Clinical trial NCT05169684
Conditions: Prostatic Neoplasms, Castration-Resistant
Keywords: BMS-986218 BMS-936558 Docetaxel Metastatic MDX1106 Nivolumab ONO-4538 TAXOTERE
Sponsor: Bristol-Myers Squibb
Start date: 2022-02-14; Completion date: 2023-12-06
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this study is to assess the safety, efficacy, tolerability, and toxicity of docetaxel alone, in combination with BMS-986218, or in combination with nivolumab plus BMS-986218 in men who have metastatic castration-resistant prostate cancer (mCRPC) that progressed after novel antiandrogen therapy and have not received chemotherapy for mCRPC.

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-986218 intervention 2: Docetaxel intervention 3: Nivolumab
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days intervention 3: Specified dose on specified days

Protocol documents:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 2, Open-label, Randomized Controlled Trial of BMS-986218 or BMS-986218 Plus 
Nivolumab in Combination with Docetaxel in Participants with Metastatic Castration-resistant 
Prostate Cancer 
 
NCT Number: NCT05169684 
Document Date (Date in which document was last revised): 18 February 2022 


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Page: 1 
Protocol Number: CA022009 
Date: 02-Sep-2021 
Revised Date: 18-Feb-2022 
 
CLINICAL PROTOCOL CA022009 
A Phase 2, Open-label, Randomized Controlled Trial of BMS-986218 or BMS-986218 Plus 
Nivolumab in Combination with Docetaxel in Participants with Metastatic Castration-resistant 
Prostate Cancer 
 
Brief Title: 
A Phase 2 Trial of BMS-986218 or BMS-986218/Nivolumab in Combination with Docetaxel in 
mCRPC 
Protocol Amendment Number: 02 
 
Clinical Trial Physician- Medical Monitor 
Bristol-Myers Squibb Company 
3401 Princeton Pike Lawrenceville, NJ 08648 
Clinical Scientist 
Bristol-Myers Squibb Company 
86 Morris Ave Summit, NJ 08648 
 
emai 
emai 
 
24-hr Emergency Telephone Number 
USA: 
International: 
 
Bristol-Myers Squibb Company 
Route 206 & Province Line Road 
Lawrenceville, NJ 08543 
Avenue de Finlande 4 
B-1420 Braine-l’Alleud, Belgium 
 
REGULATORY AGENCY IDENTIFIER NUMBER(S) 
IND: 157650 
EudraCT/EU Trial Number: 2021-003990-74 
UTN: U1111-1268-2566 
 
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 
Phone: 
: 


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CA022009 
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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. References to BMS in this protocol may apply to partners to which BMS 
has transferred obligations (eg, a Contract Research Organization [CRO]). 
 
 
 
© 2020 Bristol-Myers Squibb Company 


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DOCUMENT HISTORY 
 
Document 
Date of Issue 
Summary of Change 
Protocol 
Amendment 02 
18-Feb-2022 
The overall purpose for Protocol Amendment 02 is to provide updated 
language introducing an additional “next-generation” anti-cytotoxic T- 
lymphocyte-associated protein 4 (anti-CTLA-4) agent which may be 
incorporated into the study design via future amendment. An update was 
also made to the Bayesian Optimal Interval (BOIN) table. 
Protocol 
Amendment 01 
24-Nov-2021 
The overall purpose of Protocol Amendment 01 was to provide updates 
to increase participant safety: 
• 
Clarified dose-limiting toxicity criteria and exceptions 
• 
Updated hepatic adverse event criteria for delay, resume, and 
discontinue of study treatments 
• 
Updated inclusion/exclusion criteria related to prior radium 223 
treatment and superscans 
• 
Clarified that progression-free survival (PFS) endpoint refers to 
radiographic PFS 
Original Protocol 
02-Sep-2021 
Not applicable 


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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: 
The overall purpose for Protocol Amendment 02 is to introduce information regarding BMS- 
986288, an additional “next-generation” anti-cytotoxic T-lymphocyte-associated protein 4 (anti- 
CTLA-4) monoclonal antibody (mAb). BMS-986288 may be incorporated into the study design via 
future protocol amendment to test further the central study hypothesis that addition of next- 
generation anti-CTLA-4 agents, with or without nivolumab, will improve outcomes compared to 
docetaxel alone. BMS-986288 is another non-fucosylated next-generation anti-CTLA-4 that 
shares the Fcγ receptor (FcγR)-dependent mechanisms of BMS-986218. BMS-986288 is identical 
to BMS-986218 except for an additional “Probody” design element that could decrease toxicity 
by preventing binding to sites outside of the tumor, and thus further improve the benefit/risk profile 
as compared to BMS-986218. 
An update was also made to the Bayesian Optimal Interval (BOIN) table that eliminated criteria for 
1 or 2 participants, as enrollment will be in groups of 3 to 4 participants at a time in Part 1a and Part 
1b. 
The Protocol Summary has been revised as applicable to align with the protocol changes. 
This protocol amendment applies to all participants. 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Table 2-2: On Study Treatment 
Procedural Outline, Body 
Imaging/Bone Scan 
Table 2-3: Long-term Follow-up 
Procedural Outline, Body 
Imaging/Bone Scan 
Tumor assessments should occur 
every 9 weeks (± 7 days) from first 
dose, 
regardless 
of 
treatment 
schedule or dose delays for first 27 
weeks (instead of 24 weeks). 
Since images are completed every 9 
weeks initially, the scans should be 
done at 9, 18, and 27 weeks, and 
thereafter every 12 weeks. 
Table 2-2: On Study Treatment 
Procedural Outline, ECG 
References to the Data Management 
Electrocardiogram (ECG) 
Study 
Guidelines were deleted. 
This guideline does not exist for this 
study. 
Section 3: Introduction 
Section 3.1: Study Rationale 
Section 3.2.2: BMS-986218 and 
BMS-986288 Mechanism of Action 
Section 3.2.5: BMS-986218 and 
BMS-986288 Clinical Activity 
Section 3.3.3: Overall Benefit/Risk 
Conclusion 
Section 5.4.2.1: Rationale for 
Docetaxel and BMS-986288 or 
BMS-986288 plus Nivolumab 
Language was added introducing 
next-generation 
anti-CTLA-4 
agents. 
Based on emerging data from the 
ongoing CA043-001 study, BMS- 
986288 may be incorporated into the 
CA022-009 study design if BMS- 
986288 has a better benefit/risk 
profile than BMS-986218. 


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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02 
Section Number & Title 
Description of Change 
Brief Rationale 
Table 5.1.2-1: Safety Lead-in 
Evaluation Guidance Based on 
BOIN Design 
Columns for 1 or 2 participants were 
deleted from the BOIN table. The 
de-escalation criteria were modified. 
Three to 4 participants will enroll at 
a time into Part 1a and Part 1b (see 
protocol Section 5.1.2). Therefore, 
criteria for n = 1 and n = 2 will not 
be needed in the study. Modifying 
the de-escalation criteria allows for 
all possibilities in the table. 
Section 6.2: Exclusion Criteria, 1), 
o) 
Added list of topical steroid types. 
To clarify which types of topical 
steroids are allowed. 
Section 10.2: Sample Size 
Determination, Sample Size 
Justification for Randomized, 
Controlled Portion (Part 2) 
The percentages were corrected to 
5% in control arm, 9% in the BMS- 
986218 + docetaxel arm, and 7% in 
the BMS-986218 + nivolumab + 
docetaxel arm. 
Corrects typos. 


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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
1 
DOCUMENT HISTORY.............................................................................................. 
3 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: ............................ 
4 
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 02................ 
4 
TABLE OF CONTENTS.............................................................................................. 
6 
1 PROTOCOL SUMMARY......................................................................................... 
10 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
23 
3 INTRODUCTION ..................................................................................................... 
43 
3.1 Study Rationale ................................................................................................. 
43 
3.2 Background ....................................................................................................... 
44 
3.2.1 Indication Background............................................................................. 
44 
3.2.1.1 CTLA-4 Blockade in Prostate Cancer ............................................ 
46 
3.2.1.2 Programmed Death-1 (PD-1)/Programmed Death-ligand 1(PD-L1) 
Blockade in Prostate Cancer ................................................................ 
48 
3.2.1.3 Role for Dual Checkpoint Blockade Inhibition: (anti-CTLA-4 and 
anti-PD-1) in Prostate Cancer.............................................................. 
50 
3.2.2 BMS-986218 and BMS-986288 Mechanism of Action ............................ 
50 
3.2.3 Nivolumab Mechanism of Action ............................................................. 
51 
3.2.4 Docetaxel Mechanism of Action .............................................................. 
52 
3.2.5 BMS-986218 and BMS-986288 Clinical Activity .................................... 
52 
3.2.6 Nivolumab Clinical Activity ..................................................................... 
52 
3.2.7 Docetaxel Clinical Activity ...................................................................... 
52 
3.3 Benefit/Risk Assessment .................................................................................. 
53 
3.3.1 Risk Assessment ....................................................................................... 
53 
3.3.2 Benefit Assessment ................................................................................... 
58 
3.3.3 Overall Benefit/Risk Conclusion.............................................................. 
58 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
60 
5 STUDY DESIGN....................................................................................................... 
62 
5.1 Overall Design .................................................................................................. 
62 
5.1.1 Screening Period...................................................................................... 
63 
5.1.2 Treatment Period ..................................................................................... 
64 
5.1.3 Follow-up Period ..................................................................................... 
67 
5.1.3.1 Safety Follow-up ............................................................................. 
67 
5.1.3.2 Survival Follow-up.......................................................................... 
68 
5.1.4 Data Monitoring Committee and Other Committees............................... 
68 
5.1.4.1 Safety Monitoring for Part 1........................................................... 
68 
5.1.4.2 Data Monitoring Committee ........................................................... 
69 
5.1.4.3 Blinded Independent Central Review.............................................. 
69 
5.2 Number of Participants ..................................................................................... 
69 
5.3 End of Study Definition .................................................................................... 
70 
5.4 Scientific Rationale for Study Design............................................................... 
70 
5.4.1 Rationale for Population.......................................................................... 
70 
5.4.2 Rationale for Docetaxel and BMS-986218 or BMS-986218 plus 
Nivolumab ................................................................................................... 
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5.4.2.1 Rationale for Docetaxel and BMS-986288 or BMS-986288 plus 
Nivolumab ............................................................................................. 
5.4.3 Rationale for Two Year Duration of Treatment....................................... 
5.4.4 Rationale for Treatment Beyond Progression ......................................... 
5.4.5 Rationale for Open-label Design ............................................................. 
5.5 Justification for Dose ........................................................................................ 
5.5.1 BMS-986218 ............................................................................................ 
5.5.2 Nivolumab ................................................................................................ 
5.5.3 Rationale for Duration of Treatment with Docetaxel .............................. 
5.6 Clinical Pharmacology Summary of BMS-986218 .......................................... 
5.7 Clinical Pharmacology Summary of Nivolumab .............................................. 
6 STUDY POPULATION ............................................................................................ 
6.1 Inclusion Criteria .............................................................................................. 
6.2 Exclusion Criteria ............................................................................................. 
6.3 Lifestyle Restrictions ........................................................................................ 
6.4 Screen Failures.................................................................................................. 
6.4.1 Retesting During Screening or Lead-in Period ....................................... 
7 STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ....................... 
7.1 Study Interventions Administered .................................................................... 
7.2 Method of Study Intervention Assignment....................................................... 
7.3 Blinding............................................................................................................. 
7.4 Dosage Modification......................................................................................... 
7.4.1 Dose Modification Criteria for Nivolumab and/or BMS-986218............ 
7.4.2 Dose Delay Criteria for Docetaxel .......................................................... 
7.4.3 Criteria to Resume Treatment.................................................................. 
7.4.3.1 Criteria to Resume Treatment for Nivolumab and BMS-986218 ... 
7.4.4 Docetaxel Dose Reduction and Criteria to Resume Treatment ............... 
7.4.5 Dose-limiting Toxicities ........................................................................... 
7.4.6 Treatment of Related Infusion Reactions ................................................. 
7.4.7 Management Algorithms for Immuno-oncology Agents .......................... 
7.4.8 Docetaxel-related Hypersensitivity Reactions ......................................... 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
7.6 Treatment Compliance...................................................................................... 
7.7 Concomitant Therapy........................................................................................ 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
7.7.2 Other Restrictions and Precautions......................................................... 
7.7.3 Permitted Therapy ................................................................................... 
7.7.4 Palliative Radiation ................................................................................. 
7.7.5 Surgery ..................................................................................................... 
7.7.6 Imaging Restriction and Precautions ...................................................... 
7.8 Continued Access to Study Intervention After the End of the Study ............... 
8 DISCONTINUATION CRITERIA ........................................................................... 
8.1 Discontinuation From Study Intervention ........................................................ 
8.1.1 Discontinuation from Nivolumab and/or BMS-986128 ........................... 
8.1.2 Nivolumab and BMS-986218 Treatment Beyond Disease Progression .. 
8.1.3 Post-study Intervention Study Follow-up................................................. 
 
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8.2 Discontinuation From the Study ....................................................................... 
8.2.1 Individual Discontinuation Criteria ........................................................ 
8.3 Lost to Follow-up.............................................................................................. 
9 STUDY ASSESSMENTS AND PROCEDURES..................................................... 
9.1 Efficacy Assessments........................................................................................ 
9.1.1 Imaging Assessment for the Study............................................................ 
9.1.1.1 Methods of Measurement ................................................................ 
9.1.1.2 Imaging Assessment ........................................................................ 
9.1.1.3 BICR Confirmation of Progression ................................................ 
9.1.2 Clinical Outcomes Assessments ............................................................... 
9.1.2.1 EORTC QLQ-C30 ........................................................................... 
9.1.2.2 FACIT GP5 ..................................................................................... 
9.2 Adverse Events ................................................................................................. 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
9.2.2 Method of Detecting AEs and SAEs......................................................... 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
9.2.4 Regulatory Reporting Requirements for SAEs......................................... 
9.2.5 Pregnancy ................................................................................................ 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
9.2.7 Potential Drug-induced Liver Injury ....................................................... 
9.2.8 Other Safety Considerations .................................................................... 
9.3 Overdose ........................................................................................................... 
9.4 Safety ................................................................................................................ 
9.4.1 Physical Examinations............................................................................. 
9.4.2 Vital signs................................................................................................. 
9.4.3 Electrocardiograms ................................................................................. 
9.4.4 Clinical Safety Laboratory Assessments .................................................. 
9.4.5 Imaging Safety Assessment ...................................................................... 
9.5 Pharmacokinetics .............................................................................................. 
9.6 Immunogenicity Assessments........................................................................... 
9.7 Genetics............................................................................................................. 
9.8 Biomarkers ........................................................................................................ 
9.8.1 Peripheral Blood Biomarkers .................................................................. 
9.8.2 Exploratory Serum and Plasma Biomarkers ........................................... 
9.8.2.1 Plasma ctDNA................................................................................. 
9.8.3 Immunophenotyping................................................................................. 
9.8.3.1 T-cell Repertoire Analysis............................................................... 
9.8.3.2 Germline DNA Variants.................................................................. 
9.8.3.3 Gene Expression Profiling .............................................................. 
9.8.4 Tumor Samples......................................................................................... 
9.8.4.1 Characterization of Tumor Immune Microenvironment................. 
9.8.4.2 Characterization of Tumor T-cell Repertoire ................................. 
9.8.4.3 Gene Expression Profiling .............................................................. 
9.8.4.4 Mutational and DNA Methylation Analyses ................................... 
9.9 Additional Research.......................................................................................... 
9.10 Other Assessments .......................................................................................... 
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9.11 Health Economics OR Medical Resource Utilization and Health Economics 
........................................................................................................................... 
10 STATISTICAL CONSIDERATIONS .................................................................... 
10.1 Statistical Hypotheses ..................................................................................... 
10.2 Sample Size Determination............................................................................. 
10.3 Analysis Sets ................................................................................................... 
10.4 Statistical Analyses ......................................................................................... 
10.4.1 General Considerations ......................................................................... 
10.4.2 Primary Endpoint(s) .............................................................................. 
10.4.3 Secondary Endpoint(s)........................................................................... 
10.4.4 Exploratory Endpoint(s) ........................................................................ 
10.4.4.1 Pharmacokinetic Analysis for BMS-986218 and Nivolumab ....... 
10.4.4.2 Immunogenicity Analysis .............................................................. 
10.4.4.3 Biomarker Analysis ....................................................................... 
10.4.4.4 Clinical Outcomes Assessments .................................................... 
10.4.5 Other Safety Analysis ............................................................................. 
10.4.5.1 Continuous Safety Monitoring ...................................................... 
10.4.6 Other Analyses ....................................................................................... 
10.5 Interim Analyses ............................................................................................. 
11 REFERENCES ........................................................................................................ 
12 APPENDICES ......................................................................................................... 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP, AND REPORTING ....................................................................... 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL OF MALE PARTNERS 
DEFINITIONS AND METHODS OF CONTRACEPTION ................................. 
APPENDIX 5 PROSTATE CANCER WORKING GROUP 3 (PCWG3) 
GUIDELINES......................................................................................................... 
APPENDIX 6 ECOG PERFORMANCE STATUS ..................................................... 
APPENDIX 7 COUNTRY SPECIFIC REQUIREMENTS/DIFFERENCES .............. 
APPENDIX 8 MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 5 ............................................................................................................ 
APPENDIX 9 BOIN DESIGN DETAILS AND OPERATING CHARACTERISTICS 
................................................................................................................................. 
APPENDIX 10 CYP3A4 STRONG INHIBITOR AND INDUCER GUIDANCE ..... 
APPENDIX 11 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY 
................................................................................................................................. 
 
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1 
PROTOCOL SUMMARY 
Protocol Title: 
A Phase 2, Open-label, Randomized Controlled Trial of BMS-986218 or BMS-986218 Plus 
Nivolumab in Combination with Docetaxel in Participants with Metastatic Castration-resistant 
Prostate Cancer 
Brief Title: A Phase 2 Trial of BMS-986218 or BMS-986218/Nivolumab in Combination with 
Docetaxel in mCRPC 
Rationale: 
In 2004, 2 Phase 3 studies (TAX 327 and SWOG 99-16) demonstrated that docetaxel-based 
chemotherapy regimens improved survival in participants with metastatic castration-resistant 
prostate cancer (mCRPC) that progressed after castration therapy. More recently, most patients 
have also received treatment with at least 1 novel antiandrogen therapy (NAT) prior to use of 
docetaxel for mCRPC. The target population for this study is participants with mCRPC that 
progressed after an NAT and have not received chemotherapy for mCRPC. Treatment with 
chemotherapy in this population has a modest benefit with regard to overall survival and does not 
produce long-term disease control. Several lines of evidence support the hypothesis that addition 
of “next-generation” anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) agents, 
with or without nivolumab, will improve outcomes compared to docetaxel alone. 


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Objectives and Endpoints: 
Table 1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• 
To assess the safety, tolerability, and DLTs of 
docetaxel in combination with BMS-986218 
or in combination with BMS-986218 plus 
nivolumab in participants with mCRPC 
(Part 1) 
• 
Incidence of AEs, SAEs, AEs meeting protocol-defined 
DLT criteria, TRAEs, AEs leading to discontinuation, 
and deaths 
• 
To compare the rPFS in mCRPC participants 
treated with docetaxel and either docetaxel in 
combination with BMS-986218 or docetaxel 
in combination with BMS-986218 and 
nivolumab (Part 2) 
• 
rPFS for randomized participants is the time between 
randomization date and the first date of documented 
radiographic progression, or death due to any cause, 
whichever occurs first. The radiographic progression 
will be assessed by blinded independent central review 
(BICR) per PCWG3 
Secondary 
• 
To assess the antitumor activity of the 
combination of docetaxel with BMS-986218 
or BMS-986218 and nivolumab in mCRPC 
participants, based on ORR, TTR, and DOR 
(Part 2) 
• 
Objective response rate per PCWG3 (ORR-PCWG3) is 
the proportion of participants who have a confirmed 
complete or partial best overall response (BOR) per 
PCWG3 among randomized participants who have 
measurable disease at baseline. The BOR is defined as 
the best response designation, as determined by the 
BICR, recorded between the date of randomization and 
the date of objectively documented radiographic 
progression, or last tumor measurement, whichever 
occurs first 
• 
Time to response per PCWG3 (TTR-PCWG3) is the 
time from randomization date to the date of the first 
documented CR or PR per PCWG3, as determined by 
BICR 
• 
Duration of response per PCWG3 (DOR-PCWG3) is 
the time between the date of first response (CR/PR per 
PCWG3) to the date of first documented radiographic 
progression per PCWG3 (as determined by BICR), or 
death due to any cause 
• 
To assess PSA response rate (PSA-RR) and 
time to PSA progression (TTP-PSA; limited to 
participants with measurable PSA [defined as 
≥ 2 ng/ml] at baseline) (Part 2) 
• 
PSA-RR is the proportion of randomized participants 
with a 50% or greater decrease in PSA from baseline to 
any post-baseline PSA result. A second consecutive 
value obtained 3 or more weeks later is required to 
confirm the PSA response 
• 
TTP-PSA is the time between randomization date to the 
date of PSA progression per PCWG3 in randomized 
participants 
• 
To assess overall survival (OS) (Part 2) 
• 
OS for all randomized participants is the time between 
randomization date and the date of death from any 
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Table 1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
• 
To characterize safety of BMS-986218 in 
combination 
with 
docetaxel, 
and 
with 
nivolumab and docetaxel in Part 2 
• 
Overall safety and tolerability will be measured by the 
incidence of AEs, TRAEs, SAEs, AEs leading to 
discontinuation, and deaths 
Abbreviations: AE, adverse event; BICR, blinded independent central review; BOR, best overall response; CR, 
complete response; DLT, dose-limiting toxicity; DOR, duration of response; mCRPC, metastatic castration-resistant 
prostate cancer; ORR, objective response rate; OS, overall survival; PCWG3, Prostate Cancer Working Group 3; PR, 
partial response; PSA, prostate-specific antigen; PSA-RR, PSA response rate; rPFS, radiographic progression-free 
survival; SAE, serious adverse event; TRAE, treatment-related adverse event; TRR, time to response; TTP-PSA, time 
to PSA progression. 
 
Overall Design: 
This multi-center, randomized, controlled, open-label, Phase 2 study evaluates docetaxel alone, in 
combination with BMS-986218, or in combination with BMS-986218 plus nivolumab in men who 
have mCRPC that progressed after NAT and have not received chemotherapy for mCRPC. 
The study will be carried out in 2 parts: Part 1, a safety lead-in portion, and Part 2, a randomized, 
controlled portion. All participants will complete up to 3 study periods: screening (up to 28 days), 
treatment (up to 2 calendar years from first dose of study treatment regardless of treatment delays 
[21 days/cycle]), and follow-up. The Follow-up Period includes Safety Follow-up (comprising 
3 visits over about 100 days) and Survival Follow-up (up to 2 years from the last dose of study 
treatment) periods. The maximum duration of study participation will be approximately 4 years 
(up to 28 days of screening, treatment of up to 2 years, and follow-up of up to 2 years). Images 
will be submitted to a central imaging vendor and will undergo Blinded Independent Central 
Review (BICR). Prior to scanning the first participant, sites should be qualified and understand the 
image acquisition guidelines and submission process as outlined in the CA022009 Imaging 
Manual provided by the central imaging vendor. 
The study design schematic is presented in Figure 1 below. 


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Figure 1: 
Study Design Schema 
 
Abbreviations: CT, computed tomography; DLT, dose-limiting toxicity; I-O, immuno-oncology; mCRPC, metastatic 
castration-resistant prostate cancer; MRI, magnetic resonance imaging; N, number of participants; NAT, novel 
antiandrogen therapy; Q3W, every 3 weeks; rPD, radiographic progressive disease; Y/N, yes/no. 
a The DLT evaluation period will be 42 days (6 weeks) starting on Cycle 1 Day 1 for Part 1A and Part 1B. 
b Administer docetaxel for a maximum of 10 cycles. 
c For participants who are also receiving BMS-986218 or BMS-986218 and nivolumab, treatment with these I-O 
agents may continue beyond 10 cycles, up to 2 years (until disease progression, unacceptable toxicity, or withdrawal 
of consent). 
d In Part 1B, BMS-986218 or nivolumab may be dose reduced based on safety data. 
e In Part 2, randomization to 1 of 3 treatment arms will be stratified by measurable disease (Y/N). 
f See Crossover (Arm 2d) text below for details regarding optional crossover treatment for participants randomized 
to Part 2 Arm 2a, including maximum duration of treatments. 
 
Physical examinations, vital sign measurements, 12-lead electrocardiograms, and clinical 
laboratory evaluations will be performed at selected times throughout the dosing interval. 
Participants will be closely monitored for adverse events (AEs) throughout the study. Blood will 
be collected according to the protocol for pharmacokinetic (PK) analysis. 
Screening Period 
The screening period will be up to 28 days. Informed consent will be obtained prior to any study- 
specific procedures. All participants (Part 1 and Part 2) being screened will be evaluated based on 
inclusion and exclusion criteria and will be enrolled using an Interactive Response Technology 
(IRT) system. 


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Participants for Part 2 will be randomized to 1 of 3 treatment arms and will be stratified according 
to measurable disease status which will be assessed by investigator based on the tumor assessment 
performed during screening (Prostate Cancer Working Group 3 [PCWG3]). 
Tumor tissue must be obtained and submitted to central laboratory prior to treatment assignment 
(Part 1) or randomization (Part 2) for participants with any soft tissue lesion that is suspected to 
represent metastatic disease based on local review of imaging and is considered accessible for 
biopsy by an interventional radiologist (or other appropriate specialist). Lymph nodes must 
measure at least 1 cm in diameter along the short axis in order to be considered for biopsy. 
For participants who meet the above criteria, a pre-treatment, on-treatment, and on-progression 
biopsy are required if medically feasible (tumor sites that can be biopsied with acceptable clinical 
risk). Baseline tumor tissue is not mandatory for participants with bone metastasis only. 
Participants who have met all eligibility criteria will be enrolled to receive treatment in Part 1 or 
Part 2 as applicable. 
Treatment Period 
The treatment period for BMS-986218 and/or nivolumab will last for up to 2 calendar years from 
first dose of study treatment and up to a maximum of 10 doses for docetaxel regardless of treatment 
delays (21 days/cycle). In addition to dosing visits on Day 1 of each cycle, there are also 
non-dosing visits on Days 8 and 15 in Cycles 1 and 4 and Day 15 in Cycle 2 for 
biomarkers 
assessments. 
Part 1A will evaluate the safety and tolerability of BMS-986218 in combination with docetaxel. 
The dose-limiting toxicity (DLT) evaluation period will be 42 days (6 weeks) starting on Cycle 1 
Day 1 for Part 1A and Part 1B. The DLT evaluation during this safety lead in, including potential 
decision to escalate or to de-escalate the BMS-986218 dose level, will be guided by the Bayesian 
Optimal Interval (BOIN) design framework with a target DLT rate of 30%. In Part 1B, there is 
also a potential to de-escalate the nivolumab dose level 
 . The target DLT in Part 1A was 
selected based on an observed DLT rate of 2/6 = 33% for BMS-986218 monotherapy 
in CA022001, estimated by the basic linear ranking model (BLRM) 
design and the maximum tolerated dose not reached with 2 dose levels higher being evaluated. For 
Part 1B, the observed DLT rate was 1/9 = 11% following treatment with nivolumab 
 + 
BMS-986218 
 in the same study (CA022001). In addition, in Study CA2099KD in 
participants treated with docetaxel with nivolumab, there was a 14.3% reported frequency of 
treatment discontinuations due to Grade 3-4 treatment-related adverse events (TRAEs), with the 
most frequent TRAEs (any grade) leading to discontinuation being pneumonitis (7.1%), fatigue 
(6.0%), peripheral neuropathy (6.0%), and pneumonia (3.6%). 
The Part 1A decisions for escalation, de-escalation, or continuing evaluating at the same dose level, 
will be guided by the BOIN escalation design (Table 2). Approximately 12 DLT-evaluable 
participants are expected to be treated, depending on the number of dose levels and the number of 
observed DLTs. Dose escalation/de-escalation decisions or decision to continue enrollment at the 
current dose will be made by the Sponsor in collaboration with investigators and take into 
consideration all available safety and, if available, PK and pharmacodynamic data. Participants 


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will enroll in cohorts of 3 to 4 initially. After the first 3 to 6 participants are evaluated, additional 
cohorts of 3 to 6 participants may be enrolled, as needed, with no more than 12 participants at a 
specific dose level. Once at least 6 participants have cleared the DLT observation period at a 
tolerable dose level in Part 1A, participants will be enrolled in Part 1B to assess safety and 
tolerability of the combination of BMS-986218 + docetaxel + nivolumab, starting at a lower 
BMS-986218 dose level than in Part 1A. Additional participants may be enrolled in Part 1A at this 
dose or a higher dose in order to continue to assess safety in this combination. 
 
Table 2: 
Safety Lead-in Evaluation Guidance Based on BOIN Design 
 
 
Actions Based on Number of 
DLTs Observed 
Number of DLT-evaluable Participants Treated at Current Dose 
 
3 
4 
5 
6a 
7 
8 
9 
10 
11 
12 
Escalate Doseb if # of DLTs ≤ 
0 
0 
1 
1 
1 
1 
2 
2 
2 
2 
Stayc if # of DLTs = 
1 
1 
NA 
2 
2 
2 
3 
3 
3 
3,4 
De-escalated if # of DLTs ≥ 
2 
2 
2 
3 
3 
3 
4 
4 
4 
5 
De-escalate and Eliminatee from 
Evaluation if # of DLTs ≥ 
3 
3 
4 
4 
5 
5 
5 
6 
6 
7 
Abbreviations: BOIN, Bayesian Optimal Interval; DLT, dose-limiting toxicity; NA, not applicable (for decision). 
a A minimum of 6 DLT-evaluable participants will be required to meet acceptable DLT criteria for a dose level to be 
selected for Part 2. 
b “Escalate” indicates that a higher dose level may be evaluated. 
c “Stay” indicates that more participants need to be treated to determine tolerability. 
d “De-escalate” indicates that a lower dose level needs to be evaluated. 
e Such dose level is excessively non-tolerable and re-escalation is not allowed after de-escalation. A lower dose level 
will be evaluated. 
 
