 on follow-up 
tumor assessments for Parts 1C and 2C, 
sample collection and AE monitoring for 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
participants with known or suspected SARS- 
CoV-2 infection 
Section 3.1, Study 
Rationale 
• Added rationale for current amendment 
• To align with proposed changes to 
study design 
Section 3.2, 
Background 
• Added and/or updated text and references to 
literature and Investigator Brochures 
throughout these sections and subsections. 
• Added new Section 3.2.1.4 describing the 
preliminary safety profile for BMS-986207. 
• Updated Section 3.2.2 Nivolumab 
• Added new Section 3.2.3 Ipilimumab 
• Added new Section 3.2.4 Nivolumab 
Combined with Ipilimumab Clinical Activity 
• Aligned the description of 
background information and 
experience with study treatments 
with currently available data. 
Section 3.3, 
Benefit/Risk 
Assessment 
• Added benefit/risk assessment for treating 
non-small cell lung cancer participants 
• Added benefit/risk assessment for combination 
of BMS-986207 + nivolumab + ipilimumab 
• Added benefit/risk assessment for participants 
with confirmed SARS-CoV-2 infection 
• Additional benefit/risk information 
was added to support the changes to 
study design and to address risks 
associated with SARS-CoV-2 
infection 
Section 4, 
Objectives and 
Endpoints 
• Added primary objectives for Parts 1C and 2C 
and modified secondary 
objectives to include combination therapy with 
BMS-986207 + nivolumab + ipilimumab 
• Objectives modified to support 
changes in study design. 
• Reclassified the secondary objective related to 
assessments 
•  
objectives were 
modified because known 
downstream 
are not specific to TIGIT, 
but instead are measures of general 
increases in 
in 
the tumor. 
Section 5.1, Overall 
Design 
• Updated description of overall design 
• Added for clarity and to describe 
substudy conducted under site 
specific amendments 6, 7, and 8. 
Section 5.1.2, 
Treatment Period 
• This section was modified as follows: 
• Added description of treatment and details of 
study drug infusion for Part 2C. 
• To describe changes in study design 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
• Added Section 5.1.2.2 describing treatment in 
Part 1C and 2C 
• Updated Figure 5.1.2.2-1 (Overall Study 
Design) and added Figure 5.1.2.2-2 
(Treatment Cohorts) 
• Added Section 5.1.2.6 describing safety 
monitoring during Part 1C 
• Added description of Part 2C to Section 
5.1.2.7 Cohort Expansion 
• Section describing treatment beyond 
progression was moved to Section 5.1.4 
Section 5.1.3, Safety 
Follow-up Period 
• Added section describing 2-year duration of 
treatment for Parts 1C and 2C 
• Indicated that Section 5.1.3.4 Retreatment is 
only applicable to Parts 1A, 1B, 2A, and 2B. 
• To align with standard 2-year 
duration of treatment for nivolumab- 
containing regimens. Retreatment 
was included in Parts 1A, 1B, 2A, 
and 2B, but is not needed in Parts 
1C and 2C because of this longer 
duration of treatment. 
Section 5.1.4, 
Treatment Beyond 
Progression and 
Section 8.1.1, 
Treatment Beyond 
Progression 
• The previous Section 5.1.2.6 and previous text 
in Section 8.1.1 were relocated to Section 
5.1.4, and language related to tumor/lesion 
size was added to text describing the decision 
to continue treatment beyond progression. 
• Treatment beyond progression 
language was combined into 1 
section and relocated for clarity and 
improved readability. Text was 
added to clarify expectations for 
decisions and documentation for 
continuing treatment beyond 
progression. 
Section 5.1.5, Data 
Monitoring 
Committee and 
Other External 
Committees 
• Updated rationale for no Data Monitoring 
Committee and language describing BMS 
multi-layered process to ensure safety 
monitoring during the study. 
• Clarified BMS process to ensure 
safety monitoring. 
Section 5.2, Number 
of Participants 
• Updated to reflect additional participants to be 
enrolled in Parts 1C and 2C. 