Treatment in Part 1B may be initiated in a staggered manner relative to the BMS-986218 + 
docetaxel escalation (Part 1A). Specifically, Part 1B can be initiated upon the evaluation of a 
sufficient number of participants at a dose level in Part 1A who have cleared the DLT requirements 
(eg, 6 evaluable participants with 0 or 1 DLT), after which dose evaluation in Part 1A and Part 1B 
may proceed in parallel. At no point will the dose of BMS-986218 administered in combination 
with nivolumab and docetaxel in Part 1B exceed the highest dose determined to be tolerated in 
Part 1A. 
Part 1B will also use a BOIN design framework for the evaluation of BMS-986218 tolerability in 
combination with docetaxel and nivolumab. Approximately 12 to 18 DLT-evaluable participants 
are expected to be treated if 2 or more dose-level combinations are evaluated in this part. Initially, 
3 to 4 participants will be treated at the starting dose and subsequent decisions will be based on 


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the BOIN design framework as shown in Table 2 above, similar to Part 1A. If needed, based on 
the number of DLTs, additional participants in groups of 3 to 6 participants may be enrolled at the 
same dose level, or otherwise a lower dose level may be evaluated. 
If de-escalation is necessary based on the number of toxicities, a lower combination dose level will 
be evaluated. The specific dose level to be administered in combination will be determined based 
on the nature of the DLTs and will be either: 1) a lower dose of BMS-986218 in combination with 
the same dose levels of nivolumab and docetaxel or 2) a lower dose level of nivolumab 
in combination with the same dose levels of BMS-986218 and docetaxel. 
Once a tolerable dose has been determined for BMS-986218 in combination with docetaxel in 
Part 1A and for BMS-986218 in combination with docetaxel + nivolumab in Part 1B in at least 
6 evaluable participants, the randomized Part 2 of the study will open for enrollment. In Part 2, 
randomization 1:1:1 to 1 of 3 treatment arms will be stratified according to the following baseline 
factor: 
• Measurable disease (Y/N): Measurable disease status will be assessed by investigator based on 
the tumor assessment performed during screening (Response Evaluation Criteria in Solid 
Tumors version 1.1 [RECIST v1.1]) 
 
Crossover (Arm 2d): Participants treated in Arm 2a who demonstrate radiographic progressive 
disease (rPD) while on treatment (during active treatment with docetaxel) or after treatment (while 
in Safety or Survival Follow-up), may be eligible to crossover to optional Arm 2d and receive 
treatment of BMS-986218 in combination with nivolumab ( 
at the dose level 
chosen in Arm 2c). Further docetaxel treatment will not be administered on Arm 2d. 
In order to qualify for crossover, radiographic progression per PCWG3 must be confirmed by 
BICR and the participant must meet all inclusion criteria and exclusion criteria specified in the 
protocol (with the exception that prior treatment with docetaxel is allowed.) The BMS medical 
monitor must approve crossover to Arm 2d. 
In Arm 2d, BMS-986218 in combination with nivolumab (dose chosen in Arm 2c 
) is 
administered until disease progression, unacceptable toxicity, or withdrawal of consent, and may 
continue for a maximum of 2 calendar years from Cycle 1 Day 1 (Arm 2a) regardless of treatment 
delays (for participants who crossover during active treatment with docetaxel), or until the study 
ends, whichever occurs first. For participants who crossover after treatment (while in Safety or 
Survival Follow-up), BMS-986218 in combination with nivolumab may continue for up to 
1 calendar year from the start of crossover treatment, or for a maximum of 2 calendar years from 
Cycle 1 Day 1 (Arm 2a) regardless of treatment delays (whichever is longer), or until the study 
ends, whichever occurs first. 
Follow-up Period 
The Follow-up Period includes Safety Follow-up (comprising 3 visits over about 100 days) and 
Survival Follow-up (up to 2 years from the last dose of study treatment) periods. 


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Safety Follow-up: Upon completion of study intervention or early termination, all participants will 
enter a safety follow-up period. All participants will be evaluated for any new AEs for at least 
100 days after the last dose of study intervention. Participants who have discontinued treatment 
without having BICR-assessed disease progression will continue to have radiologic and clinical 
tumor assessments after treatment discontinuation for up to 2 years after end of treatment or until 
rPD, whichever occurs first. 
Survival Follow-up: In parallel with the safety follow-up period, participants will enter the survival 
follow-up period. Participants will be followed by phone contact or clinic visit every 12 weeks 
(± 2 weeks) from the last dose of study intervention for a period of 2 years or until death, loss to 
follow-up, withdrawal of consent, or conclusion of the study, whichever comes first. 
Number of Participants: 
Approximately 12 participants may be treated in the safety lead-in Part 1A and approximately 
12 to 18 participants in Part 1B, with a possible total of 30 DLT-evaluable participants, if 2 or 
more dose levels are evaluated. 
In addition, approximately 174 participants are expected to be randomized across 3 treatment arms 
in Part 2 of the study, to account for 21% dropout rate prior to radiographic progression across the 
3 arms. 
Study Population: 
Main Inclusion Criteria 
• Male participants, must be ≥ 18 years of age or local age of majority at the time of signing the 
informed consent. 
• Histologic confirmation of carcinoma of the prostate without small cell features. Diagnosis 
must be stated in a pathology report and confirmed by the investigator. 
• Current evidence of metastatic disease documented by either bone lesions on radionuclide bone 
scan and/or soft tissue lesions on computed tomography (CT)/magnetic resonance imaging 
(MRI). Metastases may be in regional lymph nodes (N1 per American Joint Committee on 
Cancer [AJCC] staging criteria, 8th edition) and/or distant metastases (M1 per AJCC staging 
criteria, 8th edition). 
− Participants whose disease spread is limited to regional pelvic lymph nodes (N1) measuring 
at least 2 cm in short axis will be considered eligible. 
• Documented prostate cancer progression by 1 of the following Prostate Cancer Working 
Group 3 (PCWG3) criteria while castrate, within 6 months prior to screening, and without 
initiating 
a 
new 
intervening 
systemic 
prostate 
cancer 
therapy 
(other 
than 
gonadotropin-releasing hormone [GnRH] agonist/antagonist) prior to screening: 
− Prostate-specific antigen (PSA) progression defined by a minimum of 2 rising PSA levels 
with an interval of ≥ 1 week between each determination. The PSA value at the screening 
visit should be ≥ 2 μg/L (2 ng/mL). 
− Radiographic disease progression in soft tissue based on PCWG3 criteria. 
− Radiographic disease progression in bone. 


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• Participants are chemotherapy-naïve for mCRPC and have received at least 1 second 
generation hormonal manipulations (also known as novel antiandrogen therapies [NATs], 
including but not limited to abiraterone acetate, enzalutamide, apalutamide, and darolutamide) 
in the recurrent non-metastatic setting and/or the metastatic setting. Participants must have 
progressed during treatment on an NAT or have documented intolerance to the drug (ie, 
unacceptable toxicity despite comprehensive supportive therapy). Prior docetaxel for 
metastatic castration-sensitive prostate cancer is allowed if ≥ 12 months have elapsed from last 
dose of docetaxel. Prior therapy with a poly ADP ribose polymerase (PARP) inhibitor (eg, 
olaparib, rucaparib) is also allowed. Prior radium 223 and 177Lu-prostate-specific membrane 
antigen(PSMA)-617 treatment for prostate cancer is allowed. 
• Participants with a soft tissue lesion that is suspected to represent metastatic disease based on 
local review of imaging and is considered accessible for biopsy by an interventional radiologist 
(or other appropriate specialist), must provide tumor sample from a newly-obtained (“fresh”) 
biopsy (obtained during screening, if there are tumor sites that can be biopsied with acceptable 
clinical risk). Lymph nodes must measure at least 1 cm in diameter along the short axis in order 
to be considered for biopsy. If the only site amenable to biopsy is also the only site of 
measurable disease, the investigator should prioritize maintaining a measurable target lesion 
(by RECIST v1.1) if there is a concern that the biopsy might impact tumor assessment. 
A formalin-fixed paraffin-embedded tissue block (preferred) or a minimum of 20 unstained 
slides* of tumor tissue from core biopsy, punch biopsy, excisional biopsy or surgical specimen 
obtained during screening or prior to treatment assignment (Part 1)/randomization (Part 2) 
must be sent to the central laboratory. Fine needle aspirates or other cytology samples are not 
acceptable. 
*If despite best efforts, a minimum of 20 slides is not obtainable, submission of fewer slides 
may be acceptable in some circumstances following discussion with Sponsor or designee. 
 
Main Exclusion Criteria 
• Prior treatment for biochemically recurrent or metastatic prostate cancer with an anti-cytotoxic 
T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-(ligand-)1 
(anti-PD-[L]1), or any other antibody or drug specifically targeting T-cell co-stimulation or 
checkpoint pathways. The prior use of such agents in the neoadjuvant setting is allowed. 
• Prior radiation therapy within 2 weeks prior to start of study treatment. Participants must have 
recovered (ie, Grade ≤ 1 or at baseline) from radiation-related toxicities prior to first study 
treatment. 
 
Intervention Groups and Duration: 
Participants who are assigned/randomized to a study intervention with nivolumab will receive 
nivolumab at a dose of 
over an approximately 30-minute infusion each 
treatment cycle until progression, unacceptable toxicity, withdrawal of consent, completion of 
24 months of treatment, or the study ends, whichever occurs first. If needed, flush the intravenous 
line with an appropriate amount of diluent (eg, 0.9% sodium chloride) to ensure that the complete 


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dose is administered over approximately 30 minutes. Begin study treatment within 3 calendar days 
of treatment assignment (Part 1) or randomization (Part 2). 
When study interventions BMS-986218 and docetaxel are to be administered on the same day, 
BMS-986218 should be administered first. Flush the intravenous line with an appropriate amount 
of diluent (eg, 0.9% sodium chloride) to ensure that the complete dose is administered over 
approximately 30 minutes. After the BMS-986218 infusion, there is a 30-minute delay before the 
start of the docetaxel infusion to monitor the participant for signs of possible infusion reactions 
and differentiate any such reaction from one related to the subsequent docetaxel infusion. Dosing 
of docetaxel will continue for a maximum of 10 cycles Q3W (± 3 days), until progression, 
unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first. A 
minimum of 3 to 4 cycles of docetaxel is recommended. Prednisone 5 mg twice daily will be 
administered with docetaxel in accordance with package insert/Summary of Product 
Characteristics (SmPC) guidelines. However, daily prednisone may be dose reduced or omitted at 
the discretion of the investigator if it negatively affects glycemic control or other comorbid 
conditions. Premedication with dexamethasone will also be given for docetaxel (see below). 
Dosing calculations of docetaxel should be based on the body weight assessed at baseline using 
Mosteller body surface area formula: the square root of (weight [kg] × height [cm]/3600). It is not 
necessary to re-calculate subsequent doses if the participant weight is within 10% of the weight 
used to calculate the previous dose. All doses should be rounded up or to the nearest milligram per 
institutional standard. 
When study interventions nivolumab, BMS-986218 and docetaxel (or nivolumab and 
BMS-986218 for crossover participants in Arm 2d), are to be administered on the same day, 
nivolumab is to be administered first. Nivolumab infusion must be promptly followed by a flush 
of diluent to clear the line of nivolumab before starting the BMS-986218 infusion. The second 
infusion will always be BMS-986218 and will start after the infusion line has been flushed, filters 
changed, and participant has been observed to ensure no infusion reaction has occurred. Then, 
follow the instructions above to administer docetaxel (docetaxel will not be administered for 
participants who crossover into Arm 2d). 
There will be no intra-subject dose escalations or reductions of nivolumab or BMS-986218 
allowed. For Q3W dosing cycles, participants may be dosed no less than 19 days from the previous 
dose. 
Premedication 
Premedications for BMS-986218 and nivolumab are not recommended. For docetaxel, given the 
concurrent use of prednisone (5 mg twice daily), the recommended premedication regimen is oral 
dexamethasone 8 mg (or equivalent dose of another corticosteroid) to be administered at 12, 3, and 
1 hour(s) before the docetaxel infusion; however, other corticosteroids and/or schedules and routes 
of administration are also acceptable according to local standards. Antiemetic premedication will 
be administered according to local standards. 


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Study Intervention: 
 
Study Intervention for CA022009 
Medication 
Potency 
IMP/Non-IMP/AxMP 
Docetaxel 
Various Strengths 
Non-IMP 
BMS-986218 
200 mg/vial 
IMP 
Nivolumab 
100 mg/vial 
IMP 
Abbreviations: AxMP, auxiliary medicinal product; IMP, investigational medicinal product; Non-IMP, non- 
investigational medicinal product. 
 
Statistical Methods 
Sample Size Justification for Safety Lead-in Portion (Part 1) 
Escalation/de-escalation decisions will be guided by the BOIN design. Though the exact number 
treated at a dose level will depend on the number of participants with a DLT, approximately 
12 DLT-evaluable participants may be treated in Part 1A to assess the tolerability of BMS-986218 
in combination with docetaxel (see Figure 1 for study design schema). Similarly, in Part 1B, 
approximately 12 to 18 participants may be treated with BMS-986218 in combination with 
docetaxel and nivolumab. With a maximum of 12 DLT-evaluable participants at a dose level, there 
will be above 80% probability to observe at least 1 occurrence of a safety event if the event rate in 
the population is 13%. Similarly, with 6 or 9 DLT-evaluable participants at a dose level, there will 
be above 80% probability to observe at least 1 occurrence of the safety event if the event rate in 
the population is 24% or 17%, respectively. A minimum of 6 DLT-evaluable participants and no 
more than 12 DLT-evaluable participants will be evaluated at a dose level in Part 1A or Part 1B to 
ensure tolerability prior to initiating enrollment in Part 2 at these dose levels. Therefore, a total of 
approximately 30 DLT-evaluable participants may be evaluated during the safety lead in, including 
at least 6 participants (with 0 or 1 DLT) at each of the BMS-986218 + docetaxel and 
BMS-986218 + nivolumab + docetaxel combination doses that will be evaluated in Part 2. 
Sample Size Justification for Randomized, Controlled Portion (Part 2) 
The sample size of the study is calculated to have sufficient power for the primary efficacy 
endpoint of radiographic progression-free survival (rPFS) to compare Arm 2c to Arm 2a and 
Arm 2b to Arm 2a. Assuming that Arm 2a median rPFS is 6 months and a constant hazard ratio 
(HR) of 0.55 for the Arm 2c to Arm 2a comparison (for target median rPFS = 10.9 months), a total 
of 78 rPFS events will need to be observed across these 2 arms, in order to have 91.3% power to 
show a difference at the 20% 2-sided alpha level, in this population, based on 58 participants per 
arm. Based on hierarchical testing of Arm 2b vs Arm 2a, assuming there was statistical significance 
in the Arm 2c vs Arm 2a comparison, and a constant HR of 0.62 for the Arm 2b to Arm 2a 
comparison, a total of 79 rPFS events will need to be observed across these 2 arms, with 
58 participants per arm in order to have 80% power to show a difference at the 20% 2-sided alpha 


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level. These calculations assume 18 months for accrual and a minimum of 10 months follow up. 
A total of 174 participants will need to be randomized assuming about 21% dropout rate across 
arms (5% in control arm, 9% in the BMS-986218 + docetaxel arm, and 7% in the BMS-986218 + 
nivolumab + docetaxel arm). 
The actual time of the final analysis will be based on the number of events observed, which will 
be monitored separately among Arm 2c and Arm 2a and among Arm 2b and Arm 2a during the 
study conduct. 
Primary Endpoints 
The primary endpoint for Part 1 is to assess safety based on incidence of AEs, serious adverse 
events (SAEs), AEs meeting protocol-defined DLT criteria, TRAEs, AEs leading to 
discontinuation, and deaths. In addition, the selected tolerable dose levels of BMS-986218 in 
combination with docetaxel (Part 1A) and BMS-986218 in combination with docetaxel and 
nivolumab (Part 1B) will be determined using the DLT rate within the 6-week DLT window among 
DLT-evaluable participants in Part 1A and in Part 1B. The incidence of DLTs will be calculated 
for DLT-evaluable participants and compared to the actions recommended by the BOIN design to 
guide the dose escalation/stay/de-escalation decision for the BMS-986218 + docetaxel treatment 
and for the BMS-986218 + nivolumab + docetaxel treatment. 
The primary endpoint for Part 2 is rPFS of BMS-986218 + docetaxel and BMS-986218 + 
nivolumab + docetaxel combination therapies compared to rPFS of docetaxel monotherapy 
control, in the randomized population. rPFS is defined as the time from randomization to the date 
of first documented radiographic progression per BICR using PCWG3 or death due to any cause, 
whichever occurs first. Participants who do not progress or die will be censored on the date of their 
last evaluable tumor assessment. Participants who did not have any evaluable on-study tumor 
assessments and did not die will be censored at randomization date. 
Interim Analysis 
There is no plan for an official interim analysis of efficacy in Part 2 with any adjustment of the 
type 1 error rate. 
Safety Monitoring in Part 1: 
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. This collaborative process plus a Data Monitoring 
Committee (DMC) for Part 2, 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 AE reports and analyses. Because this is an open-label 
study, WWPS representatives, the BMS medical monitor, and the investigators will have access 
to individual participants safety data necessary for safety evaluation. 


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Data Monitoring Committee: Yes 
A DMC will be used for Part 2 of this study to provide oversight of the safety. In addition, during 
the randomized Part 2 of the study, a continuous safety monitoring framework will be implemented 
by the Sponsor to monitor for DLT adverse events. 
The DMC charter will describe the procedures related to DMC operations in greater detail. 
Other Committee: Yes 
A Blinded Independent Central Review (BICR) will also be used for this study to review CT and 
bone scans, including the primary study objective. 
Brief Summary: 
CA022009 is a Phase 2, open-label, controlled, randomized, global study assessing the efficacy 
and safety of combining BMS-986218, or BMS-986218 plus nivolumab, with standard of care 
docetaxel in men who have metastatic castration-resistant prostate cancer (mCRPC) that 
progressed after a second-generation hormonal manipulation, also known as novel antiandrogen 
therapy (NAT), and have not received chemotherapy for mCRPC. The study will have a safety 
lead-in portion (Part 1) and a randomized controlled portion (Part 2). Part 2 of the study aims to 
demonstrate that addition of BMS-986218, or BMS-986218 plus nivolumab, to docetaxel 
improves clinical efficacy as assessed by radiographic progression-free survival (rPFS). Study 
details include: 
Study Duration: The maximum duration for a participant on study is 4 years (up to 2 years on 
treatment and up to 2 years on follow-up). 
Study Intervention: Each dosing cycle will last 21 days. Study intervention is administered on 
Day 1 of each cycle until disease progression or a maximum of 2 years. 
Study Visit Frequency: In each dosing cycle of 21 days, the participant will attend a dosing visit 
every 3 weeks (Q3W). In Cycle 1 and Cycle 4, participants will attend a non-dosing visit on Days 8 
and 15, and in Cycle 2, participants will attend a non-dosing visit on Day 15. Tumor assessments 
during the treatment period will be every 9 weeks (from first dose) for the first 27 weeks and then 
every 12 weeks thereafter. 


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2 
SCHEDULE OF ACTIVITIES 
Table 2-1: 
Screening Procedural Outline (CA022009) 
 
Procedure 
Screening Visit 
(Days -28 to -1) 
Notes: a 
All windows are based on calendar days 
Eligibility Assessments 
Informed Consent 
X 
A participant is considered enrolled only when a protocol-specific informed 
consent is signed. 
Must be obtained prior to performing any screening procedures. 
Study allows for re-enrollment of a participant that has discontinued the 
study as a pre-treatment failure. If re-enrolled, the participant must be 
re-consented and assigned a new participant number from IRT. 
Contact IRT 
X 
Register in Interactive Response system to obtain participant number. 
Inclusion/Exclusion Criteria 
X 
Must be confirmed prior to treatment assignment (Part 1) or randomization 
(Part 2) in IRT. 
Medical History 
X 
All medical history relevant to disease under study. Medical history will also 
include COVID-19 vaccines, toxicities of prior treatments, and known 
allergies. 
Body Imaging/Bone Scan 
X 
Technetium-99m bone scan, contrast enhanced CT of the chest, abdomen, 
pelvis, and all other known and/or suspected sites of disease, within 28 days 
prior to treatment assignment (Part 1) or randomization (Part 2). If a 
participant has a contraindication for CT intravenous contrast, then a non- 
contrast CT of the chest and a contrast-enhanced MRI of the abdomen, pelvis, 
and other known/suspected sites of disease should be obtained. 
Section 9.1.1 for further details. Please refer to Appendix 5 for PCWG3 
guidelines for tumor assessments. 
Brain Imaging 
X 
MRI of the brain without and with contrast is required for participants with 
known or suspected brain metastases, unless participant has completed an 
imaging study of the brain, within 28 days prior to treatment assignment 
(Part 1) or randomization (Part 2). CT of the brain without and with contrast 
can be performed if MRI is contraindicated. See Section 9.1.1 for further 
details. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-1: 
Screening Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
24 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Screening Visit 
(Days -28 to -1) 
Notes: a 
All windows are based on calendar days 
Prior Medications/Radiation/Surgery for Cancer 
X 
Details and dates of prior therapy, including all hormonal therapies, as well 
as prior cancer surgeries. 
Safety Assessments 
Physical Examination (PE) 
X 
If the screening PE is performed within 72 hours prior to dosing on Day 1, 
then a single exam may count as both the screening and predose evaluation. 
Physical Measurements 
X 
Includes height, weight, and BMI. 
Vital Signs 
X 
Includes body temperature, respiratory rate, oxygen saturation and seated 
blood pressure and heart rate. Blood pressure and heart rate should be 
measured after the participant has been resting quietly for at least 5 minutes. 
ECOG Performance Status 
X 
Refer to Appendix 6. 
Assessment of Signs and Symptoms 
X 
Within 14 days prior to treatment assignment (Part 1) or randomization 
(Part 2). 
Prior/Concomitant Medication Use 
X 
Within 14 days prior to treatment assignment (Part 1) or randomization 
(Part 2). 
Vaccine use within 30 days prior to Cycle 1 Day 1. 
Electrocardiogram (ECG) 
X 
Single ECG should be recorded after the participant has been supine for at 
least 5 minutes, within 14 days prior to randomization/treatment assignment. 
Laboratory Tests 
Clinical Laboratory Assessments 
X 
Must be performed within 14 days prior to treatment assignment (Part 1) or 
randomization (Part 2). 
Refer to Section 9.4.4 for list of laboratory tests to conduct. 
The following must be performed up to 28 days prior to first dose: PSA and 
testosterone (See Section 6.1, Inclusion Criteria) 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-1: 
Screening Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
25 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Screening Visit 
(Days -28 to -1) 
Notes: a 
All windows are based on calendar days 
Serology 
X 
Viral testing to be completed within 28 days prior to treatment assignment 
(Part 1) or randomization (Part 2). 
Refer to Section 9.4.4 for list of laboratory tests to conduct. 
Includes hepatitis B/C, (HBsAg, HCV antibody or HCV RNA), and HIV-1 
and HIV-2 antibody (if mandated locally; refer to Appendix 7). 
Biomarker Assessments 
See Section 9.8 for sampling schedule. 
SARS-CoV-2 Serology 
X 
Serum collected to be used for possible measurements of anti-SARS-CoV-2 
serology (anti-SARS-CoV-2 total or IgG [see Section 9.8]). Results will not 
be used to determine eligibility. 
Pre-treatment Plasma and Serum 
X 
See Section 9.8 for specification on samples and Table 9.8-1 for sampling 
schedule. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-1: 
Screening Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
26 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Screening Visit 
(Days -28 to -1) 
Notes: a 
All windows are based on calendar days 
Collection of Tumor Tissue 
X 
(See Notes) 
• 
Participants with any soft tissue lesion that is suspected to represent 
metastatic disease based on local review of imaging and is considered 
accessible for biopsy by an interventional radiologist (or other 
appropriate  specialist),  must  provide  tumor  sample  from  a 
newly-obtained (“fresh”) biopsy (obtained during screening, if there are 
tumor sites that can be biopsied with acceptable clinical risk). Lymph 
nodes must measure at least 1 cm in diameter along the short axis in order 
to be considered for biopsy. If the only site amenable to biopsy is also the 
only site of measurable disease, the investigator should prioritize 
maintaining a measurable target lesion (by RECIST v1.1) if there is a 
concern that the biopsy might impact tumor assessment. 
− 
A FFPE tissue block (preferred) or a minimum of 20 unstained 
slides* of tumor tissue from core biopsy, punch biopsy, excisional 
biopsy or surgical specimen obtained during screening or prior to 
treatment assignment (Part 1)/randomization (Part 2) must be sent to 
the central laboratory. Fine needle aspirates or other cytology 
samples are not acceptable. 
*If despite best efforts, a minimum of 20 slides is not obtainable, 
submission of fewer slides may be acceptable in some circumstances 
following discussion with Sponsor or designee. 
Please refer to Section 9.8.4 for additional details on tumor tissue 
requirements. 
− 
Consent for pre-treatment, on-treatment, and on-progression tumor 
biopsy samples are required for enrollment for participants who meet 
the above criteria. 
• 
For participants with bone-only disease, inaccessible soft tissue lesions, 
or if the biopsy procedure would pose an unacceptable clinical risk for 
the participant, submission of tumor tissue obtained from a fresh biopsy 
is not required. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-1: 
Screening Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
27 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Screening Visit 
(Days -28 to -1) 
Notes: a 
All windows are based on calendar days 
Adverse Event Reporting 
Monitor for Non-Serious Adverse Events 
X 
• 
The collection of non-serious AEs (with the exception of non-serious 
AEs related to SARS-CoV-2 infection) should begin at initiation of study 
treatment and continue during the treatment period, and for a minimum 
of 100 days following discontinuation of study treatment. 
• 
All SAEs, and all AEs (SAEs and non-serious AEs) associated with 
confirmed or suspected SARS-CoV-2 infection must be collected from 
the date of the participant’s written consent until 100 days following 
discontinuation of dosing. 
AEs are graded per NCI CTCAE v5. 
Monitor for Serious Adverse Events 
X 
All SAEs must be collected from time of consent until 100 days post 
discontinuation of dosing or participant’s participation in the study if the last 
scheduled visit occurs at a later time. 
Study Intervention 
Randomize (Part 2 only) 
X 
Within 3 days of Cycle 1 Day 1. 
Contact IRT 
X 
For Part 1 and Part 2, register in IRT system to obtain participant number 
prior to starting any screening procedures. 
After completing all screening procedures, utilize IRT to either screen fail or 
obtain treatment assignment information, as applicable. Treatment 
assignment can occur up to 3 days prior to first dose. See Section 7.2 
(Method of Study Intervention Assignment). 
 
Abbreviations: AE, adverse event; BMI, body mass index; COVID-19, coronavirus disease 2019; CRF, case report form; CT, computed tomography; ECG, 
electrocardiogram; ECOG, Eastern Cooperative Oncology Group; FFPE, formalin-fixed paraffin-embedded; HBsAg, hepatitis B surface antigen; HCV, hepatitis C 
virus; HIV, human immunodeficiency virus; IgG, immunoglobulin G; IRT, Interactive Response Technology; MRI, magnetic resonance imaging; NCI CTCAE v5, 
National Cancer Institute Common Terminology Criteria for Adverse Events version 5; PCWG3, Prostate Cancer Working Group 3; PE, physical examination; 
PSA, prostate-specific antigen; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; RNA, ribonucleic acid; SAE, serious adverse event; 
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. 
a Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required be institutional or local regulations. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
28 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
Eligibility Assessments 
Inclusion/Exclusion Criteria 
X 
Confirm eligibility prior to treatment 
assignment/randomization in IRT. 
Medical History 
X 
Update any additional medical history prior to 
participant receiving study drug (does not apply for 
participants who crossover to Arm 2d). 
Safety Assessments 
Physical Examination (PE) 
X 
If the screening PE is performed within 72 hours prior 
to dosing on Day 1, then a single exam may count as 
both the screening and predose evaluation. 
Targeted Physical Examination 
X 
X 
Includes weight and BMI. If there are any new or 
worsening clinically significant changes since the last 
examination, report changes on the appropriate non- 
serious or serious AE CRF page. 
ECOG Performance Status 
X 
X 
X 
Record on days participant is being dosed and at EOT 
or early termination (refer to Appendix 6). 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
29 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
Vital Signs 
Collected at each visit 
X 
Vital signs will be obtained within 30 (± 5) minutes 
before the start of the first infusion, and then prior to 
each additional infusion (if applicable), and at EOT or 
early termination. 
Includes body temperature, respiratory rate, oxygen 
saturation, and seated blood pressure and heart rate. 
Blood pressure and heart rate should be measured after 
the participant has been resting quietly for at least 
5 minutes. 
Assessment of Signs and Symptoms 
X 
X 
Electrocardiogram (ECGs) 
X 
X 
X 
An ECG should be recorded prior to dosing after the 
participant has been supine for at least 5 minutes. 
Concomitant Medication Use 
Collected at each visit 
X 
Record at each visit. 
Adverse Event Reportingc 
Monitor for Serious Adverse Events 
Continuously 
X 
All SAEs must be collected from the date of 
participant’s written consent until 100 days post 
discontinuation of dosing or participant’s participation 
in the study if the last scheduled visit occurs at a later 
time. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
30 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
Monitor for Non-serious Adverse Events 
Continuously 
X 
Non-serious AEs will be collected starting with the 
first dose of study medication and through 100 days 
following the last dose of study treatment. 
All AEs (SAEs or non-serious AEs), including those 
associated with SARS-CoV-2 infection, must be 
collected continuously during the treatment period. 
Laboratory Tests 
See Section 9.4.4. 
Clinical Laboratory Assessments 
X 
X 
X 
Perform on site/local laboratory testing. 
There will be a minus-72-hour window for collection 
of laboratory tests on Day 1 of each cycle. See 
Section 9.4.4 and Table 9.4.4-1. 
For the first treatment visit, labs need not be repeated if 
they were performed within 72 hours and the results 
are available and have been reviewed for eligibility. 
Thyroid Function Test 
X 
X 
X 
If thyroid function test is abnormal, free T3 and free T4 
should be collected. See Section 9.4.4 and Table 9.4.4- 
1. 
Urinalysis 
X 
X 
X 
See Section 9.4.4 and Table 9.4.4-1. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
31 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
PSA 
X 
X 
X 
Perform on Day 1 of every cycle. Participants who 
discontinue study treatment without PSA progression 
or radiographic progression will continue to have PSA 
performed at Follow-up 1, Follow-up 2, and 
Follow-up 3, and every 12 weeks thereafter. PSA 
collection will continue until PSA progression, 
radiographic progression, or end of study treatment, 
whichever occurs last. Additional PSA collection 
outside of this schedule is allowed to confirm PSA 
progression as needed, during prolonged dose delays, 
or if clinically indicated. 
 