• To reflect updates in study design 
Section 5.4, 
Scientific Rationale 
for Study Design; 
• Updated text description of overall study 
design to incorporate Parts 1C and 2C. 
• Added new Section 5.4.3 to provide rationale 
for combination of BMS-986207 + nivolumab 
+ ipilimumab 
• Added new Section 5.4.4 to provide rationale 
for triplet therapy in NSCLC 
• Updated Section 5.4.5 Rationale for Treatment 
Duration to provide a rationale for 2-year 
duration of treatment in Parts 1C and 2C 
• Updated Section 5.4.7 Rationale for Tumor 
Selection to include NSCLC 
• Updated Section 5.4.8 Rationale for Dose 
Escalation Phase Design to include Part 1C 
• To support updates to study design. 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Section 5.5.2, 
Rationale for 
Dosing Schedule 
• Updated Section 5.5.2.1 to summarize 
preliminary pharmacokinetics (PK) 
parameters for BMS-986207 at steady state 
and receptor occupancy (RO) data from Part 1 
of the study. 
• Updated Section 5.5.2.2. Changed title to 
“Nivolumab” and updated text to provide most 
current information on nivolumab dosing 
• Added Section 5.5.2.3 Ipilimumab providing 
rationale for ipilimumab dosing 
• Updated Section 5.5.2.4 to provide rationale 
for ipilimumab infusion time 
• This section has been updated to 
provide rationale for dosing in Parts 
1C and 2C and to reflect the most 
current information available for 
each of the study drugs. 
Section 6.1, 
Inclusion Criteria 
• Added inclusion criteria 2) w) i) through 2) w) 
viii) that are applicable to Part 2C participants 
only (participants with NSCLC who are 
treatment naive with PD-L1 expression ≥50%) 
• Added inclusion criterion 2) x) for participants 
with confirmed or suspected SARS-CoV-2 
• Laboratory values in 3) a) updated 
• Inclusion criterion 7) f) contraception 
requirements for male participants not 
applicable per Protocol Amendment 03 
• To align with updates to the study 
design and to reflect the most 
current safety information for 
nivolumab. 
• Contraceptive requirements for male 
participants removed to conform to 
most recent safety information for 
these investigational products 
Section 6.2, 
Exclusion Criteria 
• Exclusion criteria 1) b) and 1) c) added that 
are applicable to Part 2C participants only 
• Exclusion criteria 3) e) xii, 3) e) xiii, and 3) e) 
ix added to account for participants with 
known or suspected SARS-CoV-2 infection 
• To align with updates to the study 
design and to mitigate risks to 
participants with known or 
suspected SARS-CoV-2 infection 
Section 6.4.1, 
Retesting During 
Screening or Lead- 
In Period 
• Instruction added for management of 
participants with known or suspected SARS- 
CoV-2 infection 
• To mitigate risks to participants with 
known or suspected SARS-CoV-2 
infection 
Section 7.1, 
Treatments 
Administered 
• Table 7.1-1: Removed 40 mg vial of 
Nivolumab Solution for Injection and added 
BMS-734016 Solution for Injection 
(ipilimumab).” 
• Table 7.1-2: Added rows for 1200 mg BMS- 
896207, 360 mg nivolumab, and 1 mg/kg 
ipilimumab 
• In text, added treatment duration and 
description of dosing for Parts 1C and 2C 
• Added new study drug (ipilimumab) 
and removed dose form of 
nivolumab that is no longer in use. 
• Aligned tables and text with updates 
to study design 
Section 7.2, Method 
of Treatment 
Assignment 
• Updated text to describe treatment assignment 
for Part 2C. 
• Aligned treatment assignment 
methods with updates to the study 
design described above. 