Biomarker Assessments 
Biomarker Sample Collections for 
Blood/Serum/Plasma and Pharmacodynamic 
Sampling 
See Table 9.8-1d 
See biomarker collection table in Section 9.8 for timing 
of collections. Crossover participants in Arm 2d will 
not have any biomarkers samples drawn with the 
exception of anti-SARS-CoV-2 serology. 
Tumor Biopsy 
(See Notes) 
On-study tumor biopsy should be taken between 
Cycle 2 Day 15 and Cycle 3 Day 1 (prior to dosing; if 
there is a delay in dosing Cycle 3, biopsy can be taken 
up until Cycle 2 Day 28 as long as it is prior to the 
Cycle 3 dose), for participants with any soft tissue 
lesion that is suspected to represent metastatic disease 
based on local review of imaging and is considered 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
32 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
accessible for biopsy by an interventional radiologist 
(or other appropriate specialist). Lymph nodes must 
measure at least 1 cm in diameter along the short axis 
in order to be considered for biopsy. 
A biopsy should also be performed if medically 
feasible at the time of progression for participants on 
treatment for more than 6 cycles, for all study parts. If 
the only site amenable to biopsy is also the only site of 
measurable disease, the investigator should prioritize 
maintaining a measurable target lesion (by RECIST 
v1.1) if there is a concern that the biopsy might impact 
tumor assessment. Bone lesion biopsies are 
unacceptable for submission. 
Note: For participants who have toxicities related to 
study therapy (ie, cytopenia) that may put them at 
increased risk from the biopsy, the on-study biopsy is 
not required. 
Crossover participants in Arm 2d will not have any 
tumor biopsies performed. 
Refer to Section 9.8.4 for more details. 
SARS-CoV-2 Serology 
X (See Notes) 
X 
Serum collected approximately every 6 months during 
study treatment to be used for possible measurements 
of anti-SARS-CoV-2 serology (anti-SARS-CoV-2 total 
or IgG). Serum should also be collected approximately 
4 weeks after a documented or suspected 
SARS-COV-2 infection (see Section 9.8). 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
33 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
Efficacy Assessments 
Body Imaging/Bone Scan 
X (See Notes) 
Technetium-99m Bone Scans, Contrast enhanced CT 
of the chest, abdomen, pelvis, and all other known 
and/or suspected sites of disease. If a participant has a 
contraindication for CT intravenous contrast, then a 
non-contrast CT of the chest and a contrast-enhanced 
MRI of the abdomen, pelvis, and other 
known/suspected sites of disease should be obtained. 
Tumor assessments should occur every 9 weeks 
(± 7 days) from first dose, regardless of treatment 
schedule or dose delays for first 27 weeks. Thereafter, 
switch to every 12 weeks (± 7 days). If progression is 
not documented prior to discontinuation of study 
treatment, tumor assessments should continue every 
9 weeks (± 7 days) for the first 27 weeks from the first 
dose, and thereafter, switch to every 12 weeks 
(± 7 days). 
Imaging must continue until radiographic progression 
per PCWG3 assessed by investigator and confirmed by 
BICR, or study treatment is discontinued, whichever 
occurs later. In case subsequent therapy has begun, 
imaging must continue until radiographic progression 
per PCWG3 is confirmed by BICR. 
See Section 9.1.1 for further details. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
34 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
Brain Imaging 
X (See Notes) 
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 and at the discretion of the 
investigator). 
CT of the brain without and with contrast can be 
performed if MRI is contraindicated. Imaging must 
continue until radiographic progression per PCWG3 is 
assessed by the investigator and confirmed by BICR or 
study treatment is discontinued, whichever occurs later. 
See Section 9.1.1 for further details. 
Clinical Outcomes Assessments (Randomized Part 2 only) 
EORTC QLQ-C30 
X 
X 
Participants will complete the EORTC QLQ-C30 at 
each cycle prior to any study-related study procedures 
using electronic data capture methods. 
FACIT GP5 
Complete weekly 
Participants will complete the FACIT GP5 on a weekly 
basis for the first 12 weeks of treatment only. If data 
completion occurs on the same day as a scheduled 
clinic visit, then data collection should be prior to any 
other study procedures using electronic data capture 
methods. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-2: 
On Study Treatment Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
35 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Cycle 1 
(21 Days) 
Cycle 2 
and 
Beyond 
(each cycle 
= 21 days) 
EOT or Early 
Termination 
Notesa 
Day 1b 
Day 1b 
(± 3 days) 
Study Intervention 
Administer docetaxel (all Parts/Arms except 
Arm 2d) 
X 
X 
Participants must receive the first dose of study 
medication within 3 calendar days from vial allocation. 
Administer docetaxel for a maximum of 10 cycles. If 
participants are also receiving BMS-986218 or 
BMS-986218 and nivolumab, treatment with these I-O 
agents may continue beyond 10 cycles, up to 2 years 
(until disease progression, unacceptable toxicity, or 
withdrawal of consent). 
Prednisone 5 mg twice daily will be administered with 
docetaxel in accordance with package insert/SmPC 
guidelines. Daily prednisone may be dose reduced or 
omitted at the discretion of the investigator if it 
negatively affects glycemic control or other comorbid 
conditions. Premedication with dexamethasone will 
also be given for docetaxel. 
Administer nivolumab (Part 1B, Arm 2c, and 
Arm 2d) 
X 
X 
Participants must receive the first dose of study 
medication within 3 calendar days from vial allocation. 
Nivolumab to be supplied by BMS; vials assigned by 
IRT should be used. 
Administer BMS-986218 (Part 1A, Part 1B, 
Arm 2b, Arm 2c, and Arm 2d) 
X 
X 
Participants must receive the first dose of study 
medication within 3 calendar days from vial allocation. 
BMS-986218 to be supplied by BMS; vials assigned by 
IRT should be used. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
36 
Approved v31.0 
930173886 3.0 
 
 
Abbreviations: AE, adverse event; BICR, blinded independent central review; BMI, body mass index; BMS, Bristol-Myers Squibb; CRF, case report form; CT, 
computed tomography; DLT, dose-limiting toxicity; DM, Data Management; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; EORTC 
QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EOT, end of treatment; FACIT GP5, Functional 
Assessment of Chronic Illness Therapy General Physical Item 5; I-O, immuno-oncology; IRT, Interactive Response Technology; MRI, magnetic resonance 
imaging; PCWG3, Prostate Cancer Working Group 3; PE, physical examination; PK, pharmacokinetic; PSA, prostate-specific antigen; RECIST v1.1, Response 
Evaluation Criteria in Solid Tumors version 1.1; SAE, serious adverse event; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SmPC, Summary of 
Product Characteristics; T3, triiodothyronine; T4, thyroxine. 
a Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations. 
b If a dose is delayed, the procedures schedule for that same time point must also be delayed to coincide with when that time point’s dosing actually occurs, with 
the exception of tumor assessments which must occur as scheduled. 
c For Part 1A and Part 1B, the DLT evaluation period will be 42 days (6 weeks) starting on Cycle 1 Day 1. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-3: 
Long-term Follow-up Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
37 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Safety 
Follow-up 1 
30 days 
(±7 days)a 
Safety 
Follow-up 2 
60 days 
(±7 days)a 
Safety 
Follow-up 3 
100 days 
(±7 days)a 
Survival 
Follow-up 
(Every 
12 weeks, 
± 2 weeks)b 
Notesc 
Safety Assessments 
Targeted Physical Examination 
X 
X 
X 
Includes weight, BMI, heart rate, BP, temperature, 
and oxygen saturation. BP and heart rate should be 
measured after the participant has been resting 
quietly for at least 5 minutes. 
Vital Signs 
X 
X 
X 
Record at each visit. 
Concomitant Medication Use 
X 
X 
X 
Record at each visit. 
Subsequent Cancer Therapy 
X 
X 
X 
X 
Include documentation of subsequent cancer 
therapy (ie, systemic therapy, tumor-directed 
surgery, or radiation therapy). Continuation of 
systemic ADT with GnRH antagonist/agonist does 
not need to be documented. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-3: 
Long-term Follow-up Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
38 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Safety 
Follow-up 1 
30 days 
(±7 days)a 
Safety 
Follow-up 2 
60 days 
(±7 days)a 
Safety 
Follow-up 3 
100 days 
(±7 days)a 
Survival 
Follow-up 
(Every 
12 weeks, 
± 2 weeks)b 
Notesc 
Serious Adverse Events Assessment 
and Adverse Events Assessment 
X 
X 
X 
X* 
Per NCI CTCAE v5. Record at each visit. 
All SAEs and non-serious AEs should be collected 
continuously during the treatment period and for a 
minimum of 100 days following discontinuation 
of study treatment. 
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. 
*Beyond 100 days from the last dose of study 
therapy, participants will be followed for 
drug-related AEs/SAEs until resolution, return to 
baseline, deemed irreversible, or until the 
participant is lost to follow-up or withdraws study 
consent. 
See Section 9.2 (Adverse Events). 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-3: 
Long-term Follow-up Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
39 
Approved v31.0 
930173886 3.0 
 
 
 
 
Procedure 
Safety 
Follow-up 1 
30 days 
(±7 days)a 
Safety 
Follow-up 2 
60 days 
(±7 days)a 
Safety 
Follow-up 3 
100 days 
(±7 days)a 
Survival 
Follow-up 
(Every 
12 weeks, 
± 2 weeks)b 
Notesc 
Laboratory Tests 
See Section 9.4.4. 
Clinical Laboratory Assessments 
X 
X 
X 
Includes blood and urine samples. 
PSA 
X 
X 
X 
X 
Participants who discontinue study treatment 
without PSA progression or radiographic 
progression will continue to have PSA performed 
at follow-up visits and every 12 weeks thereafter. 
PSA collection will continue until PSA 
progression, radiographic progression, or end of 
study treatment, whichever occurs last. Additional 
PSA collection outside of this schedule is allowed 
to confirm PSA progression as needed, or if 
clinically indicated. 
PK and Immunogenicity Assessments 
PK and Immunogenicity Collections 
See Table 9.5-1 (Part 1A and Arm 2b) and Table 9.5-2 
(Part 1B and Arm 2c) 
See PK/Immunogenicity collection table in 
Section 9.5 for timing of collections. 
Efficacy Assessments 
Survival Status 
X 
X 
X 
X 
During Safety Follow-up (Follow-up Visits 1, 2, 
and 3) and every 12 weeks ± 2 weeks (clinic visit 
or by telephone) during Survival Follow-up. 
Include documentation of subsequent cancer 
therapy (ie, systemic therapy, tumor-directed 
surgery, or radiation therapy). 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 2-3: 
Long-term Follow-up Procedural Outline (CA022009) 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
40 
Approved v31.0 
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Procedure 
Safety 
Follow-up 1 
30 days 
(±7 days)a 
Safety 
Follow-up 2 
60 days 
(±7 days)a 
Safety 
Follow-up 3 
100 days 
(±7 days)a 
Survival 
Follow-up 
(Every 
12 weeks, 
± 2 weeks)b 
Notesc 
Body Imaging/Bone Scan 
X (See Notes) 
Technetium-99m Bone Scans, Contrast enhanced 
CT of the chest, abdomen, pelvis, and all other 
known and/or suspected sites of disease. If a 
participant has a contraindication for CT 
intravenous contrast, then a non-contrast CT of the 
chest and a contrast-enhanced MRI of the 
abdomen, pelvis, and other known/suspected sites 
of disease should be obtained. 
Tumor assessments should occur every 9 weeks 
(± 7 days) from first dose, regardless of treatment 
schedule or dose delays for first 27 weeks. 
Thereafter switch to every 12 weeks (± 7 days). 
If progression is not documented prior to 
discontinuation of study treatment, tumor 
assessments should continue every 9 weeks 
(± 7 days) for the first 27 weeks from the first 
dose, and thereafter, switch to every 12 weeks 
(± 7 days). 
Imaging must continue until radiographic 
progression per PCWG3 assessed by investigator 
and confirmed by BICR, or study treatment is 
discontinued, whichever occurs later. In case 
subsequent therapy has begun, imaging must 
continue until radiographic progression per 
PCWG3 is confirmed by BICR. 
See Section 9.1.1 for further details. 


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CA022009 
anti-CTLA4-NF mAb 
Table 2-3: 
Long-term Follow-up Procedural Outline (CA022009) 
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Procedure 
Safety 
Follow-up 1 
30 days 
(±7 days)a 
Safety 
Follow-up 2 
60 days 
(±7 days)a 
Safety 
Follow-up 3 
100 days 
(±7 days)a 
Survival 
Follow-up 
(Every 
12 weeks, 
± 2 weeks)b 
Notesc 
Brain Imaging 
X (See Notes) 
If progression is not documented prior to 
discontinuation of study treatment, 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 9.1.1 for further details. 
Abbreviations: ADT, androgen deprivation therapy; AE, adverse event; BICR, blinded independent central review; BMI, body mass index; BMS, Bristol-Myers 
Squibb; BP, blood pressure; CRF, case report form; CT, computed tomography; GnRH, gonadotropin-releasing hormone; MRI, magnetic resonance imaging; NCI 
CTCAE v5, National Cancer Institute Common Terminology Criteria for Adverse Events version 5; PCWG3, Prostate Cancer Working Group 3; PK, 
pharmacokinetic; PSA, prostate-specific antigen; SAE, serious adverse event; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. 
a Participants must be followed for at least 100 days after last dose of study treatment. Follow-up Visit 1 must occur 30 days from the last dose (± 7 days) or can 
be performed on the date of discontinuation if that date is greater than 30 days after last dose. Follow-up Visit 2 occurs approximately 60 days (± 7 days) from 
last dose of study medication. Follow-up Visit 3 occurs approximately 100 days ( ± 7 days) from last dose of study medication. 
b Survival Follow-up visits to occur every 12 weeks (± 2 weeks) from the last dose of study intervention (for up to 2 years) and will be performed in parallel to 
safety follow-up. Participants who crossover to Arm 2d after discontinuing docetaxel treatment and while in follow-up should only be followed for a maximum 
of 1 year from the last dose of crossover treatment. Survival visits may be conducted in clinic or by telephone. BMS may request that survival data be collected 
on all treated participants outside of the 3 month specified window. At the time of this request, each participant will be contacted to determine their survival 
status unless the participant has withdrawn consent for all contact. 
c Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulation. 


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In the event that multiple procedures are required at a single time point, the following is a list of 
procedures from highest to low priority: 
• Pharmacokinetic (PK) Sampling 
• Safety (electrocardiogram [ECG]) 
• Safety (clinical labs) 


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3 
INTRODUCTION 
CA022009 is a Phase 2, open-label, randomized, controlled global study assessing the efficacy 
and safety of combining BMS-986218, or BMS-986218 plus nivolumab, with standard of care 
docetaxel in men who have metastatic castration-resistant prostate cancer (mCRPC) that 
progressed after a second-generation hormonal manipulation, also known as novel antiandrogen 
therapy (NAT), and have not received chemotherapy for mCRPC. The study will have a safety 
lead-in portion (Part 1) and a randomized controlled portion (Part 2). Participants in Part 2 who 
are randomized to the docetaxel arm (Arm 2a) and experience radiographic disease progression 
may qualify to receive BMS-986218 and nivolumab (crossover, Arm 2d) provided they continue 
to meet eligibility criteria and after consultation with the Medical Monitor. Part 2 of the study aims 
to demonstrate that addition of BMS-986218, or BMS-986218 plus nivolumab, to docetaxel 
improves clinical efficacy as assessed by radiographic progression-free survival (rPFS). 
BMS-986218 is a fully human immunoglobulin G1 (hIgG1) monoclonal antibody (mAb) against 
cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), an inhibitory receptor expressed on 
activated effector T-cells and regulatory T-cells (Tregs). BMS-986218 belongs to a class of agents 
referred to by the Sponsor as “next-generation” anti-CTLA-4 agents, which share the ligand- 
blocking poperties of ipilumumab, but have other modifications to improve efficacy and/or 
decrease toxicity. BMS-986218 shares the same amino acid sequence as ipilimumab but is 
produced in cells deficient for alpha-(1,6)-fucosyltransferase, the enzyme that mediates 
fucosylation of N-linked carbohydrates in the antibody (Ab) fragment crystallizable (Fc) region. 
Therefore, BMS-986218 is a non-fucosylated (NF) version of ipilimumab with an increased 
affinity for Fcγ receptors (FcγRs). Compared to ipilimumab, 2 additional FcγR-dependent 
mechanisms may augment BMS-986218 anti-tumor activity: depletion of tumor-infiltrating Tregs 
and enhanced stimulation of T-cells by antigen-presenting cells (APCs). 
BMS-986288 is another non-fucosylated next-generation anti-CTLA-4 that shares the FcγR- 
dependent mechanisms of BMS-986218. BMS-986288 is identical to BMS-986218 except for 
 
. These amino acids form a 
masking peptide with a protease-cleavable linker that is selectively cleaved in the tumor 
microenvironment. The “Probody” design could therefore decrease toxicity due to antibody 
binding to target outside of the tumor. Based on emerging data evaluating this concept, BMS- 
986288 may be incorporated into the CA022-009 study design via future protocol amendment. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of the study treatments 
is provided in the respective Investigator’s Brochures (IBs) and package inserts. 
3.1 
Study Rationale 
In 2004, 2 Phase 3 studies (TAX 327 and SWOG 99-16) demonstrated that docetaxel-based 
chemotherapy regimens improved survival in participants with mCRPC that progressed after 
castration therapy.1,2 More recently, most patients have also received treatment with at least 1 NAT 
prior to use of docetaxel for mCRPC. The target population for this study is participants with 
mCRPC that progressed after an NAT and have not received chemotherapy for mCRPC. Treatment 
with chemotherapy in this population has a modest benefit with regard to overall survival (OS) 


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and does not produce long-term disease control. Several lines of evidence support the hypothesis 
that addition of next-generation anti-CTLA-4 agents, with or without nivolumab, will improve 
outcomes compared to docetaxel alone. 
3.2 
Background 
3.2.1 
Indication Background 
Prostate cancer is a leading cause of cancer mortality in men worldwide,3 with an estimated 
incidence of 1,276,106 new cases and 358,989 deaths globally4 and 191,930 new cases and 
33,330 deaths in the United States (US) in 2020.5 Prostate cancer is the most frequently diagnosed 
cancer and second most frequent cause of cancer deaths in US males. In the US, prostate cancer 
accounted for almost 1 in 5 new diagnoses of cancer in men in 2018. In Europe, prostate cancer 
was the most common primary site in men in 2018 (21.8% of the total), with 450,000 new cases 
and 107,000 deaths.6 
In 1941, Huggins and Hodges first noted the beneficial effects of castration via orchiectomy or 
injection of estrogens in patients with metastatic prostate cancer.7 Over time, androgen deprivation 
therapy (ADT) achieved through either orchiectomy or gonadotropin-releasing hormone (GnRH) 
therapy, which blocks gonadal androgen production, became the cornerstone of treatment for 
patients with metastatic disease, as well as for some patients with localized or locally advanced 
prostate cancers. ADT results in disease remission in 90% of metastatic prostate cancer patients, 
evidenced by a decline in levels of prostate-specific antigen (PSA).8 Nevertheless, most patients 
with metastatic disease progress to a state of castration-resistant prostate cancer (CRPC) at a 
median of 18 to 24 months of conventional castration therapies.9 Despite castrate levels of 
testosterone in the periphery, it has long been speculated that local sources of biological active 
androgen remain in prostate tumors. Moreover, genetic and molecular evidence suggested that 
androgen receptor (AR) gene amplification and mutations may promote AR reactivation in CRPC. 
These concepts supported the development of a new generation of androgen axis blockers to be 
utilized in combination with conventional ADT.10 
Since 2012, 4 NATs have gained approval for use in various prostate cancer disease states. 
Abiraterone, which blocks extra gonadal androgen production, first gained approval in the mCRPC 
setting and subsequently in patients with metastatic castration-sensitive prostate cancer (mCSPC). 
Enzalutamide, apalutamide, and darolutamide are all direct AR antagonists. Based on 
improvements in median overall survival (mOS), enzalutamide is approved for use in mCRPC, 
mCSPC, and non-metastatic castration-resistant prostate cancer (nmCRPC), a distinct clinical state 
in which patients demonstrate PSA progression while on ADT, despite having never demonstrated 
metastatic disease on conventional imaging.11,12,13,14 Apalutamide is approved to treat mCSPC 
and nmCRPC, and darolumatide is approved to treat nmCRPC.15,16,17 
Docetaxel became the first chemotherapeutic agent to show an OS benefit in mCRPC in 
2 randomized controlled clinical trials (TAX 327 and SWOG 99-16), and was approved in 
combination with prednisone for this indication in the US in 2004.1,2 In the landmark TAX 327 


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Phase 3 trial, 1006 participants with mCRPC were randomized to receive daily prednisone and 
either mitoxantrone 12 mg/m2 every 3 weeks (Q3W), docetaxel 75 mg/m2 Q3W, or docetaxel 
30 mg/m2 every week (QW) for 5 of every 6 weeks.1 Participants who received docetaxel Q3W 
had a median survival of 19.2 months, compared to 16.3 months in the mitoxantrone Q3W and 
17.8 months in the docetaxel QW arms. The hazard ratio (HR) for the docetaxel Q3W arm was 
0.76 (95% confidence interval [CI], 0.62 to 0.94; P = 0.009). Cabazitaxel is another taxane-based 
chemotherapy that was approved by the Food and Drug Administration (FDA) in 2010, in patients 
with mCRPC previously treated with docetaxel.18 In the FIRSTANA trial, which studied 
cabazitaxel vs docetaxel as first line (1L) therapy in chemotherapy-naïve mCRPC, different 
dosages of cabazitaxel did not show superiority over docetaxel.19 
Two radiopharmaceuticals have demonstrated an improvement in mOS in mCRPC: 1) the bone 
targeting alpha-emitting radionuclide radium-223 chloride was approved in men with symptomatic 
bone metastases but no visceral disease, based on data from the ALSYMPCA trial, which showed 
an mOS benefit (HR, 0.7; 14.9 vs 11.3 months; P < 0.001),20 and 2) 177Lu-prostate-specific 
membrane antigen(PSMA)-617, which demonstrated an improvement in rPFS and mOS in the 
VISION study leading to a Breakthrough Therapy designation by the FDA in 2021.21 
Genomic evaluation over the past few years has identified that loss of function in genes involved 
in deoxyribonucleic acid (DNA) homologous recombination repair (HRR) occurs in nearly 20% 
of mCRPC patients.22 Based on the validated concept that defects in HHR genes can sensitize 
tumor cells to poly ADP ribose polymerase (PARP) inhibitors, multiple PARP inhibitors have 
been evaluated in mCRPC. The randomized Phase 3 PROfound trial compared olaparib with 
second-generation hormonal therapy in 387 men with mCRPC harboring alterations in genes with 
roles in HRR and had experienced progression on a prior systemic therapy for metastatic disease 
with a NAT, with one prior chemotherapy agent also permitted but not required. The olaparib- 
treated men had longer OS (17.3 vs 14 months). These data supported the approval in 2020 of 
olaparib for adults with mCRPC who have disease progression following treatment with a NAT 
and have a germline or somatic pathogenic variant in an HRR gene.23 
Sipuleucel-T was the first immunotherapy to receive FDA approval in men with asymptomatic 
mCRPC based on the Phase 3 IMPACT trial, which showed a median survival of 25.8 months vs 
21.7 months (placebo arm).24 Sipuleucel-T did not improve time to objective progression or 
meaningfully increase PSA response rate (2.6% vs 1.3%). 
While the availability of these treatment options allows for tailoring therapy to patient 
characteristics such as presence or absence of symptoms, prior treatments, patient preferences, and 
life expectancy, none of these therapies result in durable clinical responses. Despite high initial 
response rates, remissions following second-generation hormone therapies are temporary due to 
the development of resistance mechanisms. At this time, with judicious sequencing and use of 
available new therapies, patients with established mCRPC have a life expectancy in the range of 
12 to 35 months. Thus, mCRPC remains a disease with a lethal outcome with the urgent need for 
treatment options that will provide durable disease control and long-term survival. Immune 


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checkpoint blockade provides clearly-established durable benefit in other indications and has also 
been evaluated in prostate cancer with encouraging signs in some patients. 
3.2.1.1 
CTLA-4 Blockade in Prostate Cancer 
The first-in-human (FIH) study of ipilimumab was in prostate cancer: an investigation of a single 
3 mg/kg dose of ipilimumab in 14 participants with CRPC.25 Ipilimumab as a single dose had 
acceptable PK and safety profiles, but only 2 of the 14 participants experienced PSA declines of 
> 50%. Results have since been reported for 6 other clinical studies of ipilimumab in mCRPC.26 
Together, these 7 trials encompassed 240 participants across multiple settings of advanced CRPC, 
roughly 20% of whom had progressed on or relapsed after docetaxel. These studies utilized 
multiple doses (ranging from 0.5 to 10 mg/kg as either monotherapy or in combination studies) 
and schedules (ranging from a single dose of ipilimumab to recurring doses every 3 weeks for 
4 cycles) and demonstrated the clinical activity of ipilimumab 3, 5, and 10 mg/kg, defined as PSA 
response, in the treatment of mCRPC (Table 3.2.1.1-1) whether used as monotherapy, with ADT 
or with other interventions such as radiotherapy, or other immunotherapeutics with different 
mechanisms of action.26 In 3 studies that included ipilimumab monotherapy at 3 mg/kg in 
mCRPC, PSA responses were observed in 6 of 46 evaluable participants (13.6%). In 1 study that 
included ipilimumab monotherapy at 10 mg/kg, PSA responses were observed in 4 of 
16 participants (25%). 


 
Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 3.2.1.1-1: 
Phase 1/2 Studies with Ipilimumab in Prostate Cancer 
 
Protocol 
Population 
Combination 
Subjects Treated/Target 
PSA 
Response 
PSA Response 
Rate (%) 
3 mg/kg: 8/6 
2 
MDX010-21 
(CA184017) 
Docetaxel failure and 
docetaxel eligible 
Monotherapy and single-dose 
radiation combination 
5 mg/kg: 6/6 
10 mg/kg:16/16 
3 mg/kg + RT: 6/6 
1 
4 
2 
13/70 evaluable 
(18.6%) 
10 mg/kg + RT: 34/34 
4 
MDX010-17 
(CA184119) 
Docetaxel eligible 
GVAX 
(CellGenesys) 
< 3 mg/kg: 6/6 
3 
5/28 (18%) 
3 mg/kg: 19/19 
5 mg/kg: 3/3 
2 
1 mg/kg: 3/3 
CTEP 7207a 
(CA184066) 
Docetaxel failure and 
docetaxel eligible 
Prostavac (fixed dose) 
3 mg/kg: 6/6 
5 mg/kg: 6/6 
1 
3 
5/28 (7%) 
10 mg/kg: 13/16 
1 
CTEP 6032 
(CA184067) 
Docetaxel eligible 
GM-CSF (on Days 1-14) 
< 3 mg/kg: 15/15 3 mg/kg: 9/9 
5 mg/kg: 5/6 
10 mg/kg: 1/16 
3 
3/30 (10%) 
MDX010-01 
(CA184009) 
Metastatic HRPC 
Monotherapy 
3 mg/kg: 14/14 
2 
2/14 (14%) 
MDX010-07 
(CA184019) 
Docetaxel eligible 
Docetaxel 
3 mg/kg alone: 24/20 
3 mg/kg + docetaxel: 20/20 
2 
1 
3/42 evaluable 
(7%) 
HRPC (subtotal) 
190/225 
31 
16% 
MDX010-06 
(CA184118) 
Unresectable PC 
(< 90 days prior hormonal Rx) 
3 months androgen ablative 
therapy 
3 mg/kg: 50/108 
11 
11/50 (22%) 
Total Subjects 
240/333 
44 
17% 
Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; HRPC, hormone-refractory prostate cancer; PC, prostate cancer; PSA, prostate- 
specific antigen; RT, radiation therapy. 
a Ongoing accrual 
 
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Two Phase 3 studies (CA184043 and CA184095) carried out subsequently have failed to show a 
clear-cut survival advantage for ipilimumab (10 mg/kg) over placebo.27,28 CA184043 was a 
double-blind, randomized Phase 3 study comparing ipilimumab plus radiotherapy to placebo plus 
radiotherapy in participants with mCRPC who had received prior treatment with docetaxel for 
their disease.27 It did not meet its primary endpoint of demonstrating a statistically significant 
prolongation of survival for the ipilimumab group compared with the placebo group. However, 
ipilimumab was associated with reductions in PSA concentration (13.1% [95% CI·9.5 to 17.5] for 
ipilimumab and 5.2% [3.0 to 8.4] for placebo) and an improvement in progression-free survival 
(PFS) compared with placebo (median 4.0 [95% CI 3.6 to 4.3] vs 3.1 [2.9 to 3.4] months; HR 0.70, 
95% CI 0.61 to 0.82; p < 0.0001). PFS was a composite endpoint based on confirmed PSA 
progression, confirmed radiological progression, clinical deterioration, or death. During an 
additional exploratory assessment at approximately 2.4 years after the primary analysis, 721/799 
participants had died. Survival analysis showed crossing of the curves at 7 to 8 months, followed 
by persistent separation of the curves beyond that point, favoring the ipilimumab arm. Given the 
lack of proportional hazards, a piecewise hazard model showed that the hazard ratio (HR) changed 
over time: the HR was 1.49 (95% CI 1.12 to 1.99) for 0 to 5 months, 0.66 (0.51 to 0.86) for 5 to 
12 months, and 0.66 (0.52 to 0.84) beyond 12 months. OS rates were higher in the ipilimumab 
versus placebo arms at 2 years (25.2% vs 16.6%), 3 years (15.3% vs 7.9%), 4 years (10.1% vs 
3.3%), and 5 years (7.9% vs 2.7%). Disease progression was the most frequent cause of death in 
both arms. In 7 participants (1.8%) in the ipilimumab arm and 1 (0.3%) in the placebo arm, the 
primary cause of death was reported as study drug toxicity. No long-term safety signals were 
identified.29 
Similarly, Study CA184095 a double-blind, randomized Phase 3 study in participants with 
asymptomatic or minimally symptomatic, chemotherapy-naïve, mCRPC with no known visceral 
metastases did not meet its primary endpoint based on intent-to-treat analysis (HR 1.11; 95.87% 
CI: 0.88, 1.39; P value = 0.3667) for OS. However, treatment with ipilimumab was associated with 
longer median PFS (defined as time to confirmed PSA or radiological progression, clinical 
deterioration, or death) in the ipilimumab group (5.6 months) versus the placebo group 
(3.8 months, HR, 0.67; 95.87% CI, 0.55 to 0.81), longer median time to non-hormonal cytotoxic 
chemotherapy (HR, 0.65; 95.87% CI, 0.52 to 0.83) and to docetaxel therapy (HR, 0.70; 95% CI, 
0.55 to 0.88) in the ipilimumab arm versus placebo. In addition, a higher PSA response rate was 
observed with ipilimumab (23%; 95% CI, 19% to 27%) compared to placebo (8%; 95% CI, 5% to 
13%). 
3.2.1.2 
Programmed Death-1 (PD-1)/Programmed Death-ligand 1(PD-L1) 
Blockade in Prostate Cancer 
In primary prostate tumors, programmed death-ligand 1 (PD-L1) expression is rare, suggesting 
that it is not a driver of primary immune resistance in primary prostate cancer. In mCRPC, PD-L1 
positivity increased with 31.6% of cases showing PD-L1-specific immunoreactivity.30 Nivolumab 
monotherapy was evaluated in a cohort of 17 participants with mCRPC.31 All participants with 
mCRPC were treated with nivolumab 10 mg/kg, and no objective responses were observed. One 
out of 10 participants evaluable for PSA response demonstrated a PSA reduction ≥ 50% from 


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baseline. Other anti-PD-(L)1 inhibitors have also demonstrated limited clinical activity in mCRPC. 
Atezolizumab monotherapy was evaluated in a Phase 1 study, including 35 participants with 
mCRPC. All 35 evaluable participants received atezolizumab after ≥ 1 prior line of therapy; 62.9% 
of participants had received ≥ 3 prior lines. One participant had a confirmed partial response (PR) 
per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and 1 participant 
had a PR per immune-related response criteria. The confirmed 50% PSA response rate was 8.6% 
(3 participants). The Phase 2 KEYNOTE-199 study included 3 cohorts of participants with 
mCRPC previously treated with docetaxel and one or more targeted endocrine therapies. Cohorts 
1 and 2 enrolled participants with RECIST-measurable PD-L1-positive and PD-L1-negative 
disease, respectively. Cohort 3 enrolled participants with bone-predominant disease, regardless of 
PD-L1 expression. All participants received pembrolizumab 200 mg every 3 weeks for up to 
35 cycles. 258 participants were enrolled: 133 in Cohort 1, 66 in Cohort 2, and 59 in Cohort 3. 
Objective response rate was 5% in Cohort 1 and 3% in Cohort 2. Disease control rate was 10% in 
Cohort 1, 9% in Cohort 2, and 22% in Cohort 3. Median OS was 9.5 months in Cohort 1, 
7.9 months in Cohort 2, and 14.1 months in Cohort 3.32 
Since single-agent PD-(L)1 inhibitors have limited anti-tumor activity in mCRPC, these agents 
have also been evaluated in combination with standard of care docetaxel chemotherapy. In 
COU-AA-302, Arm B treated 84 participants with chemotherapy-naive mCRPC with ongoing 
androgen deprivation therapy and ≤ 2 prior NATs. Participants received nivolumab 
 + 
docetaxel 75 mg/m2 Q3W + prednisone 5 mg twice a day for ≤ 10 cycles, followed by nivolumab 
until disease progression/unacceptable toxicity (up to 2 years). The 
median number of docetaxel cycles was 8; the median number of nivolumab doses was 11. Median 
follow-up was 15.2 months. There was 1 (2.2%) complete objective response and 17 (37.8%) 
partial responses in 45 participants with measurable disease. Median rPFS was 9 months overall, 
12 months in the 30 participants who had not received prior NAT, and 8.5 months in the 
54 participants previously treated with NAT. Based on the pivotal Phase 3 studies in an era prior 
to NAT development, median PFS with docetaxel would be expected to be 6 to 7 months. 
Moreover, clinical benefit of docetaxel treatment may be reduced in patients following NAT 
exposure.33 Thus, the observed PFS compares favorably and led to the ongoing randomized 
controlled Phase 3 study CheckMate 7DX to determine if the addition of nivolumab improves 
rPFS and OS compared to docetaxel alone.34 
KEYNOTE-365 Cohort B examined the safety and efficacy of pembrolizumab + docetaxel and 
prednisone in participants with mCRPC, all previously treated with NAT: 104 participants were 
treated with median time from enrollment to data cutoff of 32.4 months.35 ORR in participants 
with measurable disease was 23% and median rPFS was 8.5 months, similar to the subset of 
participants in CheckMate 9KD previously treated with NAT. These data led to the ongoing 
KEYNOTE-921 Phase 3 study evaluating pembrolizumab in combination with docetaxel in 
mCRPC. 