Section 7.4.1 Dose 
Limiting Toxicities 
• Added DLT period for Parts 1C and 2C 
• To reflect changes to the study 
design 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Section 7.4.2, 
Treatment 
Algorithms 
• Added myocarditis to the list of immune- 
related AEs 
• To align with the most recent safety 
information for nivolumab 
Section 7.4.3.3 
Criteria to Resume 
Treatment 
• Added criteria to resume treatment for 
participants with known or suspected SARS- 
CoV-2 infection 
• To mitigate risks to participants with 
known or suspected SARS-CoV-2 
infection 
Section 7.6.1, 
Prohibited and/or 
Restricted 
Treatments 
• Added live/attenuated vaccines, 
investigational vaccines, and investigational 
therapies for treatment of SARS-CoV-2 to list 
of prohibited and/or restricted treatments. 
• To align with the most recent safety 
information for nivolumab and to 
exclude investigational treatment of 
SARS-CoV-2 
Section 8.1, 
Discontinuation 
from Study 
Treatment 
Text was modified as follows: 
• Added note that under specific circumstances, 
a participant who has been imprisoned may be 
permitted to continue as a participant. 
• Modified text related to pregnancy cases to: 
o Add that BMS/Medical Monitor must be 
notified within 24 hours of a pregnancy 
event. 
o Remove text related to possible favorable 
benefit-risk ratio discussion. 
Added reference to Section 9.2.5 Pregnancy. 
• Clarified scenarios in which 
imprisoned participants may be 
permitted to continue on the study 
and expectations for reporting 
pregnancy. 
Section 9.1 Efficacy 
Assessments 
• Imaging assessments for Parts 1C and 2C 
described 
• To reflect updates to the study 
design. 
Section 9.2.3 
Follow-up of AEs 
and SAEs 
• Added instructions for follow-up of 
participants with known or suspected SARS- 
CoV-2 infection 
• To mitigate risks to participants with 
known or suspected SARS-CoV-2 
infection 
Section 9.3 
Overdose 
• Modified SAE reporting requirements for 
overdose 
• To align with updates in Appendix 3 
Section 9.5, 
Pharmacokinetics 
and 
• Added description of sample collection 
• Added Table 9.5-4 describing PK sample 
collection in Part 1C and 2C 
• Updated text to provide clarity on 
sample collection 
• Updated tables for PK and 
immunogenicity sampling schedules 
to align with updates to the study 
design. 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Section 10.1, 
Sample 
Size 
Determination 
• Added Section 10.1.2: Safety Evaluation 
Phase (Part 1C) 
• Added Section 10.1.3.2 Cohort Expansion in 
Part 2C 
• Added new sections to describe 
sample size determination in Parts 
1C and 2C. 
Section 10.3, 
Statistical Analyses 
• Modified Table 10.3.1-1: added statistical 
methods for efficacy assessment in Part 2C. 
• To align with updates to study 
design. 
Section 10.3.3, 
Pharmacokinetic 
Analyses for BMS- 
986207, Nivolumab, 
and Ipilimumab 
• Removed Ceoi as an endpoint measure 
• Cmax will be measured and derived 
to capture maximum observed 
concentration. 
Section 10.3.8, 
Interim Analyses for 
Parts 2A, 2B, and 
2C 
• Expanded to describe interim analyses for Part 
2C 
• To align with updates to study 
design 
Appendix 2: Study 
Governance 
Considerations 
Modified Good Clinical Practice section in 
Appendix 2 to: 
• Add bullet to clarify that the study will also be 
conducted in accordance with ethical 
principles derived from international 
guidelines including the Declaration of 
Helsinki and Council for International 
Organizations of Medical Sciences 
International Ethical Guidelines Good Clinical 
Practice. 
• Align with revised definition of serious breach 
to Regulation No 536/2014 of the European 
Parliament and of the Council. 
• Modified text to align with 
statement in the informed consent 
form and most current BMS 
standard language. 
Appendix 3: 
Adverse Events and 
Serious Adverse 
Events Definitions 
and Procedures for 
Recording, 
Evaluating, and 
Follow-up and 
Reporting 
Added the following sections: 
• Events Meeting the AE Definition. 
• Events Not Meeting the AE Definition. 
• Definition of SAE. 
Modified the following sections: 
• SAEs (text related to pregnancy and 
drug-induced liver injury). 
• Evaluating AEs and SAEs (updated and 
rearranged bulleted information). 