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3.2.1.3 
Role for Dual Checkpoint Blockade Inhibition: (anti-CTLA-4 and anti- 
PD-1) in Prostate Cancer 
While PD-L1 expression is low in prostate tumors, pre-clinical data has indicated that it may be 
up-regulated on tumor cells as an adaptive resistance mechanism to CTLA-4 blockade. In a clinical 
trial, an increased frequency of CD4 and CD8 T-cell infiltration was observed in tumor tissues 
from participants with localized prostate cancer who were treated with ADT plus 2 doses of 
anti-CTLA-4 antibody (ipilimumab). Treatment with ipilimumab also led to increased expression 
of PD-L1.36 
Accordingly, utilizing a combination checkpoint blockade approach with anti-CTLA-4 and 
anti-programmed death-1 (anti-PD-1) agents may be necessary to boost anti-tumor activity for 
maximum clinical benefit in prostate cancer. Combination of nivolumab 1 mg/kg plus ipilimumab 
3 mg/kg Q3W for up to 4 doses, followed by nivolumab 480 mg every 4 weeks has been evaluated 
in Cohorts B and C of CheckMate 650.37 A safety and efficacy analysis (database lock date 27- 
Nov-2018) was conducted in all treated participants with at least 24 weeks of follow-up in Cohort 
B (participants with no prior chemotherapy treatment, n = 45) and Cohort C (participants who 
progressed after prior cytotoxic chemotherapy, n = 45). Among participants with baseline 
measurable disease, ORR was 25% in Cohort B and 10% in Cohort C. 
Among participants with measurable disease, 44 participants had tumor samples that underwent 
whole exome sequencing for homologous recombination deficiency (HRD) and tumor mutational 
burden (TMB) testing (TMB “high” and “low” represent above and below the median of 
74.5 mutations per participant). In participants with TMB above versus below the median, the 
objective response rate was 50.0% versus 5.3%, PSA response rate was 30.0% versus 5.9%, 
median rPFS was 7.4 versus 2.4 months, and median OS was 19.0 versus 10.1 months. 
Confirmed/unconfirmed PSA decline ≥ 50% in participants with baseline and ≥ 1 post-baseline 
PSA result were 17.6% Cohort B and 10% in Cohort C. Grade 3-4 treatment-related adverse events 
(TRAEs) occurred in 42% and 53% of participants in Cohorts B and C, respectively; TRAEs 
leading to discontinuation occurred in 15 participants (33.3%; Grade 3–4) in Cohort 1 and 
16 (35.6%; Grade 3–4) in Cohort 2. Two treatment related deaths occurred in each cohort. Ongoing 
cohorts are exploring different dosing schedules of nivolumab in combination with ipilimumab to 
identify a dose combination which reduces toxicity and increases the potential clinical benefit from 
dual checkpoint inhibition. 
3.2.2 
BMS-986218 and BMS-986288 Mechanism of Action 
BMS-986218 is a fully human immunoglobulin G1 (hIgG1) mAb against CTLA-4, an inhibitory 
receptor expressed on activated effector T-cells and Tregs. BMS-986218 shares the same amino 
acid sequence and ligand-blocking properties as ipilimumab but is produced in cells deficient for 
alpha-(1,6)-fucosyltransferase (Fut8), the enzyme that mediates fucosylation of the Ab 
carbohydrate side chain at N-linked glycopeptides. Therefore, BMS-986218 is an NF version of 
ipilimumab, which has increased affinity for FcγRs. 
In comparison to ipilimumab which induces activation of effector CD4+ and CD8+ T-cells by 
blocking the inhibitory function of CTLA-4, BMS-986218 may increase the anti-tumor immune 


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response through 2 additional mechanisms: by depleting tumor-infiltrating Tregs and enhancing 
stimulation of T-cells by antigen-presenting cells (APCs). Increasing the affinity of the 
antibody (Ab) for FcγR increases the Ab-dependent cellular cytotoxicity of target-expressing cells 
engaged by the Ab. Antibody engagement of CTLA-4 has been shown to mediate specific 
depletion of immune suppressive Tregs at the tumor site in mouse tumor models.38,39 The 
preferential depletion of Tregs is likely due to several factors, such as higher expression of CTLA-4 
on tumor Tregs compared to Tregs in peripheral lymphoid organs, higher expression of CTLA-4 
on tumor Tregs compared to effector CD4 and CD8 T-cells, and higher FcγR (CD16-2) expression 
in tumors compared to peripheral lymphoid organs. Additionally, Fc-FcγR co-engagement by 
anti-CTLA-4 can contribute to tumoricidal activity independent of Tregs, as evidenced by studies 
in mouse models in which Tregs are first depleted by other techniques. The mechanism involves 
enhanced T-cell receptor signaling at the immunological synapse with APCs, likely through 
co-engagement of T-cells by the antigen-binding fragment with simultaneous engagement of the 
Fc to FcγR expressed on APCs.40 
BMS-986288 is another next-generation anti-CTLA-4 that is identical to BMS-986218 except for 
. These amino acids form a 
masking peptide with a protease-cleavable linker. Proteases predominantly present in the tumor 
microenvironment cleave proteolytic sites in the masking peptide linker, selectively activating the 
mAb in the tumor microenvironment. The premise of this Probody technology is to create an mAb 
that is administered in a form that has a significantly reduced ability to bind to cognate antigen 
while in circulation or normal, healthy tissue. The Probody prodrug design could therefore widen 
the therapeutic window by decreasing toxicities due to antibody binding to sites outside of the 
tumor. Based on emerging data evaluating this concept, the addition of BMS-986288 may be 
incorporated into CA022-009 via future protocol amendment. 
3.2.3 
Nivolumab Mechanism of Action 
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human monoclonal 
antibody (HuMAb; immunoglobulin G4 [IgG4]-S228P) that targets the programmed 
death-1 (PD-1) cluster of differentiation 279 (CD279) cell surface membrane receptor. PD-1 is a 
negative regulatory molecule expressed by activated T and B lymphocytes. 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 (OPDIVO™) is approved for the treatment of several types of cancer in multiple 
regions including the United States (US, Dec-2014), the European Union (Jun-2015), and Japan 
(Jul-2014). 


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3.2.4 
Docetaxel Mechanism of Action 
Docetaxel is an anti-neoplastic chemotherapeutic agent which acts by disrupting the microtubular 
network that is essential for mitotic and interphase cellular functions. See the current prescribing 
information for docetaxel (Summary of Product Characteristics [SmPC], US Prescribing 
Information [USPI], or country-specific label) for more information.41,42 
3.2.5 
BMS-986218 and BMS-986288 Clinical Activity 
Study CA022001 is an ongoing BMS study which is evaluating the safety, tolerability, and 
preliminary efficacy of intravenous (IV) doses of BMS-986218, administered as monotherapy and 
in combination with nivolumab in participants with advanced solid tumors. 
BMS-986218 monotherapy has been administered 
In addition, BMS-986218 monotherapy has also been administered 
. BMS-986218 has also been administered in combination with nivolumab 
at doses of BMS-986218 
. The maximum tolerated dose 
(MTD) of BMS-986218 as a monotherapy or in combination with nivolumab has not been reached, 
and dose escalation is currently ongoing. Overall, the safety profile of BMS-986218 as a single 
agent and in combination with nivolumab is clinically manageable. Efficacy for this ongoing study 
has not yet been evaluated. 
Study CA043-001 is an ongoing BMS study which is evaluating whether BMS-986288 by itself 
and in combination with nivolumab is safe and tolerable in the treatment of select advanced solid 
tumors. Based on clinical data, the use of BMS-986288 will be added to the CA022-009 protocol 
via future amendment, if the Sponsor seeks to test BMS-986288 in the present study. 
Additional details on the safety of BMS-986218 and BMS-986288 are summarized in their 
respective investigator brochures.43,44 
3.2.6 
Nivolumab Clinical Activity 
Nivolumab has demonstrated durable responses exceeding 6 months as monotherapy in several 
tumor types, including non-small cell lung cancer (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 colorectal cancer (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 USPI and SmPC. 
3.2.7 
Docetaxel Clinical Activity 
The safety and efficacy of docetaxel in combination with prednisone or prednisolone in 
participants with mCRPC were evaluated in a randomized Phase 3 study (TAX 327). A total of 
1006 participants were randomized to 3 different treatment arms: 1) docetaxel Q3W for 10 cycles, 
2) mitoxantrone Q3W for 10 cycles, and 3) docetaxel weekly for the first 5 weeks in a 6-week 


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cycle for 5 cycles. All regimens were administered in combination with prednisone or prednisolone 
twice daily, continuously. The primary endpoint of the study was OS. When given with 
prednisone, treatment with docetaxel Q3W led to improved rates of response in terms of pain, 
serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.1 Participants 
who received docetaxel Q3W demonstrated significantly longer OS compared to those treated with 
mitoxantrone. The median survival was 16.5 months in the mitoxantrone group and 18.9 months 
in the group given docetaxel Q3W. Respectively, for the mitoxantrone and docetaxel Q3W groups, 
32% and 45% (P < 0.001) had at least a 50% decrease in the serum PSA level, 22% and 35% 
(P = 0.01) had predefined reductions in pain, and 13% and 22% (P = 0.009) had improvements in 
the quality of life. 
3.3 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
anticipated adverse events (AEs) of BMS-986218 may be found in the Investigator’s Brochure.43 
Extensive details on the safety profile of nivolumab are available in the Investigator’s Brochure, 
and will not be repeated herein.45 
Overall, the safety profile of nivolumab monotherapy is manageable and generally consistent 
across completed and ongoing clinical trials with no MTD reached at any dose tested up to 
10 mg/kg. Most AEs were low-grade (Grade 1 to 2) with relatively few related high-grade (Grade 
3 to 4) AEs. There was no pattern in the incidence, severity, or causality of AEs with respect to 
nivolumab dose level. 
A pattern of immune-mediated adverse events (IMAEs) has been defined, for which management 
algorithms have been developed; these are provided in Appendix 8. Most high-grade events were 
manageable with the use of corticosteroids or hormone replacement therapy (endocrinopathies) as 
instructed in these algorithms. 
Additional details on the safety profile of nivolumab, including results from other clinical studies, 
are also available in the nivolumab IB. 
3.3.1 
Risk Assessment 
Study CA022009 is designed to start out with a safety lead-in portion (Part 1) prior to moving on 
to the randomized controlled portion (Part 2). The study visits allow for close monitoring of 
participants’ safety throughout the clinical trial (see Section 2, Schedule of Activities), and 
participants are encouraged to contact the investigator if an intercurrent illness develops between 
study visits. To minimize therapy-related risk to participants enrolled in the present study, the 
following safety measures will be employed throughout the conduct of the study: 
• Rigorous continuous safety monitoring by BMS to ensure participants’ safety including regular 
and systematic review of safety data, close follow-up of reported safety events, and intensive 
site and study investigator training/education on the implementation of the toxicity 
management algorithms. A BMS Safety Management Team (SMT) will review and evaluate 
all emerging data across the program for potential safety signal assessment in a timely manner. 


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BMS Worldwide Patient Safety (WWPS) is an internal group that operates independently from 
the clinical team to monitor safety across all BMS protocols (Section 5.1.4.1). 
• An independent Data Monitoring Committee (DMC) will evaluate the safety for the 
randomization phase (Section 5.1.4). This evaluation will be based on all available data with 
particular attention to AEs or other safety trends in this or any other clinical study of the study 
intervention whose character, severity, and/or frequency suggest that participants would be 
exposed to an unreasonable and significant risk of illness or injury. 
• Risks will be further minimized by adherence to inclusion and exclusion selection criteria 
(Section 6), avoidance of prohibited medication (Section 7.7), close safety monitoring 
(Section 9.2 and Section 9.4), and dose adjustment guidelines (Section 7.4). These will also be 
clearly discussed and highlighted during site visits. 
• Study treatment administration will occur at infusion centers with medical monitoring and the 
capability to manage infusion reactions or anaphylaxis. The protocol provides a treatment 
algorithm for infusion reactions. In addition to conventional safety measures for infusion of 
biologic agents, all participants will undergo observation and assessment for signs of infusion 
reaction for 30 minutes post infusion after all infusions of BMS-986218. 
 
Selected important clinically significant risks for BMS-986218, nivolumab and docetaxel are 
presented in Table 3.3.1-1. 
Table 3.3.1-1: 
Risk Assessment 
 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Study Intervention: BMS-986218 
Overall Safety Profile 
The safety profile of BMS-986218 
is based on the data from Study 
CA022001, the Phase 1/2a first-in- 
human (FIH) clinical study for this 
drug product. Both as a 
monotherapy and in combination 
with nivolumab, its observed 
toxicity profile thus far is similar to 
that observed with ipilimumab, 
which is anticipated based on the 
mechanism of action. 
Reference Safety Information in 
IB.43 
See Section 7.4.1 and Table 7.4.1-1 
for dose modification criteria and 
AE criteria for delay, resume and 
discontinuation of nivolumab and 
BMS-986218. 
Diarrhea 
Pneumonitis 
These events were commonly 
reported and are considered 
important identified risks. 
Reference Safety Information in 
IB.43 
Recommended management 
algorithms are included in 
Appendix 8. 
Study Interventions: BMS-986218 and Nivolumab 
Increased Toxicity Combining 
Multiple Checkpoint Inhibitors, 
The paradigm of combining of 
ipilimumab and nivolumab with 
The toxicity profile with the 
combination was consistent with 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
(anti-CTLA-4 [ipilimumab] and 
anti-PD-1 [nivolumab]), with 
Chemotherapy 
chemotherapy was established by 
the Phase 3 CheckMate 9LA study, 
an open-label, multi-center, 
randomized Phase 3 trial evaluating 
ipilimumab plus nivolumab 
combined with platinum doublet 
chemotherapy compared to 
chemotherapy alone as 1L 
treatment for patients with 
metastatic NSCLC. The addition of 
ipilimumab and nivolumab 
increased toxicity: Grade 3 or 4 
TRAEs were reported in 48% of 
patients who received ipilimumab 
and nivolumab with chemotherapy 
and in 38% of patients who 
received chemotherapy only. 
that of the treatment components 
and was acceptable based on 
improved clinical activity, leading 
to approval of the combination as 
1L treatment for adult patients with 
metastatic or recurrent non-small 
cell lung cancer with no epidermal 
growth factor receptor (EGFR) or 
ALK genomic tumor aberrations. 
IMAEs 
The frequency and types of 
immune-mediated adverse reactions 
are similar across multiple types of 
tumors. Unanticipated side effect 
events may also occur. 
Reference Safety Information in 
IB.45 
Recommended management 
algorithms are included in 
Appendix 8. 
Diarrhea 
Colitis 
Pneumonitis 
These events were commonly 
reported and are considered 
important identified risks. 
Reference Safety Information in IB. 
Recommended management 
algorithms are included in 
Appendix 8. 
Study Intervention: Docetaxel 
Well-characterized AE Profile as a 
Cytotoxic Chemotherapy: 
Pancytopenia, Fluid Retention, 
Peripheral Neuropathies, Diarrhea, 
Nausea, and Vomiting 
The safety and tolerability of 
docetaxel in combination with 
pembrolizumab in patients with 
mCRPC appeared to be acceptable. 
Grade 3 to 5 treatment-related AEs 
(TRAEs) occurred in 27 (38%) of 
patients, including 2 deaths from 
TRAEs (pneumonitis). The most 
commonly reported Grade ≥ 3 
TRAEs were febrile neutropenia 
(12%), decreased neutrophil count 
(6%), colitis (4%), and pneumonitis 
(4%). Most immune-mediated AEs 
(IMAEs) were low grade with the 
most common being infusion- 
related reactions (11%) and colitis 
(10%). Of the 104 treated 
participants, treatment-related 
adverse events (TRAEs) occurred 
See Section 7.4.2 and Table 7.4.2-1 
for dose modification criteria and 
AE criteria for delay, resume and 
discontinuation of docetaxel. 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
in 100 participants (96.2%); the 
most frequent (≥ 30%) were 
diarrhea (41.3%), fatigue (41.3%), 
and alopecia (40.4%). Grade 3-5 
TRAEs occurred in 46 participants 
(44.2%). Five participants (4.8%) 
died of AEs; 2 were treatment- 
related pneumonitis.35 
Docetaxel was also tested in 
combination with nivolumab in 
Arm B of the ongoing Phase 2 
CA2099KD study (NCT03338790). 
Of 84 treated patients with a 
median age of 71 years (range: 53 
to 88 years), 47.6% of patients 
experienced Grade 3-4 TRAEs, 
most commonly neutropenia 
(16.7%). TRAEs led to 
discontinuation in 29.8% of 
patients. The most common 
immune-related AEs were GI 
(35.7%) or skin-related (26.2%). 
There were 3 treatment-related 
deaths (1 pneumonitis related to 
nivolumab; 2 pneumonias related to 
docetaxel).34 
Study Procedures 
Biopsies 
The biopsies pose limited risk to the 
participant and include discomfort, 
pain, and bleeding. 
Section 9.8 gives guidance on 
lesions that are appropriate for a 
research biopsy and when no 
appropriate lesion is identified 
participants are still able 
participate. Because of the need for 
development of predictive 
biomarkers for participants treated 
with BMS-986218 in future studies, 
the limited risk of a research biopsy 
in selected (low-risk) participants is 
considered appropriate in a Phase 2 
research setting. 
Blood Sampling 
The amount of blood sampling 
poses limited risk to the participant 
and includes discomfort, pain, and 
bleeding. 
The amount of total blood is 
reduced to the minimal quantity 
required to address the need of 
safety monitoring, standard of care, 
PK/anti-drug antibodies (ADAs), 
and biomarker needs and is below 
the recommended daily limits for 
each treatment day. 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Other 
SARS-CoV-2 Infection 
The global coronavirus disease 
2019 (COVID-19) pandemic has 
been identified as a potential risk to 
clinical trial participants in general. 
Whether BMS-986218 in 
combination with docetaxel or 
docetaxel plus nivolumab 
administration increases the risk for 
contracting SARS-CoV-2 infection 
or increases the severity or duration 
of symptoms is currently unknown. 
This unknown risk must be 
considered when enrolling a 
participant. 
No additional safety monitoring or 
routine screening tests will be 
required due to the SARS-CoV-2 
pandemic. Participants with recent 
or acute infections will be excluded 
or delay start of treatment as 
defined in Section 6.2. If a 
participant has a confirmed 
SARS-CoV-2 infection while on 
study treatment, dose delay or 
interruption of study treatment is 
required as described in 
Section 7.4. An exploratory 
analysis of the impact of SARS- 
CoV-2 serologic status on 
participants receiving BMS-986218 
in combination with docetaxel or 
docetaxel plus nivolumab may be 
performed. 
The study has been designed with 
study visits that allow for close 
monitoring of participants’ safety 
throughout the clinical trial 
(Section 9.4), and participants are 
encouraged to contact the 
investigator if an intercurrent illness 
develops between study visits. 
Testing for COVID-19 to inform 
decisions about clinical care during 
the study should follow local 
standard practice. 
Non-live COVID-19 vaccination is 
considered a simple concomitant 
medication within the study. 
However, the efficacy and safety of 
non-live vaccines (including non- 
live COVID-19 vaccines) in 
participants receiving BMS-986218 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
in combination with docetaxel or 
docetaxel plus nivolumab is 
unknown. 
Abbreviations: 1L, first line; ADA, anti-drug antibody; AE, adverse event; ALK, anaplastic lymphoma kinase; 
COVID-19, coronavirus disease 2019; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; EGFR, epidermal 
growth factor receptor; FIH, first-in-human; GI, gastrointestinal; IB, Investigator’s Brochure; IMAE, immune- 
mediated adverse event; mCRPC, metastatic castration-resistant prostate cancer; NSCLC, non-small cell lung cancer; 
PD-1, programmed death-1; PK, pharmacokinetic; SARS-CoV-2, severe acute respiratory syndrome coronavirus 
disease 2; TRAE, treatment-related adverse event. 
 
 
3.3.2 
Benefit Assessment 
Although multiple new agents have been approved for mCRPC over the last decade, benefits 
remain modest and the median survival of patients with mCRPC is unsatisfactory at approximately 
12 to 35 months.11,18,20,46,47,48 Participants with mCRPC who received docetaxel Q3W had a 
median survival of 19.2 months, compared to 16.3 months in the mitoxantrone Q3W and 
17.8 months in the docetaxel QW arms. The hazard ratio (HR) for the docetaxel Q3W arm was 
0.76 (95% CI, 0.62 to 0.94; P = 0.009). Furthermore, OS may be shorter in patients who received 
prior treatment with NAT.49,50 It is clear that there is an urgent need for new therapeutic options 
that offer further improvement in cancer control and OS. Ipilimumab has demonstrated anti-tumor 
activity in mCPRC when administered to patients who have not yet received chemotherapy or in 
patients previously treated with docetaxel, and the activity may be augmented by combination with 
nivolumab. The additional mechanisms of anti-tumor activity provided by BMS-986218 compared 
to ipilumumab could provide greater benefit. Moreover, two Phase 2 studies, KEYNOTE-365 and 
CheckMate 9KD have suggested that addition of PD-1 blockade to docetaxel improves mPFS 
compared to historical data, providing further support for combining chemotherapy and 
immunotherapy in mCRPC.35,34 
3.3.3 
Overall Benefit/Risk Conclusion 
In conclusion, treatment with BMS-986218 and nivolumab in combination with docetaxel in men 
with mCRPC is expected to be tolerable, and toxicities of the treatment are expected to be 
manageable and reversible upon dose reduction, treatment interruption, or discontinuation. 
IMAE-related toxicities may require use of immunosuppressive agents. For management 
algorithms for AEs related to immuno-oncology (I-O) agents, refer to Appendix 8. Together, the 
potential for 1) CTLA-4 blockade to induce long-term disease control and improve survival in a 
subset of patients as a monotherapy,29 2) better response to CTLA-4 blockade when combined 
with nivolumab,37 3) longer term disease control when immunotherapy is added to 
chemotherapy,34,35 and 4) better anti-tumor activity and less relative toxicity with BMS-986218 
compared to ipilimumab all support the likelihood of substantial benefit to patients when treated 


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with the combination of docetaxel with BMS-986218 or BMS-986218 plus nivolumab. The overall 
risk-benefit of the combination is deemed acceptable. 
Lastly, due to the Probody design, BMS-986288 may have a better benefit/risk profile than BMS- 
986218. If emerging data from Study CA043-001 support its potential, the Sponsor may elect to 
incorporate BMS-986288 into the CA022-009 study design via future protocol amendment. 
Detailed information about the known and expected benefits and risks and reasonably anticipated 
AEs of BMS-986218, BMS-986288, and nivolumab may be found in their respective IBs.43,45,45 
Similar information is provided for docetaxel in the associated Patient Information Leaflet, USPI, 
country-specific label, Development Safety Update Report, or SmPC.41,42 


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4 
OBJECTIVES AND ENDPOINTS 
Table 4-1: 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• 
To assess the safety, tolerability, and DLTs of 
docetaxel in combination with BMS-986218 or 
in combination with BMS-986218 plus 
nivolumab in participants with mCRPC 
(Part 1) 
Primary 
• 
Incidence of AEs, SAEs, AEs meeting protocol-defined 
DLT criteria, TRAEs, AEs leading to discontinuation, 
and deaths 
• 
To compare the rPFS in mCRPC participants 
treated with docetaxel and either docetaxel in 
combination with BMS-986218 or docetaxel in 
combination with BMS-986218 and nivolumab 
(Part 2) 
• 
rPFS for randomized participants is the time between 
randomization date and the first date of documented 
radiographic progression, or death due to any cause, 
whichever occurs first. The radiographic progression 
will be assessed by blinded independent central review 
(BICR) per PCWG3 
Secondary 
• 
To assess the antitumor activity of the 
combination of docetaxel with BMS-986218 or 
BMS-986218 and nivolumab in mCRPC 
participants, based on ORR, TTR, and DOR 
(Part 2) 
Secondary 
• 
Objective response rate per PCWG3 (ORR-PCWG3) is 
the proportion of participants who have a confirmed 
complete or partial best overall response (BOR) per 
PCWG3 among randomized participants who have 
measurable disease at baseline. The BOR is defined as 
the best response designation, as determined by the 
BICR, recorded between the date of randomization and 
the date of objectively documented radiographic 
progression, or last tumor measurement, whichever 
occurs first 
• 
Time to response per PCWG3 (TTR-PCWG3) is the 
time from randomization date to the date of the first 
documented CR or PR per PCWG3, as determined by 
BICR 
• 
Duration of response per PCWG3 (DOR-PCWG3) is 
the time between the date of first response (CR/PR per 
PCWG3) to the date of first documented radiographic 
progression per PCWG3 (as determined by BICR), or 
death due to any cause 
• 
To assess PSA response rate (PSA-RR) and 
time to PSA progression (TTP-PSA; limited to 
participants with measurable PSA [defined as 
≥ 2 ng/ml] at baseline) (Part 2) 
• 
PSA-RR is the proportion of randomized participants 
with a 50% or greater decrease in PSA from baseline to 
any post-baseline PSA result. A second consecutive 
value obtained 3 or more weeks later is required to 
confirm the PSA response 
• 
TTP-PSA is the time between randomization date to the 
date of PSA progression per PCWG3 in randomized 
participants 
• 
To assess overall survival (OS) (Part 2) 
• 
OS for all randomized participants is the time between 
randomization date and the date of death from any cause 
• 
To characterize safety of BMS-986218 in 
combination 
with 
docetaxel, 
and 
with 
nivolumab and docetaxel in Part 2 
• 
Overall safety and tolerability will be measured by the 
incidence of AEs, TRAEs, SAEs, AEs leading to 
discontinuation, and deaths 


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Objectives 
Endpoints 
Exploratory 
• 
To characterize the PK of BMS-986218 when 
administered in combination with docetaxel 
only or in combination with docetaxel and 
nivolumab 
Exploratory 
• 
Summary of PK parameters of BMS-986218 
• 
To 
characterize 
the 
immunogenicity 
of 
BMS-986218 
when 
administered 
in 
combination with docetaxel only or in 
combination with docetaxel and nivolumab 
• 
Summary of ADA incidence to BMS-986218 
• 
To characterize the PK of nivolumab when 
administered in combination with docetaxel 
and BMS-986218 
• 
Summary of PK parameters of nivolumab 
• 
To 
characterize 
the 
immunogenicity 
of 
nivolumab when administered in combination 
with docetaxel and BMS-986218 
• 
Summary of ADA incidence to nivolumab 
• 
To estimate the time to initiation of subsequent 
systemic therapy (TT-SST) 
• 
TT-SST is the time from treatment assignment (Part 1) 
or randomization date (Part 2) to the start of subsequent 
systemic 
therapy, 
including 
hormonal 
therapy 
(excluding 
continued 
ADT 
with 
GnRH 
agonist/antagonist), chemotherapy, immunotherapy, or 
investigational therapy 
• 
To investigate the time to first symptomatic 
skeletal events (TT-SSEs) 
• 
TT-SSE is the time between treatment assignment 
(Part 1) or randomization (Part 2) and the date of first 
symptomatic fracture, radiation or surgery to bone, or 
spinal cord compression 
• 
To evaluate the change in health-related quality 
of life domains (Part 2 only) 
• 
Change in baseline mean scores (total, subscale and 
symptoms scores) as assessed by EORTC QLQ-C30 
• 
To evaluate the change in perceptions of 
bothersomeness in treatment-related symptoms 
(Part 2 only) 
• 
Proportion of participants endorsing each response 
category of the single item FACIT GP5 at baseline and 
post-baseline administration 
• 
To explore measures of clinical activity in 
participants in Part 1 
• 
Based on ORR, TTR and DOR 
• 
To explore measures of clinical activity in 
participants receiving the crossover treatment 
(Arm 2d in Part 2), based on ORR and 
PSA-RR 
• 
ORR and PSA-RR based on clinical activity after 
initiation of crossover treatment 
• 
To explore the time to and duration of PSA 
response 
• 
Time to PSA response (TTR-PSA) is defined for PSA 
responders as the time from treatment assignment 
(Part 1) or randomization date (Part 2) to the date of the 
first PSA response. Duration of PSA response 
(DOR-PSA) is defined for PSA responders as the time 
between the date of first confirmed PSA response and 
the date of PSA progression 


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Objectives 
Endpoints 
• 
To explore pharmacodynamic biomarkers in 
blood (cytokines, circulating immune subsets) 
and tumor (immune cell subsets in tumor 
microenvironment) and explore the association 
between baseline and other markers with 
response following Part 1 and Part 2 treatment 
• 
Summary measures for key baseline blood and tumor 
biomarkers and change (or % change) from baseline and 
measure of association of anti-tumor response and 
pharmacodynamic markers 
• 
To assess the impact of SARS-CoV-2 serologic 
status on participants with mCRPC who are 
receiving study intervention(s) 
• 
Exploratory measurements of SARS-CoV-2 serology 
(anti-SARS-CoV-2 total or IgG), from serum samples 
collected at baseline and specified timepoints 
• 
To explore the potential association of ctDNA 
(HRD, DDR and TMB) in peripheral blood 
with anti-tumor activity prior to treatment and 
following administration of docetaxel alone or 
in 
combination 
with 
BMS-986218 
or 
BMS-986218 plus nivolumab 
• 
Summary measures of anti-tumor activity by 
pre-treatment level of ctDNA, measure of association of 
anti-tumor activity and change (or % change) from 
baseline with ctDNA 
Abbreviations: ADA, anti-drug antibody; ADT, androgen deprivation therapy; AE, adverse event; BICR, blinded 
independent central review; BOR, best overall response; CR, complete response; ctDNA, circulating tumor DNA; 
DNA, deoxyribonucleic acid; DDR, DNA damage repair; DLT, dose-limiting toxicity; DOR, duration of response; 
EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; 
FACIT GP5, Functional Assessment of Chronic Illness Therapy General Physical Item 5; GnRH, gonadotropin- 
releasing hormone; HRD, homologous recombination deficiency; IgG, immunoglobulin G; mCRPC, metastatic 
castration-resistant prostate cancer; ORR, objective response rate; OS, overall survival; PCWG3, Prostate Cancer 
Working Group 3; PK, pharmacokinetic; PR, partial response; PSA, prostate-specific antigen; PSA-RR, PSA response 
rate; rPFS, radiographic progression-free survival; SAE, serious adverse event; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus 2; TMB, tumor mutational burden; TRAE, treatment-related adverse event; TTP-PSA, time to 
PSA progression; TTR, time to response; TTR-PSA, time to PSA response; TT-SSE, time to first symptomatic skeletal 
event; TT-SST, time to initiation of subsequent systemic therapy. 
 
5 
STUDY DESIGN 
5.1 
Overall Design 
This multi-center, randomized, controlled, open-label, Phase 2 study evaluates docetaxel alone, in 
combination with BMS-986218, or in combination with BMS-986218 plus nivolumab in men who 
have mCRPC that progressed after NAT and have not received chemotherapy for mCRPC. 
The study will be carried out in 2 parts: Part 1, a safety lead-in portion, and Part 2, a randomized, 
controlled portion. All participants will complete up to 3 study periods: screening (up to 28 days), 
treatment (up to 2 calendar years from first dose of study treatment regardless of treatment delays 
[21 days/cycle]), and follow-up. The Follow-up Period includes Safety Follow-up (comprising 
3 visits over about 100 days) and Survival Follow-up (up to 2 years from the last dose of study 
treatment) periods. The maximum duration of study participation will be approximately 4 years 
(up to 28 days of screening, treatment of up to 2 years, and follow-up of up to 2 years). Images 
will be submitted to a central imaging vendor and will undergo Blinded Independent Central 
Review (BICR). Prior to scanning the first participant, sites should be qualified and understand the 
image acquisition guidelines and submission process as outlined in the CA022009 Imaging 
Manual provided by the central imaging vendor. 


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The study design schematic is presented in Figure 5.1-1. 
Figure 5.1-1: 
Study Design Schema 
 
Abbreviations: CT, computed tomography; DLT, dose-limiting toxicity; I-O, immuno-oncology; mCRPC, metastatic 
castration-resistant prostate cancer; MRI, magnetic resonance imaging; N, number of participants; NAT, novel 
antiandrogen therapy; Q3W, every 3 weeks; rPD, radiographic progressive disease; Y/N, yes/no. 
a The DLT evaluation period will be 42 days (6 weeks) starting on Cycle 1 Day 1 for Part 1A and Part 1B. 
b Administer docetaxel for a maximum of 10 cycles. 
c For participants who are also receiving BMS-986218 or BMS-986218 and nivolumab, treatment with these I-O 
agents may continue beyond 10 cycles, up to 2 years (until disease progression, unacceptable toxicity, or withdrawal 
of consent). 
d In Part 1B, BMS-986218 or nivolumab may be dose reduced based on safety data. 
e In Part 2, randomization to 1 of 3 treatment arms will be stratified by measurable disease (Y/N). 
f See Section 5.1.2 for details regarding optional crossover treatment (Arm 2d) for participants randomized to Part 2 
Arm 2a, including maximum duration of treatments. 
 
Physical examinations, vital sign measurements, 12-lead ECGs, and clinical laboratory evaluations 
will be performed at selected times throughout the dosing interval (see Section 2, Schedule of 
Activities). Participants will be closely monitored for AEs throughout the study. Blood will be 
collected according to Section 9.5 for PK analysis. 
5.1.1 
Screening Period 
The screening period will be up to 28 days. Informed consent will be obtained prior to any 
study-specific procedures. All participants (Part 1 and Part 2) being screened will be evaluated 
based on inclusion and exclusion criteria (Section 6.1 and Section 6.2) and will be enrolled using 
an Interactive Response Technology (IRT) system (Section 7.2). 


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Participants for Part 2 will be randomized to 1 of 3 treatment arms and will be stratified according 
to measurable disease status which will be assessed by investigator based on the tumor assessment 
performed during screening (Prostate Cancer Working Group 3 [PCWG3]; refer to Appendix 5). 
Tumor tissue must be obtained and submitted to central laboratory prior to treatment assignment 
(Part 1) or randomization (Part 2) for participants with any soft tissue lesion that is suspected to 
represent metastatic disease based on local review of imaging and is considered accessible for 
biopsy by an interventional radiologist (or other appropriate specialist). Lymph nodes must 
measure at least 1 cm in diameter along the short axis in order to be considered for biopsy. See 
Section 6.1 (Inclusion Criteria) and Section 9.8 (Biomarkers) for specifications. 
For participants who meet the above criteria, a pre-treatment, on-treatment, and on-progression 
biopsy are required if medically feasible (tumor sites that can be biopsied with acceptable clinical 
risk). Baseline tumor tissue is not mandatory for participants with bone metastasis only. 
Participants who have met all eligibility criteria will be enrolled to receive treatment in Part 1 or 
Part 2 as applicable. 
5.1.2 
Treatment Period 
The treatment period for BMS-986218 and/or nivolumab will last for up to 2 calendar years from 
first dose of study treatment and up to a maximum of 10 doses for docetaxel regardless of treatment 
delays (21 days/cycle). In addition to dosing visits on Day 1 of each cycle, there are also 
non-dosing visits on Days 8 and 15 in Cycles 1 and 4 and Day 15 in Cycle 2 for 
biomarkers 
assessments (see Section 9.5 and Section 9.8). 
Part 1A will evaluate the safety and tolerability of BMS-986218 in combination with docetaxel. 
The dose-limiting toxicity (DLT) evaluation period will be 42 days (6 weeks) starting on Cycle 1 
Day 1 for Part 1A and Part 1B. The DLT evaluation during this safety lead-in, including potential 
decision to escalate or to de-escalate the BMS-986218 dose level, will be guided by the Bayesian 
Optimal Interval (BOIN) design framework (refer to Appendix 9) with a target DLT rate of 30%.51 
In Part 1B, there is also a potential to de-escalate the nivolumab dose level 
. The target 
DLT in Part 1A was selected based on an observed DLT rate of 2/6 = 33% for BMS-986218 
monotherapy at the 
 dosing in CA022001, estimated by the basic linear ranking model 
(BLRM) design and the MTD not reached with 2 dose levels higher being evaluated. For Part 1B, 
the observed DLT rate was 1/9 = 11% following treatment with nivolumab 
 + BMS-986218 
in the same study (CA022001). In addition, in Study CA2099KD in participants 
treated with docetaxel with nivolumab, there was a 14.3% reported frequency of treatment 
discontinuations due to Grade 3-4 TRAEs, with the most frequent TRAEs (any grade) leading to 
discontinuation being pneumonitis (7.1%), fatigue (6.0%), peripheral neuropathy (6.0%), and 
pneumonia (3.6%). 
The Part 1A decisions for escalation, de-escalation, or continuing evaluating at the same dose level, 
will be guided by the BOIN escalation design (Table 5.1.2-1). Approximately 12 DLT-evaluable 
participants are expected to be treated, depending on the number of dose levels and the number of 
observed DLTs. Dose escalation/de-escalation decisions or decision to continue enrollment at the 
current dose will be made by the Sponsor in collaboration with investigators and take into 


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consideration all available safety and, if available, PK and pharmacodynamic data. Participants 
will enroll in cohorts of 3 to 4 initially. After the first 3 to 6 participants are evaluated, additional 
cohorts of 3 to 6 participants may be enrolled, as needed, with no more than 12 participants at a 
specific dose level. Once at least 6 participants have cleared the DLT observation period at a 
tolerable dose level in Part 1A, participants will be enrolled in Part 1B to assess safety and 
tolerability of the combination of BMS-986218 + docetaxel + nivolumab, starting at a lower 
BMS-986218 dose level than in Part 1A. Additional participants may be enrolled in Part 1A at this 
dose or a higher dose in order to continue to assess safety in this combination. 
Table 5.1.2-1: 
Safety Lead-in Evaluation Guidance Based on BOIN Design 
 
 
Actions Based on Number of 
DLTs Observed 
Number of DLT-evaluable Participants Treated at Current Dose 
 
3 
4 
5 
6a 
7 
8 
9 
10 
11 
12 
Escalate Doseb if # of DLTs ≤ 
0 
0 
1 
1 
1 
1 
2 
2 
2 
2 
Stayc if # of DLTs = 
1 
1 
NA 
2 
2 
2 
3 
3 
3 
3,4 
De-escalated if # of DLTs ≥ 
2 
2 
2 
3 
3 
3 
4 
4 
4 
5 
De-escalate and Eliminatee from 
Evaluation if # of DLTs ≥ 
3 
3 
4 
4 
5 
5 
5 
6 
6 
7 
Abbreviations: BOIN, Bayesian Optimal Interval; DLT, dose-limiting toxicity; NA, not applicable (for decision). 
a A minimum of 6 DLT-evaluable participants will be required to meet acceptable DLT criteria for a dose level to be 
selected for Part 2. 
b “Escalate” indicates that a higher dose level may be evaluated. 
c “Stay” indicates that more participants need to be treated to determine tolerability. 
d “De-escalate” indicates that a lower dose level needs to be evaluated. 
e Such dose level is excessively non-tolerable and re-escalation is not allowed after de-escalation. A lower dose level 
will be evaluated. 
 
Treatment in Part 1B may be initiated in a staggered manner relative to the BMS-986218 + 
docetaxel escalation (Part 1A). Specifically, Part 1B can be initiated upon the evaluation of a 
sufficient number of participants at a dose level in Part 1A who have cleared the DLT requirements 
(eg, 6 evaluable participants with 0 or 1 DLT), after which dose evaluation in Part 1A and Part 1B 
may proceed in parallel. At no point will the dose of BMS-986218 administered in combination 
with nivolumab and docetaxel in Part 1B exceed the highest dose determined to be tolerated in 
Part 1A. 
Part 1B will also use a BOIN design framework for the evaluation of BMS-986218 tolerability in 
combination with docetaxel and nivolumab. Approximately 12 to 18 DLT-evaluable participants 
are expected to be treated if 2 or more dose-level combinations are evaluated in this part. Initially, 
3 to 4 participants will be treated at the starting dose and subsequent decisions will be based on 
the BOIN design framework as shown in Table 5.1.2-1 above, similar to Part 1A. If needed, based 


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on the number of DLTs, additional participants in groups of 3 to 6 participants may be enrolled at 
the same dose level, or otherwise a lower dose level may be evaluated. 
If de-escalation is necessary based on the number of toxicities, a lower combination dose level will 
be evaluated. The specific dose level to be administered in combination will be determined based 
on the nature of the DLTs and will be either: 1) a lower dose of BMS-986218 in combination with 
the same dose levels of nivolumab and docetaxel or 2) a lower dose level of nivolumab 
in combination with the same dose levels of BMS-986218 and docetaxel. 
Once a tolerable dose has been determined for BMS-986218 in combination with docetaxel in 
Part 1A and for BMS-986218 in combination with docetaxel + nivolumab in Part 1B in at least 
6 evaluable participants, the randomized Part 2 of the study will open for enrollment. In Part 2, 
randomization 1:1:1 to 1 of 3 treatment arms will be stratified according to the following baseline 
factor: 
• Measurable disease (Y/N): Measurable disease status will be assessed by investigator based on 
the tumor assessment performed during screening (RECIST v1.1). 
 
Optional Crossover Treatment (Arm 2d) for Participants Randomized to Part 2 Arm 2a: 
Participants treated in Arm 2a who demonstrate radiographic progressive disease (rPD) while on 
treatment (during active treatment with docetaxel) or after treatment (while in Safety or Survival 
Follow-up) may be eligible to crossover to optional Arm 2d and receive treatment of BMS-986218 
in combination with nivolumab (Q3W at the dose level chosen in Arm 2c). Further docetaxel 
treatment will not be administered in Arm 2d. 
In order to qualify for crossover, radiographic progression per PCWG3 must be confirmed by 
BICR and the participant must meet all inclusion criteria and exclusion criteria specified in 
Section 6.1 and Section 6.2 (with the exception that prior treatment with docetaxel is allowed). 
The BMS medical monitor must approve crossover to Arm 2d. 
At least a 3-week period from the last dose of docetaxel is required prior to the first dose of 
crossover treatment. Participants who are receiving treatment in Arm 2d should restart the 
Schedule of Activities (Section 2, Table 2-2) at Cycle 1 Day 1. The imaging tumor assessments 
performed at progression while on Arm 2a may serve as the new baseline by which to assess 
response during crossover and will be submitted to BICR. 
The following assessments will not be repeated for crossover participants: 
• Crossover participants in Arm 2d will not have any biomarkers samples drawn or tumor 
biopsies performed with the exception of anti-severe acute respiratory syndrome coronavirus 
2 (anti-SARS-CoV-2) serology, which should follow Table 9.8-1. 
 
In Arm 2d, BMS-986218 in combination with nivolumab (dose chosen in Arm 2c Q3W) is 
administered until disease progression, unacceptable toxicity, or withdrawal of consent, and may 
continue for a maximum of 2 calendar years from Cycle 1 Day 1 (Arm 2a) regardless of treatment 
delays (for participants who crossover during active treatment with docetaxel) or until the study 


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ends, whichever occurs first. For participants who crossover after treatment (while in Safety or 
Survival Follow-up), BMS-986218 in combination with nivolumab may continue for up to 
1 calendar year from the start of crossover treatment, or for a maximum of 2 calendar years from 
Cycle 1 Day 1 (Arm 2a) regardless of treatment delays (whichever is longer), or until the study 
ends, whichever occurs first. Treatment for crossover participants beyond radiographic 
progression per PCWG3 criteria is permitted if the participant has investigator-assessed clinical 
benefit and is tolerating the treatment, as specified in Section 8.1.2. 
Upon discontinuation of crossover treatment, participants will enter or re-enter the Follow-Up 
Period (Safety Follow-up and Survival Follow-up). Participants who crossover during the 
treatment portion (during active treatment with docetaxel) of the study should proceed with 
follow-up guidelines in Section 5.1.3 and Table 2-3. 
Participants who crossover after discontinuing docetaxel treatment and while in follow-up should 
only be followed for a maximum of 1 year from the last dose of crossover treatment. 
For participants re-entering the Follow-up Period, the following guidelines apply: 
• The 3 Safety Follow-up visits will be conducted (30, 60, and 100 days ± 7 days [see Table 2- 
3]). 
• 
Survival Follow-up visits to occur every 12 weeks (± 2 weeks) from the last dose of crossover 
intervention and will be performed in parallel to safety follow-up (for a maximum of 1 year 
from the last dose of crossover treatment) or until death, loss to follow-up, withdrawal of 
consent, or conclusion of the study, whichever comes first. Survival visits may be conducted 
in clinic or by telephone (see Table 2-3). 
• Participants who have discontinued treatment without having BICR-assessed disease 
progression (during the crossover) will continue to have radiologic and clinical tumor 
assessments after crossover treatment discontinuation for up to a maximum of 1 calendar year 
or until rPD, whichever occurs first. 
 
5.1.3 
Follow-up Period 
The Follow-up Period includes Safety Follow-up (comprising 3 visits over about 100 days) and 
Survival Follow-up (up to 2 years from the last dose of study treatment) periods. 
Participants in Arm 2d who crossover after discontinuing docetaxel treatment and while in 
follow-up should only be followed for a maximum of 1 year from the last dose of crossover 
treatment. 
5.1.3.1 
Safety Follow-up 
Upon completion of study intervention or early termination, all participants will enter a safety 
follow-up period. All participants will be evaluated for any new AEs for at least 100 days after the 
last dose of study intervention. Participants who have discontinued treatment without having 
BICR-assessed disease progression will continue to have radiologic and clinical tumor assessments 
after treatment discontinuation for up to 2 years after end of treatment (EOT) or until rPD, 
whichever occurs first. 


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Participants in Arm 2d who crossover after discontinuing docetaxel treatment and who re-enter the 
follow-up period will repeat the 100-day Safety Follow-up visits (Day 30, 60, and 100). 
Participants who have discontinued treatment without having BICR-assessed disease progression 
(during the crossover), will continue to have radiologic and clinical tumor assessments after 
crossover treatment discontinuation for up to a maximum of 1 calendar year or until rPD, 
whichever occurs first. 
5.1.3.2 
Survival Follow-up 
In parallel with the safety follow-up period, participants will enter the survival follow-up period. 
Participants will be followed by phone contact or clinic visit every 12 weeks (± 2 weeks) from the 
last dose of study intervention for a period of 2 years or until death, loss to follow-up, withdrawal 
of consent, or conclusion of the study, whichever comes first. 
Participants in Arm 2d who crossover after discontinuing docetaxel treatment and who re-enter the 
Survival Follow-up period, the visits will occur every 12 weeks (± 2 weeks) from the last dose of 
crossover intervention and will be performed in parallel to Safety Follow-up (for a maximum of 
1 year from the last dose of crossover treatment) or until death, loss to follow-up, withdrawal of 
consent, or conclusion of the study, whichever comes first. Survival visits may be conducted in 
clinic or by telephone. 
The Sponsor may decide to terminate the Survival Follow-up period once all participants have 
completed the Safety Follow-up period. 
5.1.4 
Data Monitoring Committee and Other Committees 
5.1.4.1 
Safety Monitoring for Part 1 
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 plus a DMC for 
Part 2, 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 AE reports and analyses. Because this is an open-label 
study, WWPS representatives, the BMS medical monitor, and the investigators will have access 
to individual participants safety 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. Within BMS, an SMT is established for investigational therapies 
under clinical development, and a member of WWPS chairs this team. In addition, signal detection 
is performed at least monthly and ad hoc throughout the study by the SMT, composed, at a 
minimum, of the WWPS medical safety assessment physician (Chair of the SMT), the Clinical 
Development Lead and/or Medical Affairs Lead, Global Regulatory Lead, and Pharmacovigilance 
Scientist. Furthermore, the SMT routinely monitors for actual or potential issues related to 
participant safety that could result in a change in the medical risk-benefit balance associated with 
the use of study treatment(s). 


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5.1.4.2 
Data Monitoring Committee 
A DMC will be used for Part 2 of this study. The DMC charter will describe the procedures related 
to the committee operations in greater detail. 
The independent DMC will be utilized to provide general oversight and safety evaluations during 
the randomized portion (Part 2) of the study. In addition, during the randomized Part 2 of the study, 
a continuous safety monitoring framework will be implemented by the Sponsor to monitor for 
adverse events (see Section 10.4.5.1). 
The independent DMC will provide advice to the Sponsor regarding actions the committee deems 
necessary for the continuing protection of participants enrolled in this study. The independent 
DMC will be charged with assessing such actions in light of an acceptable benefit-risk profile for 
nivolumab, BMS-986218, and docetaxel. The independent DMC will act in an advisory capacity 
to BMS and will monitor participant safety data of the study. BMS will have responsibility for the 
overall conduct of the study, including managing the communication of study data. BMS will be 
responsible for promptly reviewing the DMC recommendations, for providing guidance regarding 
the continuation or termination of the study, and for determining whether amendments to the 
protocol or changes to the study conduct are required. The DMC charter will describe the 
procedures related to the committee operations in greater detail. The DMC will meet on a regular 
basis, which will be defined in the charter, and on an ad hoc basis as necessary throughout study 
conduct 
Decisions related to the continuation or any changes to study conduct based on safety, toxicity, 
and benefit-risk will be solely the responsibility of BMS and will take account of the totality of 
the data available and in consideration of any DMC recommendations. 
5.1.4.3 
Blinded Independent Central Review 
A Blinded Independent Central Review (BICR) will also be used for this study to review computed 
tomography (CT) and bone scans, including the primary study objective. A BICR is recommended 
by regulatory agencies in situations where clinical site image interpretation is variable and results 
of image measurements are important for eligibility determination, safety, and/or efficacy 
endpoints. Specifically, BICR review of scans may mitigate bias regarding endpoint assessment 
due to the subjectivity involved in lesion measurement and interpretation of rPFS. Sites must 
submit all images to BICR on a continuing basis. Treatment decisions for the individual 
participants will be based on investigator assessment and not the BICR results. 
Prior to scanning the first participant, sites should be qualified and understand the image 
acquisition guidelines and submission process as outlined in the CA022009 Imaging Manual 
provided by the central imaging vendor. 
5.2 
Number of Participants 
Approximately 12 participants may be treated in the safety lead-in Part 1A and approximately 
12 to 18 participants in Part 1B, with a possible total of 30 DLT-evaluable participants, if 2 or 
more dose levels are evaluated. In addition, approximately 174 participants are expected to be 


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randomized across 3 treatment arms in Part 2 of the study, to account for 21% dropout rate prior 
to radiographic progression across the 3 arms. 
5.3 
End of Study Definition 
The start of the trial is defined as the first participant first visit. 
End of trial is defined as the last participant last visit or scheduled procedure shown in the Schedule 
of Activities for the last participant. 
Study completion is defined as the final date on which data for the primary endpoint were or are 
expected to be collected, if this is not the same. 
A participant is considered to have completed the study if he/she has completed the last visit or 
the last procedure shown in the Schedule of Activities. 
5.4 
Scientific Rationale for Study Design 
BMS-986218 is being investigated in males with mCRPC, either in combination with docetaxel 
or in combination with docetaxel and nivolumab. The study design (Figure 5.1-1) includes the 
following: 
• A 28-day screening period 
• A treatment period that can last up to 2 calendar years for BMS-986218 (Q3W) and/or 
nivolumab 
 , and up to a maximum of 10 doses for docetaxel (Q3W) 
• Safety lead-in portion (Part 1; includes Part 1A and Part 1B) 
• Randomized controlled portion (Part 2) 
• Safety follow-up (100 days over 3 visits) 
• Survival follow-up (up to 2 years after last dose) 
• Optional crossover for participants in Arm 2a who demonstrate rPD 
 
5.4.1 
Rationale for Population 
Men with mCRPC who have progressed after NAT(s) and have not received chemotherapy for 
mCRPC will be included in this study. Although many patients without symptoms are not treated 
with chemotherapy, the survival benefit reported with docetaxel applies to those with or without 
symptoms. National Comprehensive Cancer Network (NCCN) guidelines recommend docetaxel 
(category 1) as the preferred first line (1L) chemotherapy in men with symptomatic mCRPC and 
in patients with signs of rapid progression or visceral metastases despite lack of symptoms.52 
Docetaxel also has a category 1 recommendation in mCRPC following enzalutamide/abiraterone 
therapy. Clinical data from a number of small retrospective cohort studies suggests that once 
participants with mCRPC progress on NAT therapy, response rates to abiraterone after 
enzalutamide and conversely enzalutamide after abiraterone are low and no robust clinical criteria 
exist to select one drug rather than the other.49 Given that abiraterone and enzalutamide are the 
preferred 1L option for men with asymptomatic, chemotherapy-naïve mCRPC and the recent 
approvals of NATs in mCSPC and nmCRPC settings, it is expected that most patients will have 
received one NAT prior to consideration of docetaxel for treatment of mCRPC. Therefore, the 


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current study will include chemotherapy-naïve mCRPC participants who have been previously 
treated with NAT. 
5.4.2 
Rationale for Docetaxel and BMS-986218 or BMS-986218 plus 
Nivolumab 
Docetaxel, a second-generation semisynthetic taxane analog, became the first chemotherapeutic 
agent to show an OS benefit in mCRPC in 2 randomized controlled clinical trials (TAX 327 and 
SWOG 99-16), and was approved in combination with prednisone for this indication in the US in 
2004.1,2 In addition to inducing direct tumor cell cytotoxicity, it is hypothesized that chemotherapy 
may modify the immune response to tumors by influencing multiple mechanisms, including 
inducing immunogenic cell death, stimulating release of tumor antigens, and/or depleting 
immuno-suppressive Tregs. 
CTLA-4 blockade has demonstrated clinical activity against mCPRC, but it is not yet a standard 
treatment. Two Phase 3 studies demonstrated that ipilimumab (10 mg/kg) improved PFS when 
administered either prior (CA184095) or following (CA184043) chemotherapy, but failed to show 
a statistically significant survival benefit.28,29 After longer follow-up, retrospective analysis of 
CA184043, which specifically compared radiotherapy to radiotherapy plus ipilimumab, showed 
ipilimumab significantly improved landmark OS at 2, 3, 4, and 5 years. PD-(L)1 directed therapy 
has not shown meaningful clinical activity against mCRPC in monotherapy studies. Prostate 
cancer tumor cells have been shown to have low expression of PD-L1, but its expression is 
up-regulated in response to inflammatory cytokines, induced by CTLA-4.36 PD-1 blockade 
therefore may augment clinical activity when administered in combinations. In support, ~25% of 
participants with mCRPC, that were not previously treated with chemotherapy, demonstrated an 
objective response to ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg). Moreover, addition of 
nivolumab or pembrolizumab to docetaxel is associated with a longer-than-expected PFS 
compared with historical studies of docetaxel alone, serving as the rationale for 2 ongoing Phase 3 
studies comparing docetaxel to docetaxel plus PD-1 blockade.1,2,34,35 The additional mechanisms 
of anti-tumor activity of BMS-986218 compared to ipilimumab, which may improve its anti-tumor 
activity relative to toxicity, and its use in combinations with other immune-modulating agents, 
have the potential to meaningfully improve outcomes in mCRPC. 
5.4.2.1 
Rationale for Docetaxel and BMS-986288 or BMS-986288 plus 
Nivolumab 
BMS-986288 is not evaluated in the current CA022-009 study design but may be introduced via 
future protocol amendment. BMS-986288 is a non-fucosylated anti-CTLA-4 agent identical to 
BMS-986218, but with an additional Probody element (see Section 3.2.2). BMS-986288 has the 
same enhanced Fc engagement as BMS-986218, and the Probody aspect may further improve the 
benefit/risk profile, as compared to BMS-986218, by enabling selective CTLA-4 blockade in the 
tumor microenvironment. If emerging clinical data support improved clinical utility, the Sponsor 
may amend CA022-009 to test docetaxel and BMS-986288 or docetaxel and BMS-986288 plus 
nivolumab. 