• Reporting of SAEs to Sponsor or Designee 
(updated and rearranged bulleted information 
related to pregnancy and paper report forms). 
• Modifications made to information 
related to AEs and SAEs to align 
with the most current BMS standard 
language, regulatory definition 
EMA GVP Module VI 
(EMA/873138/2011) and ICH E2A, 
and clarify the instructions for 
reporting pregnancy. 
Appendix 4: 
Women of 
Childbearing 
Potential and 
• Added additional details for hormonal, oral, 
intravaginal, and intrauterine 
hormone-releasing system contraceptive 
methods. 
• Clarified contraceptive methods for 
women of childbearing potential and 
male participants. 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 03 
Section Number & 
Title 
Description of Change 
Brief Rationale 
Methods of 
Contraception 
• Removed contraceptive requirements for male 
participants 
Appendix 6: 
Management 
Algorithms for 
Immuno-oncology 
Agents 
• Modified the footnote in the Hepatic Adverse 
Event Management algorithm. 
• Added an additional algorithm for 
management of myocarditis. 
• Language was modified to align 
protocol with current study 
treatment Investigator Brochures 
and program safety parameters. 
Appendix 12: 
Statistical 
Methodology 
• Added additional details to the escalation 
design simulation for Part 1C 
• Clarified use of the Bayesian 
Optimal Interval design to guide 
determination of the maximum 
tolerated dose in Part 1C. 
All 
• Minor formatting and typographical 
corrections. 
• Corrections for clarity and 
consistency within the document 
were minor, and therefore have not 
been summarized. 
 
Overall Rationale for the Revised Protocol 02, 06-Jul-2017 
The main purpose of this amendment is to add q4w dosing regimen to both the BMS-986207 
monotherapy and the combination nivolumab and BMS-986207 dosing schedule. The less frequent 
The main purpose of this amendment is to add q4w dosing regimen to both the BMS-986207 
monotherapy and the combination nivolumab and BMS-986207 dosing schedule. The less frequent 
q4w dosing schedule may benefit patients by decreasing the number of time drug is infused and 
will also reduce the potential medical burden from the care givers and cancer treatment institutions. 
Additional changes to the protocol provide clarity in executing the clinical study. 
Revisions apply to future participants enrolled in the study. 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 1 Synopsis 
Section 2 Schedule of Activities 
Section 5 Study Design 
Addition of q4w dosing 
regimen 
The addition of q4w dosing regimen will 
provide data for more convenience dosing 
regimens in the future 
Section 7 Treatment 
Section 9 Study Assessment and 
Procedures 
Section 6 Study Population 
Inclusion criteria numbering 
for the Target Population was 
changed. 
Inclusion criteria numbering changed to 
ensure clear identification of specific 
inclusion criteria. 
Section 6 Population 
Inclusion criteria 3c) changed 
to include subjects that have 
clinical stable thyroid 
Criteria was updated to ensure appropriate 
review of subjects and to ensure eligible 
subjects are not excluded unnecessarily. 


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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 02 
Section Number & Title 
Description of Change 
Brief Rationale 
function and Exclusion 
criteria 3e, x) was modified to 
include “unless agreed by the 
medical monitor” 
Section 2 Schedule of Activities 
Extension of the window 
period for all Laboratory 
collections to 72 hours 
Logistically it is difficult to collect samples 
within 24 hours. 
Section 9 Study Assessment and 
Procedures 
Table 9.4.4-1 
Clarification of reflex 
assessments 
Addition of D0 assessments 
for Retreatment eligible 
subjects where applicable 
Section 9 Study Assessment and 
Procedures 
Table 9.5-2 Removal of some 
erroneous samples and 
clarification on time points. 
Addition of Table 9.5.3 for 
the q4w dosing 
Section 9 Study Assessment and 
Procedures 
to the US 
and Canada sites. 
are out of scope for the 
plan for this clinical study 
To ensure the integrity of 
only 
samples from US and Canada sites will be 
collected. 
All 
Minor formatting and 
typographical corrections