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5.4.3 
Rationale for Two Year Duration of Treatment 
The optimal duration of immunotherapy is an important question and continues to be investigated. 
Clinical trials across different tumor types in the nivolumab and ipilimumab development program 
indicate that most of the responses occur early, with a median time to response of 2 to 4 months, 
and emerging data suggests that benefit can be maintained in the absence of continued treatment. 
A retrospective pooled analysis of two melanoma studies suggest the majority of patients who 
discontinue nivolumab and/or ipilimumab for toxicity maintain disease control in the absence of 
further treatment.53 Furthermore, a limited duration of ipilimumab, including only 4 induction 
doses, resulted in long term survival in patients with metastatic melanoma, with a sustained plateau 
in survival starting around 2 years after the start of treatment.54 
Accumulating data suggest that 2 years of PD-1 checkpoint inhibitor treatment may be sufficient 
for long term benefit. CA209003, a dose-escalation cohort expansion trial evaluating the safety 
and clinical activity of nivolumab in patients with previously treated advanced solid tumors 
(including 129 patients with NSCLC), specified a maximum treatment duration of 2 years. Among 
16 patients with non-small cell lung cancer (NSCLC) who discontinued nivolumab after 
completing 2 years of treatment, 12 patients were alive >5 years and remained progression-free 
without any subsequent therapy. In the CA209003 NSCLC cohort, the OS curve begins to plateau 
after 2 years, with an OS rate of 25% at 2 years and 18% at 3 years.55 These survival outcomes are 
similar to Phase 3 studies in previously treated NSCLC, in which nivolumab treatment was 
continued until progression or unacceptable toxicity (2 year OS rates of 23% and 29%, and 3 year 
OS rates of 16%-18% for squamous and non-squamous NSCLC respectively).56 
Taken together, these data suggest that treatment beyond 2 years is unlikely to confer additional 
clinically meaningful benefit and that the risk of progression after discontinuing treatment at 
2 years is low. 
In contrast, a shorter duration of nivolumab of only 1 year was associated with increased risk of 
progression in previously treated patients with NSCLC, suggesting that treatment beyond 1 year 
is likely needed. In CA209153, patients with previously treated advanced NSCLC who completed 
1 year of nivolumab therapy were randomized to either continue or stop treatment, with the option 
of retreatment upon progression. Among 163 patients still on treatment at 1 year and without 
progression, those who were randomized to continue nivolumab had significant improvement in 
PFS compared to those who were randomized to stop treatment, with median PFS (post- 
randomization) not reached vs 10.3 months, respectively; hazard ratio (HR)=0.42 (95% CI, 0.25 
to 0.71). With a median follow-up of 14.9 months post-randomization, there also was a trend for 
patients on continued treatment to live longer (OS HR = 0.63 [95% CI: 0.33, 1.20]). Of note, the 
PFS curves in both groups plateau approximately 1 year after randomization (ie, 2 years after 
treatment initiation), suggesting that there may be minimal benefit in extending treatment beyond 
a total of 2 years.57 
Collectively, these data suggest that there is minimal if any benefit derived from continuing I-O 
treatment beyond two years in advanced tumors. Even though immunotherapy is well tolerated, 
patients will be at risk for additional toxicity with longer-term treatment. Therefore, in this study, 


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AEs are consistent with those observed with ipilimumab. Preliminary analysis supports 
BMS-986218 and nivolumab will be given for a maximum of 2 years from the start of study 
treatment. 
5.4.4 
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 stable 
disease (SD). Two distinct non-conventional patterns have been reported: 1) a reduction in target 
tumor burden despite the appearance of new lesion(s), and 2) a transient increase in target tumor 
burden in an initial phase, followed by subsequent tumor shrinkage. These phenomena were 
observed in the BMS Phase 2 study (CA209003) of nivolumab in patients with solid tumors. Two 
hypotheses potentially explain these phenomena. First, enhanced inflammation within tumors 
could lead to an increase in tumor size, which would appear as enlarged index lesions and as 
newly-visible small non-index lesions. Over time, both the malignant and inflammatory portions 
of the mass may then decrease, leading to overt signs of clinical improvement. Alternatively, in 
some individuals, the kinetics of tumor growth may initially outpace anti-tumor immune activity. 
With sufficient time, the anti-tumor activity will dominate and become clinically apparent. 
Therefore, it is important to avoid premature discontinuation of the study treatment that might 
induce a non-conventional response pattern in some patients. 
5.4.5 
Rationale for Open-label Design 
This study will use an open-label design to ensure that immune-related toxicities in participants 
receiving immunotherapy are promptly identified and managed. Scans will be submitted to an 
imaging core laboratory for review by BICR. BICR review of scans may mitigate bias regarding 
endpoint assessment due to the subjectivity involved in lesion measurement and interpretation of 
rPFS. Treatment decisions for the study will be based on investigator assessment and not the BICR 
results. 
5.5 
Justification for Dose 
5.5.1 
BMS-986218 
CA022009 is the first study combining BMS-986218 or BMS-986218 plus nivolumab with 
chemotherapy. Study CA022001 is an ongoing Phase 1/2a, FIH study that has evaluated 
BMS-986218 as monotherapy and in combination with nivolumab in multiple solid tumor 
 
preliminary as the study remains ongoing. 
As a monotherapy, the MTD for BMS-986218 has not yet been defined and the most common 
indications. 
All data presented below from the CA022001 study should be considered 


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Similar data was 
collected from CA184169, which evaluated ipilimumab at 3 mg/kg and 10 mg/kg in participants 
 
The proposed starting dose of BMS-986218 (50 mg Q3W, 
) in combination with docetaxel is at least 2 dose levels below the maximum administered 
dose (MAD) of 
in the CA022001 study (study is ongoing 
and may continue to dose escalate). Based on preliminary analysis, median duration of treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ipilimumab, where clinical anti-tumor activity in mCRPC was demonstrated. In the CA022009 
study, BMS-986218 will be administered at 
dose of 50 mg Q3W 
will be 
based on the totality of the data available at that time including safety data as well as efficacy and 
biomarker data from the CA022001 study BMS-986218 monotherapy treatments and the present 
study. 
Flat dose nivolumab 
 has been established to be tolerable in combination with 
docetaxel (see Section 5.5.2) and the tolerability of BMS-986218 in combination with docetaxel 
will be tested in Part 1A prior to initiating BMS-986218 + nivolumab + docetaxel therapy in 
Part 1B. In Part 1B, BMS-986218 will be initiated at a dose no higher 
and at least 1 dose level below that, which was 
demonstrated to be tolerable in at least 6 participants in Part 1A. In CA022001, 
 
 in combination with flat dose nivolumab 
has been administered to 
15 participants with acceptable tolerability. Median duration of treatment based on a 
in combination with nivolumab 
. 
No participants remain on study treatment. 
with melanoma, enabling estimation of activity equivalency for BMS-986218 based on 
of participants 
Fifteen participants have discontinued 
treatment due to progression of disease. 
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BMS-986218 dose evaluation in combination with 
remains 
ongoing on the CA022001 study at doses above the proposed starting dose for Part 1B of the 
CA022009 study. A decision to dose escalate (to BMS-986218 30 mg Q3W) will be based on the 
totality of the data available at that time including safety data as well as efficacy and biomarker 
data from the CA022001 study evaluating BMS-986218 with nivolumab and the present study. 
The MAD of BMS-986218 dose in Part 1B will not exceed that given in Part 1A and may be lower. 
Similarly, the dose selected of BMS-986218 for Part 2 Arm 2c may be lower than that selected for 
Arm 2b. Lastly, the dose of BMS-986218 in combination with flat dose nivolumab and docetaxel 
will not exceed the equivalent of dose demonstrated to be tolerable in combination with nivolumab 
in the on-going CA022001 study. 
5.5.2 
Nivolumab 
The nivolumab dose 
 was selected based on clinical data and modeling and 
simulation approaches using population PK (PPK) and exposure-response analyses of data from 
studies in multiple tumor types. 
Nivolumab PK has been extensively studied in multiple tumor types, including melanoma, 
NSCLC, RCC, cHL, SCCHN, CRC and urothelial carcinoma and has been safely administered at 
doses 
. Nivolumab monotherapy was originally approved as a body-weight 
based dose 
 , and was updated to 
 or 
 in multiple 
indications.58,59 Nivolumab  
has recently been approved in malignant pleural 
mesothelioma as monotherapy, metastatic non-small cell lung cancer in combination with 
ipilimumab 1 mg/kg every 6 weeks and 2 cycles of platinum-doublet chemotherapy, and in gastric 
cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, in combination with 
fluoropyrimidine- and platinum-containing chemotherapy. Less frequent 
 and 
dosing regimens can reduce the burden to patients of frequent, lengthy IV treatments 
and allow combination of nivolumab with other agents using alternative dosing regimens. 
Nivolumab 
was accordingly administered in the CheckMate 9KD 
which is administered every 3 weeks for the treatment of mCRPC. 
The benefit-risk profiles of nivolumab 
are predicted 
to be comparable to 
 . This assessment is based on a comprehensive characterization 
of nivolumab PK, safety, efficacy, and exposure-response relationships across indications. 
Population PK (PPK) analyses have shown that the PK of nivolumab is linear with proportional 
exposures over a dose range of 0.1 to 10 mg/kg; no clinically meaningful differences in PK across 
ethnicities and tumor types were observed. Using the PPK model, the exposures following 
administration of several dosing regimens of nivolumab administered as a flat dose were 
simulated, including 
. The simulated average serum 
concentration at steady state [Cavgss] following administration of nivolumab 
 and 
are predicted to be similar to those following administration of nivolumab 
and nivolumab 
 administered to patients over a wide body weight 
range (34-180 kg) across tumor types. 


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Additional details on nivolumab posologies and risk-benefit can be found in the Investigator’s 
Brochure. 
5.5.3 
Rationale for Duration of Treatment with Docetaxel 
The duration of treatment for docetaxel should be based on the assessment of benefit and toxicities. 
In a pivotal trial establishing the survival advantage of docetaxel chemotherapy, participants 
received up to 10 cycles of treatment.1 Administering more than 10 cycles of docetaxel has not 
demonstrated any further improvement in survival and is associated with more adverse effects.60,61 
Therefore, in the present study, docetaxel will be administered for a maximum of 10 cycles, or 
until disease progression, unacceptable toxicity, withdrawal of participant consent, or the end of 
the study, whichever occurs sooner. Please consult the current prescribing information for 
docetaxel for further details concerning administration. 
5.6 
Clinical Pharmacology Summary of BMS-986218 
Preliminary PK analysis from the ongoing study CA022001 was based on available data as of 
05-Jan-2021. Preliminary PK analysis showed the maximum observed concentration (Cmax) and 
the area under the concentration-time curve in 1 dosing interval (AUC[TAU]) of BMS-986218 in 
serum 
as monotherapy 
treatment. 
 
 
Full details on the 
clinical pharmacology aspects of BMS-986218 can be found in the Investigator’s Brochure. 
5.7 
Clinical Pharmacology Summary of Nivolumab 
Nivolumab pharmacokinetics (PK) was assessed using a population PK approach for both 
single-agent nivolumab and nivolumab with ipilimumab. 
Nivolumab as a single agent: The PK of single-agent nivolumab was studied in patients over a 
dose range of 0.1 to 20 mg/kg administered as a single dose or as multiple doses of nivolumab 
every 2 or 3 weeks. Nivolumab clearance (CL) decreases over time, with a mean maximal 
reduction (% coefficient of variation [CV%]) from baseline values of 24.5% (47.6%) resulting in 
a geometric mean steady-state clearance (CLss) (CV%) of 8.2 mL/h (53.9%) in patients with 
metastatic tumors; the decrease in CLss is not considered clinically relevant. The geometric mean 
volume of distribution at steady state (Vss) (CV%) is 6.8 L (27.3%), and geometric mean 
elimination half-life (t1/2) is 25 days (77.5%). Steady-state concentrations of nivolumab were 
reached by 12 weeks when administered at 3 mg/kg every 2 weeks, and systemic accumulation 
was 3.7-fold. The exposure to nivolumab increases dose proportionally over the dose range of 0.1 
to 10 mg/kg administered every 2 weeks. 
Nivolumab with ipilimumab: When nivolumab 1 mg/kg was administered in combination with 
ipilimumab 3 mg/kg, the CL of nivolumab was increased by 29%, and the CL of ipilimumab was 
unchanged compared to nivolumab administered alone. When nivolumab 3 mg/kg was 
administered in combination with ipilimumab 1 mg/kg, the CL of nivolumab and ipilimumab were 


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unchanged. These results are unlikely to be clinically relevant given the flat dose-response 
observed between nivolumab and efficacy and safety. 
Renal Impairment: The effect of renal impairment on the clearance of nivolumab was evaluated 
by a population PK analysis in patients with mild (estimated glomerular filtration rate 
[eGFR] 60 to 89 mL/min/1.73 m2), moderate (eGFR 30 to 59 mL/min/1.73 m2), or severe (eGFR 
15 to 29 mL/min/1.73 m2) renal impairment. No clinically important differences in the clearance 
of nivolumab were found between patients with renal impairment and patients with normal renal 
function. 
Hepatic Impairment: The effect of hepatic impairment on the clearance of nivolumab was 
evaluated by population PK analyses in patients with HCC and in patients with other tumors with 
mild hepatic impairment (total bilirubin [TB] less than or equal to the ULN and AST greater than 
ULN or TB greater than 1 to 1.5 times ULN and any AST) and in HCC patients with moderate 
hepatic impairment (TB greater than 1.5 to 3 times ULN and any AST). No clinically important 
differences in the clearance of nivolumab were found between patients with mild/moderate hepatic 
impairment. 
Full details on the clinical pharmacology aspects of nivolumab can be found in the Investigator’s 
Brochure and product label. 
Nivolumab 
 is approved in malignant pleural mesothelioma as monotherapy, 
metastatic non-small cell lung cancer in combination with ipilimumab 1 mg/kg every 6 weeks and 
2 cycles of platinum-doublet chemotherapy, and in gastric cancer, gastroesophageal junction 
cancer, and esophageal adenocarcinoma, in combination with fluoropyrimidine- and 
platinum-containing chemotherapy. Nivolumab 
dosing will be the starting dose used 
in this study (in Part 1B). 
6 
STUDY POPULATION 
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. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
6.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1) Signed Written Informed Consent 
a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC) approved written informed consent form (ICF) in accordance with 
regulatory and institutional guidelines. This must be obtained before the performance of 
any protocol-related procedures that are not part of normal patient care. 
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory testing, and other requirements of the study. 


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2) Type of Participant and Target Disease Characteristics 
a) Histologic confirmation of carcinoma of the prostate without small cell features. Diagnosis 
must be stated in a pathology report and confirmed by the investigator. 
b) Current evidence of metastatic disease documented by either bone lesions on radionuclide 
bone scan and/or soft tissue lesions on CT/magnetic resonance imaging (MRI). Metastases 
may be in regional lymph nodes (N1 per American Joint Committee on Cancer [AJCC] 
staging criteria, 8th edition) and/or distant metastases (M1 per AJCC staging criteria, 8th 
edition).62 
i) Participants whose disease spread is limited to regional pelvic lymph nodes (N1) 
measuring at least 2 cm in short axis will be considered eligible. 
c) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. 
d) Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone 
(GnRH) agonist/antagonist or bilateral orchiectomy (ie, surgical or medical castration) 
confirmed by testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit. Castrate 
levels of testosterone must be maintained by surgical or medical means (GnRH 
agonist/antagonist) throughout the conduct of the study. For participants who have not had 
an orchiectomy but maintained castrate levels of testosterone without ongoing medical 
therapy, GnRH agonist/antagonist must be reinitiated at least 4 weeks prior to first dose of 
study treatment and continued throughout the study on a standard dosing schedule. 
e) Documented prostate cancer progression by 1 of the following Prostate Cancer Working 
Group 3 (PCWG3) criteria while castrate, within 6 months prior to screening, and without 
initiating a new intervening systemic prostate cancer therapy (other than GnRH 
agonist/antagonist) prior to screening: 
i) Prostate-specific antigen (PSA) progression defined by a minimum of 2 rising PSA 
levels with an interval of ≥ 1 week between each determination. The PSA value at the 
screening visit should be ≥ 2 μg/L (2 ng/mL). 
ii) Radiographic disease progression in soft tissue based on PCWG3 criteria. 
iii) Radiographic disease progression in bone. 
f) Participants  are  chemotherapy-naïve  for  mCRPC  and  have  received  at  least 
1 second-generation hormonal manipulations (also known as novel antiandrogen therapies 
[NAT], including but not limited to abiraterone acetate, enzalutamide, apalutamide, and 
darolutamide) in the recurrent non-metastatic setting and/or the metastatic setting. 
Participants must have progressed during treatment on an NAT or have documented 
intolerance to the drug (ie, unacceptable toxicity despite comprehensive supportive 
therapy). Prior docetaxel for metastatic castration-sensitive prostate cancer is allowed if 
≥ 12 months have elapsed from last dose of docetaxel. Prior therapy with a PARP inhibitor 
(eg, olaparib, rucaparib) is also allowed. Prior radium 223 and 177Lu-PSMA-617 treatment 
for prostate cancer is allowed. 
g) Prior prostate cancer vaccine therapy (eg, sipuleucel-T), second-generation hormonal 
manipulations (eg, abiraterone acetate, enzalutamide, apalutamide, and darolutamide), 
antiandrogens (eg, flutamide), ketoconazole, and diethylstilbestrol or other estrogens are 
allowed if treatment was completed at least 28 days prior to start of study treatment. Note: 
bicalutamide or nilutamide must be discontinued at least 6 weeks prior to the start of study 
treatment. 


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h) Participants with a soft tissue lesion that is suspected to represent metastatic disease based 
on local review of imaging and is considered accessible for biopsy by an interventional 
radiologist (or other appropriate specialist), must provide tumor sample from a 
newly-obtained (“fresh”) biopsy (obtained during screening, if there are tumor sites that 
can be biopsied with acceptable clinical risk). Lymph nodes must measure at least 1 cm in 
diameter along the short axis in order to be considered for biopsy. If the only site amenable 
to biopsy is also the only site of measurable disease, the investigator should prioritize 
maintaining a measurable target lesion (by RECIST v1.1) if there is a concern that the 
biopsy might impact tumor assessment. 
A formalin-fixed paraffin-embedded (FFPE) tissue block (preferred) or a minimum of 20 
unstained slides* of tumor tissue from core biopsy, punch biopsy, excisional biopsy or 
surgical specimen obtained during screening or prior to treatment assignment 
(Part 1)/randomization (Part 2) must be sent to the central laboratory. Fine needle aspirates 
or other cytology samples are not acceptable. 
*If despite best efforts, a minimum of 20 slides is not obtainable, submission of fewer 
slides may be acceptable in some circumstances following discussion with Sponsor or 
designee. 
Please refer to Section 9.8.4 for additional details on tumor tissue requirements. 
3) Age of Participant 
a) Participant must be male and ≥ 18 years of age or local age of majority at the time of 
signing the informed consent. 
4) Reproductive Status 
a) Male Participants: Males who are sexually active with women of childbearing potential 
(WOCBP) must agree to follow instructions for method(s) of contraception as defined in 
Appendix 4 and as described below. 
i) Azoospermic males are not exempt from contraceptive requirements and will be 
required to always use a latex or other synthetic condom during any sexual activity 
(eg, vaginal, anal, oral) with WOCBP, even if the participant has undergone a 
successful vasectomy or if the partner is pregnant. 
ii) Male participants will be required to always use a latex or other synthetic condom 
during any sexual activity (eg, vaginal, anal, oral) with WOCBP, even if the 
participants have undergone a successful vasectomy or if their partner is already 
pregnant or breastfeeding. Males should continue to use a condom during the 
intervention period and for at least 3 months after the last dose of study intervention. 
iii) Female partners of males participating in the study should be advised to use highly 
effective methods of contraception during the intervention period and for at least 3 
months after the last dose of study intervention in the male participant. 
iv) Male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from sexual activity or use a male condom during any sexual activity 
(eg, vaginal, anal, oral), even if the participants have undergone a successful 
vasectomy, during the intervention period and for at least 3 months after the last dose 
of study intervention. 
v) Male participants must refrain from donating sperm during the intervention period and 
for at least 3 months after the last dose of study intervention. 


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vi) Breastfeeding partners should be advised to consult their health care providers about 
using appropriate highly effective contraception during the time the participant is 
required to use condoms. 
6.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1) Medical Conditions 
a) Concurrent malignancy (present during screening) requiring treatment or history of prior 
malignancy active within 2 years prior to treatment assignment in Part 1 or randomization 
in Part 2 (ie, participants with a history of prior malignancy are eligible if treatment was 
completed at least 2 years before treatment assignment [Part 1] or randomization [Part 2] 
and the participant has no evidence of disease). Participants with history of prior early stage 
basal/squamous cell skin cancer, superficial bladder cancer, or other non-invasive or in situ 
cancers that have undergone definitive treatment at any time are also eligible. 
b) Untreated central nervous system (CNS) metastases. Participants are eligible if CNS 
metastases have been treated and participants have neurologically returned to baseline 
(except for residual signs or symptoms related to the CNS treatment). In addition, 
participants must have been either off corticosteroids, or on a stable or decreasing dose of 
≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment assignment 
(Part 1) or randomization (Part 2). Imaging performed within 28 days prior to treatment 
assignment (Part 1) or randomization (Part 2) must document radiographic stability of CNS 
lesions and be performed after completion of any CNS directed therapy. 
c) Leptomeningeal metastases 
d) Participants must have recovered from the effects of major surgery requiring general 
anesthesia or significant traumatic injury at least 14 days before start of study treatment. 
e) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must 
have resolved to Grade 1 or baseline before administration of study treatment. Participants 
with toxicities attributed to prior anti-cancer therapy that are not expected to resolve and 
result in long-lasting sequelae not anticipated to impact tolerance of study treatments (ie, 
hearing loss, Grade 2 erectile dysfunction etc.), are permitted to enroll as long as they meet 
all other eligibility criteria. 
f) Participants who have ≥ Grade 2 peripheral neuropathy are excluded. 
g) Participants with an active, known or suspected autoimmune disease. Participants with 
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin 
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or 
conditions not expected to recur in the absence of an external trigger are permitted to enroll. 
i) Euthyroid participants with a history of Grave’s disease (participants with suspected 
autoimmune thyroid disorders must be negative for thyroglobulin and thyroid 
peroxidase antibodies and thyroid stimulating immunoglobulin [Ig] prior to the first 
dose of study treatment). 
h) History of (non-infectious) pneumonitis or has current pneumonitis or a history of 
symptomatic chronic interstitial lung disease 
i) Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 
20 days for severe/critical illness prior to Cycle 1 Day 1. 


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i) Acute symptoms must have resolved and based on investigator assessment in 
consultation with the medical monitor, there are no sequelae that would place the 
participant at a higher risk of receiving study treatment. 
j) Altered mental status, or any psychiatric condition that would prohibit the understanding 
or rendering of informed consent or completing quality of life questionnaire. 
k) Active viral hepatitis, including the following: 
i) Any positive test result for hepatitis B virus (HBV) indicating presence of virus, eg, 
hepatitis B surface antigen (HBsAg, Australia antigen) positive. 
ii) Any positive test result for hepatitis C virus (HCV) indicating presence of active viral 
replication (detectable HCV-RNA). 
(1) Participants with positive HCV antibody and an undetectable HCV RNA are 
eligible to enroll. 
(2) Additional testing or substitute testing per institutional guidelines to rule out 
infection is permitted. 
iii) History of resolved hepatitis A virus infection is not an exclusion criterion. 
l) Known human immunodeficiency virus (HIV) positive with an AIDS defining 
opportunistic infection within the last year, or a current CD4 count < 350 cells/μL. 
Participants with HIV are eligible if: 
i) They have received antiretroviral therapy (ART) for at least 4 weeks prior to 
randomization/treatment assignment as clinically indicated while enrolled on study 
(see Section 7.7.2 for CYP3A4 restriction) 
ii) They continue on ART as clinically indicated while enrolled on study 
iii) CD4 counts and viral load are monitored per standard of care by a local health care 
provider. 
NOTE: Testing for HIV must be performed at sites where mandated locally. HIV positive 
participants must be excluded where mandated locally (see Appendix 7). 
m) Participants with serious or uncontrolled medical disorders that, in the opinion of the 
investigator, would impair the ability of the participant to receive protocol therapy or 
obscure the interpretation of AEs, such as a condition associated with frequent diarrhea. 
n) Psychiatric illness/social situations that would limit compliance with study requirements. 
o) Participants with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalent) within 14 days or other immunosuppressive 
medications within 30 days of treatment assignment (Part 1) or randomization (Part 2). 
Inhaled or topical steroids (including ocular, intra-articular, and intranasal), and adrenal 
replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the 
absence of active autoimmune disease. 
p) Participant has any condition, including, but not limited to, active or uncontrolled infection, 
the presence of laboratory abnormalities, history of congestive heart failure, unstable 
angina pectoris, or cardiac arrhythmia, which places the subject at unacceptable risk if he 
were to participate in the study. 
q) Participants with superscan on Technetium-99m radionuclide bone scans are not eligible 
for the study. Superscan is defined as a bone scan which demonstrates markedly increased 


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skeletal radioisotope uptake relative to soft tissue in association with absence of faint renal 
activity (absent kidney sign). 
2) Prior/Concomitant Therapy 
a) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7 
(Concomitant Therapy). 
b) Treatment with complementary medications (eg, herbal supplements or traditional Chinese 
medicines) to treat the disease under study within 2 weeks prior to first study treatment. 
Such medications are permitted if they are used as supportive care. Refer to Section 7.7.1 
for prohibited therapies. As some herbal supplements may modulate CYP3A4, see 
Section 7.7.2 for CYP3A4 restrictions. 
c) Treatment with any live/attenuated vaccine, including SARS-CoV-2 vaccine, within 
30 days of first study treatment. 
d) Previous SARS-CoV-2 vaccine within 14 days of Cycle 1 Day 1. For vaccines requiring 
more than 1 dose, the full series (eg, both doses of a 2-dose series) should be completed 
prior to Cycle 1 Day 1 when feasible and when a delay in Cycle 1 Day 1 would not put the 
study participant at risk. 
e) Prior treatment for biochemically recurrent or metastatic prostate cancer with an 
anti-CTLA-4, anti-PD-(L)1, or any other antibody or drug specifically targeting T-cell 
co-stimulation or checkpoint pathways. The prior use of such agents in the neoadjuvant 
setting is allowed. 
f) Prior radiation therapy within 2 weeks prior to start of study treatment. Participants must 
have recovered (ie, Grade ≤ 1 or at baseline) from radiation-related toxicities prior to first 
study treatment. 
3) Physical and Laboratory Test Findings 
a) White blood cells (WBCs) < 2000/μL 
b) Neutrophils < 1500/μL 
c) Platelets < 100 × 103/μL 
d) Hemoglobin < 9.0 g/dL (blood transfusion within 2 weeks of screening labs is not allowed) 
e) Serum creatinine > 1.5× upper limit of normal (ULN), unless creatinine clearance 
≥ 40 mL/min (measured or calculated using the Cockroft-Gault formula) 
f) AST/ALT > 3.0× ULN OR AST and/or ALT > 1.5× ULN concomitant with alkaline 
phosphatase > 2.5× ULN in the absence of bone metastasis 
g) Total bilirubin > 1.0× ULN (except participants with Gilbert’s syndrome, if the T.bili is 
< 2× ULN and direct bilirubin is in the normal range) 
4) Allergies and Adverse Drug Reaction 
a) History of allergy or hypersensitivity to study drug components 
b) History of hypersensitivity to docetaxel or polysorbate 80 
c) 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, hypothyroidism) 


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5) Other Exclusion Criteria 
a) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply, and BMS approval is required.) 
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness. 
c) Inability to comply with restrictions as listed in Section 6.3 (Lifestyle Restrictions). 
d) Participation in another clinical trial concurrent with this study. 
 
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 
Participants receiving docetaxel should be advised to use appropriate sun protection due to the 
potential risk of photosensitivity which may cause sunburn with minimal sun exposure. 
6.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, as applicable, and to respond to queries from regulatory authorities. 
Minimal information includes date of consent, demography, screen failure details, eligibility 
criteria, and any serious AEs. 
6.4.1 
Retesting During Screening or Lead-in Period 
Participant Re-enrollment: This study permits the re-enrollment of a participant who has 
discontinued the study as a pretreatment failure (ie, participant has not been randomized/has not 
been treated). If re-enrolled, the participant must be re-consented. 
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in period will be permitted (in addition to any parameters that require a confirmatory value). 
The most current result prior to administration of study intervention is the value by which study 
inclusion will be assessed, because it represents the participant’s most current clinical state. 
Laboratory parameters and/or assessments that are included in Section 2 Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant. 
Testing for asymptomatic SARS-CoV-2 infection by reverse transcriptase polymerase chain 
reaction (RT-PCR) or viral antigen is not required. However, some participants may develop 


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suspected or confirmed symptomatic SARS-CoV-2 infection, or be discovered to have 
asymptomatic SARS-CoV-2 infection during the screening period. In such cases, participants may 
be considered eligible for the study after meeting all inclusion/exclusion criteria related to active 
infection, and after meeting the following criteria: 
• At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive RT-PCR or viral antigen test result, and 
• At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and 
• Acute symptoms (eg, cough, shortness of breath) have resolved and 
• In the opinion of the investigator, there are no SARS-CoV-2 infection sequelae that may place 
the participant at a higher risk of receiving investigational treatment 
• In the instance of a SARS-CoV-2 infection during screening, the screening period may be 
extended up to 4 additional weeks beyond the protocol-specified timeframe with MM approval. 
• Any screening tests already performed which could potentially be affected by the 
SARS-CoV-2 infection or its complications on an individual basis and agreed upon with the 
MM (including but not limited to safety labs, SpO2, chest CT scan) should be repeated. 
 
7 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), placebo, 
procedure(s) or medical device intended to be administered to a study participant according to the 
study protocol. 
Study intervention includes both Investigational [Medicinal] Product (IP/IMP) and 
Non-investigational/Auxiliary [Medicinal] Product (Non-IP/Non-IMP/AxMP) as indicated in 
Table 7.1-1 and Table 7.1-2. 
An IP, also known as IMP in some regions, is defined a pharmaceutical form of an active substance 
or placebo being tested or used as a reference in a clinical study, including products already with 
a marketing authorization but used or assembled (formulated or packaged) differently from the 
authorized form, or used for an unauthorized indication, or when used to gain further information 
about the authorized form. 
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as 
Non-IPs/AxMPs. 
7.1 
Study Interventions Administered 
The selection and timing of dose for each participant are as shown in Table 7.1-1 (Part 1) and 
Table 7.1-2 (Part 2). 


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Table 7.1-1: 
Study Interventions - Part 1 
 
Part Name 
Part 1A 
Part 1B 
Intervention Name 
Docetaxela,b + BMS-986218c 
Docetaxela,b + BMS-986218c + Nivolumabc 
Type 
Drug + Biologic 
Drug + Biologic + Biologic 
Dose Formulation 
Solutions in a single-use vial 
Solutions in a single-use vial 
Unit Dose Strength(s) 
Various strengths + 
200 mg/vial 
Various strengths + 200 mg/vial + 
100 mg/vial 
Dosage Level(s) 
Docetaxel 75 mg/m2 Q3W + 
BMS-986218 50 mg Q3W 
BMS-986218 may be 
de-escalated 
(30 mg Q3W) 
Docetaxel 75 mg/m2 Q3W + BMS-986218 
 
BMS-986218 may be escalated (30 mg 
Q3W) 
Route of Administration 
IV infusions 
IV infusions 
Use 
SOC + experimental 
SOC + experimental (BMS-986218 + 
Nivolumab) 
IMP and Non-IMP/AxMP 
Non-IMP + IMP 
Non-IMP + IMP + IMP 
Sourcing 
Provided locally by the trial 
sited + Provided centrally by 
the Sponsor 
Provided locally by the trial sited + Provided 
centrally by the Sponsor (BMS-986218 + 
Nivolumab) 
Packaging and Labeling 
Study interventions will be 
provided in vials. Each vial 
will be labeled as required per 
country requirement. 
Study interventions will be provided in vials. 
Each vial will be labeled as required per 
country requirement. 
Current/Former Name(s) or 
Alias(es) 
1) Docetaxel or TAXOTERE 
2) BMS-986218 or 
anti-CTLA-4-NF 
1) Docetaxel or TAXOTERE 
2) BMS-986218 or anti-CTLA-4-NF 
3) Nivolumab or BMS-936558 or 
MDX1106 or ONO-4538 
Abbreviations: AxMP, auxiliary medicinal product; CTLA-4-NF, cytotoxic T-lymphocyte-associated protein 4 
non-fucosylated; IMP, investigational medicinal product; IV, intravenous; Q3W, every 3 weeks; SOC, standard of 
care; SmPC, Summary of Product Characteristics. 
a Prednisone 5 mg twice daily will be administered with docetaxel in accordance with package insert/SmPC 
guidelines. Daily prednisone may be dose reduced or omitted at the discretion of the investigator if it negatively 
affects glycemic control or other comorbid conditions. Premedication with dexamethasone will also be given for 
docetaxel (for more details, see additional text in Section 7.1, below). 
b A minimum of 3 to 4 cycles of docetaxel is recommended and up to 10 cycles is allowed per the package insert and 
SOC. 
c The treatment period for BMS-986218 and/or nivolumab will last for up to 2 calendar years from first dose of study 
treatment. 
d Sponsor may provide docetaxel in regions where it is not available through insurance or as part of SOC. 


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Table 7.1-2: 
Study Interventions - Part 2 
 
Arm Name 
Arm 2aa 
Arm 2b 
Arm 2c 
Intervention Name 
Docetaxelb,c 
Docetaxelb,c + 
BMS-986218d 
Docetaxelb,c + 
BMS-986218d + 
Nivolumabd 
Type 
Drug 
Drug + Biologic 
Drug + Biologic + 
Biologic 
Dose Formulation 
Solutions in a single-use 
vial 
Solutions in a single-use 
vial 
Solutions in a single-use 
vial 
Unit Dose Strength(s) 
Various strengths 
Various strengths + 
200 mg/vial 
Various strengths + 
200 mg/vial + 
100 mg/vial 
Dosage Level(s) 
75 mg/m2 Q3W 
75 mg/m2 Q3W + 
BMS-986218 at or below 
dose chosen in Part 1A 
Q3W 
75 mg/m2 Q3W + 
BMS-986218 at or below 
dose chosen in Part 1B 
Q3W + Nivolumab 
Route of Administration 
IV infusion 
IV infusions 
IV infusions 
Use 
SOC 
SOC + experimental 
SOC + experimental 
(BMS-986218 + 
Nivolumab) 
IMP and Non- 
IMP/AxMP 
Non-IMP 
Non-IMP + IMP 
Non-IMP + IMP + IMP 
Sourcing 
Provided locally by the 
trial sitee + Provided 
centrally by the Sponsor 
Provided locally by the 
trial sitee + Provided 
centrally by the Sponsor 
Provided locally by the 
trial sitee + Provided 
centrally by the Sponsor 
(BMS-986218 + 
Nivolumab) 
Packaging and Labeling 
Study interventions will 
be provided in vials. Each 
vial will be labeled as 
required per country 
requirement. 
Study interventions will 
be provided in vials. Each 
vial will be labeled as 
required per country 
requirement. 
Study interventions will 
be provided in vials. Each 
vial will be labeled as 
required per country 
requirement. 
Current/Former 
Name(s) or Alias(es) 
1) Docetaxel or 
TAXOTERE 
1) Docetaxel or 
TAXOTERE 
2) BMS-986218 or 
anti-CTLA-4-NF 
1) Docetaxel or 
TAXOTERE 
2) BMS-986218 or 
anti-CTLA-4-NF 
3) Nivolumab or 
BMS-936558 or 
MDX1106 or 
ONO-4538 
Abbreviations: AxMP, auxiliary medicinal product; CTLA-4-NF, cytotoxic T-lymphocyte-associated protein 4 
non-fucosylated; IMP, investigational medicinal product; IV, intravenous; Q3W, every 3 weeks; SOC, standard of 
care; SmPC, Summary of Product characteristics. 


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a Participants in Arm 2a who experience rPD can receive BMS-986218 (same dose as Arm 2c) + nivolumab (same 
dose as Arm 2c) as crossover treatment in Arm 2d (see column above for Arm 2c minus the docetaxel study 
intervention). 
b Prednisone 5 mg twice daily will be administered with docetaxel in accordance with the package insert/SmPC 
guidelines. Daily prednisone may be dose reduced or omitted at the discretion of the investigator if it negatively 
affects glycemic control or other comorbid conditions. Premedication with dexamethasone will also be given for 
docetaxel (for more details, see additional text in Section 7.1, below). 
c A minimum of 3 to 4 cycles of docetaxel is recommended and up to 10 cycles is allowed per the package insert and 
SOC. 
d The treatment period for BMS-986218 and/or nivolumab will last for up to 2 calendar years from first dose of study 
treatment. 
e Sponsor may provide docetaxel in regions where it is not available through insurance or as part of SOC. 
 
Participants who are assigned/randomized to a study intervention with nivolumab will receive 
nivolumab at a dose of 
over an approximately 30-minute infusion each 
treatment cycle until progression, unacceptable toxicity, withdrawal of consent, completion of 
24 months of treatment, or the study ends, whichever occurs first. If needed, flush the intravenous 
line with an appropriate amount of diluent (eg, 0.9% sodium chloride) to ensure that the complete 
dose is administered over approximately 30 minutes. Begin study treatment within 3 calendar days 
of treatment assignment (Part 1) or randomization (Part 2). 
When study interventions BMS-986218 and docetaxel are to be administered on the same day, 
BMS-986218 should be administered first. Flush the intravenous line with an appropriate amount 
of diluent (eg, 0.9% sodium chloride) to ensure that the complete dose is administered over 
approximately 30 minutes. After the BMS-986218 infusion, there is a 30-minute delay before the 
start of the docetaxel infusion to monitor the participant for signs of possible infusion reactions 
and differentiate any such reaction from one related to the subsequent docetaxel infusion. Dosing 
of docetaxel will continue for a maximum of 10 cycles Q3W (± 3 days), until progression, 
unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first. A 
minimum of 3 to 4 cycles of docetaxel is recommended. Prednisone 5 mg twice daily will be 
administered with docetaxel in accordance with package insert/SmPC guidelines. However, daily 
prednisone may be dose reduced or omitted at the discretion of the investigator if it negatively 
affects glycemic control or other comorbid conditions. Premedication with dexamethasone will 
also be given for docetaxel (see below). 
Dosing calculations of docetaxel should be based on the body weight assessed at baseline using 
Mosteller body surface area formula: the square root of (weight [kg] × height [cm]/3600). It is not 
necessary to re-calculate subsequent doses if the participant weight is within 10% of the weight 
used to calculate the previous dose. All doses should be rounded up or to the nearest milligram per 
institutional standard. 
When study interventions nivolumab, BMS-986218 and docetaxel (or nivolumab and 
BMS-986218 for crossover participants in Arm 2d), are to be administered on the same day, 
nivolumab is to be administered first. Nivolumab infusion must be promptly followed by a flush 
of diluent to clear the line of nivolumab before starting the BMS-986218 infusion. The second 


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infusion will always be BMS-986218 and will start after the infusion line has been flushed, filters 
changed, and participant has been observed to ensure no infusion reaction has occurred. Then, 
follow the instructions above to administer docetaxel (docetaxel will not be administered for 
participants who crossover into Arm 2d). 
There will be no intra-subject dose escalations or reductions of nivolumab or BMS-986218 
allowed. For Q3W dosing cycles, participants may be dosed no less than 19 days from the previous 
dose. 
Monitor participants carefully for infusion reactions during nivolumab administration. If an acute 
infusion reaction is noted, manage participants according to Section 7.4.6. 
Doses of study drug(s) may be interrupted, delayed, or discontinued depending on how well the 
participant tolerates the treatment. Dosing visits are not skipped, only delayed. 
Please refer to the current Investigator Brochure and/or Pharmacy Manual for further details 
regarding storage, preparation, and administration of nivolumab. 
Care must be taken to assure sterility of the prepared solution as the product does not contain any 
antimicrobial preservative or bacteriostatic agent. 
For details regarding BMS-986218 storage, preparation and administration, please refer to the 
current Investigator’s Brochure and/or Pharmacy Manual. 
Use separate infusion bags and filters when administering the study interventions on the same day. 
Premedication: 
Premedications for BMS-986218 and nivolumab are not recommended. For docetaxel, given the 
concurrent use of prednisone (5 mg twice daily), the recommended premedication regimen is oral 
dexamethasone 8 mg (or equivalent dose of another corticosteroid) to be administered at 12, 3, and 
1 hour(s) before the docetaxel infusion; however, other corticosteroids and/or schedules and routes 
of administration are also acceptable according to local standards. Antiemetic premedication will 
be administered according to local standards. 
Participants should be carefully monitored for infusion reactions during BMS-986218, docetaxel, 
and nivolumab administration. If an acute infusion reaction is noted, participants should be 
managed according to Section 7.4.6 and Section 7.4.8. 
7.2 
Method of Study Intervention Assignment 
Study using Interactive Response Technology (IRT): All participants will be centrally assigned to 
treatment (Part 1) or randomized (Part 2) using IRT. Before the study is initiated, each user will 
receive log-in information and directions on how to access the IRT. 
Study intervention will be dispensed at the study visits as listed in Schedule of Activities 
(Section 2). 
Participants in Part 2 will be randomized to receive 1 of 3 study interventions (Q3W) as follows: 
Arm 2a- docetaxel; Arm 2b- docetaxel and BMS-986218; Arm 2c- docetaxel, BMS-986218, and 
nivolumab. Randomization is done according to a computer-generated randomization scheme 


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prepared by a Randomization Coordinator within the Drug Supply Management Department of 
BMS Research and Development and will be stratified by presence of measurable disease (Y/N). 
During the screening visit, the investigative site will call into the enrollment option of the IRT 
designated by BMS for assignment of a 5-digit participant number that will be unique across all 
sites. Enrolled participants, including those not dosed, will be assigned sequential participant 
numbers starting with 
 (eg, 
). The patient identification 
number (PID) will ultimately comprise the site number and participant number. For example, the 
first participant screened (ie, enrolled) at site number 1 will have a PID of 
 . Once it is 
determined that the participant meets the eligibility criteria following the screening visit, the 
investigative site will call the IRT to assign (Part 1) or randomize (Part 2) the participant into the 
open dose panel. 
7.3 
Blinding 
This is an open-label study; participants in Part 1 will be assigned to treatment and participants in 
Part 2 will be randomized to treatment. It has been determined that blinding could negatively 
impact participant safety management, therefore blinding procedures are not applicable. The 
specific treatment to be taken by a participant will be assigned using IRT. The site will contact the 
Interactive Response System prior to the start of study intervention administration for each 
participant. The site will record the treatment assignment on the applicable case report form (CRF), 
if required. 
Release of Treatment Assignment: 
Access to randomized treatment codes will be restricted from BMS personnel (with exceptions 
noted below) prior to the final analysis. Access to the participants’ individual treatment assignment 
as recorded on the CRF will be allowed in order to monitor and manage potential safety risks that 
may be specific to the treatment received. 
Since this is an open-label study, blinding procedures are not applicable to global sites; however, 
the specific treatment to be taken by a participant will be assigned using an IRT. The site will 
contact the IRT prior to the start of study treatment administration for each participant. The site 
will record the treatment assignment on the applicable CRF. 
In order to monitor safety, designated staff of BMS Research & Development (R&D) will have 
access to the treatment codes prior to the final database lock. Specific safety events may be 
tabulated by treatment (for Arm 2b and Arm 2c) in order to assess whether toxicity boundaries 
have been reached, based on the continuous safety monitoring plan. To prevent bias and to protect 
the data integrity of the study, efficacy data will not be summarized by treatment arm prior to the 
final database lock, unless otherwise specified. In order to plan the time of the final efficacy 
analysis, designated Sponsor representatives will periodically monitor the total number of events 
between Arm 2a and Arm 2c (or Arm 2a and Arm 2b) relative to the pre-specified events needed 
for the planned analysis. In addition, designated staff of BMS R&D, such as Clinical 
Pharmacology and Pharmacometrics scientist, or Informatics and Predictive Sciences 
representatives may have access to the treatment assignment prior to database lock to facilitate the 
analysis of PK, biomarker, and immunogenicity samples. A bioanalytical scientist in the 


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Bioanalytical Sciences department of BMS R&D (or a designee in the external central 
bioanalytical laboratory) will have access to the randomized treatment assignments in order to 
minimize unnecessary bioanalytical analysis of samples for PK and immunogenicity. 
7.4 
Dosage Modification 
Dosing for all drugs should initially be delayed if any criteria in Table 7.4.1-1 (for BMS-986218 
and/or nivolumab) or Table 7.4.2-1 (for docetaxel) are met. That is, immunotherapy should also 
be delayed if criteria for delay of docetaxel are met and docetaxel should also be delayed if criteria 
for immunotherapy are met. Circumstances in which chemotherapy or immunotherapy can be 
independently resumed are discussed in Section 7.4.3. 
7.4.1 
Dose Modification Criteria for Nivolumab and/or BMS-986218 
The criteria for dose delay, resumption, and discontinuation in Table 7.4.1-1 applies to nivolumab 
and/or BMS-986218. 
In addition, delay nivolumab and BMS-986218 dosing for any adverse event, laboratory 
abnormality, or intercurrent illness which, in the judgment of the investigator, warrants delaying 
the dose of study medication. 
For participants who require delay of nivolumab and BMS-986218, re-evaluate weekly, or more 
frequently, if clinically indicated and resume dosing when criteria to resume treatment are met (see 
Section 7.4.3). Continue tumor assessments per protocol even if dosing is delayed. 
There will be no dose modifications permitted for nivolumab or BMS-986218. Administration of 
either nivolumab and/or BMS-986218 is permitted when docetaxel is discontinued due to toxicity 
if the treating investigator determines that it is the best interest of the participant. 


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Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
Gastrointestinal 
Colitis and Diarrhea 
Grade 2 
Delay dose 
Dosing may resume after AE returns to baseline 
Grade 3 
Permanently discontinue 
BMS-986218 
Nivolumab may be resumed when AE resolves to baseline. If 
Grade 3 diarrhea or colitis recurs while on nivolumab without 
BMS-986218 permanently discontinue 
Grade 4 
Permanently discontinue 
Renal 
Serum Creatinine Increased 
Grade 2 or 3 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline 
value. 
Grade 4 
Permanently discontinue 
Pulmonary 
Pneumonitis 
Grade 2 
Delay dose 
Dosing may resume after pneumonitis has resolved to ≤ Grade 1. 
Grade 3 or 4 
Permanently discontinue 
Hepatic 
AST, ALT or T.bilia Increased 
AST or ALT > 
3× and ≤ 5× ULN 
or T.bili > 1.5× 
and ≤ 3× ULN, 
regardless of 
baseline value 
Delay dose 
Dosing may resume when laboratory values return to baseline. 
Exception: Permanently discontinue if the increase is associated with 
new clinical signs/symptoms of liver inflammation (eg, right upper 
quadrant tenderness, fatigue, nausea, vomiting, fever, rash, and/or 
eosinophilia). 
AST or ALT > 
5× ULN or T.bili 
> 3× ULN, 
regardless of 
baseline value 
Permanently discontinue 
In most cases of AST or ALT > 5× ULN, study treatment will be 
permanently discontinued. If the investigator determines a possible 
favorable benefit/risk ratio that warrants continuation of study 
treatment, a discussion between the investigator and the Medical 
Monitor/ designee must occur and approval from Medical Monitor 
prior to resuming therapy. 


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Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
Concurrent AST 
or ALT > 3× 
ULN and T.bili 
> 2× ULN or 
INR > 1.5, 
regardless of 
baseline value 
Permanently discontinue 
Endocrinopathy 
Adrenal Insufficiency 
Grade 2 adrenal 
insufficiency 
Delay dose 
Dosing may resume after adequately controlled with hormone 
replacement. 
Grade 3 or 4 
adrenal 
insufficiency or 
adrenal crisis 
Delay dose or permanently 
discontinue 
Mandatory discussion with and approval from the Medical Monitor 
needed prior to resuming therapy. If adrenal insufficiency resolves or 
is adequately controlled with physiologic hormone replacement, 
participant may not require discontinuation of study drug. 
Hyperglycemia 
Hyperglycemia 
requiring 
initiation or 
change in daily 
management 
(Grade 2 or 3) 
Delay dose 
Dosing may resume if hyperglycemia resolves to Grade ≤ 1 or 
baseline value, or is adequately controlled with glucose-controlling 
agents. 
Grade 4 
Delay dose or permanently 
discontinue 
Mandatory discussion with and approval from the Medical Monitor 
needed prior to resuming therapy. If hyperglycemia resolves, or is 
adequately controlled with glucose-controlling agents, participant 
may not require discontinuation of study drug. 
Hypophysitis/Hypopituitarism 
Symptomatic 
Grade 1-3 that is 
also associated 
with 
corresponding 
abnormal lab 
Delay dose 
Dosing may resume if endocrinopathy resolves to be asymptomatic, 
or is adequately controlled with only physiologic hormone 
replacement. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.1-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986218 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
and/or pituitary 
scan 
Grade 4 
Delay dose or permanently 
discontinue 
Mandatory discussion with and approval from the Medical Monitor 
needed prior to resuming therapy. If endocrinopathy resolves or is 
adequately controlled with physiologic hormone replacement, 
participant may not require discontinuation of study drug. 
Hyperthyroidism or 
Hypothyroidism 
Grade 2 or 3 
Delay dose 
Dosing may resume if endocrinopathy resolves to be asymptomatic 
or is adequately controlled with only physiologic hormone 
replacement or other medical management. 
Grade 4 
Delay dose or permanently 
discontinue 
Mandatory discussion with and approval from the Medical Monitor 
needed prior to resuming therapy. If endocrinopathy resolves or is 
adequately controlled with physiologic hormone replacement or 
other medical management, participant may not require 
discontinuation of study drug. 
Skin 
Rash 
Grade 2 rash 
covering > 30% 
body surface area 
or Grade 3 rash 
Delay dose 
Dosing may resume when rash reduces to ≤ 10% body surface area. 
Exception: Permanently discontinue for Grade 3 rash that does not 
reduce to ≤ Grade 1 after 2-week treatment delay. 
Suspected 
Stevens-Johnson 
syndrome (SJS), 
toxic epidermal 
necrolysis (TEN) 
or drug reaction 
with eosinophilia 
and systemic 
symptoms 
(DRESS) 
Delay dose 
Dosing may resume if SJS, TEN, or DRESS is ruled out and rash 
reduces to ≤ 10% body surface area. 
Grade 4 rash or 
confirmed 
Permanently discontinue 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.1-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986218 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
SJS,TEN, or 
DRESS 
Neurological 
Guillain-Barre Syndrome (GBS) 
Any Grade 
Permanently discontinue 
Myasthenia Gravis (MG) 
Any Grade 
Permanently discontinue 
Encephalitis 
Any Grade 
encephalitis 
Delay dose 
After workup for differential diagnosis, (ie, infection, tumor-related), 
if encephalitis is not drug related, then dosing may resume when AE 
resolves. 
Any Grade 
drug-related 
encephalitis 
Permanently discontinue 
Myelitis 
Any Grade 
myelitis 
Delay dose 
After workup for differential diagnosis, (ie, infection, tumor-related), 
if myelitis is not drug related, then dosing may resume when AE 
resolves. 
Any Grade drug 
related myelitis 
Permanently discontinue 
Neurological (other than GBS, 
MG, encephalitis, or myelitis) 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to baseline 
Grade 3 or 4 
Permanently discontinue 
Myocarditis 
Myocarditis 
Symptoms 
induced from 
mild to moderate 
activity or 
exertion 
Delay dose 
Dosing may resume after myocarditis has resolved. Mandatory 
discussion with and approval from the Medical Monitor needed prior 
to resuming therapy. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.1-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986218 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Approved v31.0 
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Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
Severe or life 
threatening, with 
symptoms at rest 
or with minimal 
activity or 
exertion, and/or 
where 
intervention 
indicated. 
Permanently discontinue 
Other Clinical AE 
Pancreatitis: Amylase or Lipase 
Increased 
Grade 3 with 
symptoms 
Delay dose 
Note: Grade 3 increased amylase or lipase without signs or 
symptoms of pancreatitis does not require dose delay. Dosing may 
resume when participant becomes asymptomatic. 
Grade 4 
Permanently discontinue 
Uveitis 
Grade 2 uveitis 
Delay dose 
Dosing may resume if uveitis responds to topical therapy (eye drops) 
and after uveitis resolves to Grade ≤ 1 or baseline. If participant 
requires oral steroids for uveitis, then permanently discontinue study 
drug. 
Grade 3 or 4 
uveitis 
Permanently discontinue 
Other Drug-related AE (not 
listed above [non-laboratory 
AEs, see below for other 
laboratory drug-related AEs]) 
Grade 2 non-skin 
AE, except 
fatigue 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline 
value 
Grade 3 AE - 
First occurrence 
lasting ≤ 7 days 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline 
value. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.1-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986218 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
Grade 3 AE- First 
occurrence 
lasting > 7 days 
Permanently discontinue 
Recurrence of 
Grade 3 AE of 
any duration 
Permanently discontinue 
Exception: Recurrent Grade 3 fatigue may resume treatment after 
resolution to Grade 2 or lower. 
Grade 4 or 
Life-threatening 
adverse reaction 
Permanently discontinue 
Other Laboratory Abnormalities 
Other Drug-Related Lab 
Abnormality (not listed above) 
Not Attributed to Docetaxel 
Grade 3 
Delay dose 
Exceptions: 
No delay required for: Grade 3 lymphopenia or Grade 3 anemia 
related to underlying disease that responds to red blood cell 
transfusion. 
Permanent Discontinuation for: Grade 3 thrombocytopenia > 7 days 
or associated with bleeding. Grade ≥ 3 hemolysis. 
Grade 4 
Permanently discontinue 
Exceptions: The following events do not require discontinuation of 
study drug: 
• 
Grade 4 neutropenia ≤ 7 days 
• 
Grade 4 lymphopenia or leukopenia 
• 
Grade 4 isolated electrolyte imbalances/abnormalities that are not 
associated with clinical sequelae and are responding to 
supplementation/appropriate management within 72 hours of 
their onset 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.1-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986218 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
97 
Approved v31.0 
930173886 3.0 
 
 
 
 
Drug-related AE per CTCAE 
V5 
Severity 
Action Taken for 
BMS-986218 and/or 
Nivolumab 
Clarifications, Exceptions, and Resume Criteria 
Infusion Reactions (manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other 
allergic-like reactions.) 
Hypersensitivity Reaction or 
Infusion Reaction 
Grade 3 or 4 
Permanently discontinue except 
as described in Section 7.4.6 
Refer to Section 7.4.6 on Treatment of Related Infusion Reactions 
SARS-CoV-2 Infection Either 
Confirmed or Suspected 
Delay dose 
Participants with SARS-CoV-2 infection (either confirmed or 
suspected) may resume treatment after 1) at least 10 days (20 days 
for severe/critical illness) have passed since symptoms first appeared 
or positive test result (eg, RT-PCR or viral antigen), 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 with the BMS Medical Monitor. 
For suspected cases, treatment may also resume if SARS-CoV-2 
infection is ruled-out as per institutional policy for testing of 
SARS-CoV-2 and other criteria to resume treatment are met. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMS, Bristol-Myers Squibb; CTCAE V5, Common 
Terminology Criteria for Adverse Events version 5; DRESS, drug reaction with eosinophilia and systemic symptoms; GBS, Guillain-Barre Syndrome; 
INR, international normalized ratio; MG, myasthenia gravis; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus disease 2; SJS, Steven-Johnson syndrome; T.bili, total bilirubin; TEN, toxic epidermal necrolysis; ULN, upper limit of normal. 
a For participants with Gilbert’s syndrome, direct bilirubin should be monitored and utilized in place of T.bili for toxicity assessments. 


 
Clinical Protocol 
CA022009 
BMS-986218 
anti-CTLA4-NF mAb 
7.4.2 
Dose Delay Criteria for Docetaxel 
The criteria for dose delay, resumption, and discontinuation in Table 7.4.2-1 applies to docetaxel. 
In addition, delay docetaxel for any AE, laboratory abnormality, or intercurrent illness which, in 
the judgment of the investigator, warrants delaying the dose of study medication. 
For participants who require delay of docetaxel re-evaluate weekly, or more frequently, if 
clinically indicated and resume dosing when criteria to resume treatment are met (see 
Section 7.4.3). Continue tumor assessments per protocol even if dosing is delayed. Dose 
modifications of docetaxel are permissible (see Section 7.4.4). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 02 
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Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.2-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per 
CTCAE V5 
Severity 
Action Taken for 
docetaxel 
Clarifications, Exceptions, and Resume Criteria 
Hematological 
Neutropenia 
Grade 2 
Delay dose/reduce 
dosea 
If not recovered on the day of administration, delay next infusion until neutrophil 
counts ≥ 1.5 × 109/L. 
• 
1st episode: no dose reduction is required. 
• 
2nd episode: consider dose reduction by 1 dose level.a 
Granulocyte colony-stimulating factor (G-CSF) may be administered at the 
discretion of the investigator and following local guidelines. 
Grade 3 or 4 
Delay dose/reduce 
dosea or 
permanently 
discontinue 
Delay next infusion until neutrophil counts ≥ 1.5 × 109/L. 
No dose reduction if isolated and duration ≤ 7 days and recovered by Day 22 to 
≤ Grade 1. 
If duration > than 7 days or not recovered on Day 22 to ≤ Grade 1: 
• 
1st episode: consider prophylactic G-CSF in subsequent cycles. 
• 
2nd episode or 1st episode despite prophylactic G-CSF: Reduce dose by 1 
dose level.a 
• 
3rd episode or 2nd episode despite prophylactic G-CSF: permanently 
discontinue. 
Febrile neutropenia or 
neutropenic infection 
Grade 3 or 4 
Delay dose/reduce 
dosea or 
permanently 
discontinue 
Delay next infusion until neutrophil counts ≥ 1.5 × 109/L. 
• 
1st episode: reduce the dosea and consider prophylactic G-CSF in subsequent 
cycles. 
• 
2nd episode: permanently discontinue. 
Thrombocytopenia 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline. 
Grade 3 or 4 
Delay dose/reduce 
dosea or 
permanently 
discontinue 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline. If Grade 3 
without delay, no dose reduction required. If Grade 4, or Grade 3 with delay: 
• 
1st episode: reduce dose by 1 dose level.a 
• 
2nd episode: permanently discontinue. 
Permanent discontinuation for: Grade 3 thrombocytopenia > 7 days or associated 
with bleeding. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.2-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per 
CTCAE V5 
Severity 
Action Taken for 
docetaxel 
Clarifications, Exceptions, and Resume Criteria 
Gastrointestinal 
Diarrhea 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to baseline. 
Grade 3 
Delay dose/reduce 
dosea or 
permanently 
discontinue 
• 
1st episode: reduce dose by 1 dose level.a 
• 
2nd episode: permanently discontinue. 
Grade 4 
Permanently 
discontinue 
Colitis or enterocolitis 
Grade 2 
Delay dose 
Dosing may resume when AE resolves to baseline 
Grade 3 or 4 
Delay dose/reduce 
dosea or 
permanently 
discontinue 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline. 
• 
1st episode: reduce dose by 1 dose level.a 
• 
2nd episode: permanently discontinue. 
Skin 
Rash 
Grade 2 rash 
covering < 30% of 
body surface 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline. 
Dosing may resume when rash reduces to ≤ 10% body surface area. 
Grade 2 rash 
covering > 30% 
body surface area 
or Grade 3 rash 
Delay dose/reduce 
dose,a or 
permanently 
discontinue 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline. 
• 
1st episode: reduce dose by 1 dose level.a 
• 
2nd episode: permanently discontinue. 
Grade 4 
Permanently 
discontinue 
Neurological 
Peripheral neuropathy 
Grade 2 
Reduce dosea 
Reduce dose by 1 dose level.a 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.2-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per 
CTCAE V5 
Severity 
Action Taken for 
docetaxel 
Clarifications, Exceptions, and Resume Criteria 
Grade 3 or 4 
Permanently 
discontinue 
Hepatic 
Aspartate aminotransferase 
(AST), alanine 
aminotransferase (ALT), or 
total bilirubin (T.bili)b 
increased with or without 
alkaline phosphatase increase 
AST or ALT > 3× 
and ≤ 5× upper 
limit of normal 
(ULN) or T.bili > 
1.5× and ≤ 3× 
ULN, regardless of 
baseline value or 
T.bili > ULN 
and/or AST/ALT > 
1.5× ULN 
associated with 
alkaline 
phosphatase > 2.5× 
ULN (in the 
absence of bone 
metastasis) 
Delay dose/reduce 
dosea 
Dose reduction may be considered at the discretion of the investigator and 
following local guidelines.a 
Dosing may resume when laboratory values return to baseline. 
AST or ALT > 5× 
ULN or T.bili > 3× 
ULN, regardless of 
baseline value or 
concurrent AST or 
ALT > 3× ULN 
and T.bili > 2× 
ULN or INR > 1.5, 
regardless of 
baseline value 
Permanently 
discontinue 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.2-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per 
CTCAE V5 
Severity 
Action Taken for 
docetaxel 
Clarifications, Exceptions, and Resume Criteria 
Infusion Reactions (manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other 
allergic-like reactions.) 
Hypersensitivity reaction or 
infusion reaction 
Grade 3 or 4 
Permanently 
discontinue 
Refer to Section 7.4.8: Docetaxel-related Hypersensitivity Reactions. 
Other Clinical AE 
Cystoid macular oedema 
(CMO) diagnosed by 
ophthalmologic examination 
Any grade 
Permanently 
discontinue 
CMO has been reported in participants treated with docetaxel. Participants with 
impaired vision should undergo a prompt and complete ophthalmologic 
examination. In case CMO is diagnosed, docetaxel treatment should be 
discontinued and appropriate treatment initiated. 
Other drug-related AE (not 
listed above) 
Grade 2 non-skin 
AE, except fatigue 
Delay dose 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline value. 
Grade 3 
Delay dose/reduce 
dosea or 
permanently 
discontinue 
Dosing may resume when AE resolves to Grade ≤ 1 or baseline value. 
• 
1st episode: dose reduction may be considered at the discretion of the 
investigator.a 
• 
2nd episode: permanently discontinue. 
Grade 4 or 
life-threatening 
adverse reaction 
Permanently 
discontinue 
Other Laboratory Abnormalities 
Other drug-related lab 
abnormality (not listed 
above) 
Grade 3 
Delay dose/reduce 
dosea 
Dose reduction may be considered at the discretion of the investigator and 
following local guidelines.a 
Exceptions: No delay required for: Grade 3 lymphopenia. 
Grade 4 
Permanently 
discontinue 
Exceptions: The following events do not require discontinuation of study drug: 
• 
Grade 4 lymphopenia or leukopenia. 
• 
Grade 4 isolated electrolyte imbalances/abnormalities that are not associated 
with clinical sequelae and are responding to supplementation/appropriate 
management within 72 hours of their onset. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Table 7.4.2-1: 
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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Drug-related AE per 
CTCAE V5 
Severity 
Action Taken for 
docetaxel 
Clarifications, Exceptions, and Resume Criteria 
SARS-CoV-2 Infection 
Either Confirmed or 
Suspected 
Delay dose 
Participants with SARS-CoV-2 infection (either confirmed or suspected) may 
resume treatment after 1) at least 10 days (20 days for severe/critical illness) 
have passed since symptoms first appeared or positive test result (eg, RT-PCR or 
viral antigen), 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 with the BMS Medical Monitor. 
For suspected cases, treatment may also resume if SARS-CoV-2 infection is 
ruled-out as per institutional policy for testing of SARS-CoV-2 and other criteria 
to resume treatment are met. 
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CMO, cystoid macular oedema; CTCAE V5, Common 
Terminology Criteria for Adverse Events version 5; G-CSF, granulocyte colony-stimulating factor; INR, international normalized ratio; RT-PCR, reverse 
transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus disease 2; T.bili, total bilirubin; ULN, upper limit of normal. 
a See Section 7.4.4 for instructions on docetaxel dose reduction. 
b For patients with Gilbert’s syndrome, direct bilirubin should be monitored and utilized in place of T.bili for toxicity assessments. 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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7.4.3 
Criteria to Resume Treatment 
Dosing for all drugs should be delayed if any criteria in Table 7.4.1-1 (for BMS-986218 and/or 
nivolumab) or Table 7.4.2-1 (for docetaxel) are met. That is, immunotherapy should also be 
delayed if criteria for delay of docetaxel are met and docetaxel should also be delayed if criteria 
for immunotherapy are met. Participants may resume dosing when resuming criteria for BOTH 
immunotherapy and docetaxel are met. That is, immunotherapy and docetaxel will generally be 
administered together until completion of Cycle 10 or until one of the agents is permanently 
discontinued. The exception is immune-related toxicities that require prolonged immunotherapy 
delay (ie, toxicities treated with a prolonged corticosteroid taper). In such cases, dosing with 
docetaxel may resume prior to immunotherapy, when the criteria to resume dosing for docetaxel 
have been met. Immunotherapy dosing may be resumed later, after completion of the corticosteroid 
taper and when criteria to resume nivolumab or BMS-986218 dosing have been met. 
Administration of either immunotherapy or docetaxel only is permitted, if the other study 
treatment(s) is (are) permanently discontinued due to toxicity, and the treating investigator assesses 
continued therapy to have a favorable likelihood of benefit compared to risk. For participants 
undergoing immunotherapy treatment with BMS-986218 and nivolumab, both agents should 
typically be administered or discontinued together. In circumstances where a toxicity is attributable 
to 1 immunotherapy agent (eg, infusion reaction), administration of only 1 immunotherapy agent 
is permitted after discussion with the BMS medical monitor or designee. 
Participants with confirmed SARS-CoV-2 infection may resume treatment with BMS-986218 or 
BMS-986218 plus nivolumab, in combination with docetaxel after 1) at least 10 days (20 days for 
severe/critical illness) have passed since symptoms first appeared, positive RT-PCR test result, or 
positive viral antigen test result, 2) resolution of acute symptoms (including at least 24 hours has 
passed since last fever without fever reducing medications), 3) evaluation by the Investigator with 
confirmation that there are no sequelae that would place the participant at a higher risk of receiving 
investigational treatment, and 4) consultation by the medical monitor. For suspected cases, 
treatment may also resume if SARS-CoV-2 infection is ruled-out and other criteria to resume 
treatment are met. 
Prior to re-initiating on-study treatment in a participant with a dosing delay lasting 8 weeks due to 
SARS-CoV-2 infection, the medical monitor/designee must be consulted. 
7.4.3.1 
Criteria to Resume Treatment for Nivolumab and BMS-986218 
Participants may resume treatment with study drug if they have completed AE management (ie, 
corticosteroid taper) or are on ≤ 10 mg prednisone or equivalent, and meet the requirements per 
Table 7.4.1-1. 
Prior to re-initiating treatment in a participant with a dosing delay lasting > 8 weeks, the Medical 
Monitor (or designee) must be consulted. Continue tumor assessments per protocol even if dosing 
is delayed. Continue periodic study visits to assess safety and laboratory studies weekly or more 
frequently if clinically indicated during such dosing delays. 


Clinical Protocol 
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CA022009 
anti-CTLA4-NF mAb 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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In circumstances where a toxicity is attributable to one immunotherapy agent (eg, infusion 
reaction), administration of only 1 immunotherapy agent is permitted after discussion with the 
BMS medical monitor or designee. 
7.4.4 
Docetaxel Dose Reduction and Criteria to Resume Treatment 
The docetaxel dose can be reduced when necessary as described in Table 7.4.4-1. The dose which 
has been reduced for toxicity must not be re-escalated. Up to a maximum of 1 dose reduction will 
be allowed per participant. If a second dose reduction is required per the modifications above, the 
participant should discontinue study treatment. Participants who experience an event related to 
docetaxel necessitating discontinuation of chemotherapy may continue to receive other study 
treatments. See Section 7.4.2 for criteria on resuming docetaxel treatment after a dose delay. 
 
Table 7.4.4-1: 
Dose Reductions for Docetaxel 
Dose Level 
Docetaxel 
Starting dose 
First dose reduction 
75 mg/m2 
60 mg/m2 
Second dose reduction 
Discontinue docetaxel 
 
7.4.5 
Dose-limiting Toxicities 
For DLT evaluation, all AEs should be considered except those that are clearly and 
incontrovertibly due to disease progression or extraneous causes. 
 
DLTs will be defined as: 
• Any treatment-related AEs for which a participant permanently discontinues a study treatment 
(other than daily prednisone) based on the criteria listed in Table 7.4.1-1 and Table 7.4.2-1 and 
that occurs during the first 2 cycles of treatment 
• Any death not clearly due to the underlying disease or extraneous causes and that occurs during 
the first 2 cycles of treatment 
• Greater than or equal to Grade 2 pneumonitis lasting greater than 5 days despite appropriate 
medical therapy and that occurs during the first 2 cycles of treatment 
• Any neutropenic fever as well as Grade 4 neutropenia or thrombocytopenia for > 7 days that 
occurs during the first 2 cycles of treatment 
• Any treatment-related AE that delays initiation of Cycle 2 or Cycle 3 of treatment by greater 
than 2 consecutive weeks 
• Any Grade 3 or higher non-hematologic toxicity not specifically addressed elsewhere with the 
following exceptions: 
− Grade 3 or Grade 4 electrolyte abnormalities that are not complicated by associated clinical 
adverse experiences, last less than 72 hours, and either resolve spontaneously or respond 
to conventional medical intervention 


Clinical Protocol 
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CA022009 
anti-CTLA4-NF mAb 
Protocol Amendment No.: 02 
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− Grade 3 nausea, vomiting, or diarrhea that lasts less than 72 hours and either resolves 
spontaneously or responds to conventional medical intervention 
− Grade 3 elevation of amylase or lipase not associated with clinical or radiographic evidence 
of pancreatitis 
− 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 
− Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to sites of known or 
suspected tumor) 
− Grade 3 fatigue unless > 7 days 
− Grade 3 infusion reaction that returns to Grade 1 in < 6 hours 
 
Note: For participants who experience a DLT, further treatment will be based on Table 7.4.1-1 and 
Table 7.4.2-1 and the criteria to resume treatment in Section 7.4.3 and Section 7.4.4. 
 
DLT Exception: 
Infusion reactions attributed to docetaxel will not be considered DLTs. 
AEs will be graded according to the National Cancer Institute (NCI) Common Terminology 
Criteria for Adverse Events (CTCAE) v5. 
7.4.6 
Treatment of Related Infusion Reactions 
Since nivolumab and BMS-986218 contain only human immunoglobulin 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, 
arthralgias, hypotension, hypertension, bronchospasm, or other allergic-like reactions. Report all 
Grade 3 or 4 infusion reactions within 24 hours as an SAE if it meets the criteria. 
Treatment recommendations are provided below based on CTCAE v5 grading definitions and may 
be modified based on local treatment standards and guidelines, as appropriate: 
For Grade 1 symptoms (mild reaction; infusion interruption not indicated; intervention not 
indicated): 
• Remain at bedside and monitor participant until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg at least 30 minutes before 
additional nivolumab and/or BMS-986218 administrations. 
 
For Grade 2 symptoms: (Therapy or infusion interruption indicated but responds promptly to 
symptomatic treatment (eg, antihistamines, nonsteroidal anti-inflammatory drugs [NSAIDS], 
narcotics, IV fluids); prophylactic medications indicated for ≤ 24 hrs): 


Clinical Protocol 
BMS-986218 
CA022009 
anti-CTLA4-NF mAb 
Protocol Amendment No.: 02 
Date: 18-Feb-2022 
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• 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 study medication will be administered at that visit. 
• For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg 
administered at least 30 minutes before nivolumab and/or BMS-986218 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 [eg, not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following 
initial improvement; hospitalization indicated for clinical sequelae. Grade 4: Life-threatening 
consequences; urgent intervention 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. Monitor participant until the 
Investigator judges that the symptoms will not recur. Study drug will be permanently 
discontinued. Follow institutional guidelines for the treatment of anaphylaxis. Remain at 
bedside and monitor participant until recovery of the symptoms. 
 
In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine or corticosteroids). 
7.4.7 
Management Algorithms for Immuno-oncology Agents 
Immuno-oncology (I-O) agents are associated with IMAEs that can differ in severity and duration 
from AEs caused by other therapeutic classes. BMS-986218 and nivolumab are considered I-O 
agents in this protocol. Early recognition and management of IMAEs associated with I-O agents 
may mitigate severe toxicity. Management algorithms have been developed from extensive 
experience with ipilimumab and nivolumab to assist investigators in assessing and managing the 
following groups of IMAEs: 
• Gastrointestinal 
• Renal 
• Pulmonary 
• Hepatic 


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• Endocrinopathies 
• Skin 
• Neurological 
• Myocarditis 
 
The clinical nature of AEs noted with BMS-986218 will determine the role of the algorithms for 
use in toxicities related to its use in this study. The algorithms recommended for the management 
of IMAEs in this protocol can be found in Appendix 8. 
7.4.8 
Docetaxel-related Hypersensitivity Reactions 
Participants should be observed closely for hypersensitivity reactions especially during the first 
and second infusions. Hypersensitivity reactions may occur within a few minutes following the 
initiation of the infusion of docetaxel, thus facilities for the treatment of hypotension and 
bronchospasm should be available. If hypersensitivity reactions occur, minor symptoms such as 
flushing or localized cutaneous reactions do not require interruption of therapy. However, severe 
reactions ( ≥ Grade 3), such as severe hypotension, bronchospasm, or generalized rash/erythema 
require immediate discontinuation of docetaxel and appropriate therapy. Participants who have 
developed severe hypersensitivity reactions should not be re-challenged with docetaxel. 
Participants who have previously experienced a hypersensitivity reaction to paclitaxel may be at 
risk to develop hypersensitivity reaction to docetaxel, including more severe hypersensitivity 
reaction. These participants should be closely monitored during initiation of docetaxel therapy. 
7.5 
Preparation/Handling/Storage/Accountability 
The IP/AxMP must be stored in a secure area according to local regulations. It is the responsibility 
of the investigator, or designee where permitted, to ensure that IP/AxMP is only dispensed to study 
participants. The IP/AxMP must be dispensed only from official study sites by authorized 
personnel according to local regulations. 
The product storage manager should ensure that the study intervention 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 intervention arise, the study intervention 
should not be dispensed, and BMS should be contacted immediately. 
Study intervention not supplied by BMS will be stored in accordance with the package insert. 
IP/AxMP documentation (whether supplied by BMS or not) must be maintained that includes all 
processes required to ensure the 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). 
• The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention. 


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• The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
• Further guidance and information for the final disposition of unused study interventions are 
provided in Appendix 2. 
• Further preparation/administration and handling instruction will be provided in the Pharmacy 
Manual 
 
For study interventions not provided by BMS and obtained commercially by the site, storage 
should be in accordance with the product label. 
7.6 
Treatment Compliance 
Not applicable. 
7.7 
Concomitant Therapy 
7.7.1 
Prohibited and/or Restricted Treatments 
The following medications and treatments are prohibited during the study (unless utilized to treat 
a drug-related adverse event): 
• Immunosuppressive agents 
• Immunosuppressive doses of systemic corticosteroids. Participants are permitted the use of 
topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal 
systemic absorption). Adrenal replacement steroid doses > 10 mg daily prednisone are 
permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast 
dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity 
reaction caused by a contact allergen) is permitted. Premedication with corticosteroids for 
docetaxel therapy is allowed as detailed in Section 7.1. 
• Any concurrent systemic anti-neoplastic therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents for treatment of mCRPC) 
o Approved bisphosphonates and receptor activator of nuclear factor kappa-B ligand 
(RANKL) inhibitors are allowed 
• Any non-palliative radiation therapy. Radiation therapy administered with palliative intent (ie, 
for pain, bleeding, spinal cord compression, brain metastasis, new or impending pathologic 
fracture, superior vena-cava syndrome, or obstruction) is permitted. 
• Megestrol acetate 
• Any complementary medications (eg herbal supplements or traditional Chinese medicines) 
intended to treat the disease under study. Such medications are permitted if they are used as 
supportive care. 
• Any live/attenuated vaccine (eg varicella, zoster, yellow fever, rotavirus, oral polio and 
measles, mumps, rubella [MMR]) during treatment and until 100 days post last dose. 
• Administration of investigational SARS-CoV-2 vaccines is not allowed during the study. 


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• Participants may receive authorized or approved SARS-CoV-2 vaccines while continuing on 
study treatment at the discretion of the Investigator. 
o Live COVID-19 vaccines should not be administered to a participant during the study, 
including during the treatment, safety follow-up period, and within 3 months following 
the last dose of IMP. In addition, the administration of a live COVID-19 vaccine is 
prohibited up to 30 days prior to the initiation of study treatment. 
• Treatment of active SARS-CoV-2 infections or high risk exposures, including use of 
investigational therapies, is allowed and should be discussed with the medical monitor. 
 
7.7.2 
Other Restrictions and Precautions 
Strong CYP3A4 inhibitors and inducers should be avoided during the treatment with docetaxel. 
Please refer to Appendix 10 for a list of common strong CYP3A4 inhibitors and inducers. 
7.7.3 
Permitted Therapy 
Participants are permitted the use of the following treatments: 
• In the absence of active autoimmune disease, ocular, intra-articular, intra-nasal, inhaled or 
topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent 
are permitted. 
• A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast dye allergy) 
or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction 
caused by a contact allergen). 
• Participants receiving docetaxel may receive growth factors (including granulocyte 
colony-stimulating factor [G-CSF] and erythropoietin) at the discretion of the investigator and 
following local guidelines. 
7.7.4 
Palliative Radiation 
Palliative local therapy, including palliative radiotherapy and palliative surgical resection, to 
symptomatic tumor lesions is permitted. Participants requiring palliative local therapy should be 
evaluated (by CT/MRI and bone scan if clinically indicated) for objective evidence of disease 
progression prior to the initiation of such therapy, particularly if the most recent tumor assessment 
was more than 4 weeks prior to the planned start of local therapy. If progression per PCWG3 is 
identified prior to the initiation of palliative local therapy, then participants must either discontinue 
study treatment or they must meet criteria to continue treatment beyond progression (Section 8.1.2) 
in order to resume study treatment after the completion of palliative local therapy. Participants in 
Arm 2a who meet progression criteria prior to palliative radiation may proceed to the crossover 
arm (Arm 2d) following radiation. Participants receiving palliative radiation of target lesions will 
no longer be evaluable for the determination of response subsequent to the date palliative radiation 
occurs. In cases where palliative radiotherapy is required, BMS-986218 and nivolumab dosing 
should be withheld for at least 1 week before (if radiation can be safely delayed based on the 
clinical scenario), during, and 1 week after radiotherapy. Participants should be closely monitored 
for any radiation-related toxicity during and after receiving radiotherapy, and such AEs should 


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resolve to baseline or less than or equal to Grade 1 prior to resuming BMS-986218 or nivolumab. 
For docetaxel resumption, local standard of care guidelines should be followed. 
7.7.5 
Surgery 
Participants undergoing major surgery for any reason while on study should have BMS-986218, 
docetaxel, and/or nivolumab held for at least 4 weeks after surgery, and these study treatments 
should not be resumed until wound healing has occurred and it is considered safe to do so in the 
assessment of the investigator. Wound healing must be evaluated by the surgeon prior to resuming 
study treatment. Prior to resuming study treatment, surgically related AEs should resolve to 
Grade 1 or baseline, and participants must meet relevant eligibility criteria as determined by the 
BMS Medical Monitor (or designee) in discussion with the investigator. 
7.7.6 
Imaging Restriction and Precautions 
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history, and renal status), the appropriate imaging modality and 
contrast regimen per imaging study. Imaging contraindications and contrast risks are to be 
considered in this assessment. Participants with renal insufficiency are to be assessed as to whether 
or not they should receive contrast and if so, which contrast agent and dose is appropriate. Specific 
to MRI, participants with severe renal insufficiency (ie, estimated glomerular filtration rate 
[eGFR] < 30 mL/min/1.73 m2) are at increased risk of nephrogenic systemic fibrosis, therefore 
MRI contrast is contraindicated. In addition, participants may be excluded from MRI if they have 
tattoos, metallic implants, pacemakers, etc. This will be outlined in the imaging manual. 
Gentle hydration before and after IV contrast should follow local standard of care. The ultimate 
decision to perform MRI in an individual participant in this study rests with the site radiologist, 
the investigator, and standards set by the local Ethics Committee. 
7.8 
Continued Access to Study Intervention After the End of the Study 
At the end of the study, BMS will not continue to provide BMS-supplied study intervention to 
participants/investigators unless BMS chooses to extend the study. The investigator should ensure 
that the participant receives appropriate standard of care to treat the condition under study. 
BMS reserves the right to terminate access to BMS-supplied study intervention if any of the 
following occur: a) the study is terminated due to safety concerns; b) the development of 
BMS-986218 is terminated for other reasons, including, but not limited to, lack of efficacy and/or 
not meeting the study objectives; c) the participant can obtain medication from a 
government-sponsored or other health program. In all cases, BMS will follow local regulations. 
8 
DISCONTINUATION CRITERIA 
8.1 
Discontinuation From Study Intervention 
Participants MUST discontinue IP (and Non-IP/AxMP at the discretion of the investigator) for any 
of the following reasons: 
• Participant’s request to stop study intervention. Participants who request to discontinue study 
intervention will remain in the study and must continue to be followed for protocol-specified 


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follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by the participant 
to provide this information 
• Any clinical AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant 
• Termination of the study by BMS 
• Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness. (Note: Under 
specific circumstances and only in countries where local regulations permit, a participant who 
has been imprisoned may be permitted to continue as a participant. Strict conditions apply, and 
BMS approval is required.) 
• Significant noncompliance with protocol (eg, procedures, assessments, medications, etc). The 
investigator should discuss such issues with the Medical Monitor. 
• Radiographic progression of disease per PCWG3 criteria; however, participants who meet 
criteria for treatment beyond progression or who qualify for crossover into Arm 2d (from 
Arm 2a) may continue to receive study intervention. 
• Clinical deterioration attributed to disease progression, without radiographic progression per 
PCWG3, that in the judgment of the investigator makes it unsafe for the participant to continue 
with study intervention. 
 
Refer to the Schedule of Activities for data to be collected at the time of treatment discontinuation 
and follow-up and for any further evaluations that can be completed. 
All participants who discontinue study intervention 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 (eg, is imprisoned or involuntarily incarcerated for the 
treatment of either a psychiatric or physical illness). 
If study intervention 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 per local 
regulatory requirements in each region/country and entered on the appropriate CRF page. 
For all participants, global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as ‘symptomatic 
deterioration’ in the source data and in the electronic case report form (eCRF). Tumor assessments 
for participants who discontinue study intervention without radiographic progression, confirmed 
by BICR (Section 5.1.4.3), should continue as per protocol until radiographic progression is 
determined by BICR. 
8.1.1 
Discontinuation from Nivolumab and/or BMS-986128 
Nivolumab and/or BMS-986218 treatment must be permanently discontinued per criteria in Table 
7.4.1-1 in Section 7.4.1. Discontinue nivolumab and/or BMS-986218 for any adverse event, 


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laboratory abnormality, or intercurrent illness which, in the judgment of the Investigator, presents 
a substantial clinical risk to the participant with continued nivolumab dosing and/or BMS-986218. 
Any event that leads to delay in dosing lasting > 8 weeks from the previous dose requires 
discontinuation of study drug, with the following exceptions: 
• Dosing delays to allow for prolonged steroid tapers to manage drug-related adverse events are 
allowed. 
• Dosing delays lasting > 8 weeks from the previous dose that occur for non-drug-related reasons 
may be allowed if approved by the Medical Monitor (or designee). 
 
8.1.2 
Nivolumab and BMS-986218 Treatment Beyond Disease Progression 
Accumulating evidence indicates a minority of participants treated with immunotherapy may 
derive clinical benefit despite initial evidence of PD.63 
Participants treated with BMS-986218 or nivolumab will be permitted to continue with their 
assigned treatment beyond radiographic progression per PCWG3 criteria, assessed by the 
investigator up to a maximum of 24 months from date of first dose as long as they meet the 
following criteria: 
• Investigator-assessed clinical benefit 
• Tolerance of study treatment 
• Stable performance status 
• Participant provides written informed consent prior to receiving additional study treatment. All 
other elements of the main consent including description of reasonably foreseeable risks or 
discomforts, or other alternative treatment options will still apply. 
 
Treatment beyond progression may be administered during or after localized interventions 
(surgery/radiation therapy) after discussion with the Medical Monitor. 
Continue radiographic assessment/scan(s) in accordance with the Section 2 Schedule of Activities 
for the duration of the treatment beyond progression and submit to the central imaging vendor. 
Balance the assessment of clinical benefit with clinical judgment as to whether the participant is 
clinically deteriorating and unlikely to receive any benefit from continued study treatment. 
For the participants who continue study therapy beyond progression, further progression is defined 
as an additional 10% increase in tumor burden with a minimum 5 mm absolute increase from time 
of initial PD. This includes an increase in the sum of diameters of all target lesions and/or the 
diameters of new measurable lesions compared to the time of initial PD. Further progression in 
bone is defined as the development of 2 new bone lesions. Confirmatory bone imaging is not 
required to define further progression in bone. Upon documentation of further progression, 
permanently discontinue study treatment unless the clinical judgement of the investigator is that 
continuing treatment is in the patient’s best interest. 


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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-measureable at the time of initial progression may 
become measureable 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. 
8.1.3 
Post-study Intervention Study Follow-up 
In this study, rPFS is a key endpoint of the study. Post-study follow-up is of critical importance 
and is essential to preserving participant safety and the integrity of the study. Participants who 
discontinue study intervention must continue to be followed (in this study or a rollover study) for 
collection of outcome and/or survival follow-up data as required and in line with Section 5 until 
death or the conclusion of the study. 
If progression has not occurred before treatment discontinuation, tumor assessments should 
continue according to the Schedule of Activities. 
Participants should undergo 100 days of safety follow-up post last dose of study intervention 
(follow-up Day 30, 60, and 100). All participants who received study interventions will also be 
followed for survival data. 
Participants in Arm 2d who crossover after discontinuing docetaxel treatment and who re-enter the 
follow-up period will repeat the 100-day Safety Follow-up visits (Day 30, 60, and 100). 
Participants who discontinue study intervention may continue to be followed. 
BMS may request that survival data be collected on all treated/randomized participants outside of 
the protocol defined window (Table 2-3). At the time of this request, each participant will be 
contacted to determine their survival status unless the participant has withdrawn consent for all 
contact or is lost to follow-up. 
8.2 
Discontinuation From the Study 
Participants who request to discontinue study intervention 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. 
• 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 intervention 
only or also from study procedures and/or post-treatment study follow-up, and entered on the 
appropriate CRF page. 


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• In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law. 
• If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
 
8.2.1 
Individual Discontinuation Criteria 
• A participant may withdraw completely from the study at any time at his/her own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons. This is expected to be uncommon. Stopping study 
intervention is not considered withdrawal from the study. 
• At the time of discontinuing from the study, if possible, an early termination visit should be 
conducted, as shown in the Schedule of Activities. See the Schedule of Activities for data to 
be collected at the time of study discontinuation and follow-up and for any further evaluations 
that need to be completed. 
• The participant will be permanently discontinued both from the study intervention and from 
the study at that time. 
• 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 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
• All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant. 
• Lost to follow-up is defined by the inability to reach the participant after a minimum of 
three (3) documented phone calls, faxes, or emails, as well as lack of response by participant 
to one (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 the investigator’s use of third-party representative to assist in the follow-up portion of the 
study has been included in the participant’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining the 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 (Section 2). 
• Protocol waivers or exemptions are not allowed. 
• All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
treatment. 
• Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before treatment assignment (Part 1) and randomization 
(Part 2). 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. 
• Images will be submitted to a central imaging vendor for BICR at any time during the study. 
Prior to scanning the first participant, sites should be qualified and understand the image 
acquisition guidelines and submission process as outlined in the CA022009 Imaging Manual 
provided by the central imaging vendor. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
• Perform additional measures, including non-study required laboratory tests, as clinically 
indicated or to comply with local regulations. Laboratory toxicities (eg, suspected drug induced 
liver enzyme evaluations) will be monitored during the follow-up phase via on-site/local labs 
until all study drug-related toxicities resolve, return to baseline, or are deemed irreversible. 
• Evaluate participant immediately to rule out cardiac or pulmonary toxicity if participant shows 
cardiac or pulmonary-related signs (hypoxia, abnormal heart rate or changes from baseline) or 
symptoms (eg, dyspnea, cough, chest pain, fatigue, palpitations). 
• Some of the assessments referred to in this section may not be captured as data in the eCRF. 
They are intended to be used as safety monitoring by the treating physician. Additional testing 
or assessments may be performed as clinically necessary or where required by institutional or 
local regulations. 
 
9.1 
Efficacy Assessments 
9.1.1 
Imaging Assessment for the Study 
Images will be submitted to a central imaging vendor for blinded independent central review 
(BICR) during the study. Prior to scanning the first participant, sites should be qualified and 
understand the image acquisition guidelines and submission process as outlined in the CA022009 
Imaging Manual provided by the central imaging vendor. Screening and on study images should 


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be acquired as outlined in Section 2 (Schedule of Activities). Tumor assessments at other 
timepoints may be performed if clinically indicated and should be submitted to the central imaging 
vendor as soon as possible. Unscheduled bone scans and CT/MRI should be submitted to the 
central imaging vendor. X-rays that clearly demonstrate interval progression of disease, for 
example most commonly as unequivocal lesions that are unmistakably new since the prior 
CT/MRI, should be submitted to the central imaging vendor. Otherwise, they do not need to be 
submitted centrally. 
Collect any additional imaging that may demonstrate tumor response or progression (including 
scans performed at unscheduled timepoints and/or at an outside institution) for PCWG3 tumor 
assessment and submit to the BICR. 
9.1.1.1 
Methods of Measurement 
Bone lesions, including those with soft tissue component, will be assessed using Technetium-99m 
(Tc-99m) based radionuclide bone scans and not by CT or MRI. 
Contrast-enhanced CT of the, chest, abdomen, pelvis, and all other known and/or suspected sites 
of disease should be performed for tumor assessments. Images should be acquired with slice 
thickness of 5 mm or less with no intervening gap (contiguous). Every attempt should be made to 
image each participant using an identical acquisition protocol on the same scanner for all imaging 
timepoints. Tumor measurements should be made by the same investigator or radiologist for each 
assessment, whenever possible. Change in tumor measurements and tumor response to guide 
ongoing study treatment decisions will be assessed by the investigator using the PCWG3 criteria 
(refer to Appendix 5). 
If a participant has a contraindication for CT intravenous contrast, then a non-contrast CT of the 
chest and a contrast-enhanced MRI of the abdomen, pelvis, and other known/suspected sites of 
disease should be obtained. 
If a participant has a contraindication for both MRI and CT intravenous contrasts, then a 
non-contrast CT of the chest and a non-contrast MRI of the abdomen, pelvis, and other 
known/suspected sites of disease should be obtained. 
If a participant has a contraindication for MRI (eg, incompatible pacemaker) in addition to 
contraindication to CT intravenous contrast, then a non-contrast CT of the chest, abdomen, pelvis, 
and other known/suspected sites of disease is acceptable. 
MRI of brain (without and with contrast) should be acquired as outlined in Section 2 (Schedule of 
Activities). CT of the brain (without and with contrast) can be performed if MRI is contraindicated. 
9.1.1.2 
Imaging Assessment 
Tumor assessments should continue even if dosing is delayed or discontinued. Changes in tumor 
measurements and tumor responses will be assessed by the same investigator or designee using 
PCWG3 criteria (refer to Appendix 5). Assessments of PR and CR must be confirmed at least 
4 weeks (28 days) after initial response. A best overall response (BOR) of SD requires a minimum 
of 56 days on study from date of randomization to the date of the first imaging assessment. 


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9.1.1.3 
BICR Confirmation of Progression 
Sites should submit scans to the central imaging vendor on a rolling basis, throughout the duration 
of the study. BICR of scans will occur on a rolling basis, blinded to treatment arm, clinical data, 
and investigator assessment of submitted scans. When progression per PCWG3 criteria (refer to 
Appendix 5) is assessed by the investigator, the site will inform the central imaging vendor, in 
order for BICR assessment of progression to be performed. The BICR will be completed and the 
results provided to the site as specified in the imaging vendor documents, provided there are no 
pending imaging queries to the site. All details on the timelines and associated process 
requirements will be outlined in the Imaging Manual. 
Participants whose radiographic progression is not confirmed by the BICR will be required to 
continue tumor assessments (if clinically feasible) according to the protocol-specified schedule, or 
sooner if clinically indicated. Also, if participants discontinue treatment without radiographic 
progression, tumor assessments will continue according to the protocol-specified schedule, as 
noted in Section 2 (Schedule of Activities) until progression has been confirmed by BICR. In case 
subsequent therapy has begun, imaging must continue until radiographic progression per PCWG3 
is confirmed by BICR. 
All study treatment decisions will be based on the investigator’s assessment of tumor images and 
not on the BICR assessment. 
9.1.2 
Clinical Outcomes Assessments 
The evaluation of clinical outcomes assessments (COAs) is an increasingly important aspect of 
clinical efficacy in oncology trials. Such data provide an understanding of the impact of treatment 
from the participant’s perspective and offer insights into patient experience that may not be 
captured through physician reporting. Participants in Part 2 will complete the European 
Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life 
Questionnaire-Core 30 (QLQ-C30) and the single item Functional Assessment of Chronic Illness 
Therapy General Physical Item 5 (FACIT GP5) as indicated in Section 2 (Schedule of Activities). 
The questionnaires will be provided in the participant’s preferred language, if available, and may 
be administered using electronic devices or a web-based platform. 
If exceptional circumstances preclude the continued administration of measures using planned 
modalities, then alternate administration methods may be required, after consultation with the 
Sponsor or the Sponsor’s representative. 
9.1.2.1 
EORTC QLQ-C30 
The European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life 
Questionnaire–Core 30 (QLQ-C30) will be used to assess the effects of disease symptoms on 
functioning and well-being.64 The EORTC QLQ-C30 is the most commonly used quality of life 
instrument in oncology trials. The instrument’s 30 items are divided among 5 functional scales 
(physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, 
nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial 
difficulties), and a global health/quality of life scale. With the exception of 2 items included in the 


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global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), 
item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the QLQ-C30 are 
transformed to a 0 to 100 metric such that higher values indicate better functioning or quality of 
life or a higher level of symptoms. A score difference of 10 will be used as an estimate of the 
minimally important difference (MID) for the subscales of the EORTC QLQ-C30.65 
The EORTC QLQ-C30 will be administered during the treatment period only and not in Safety or 
Survival Follow-up periods. 
9.1.2.2 
FACIT GP5 
The Functional Assessment of Chronic Illness Therapy - GP5 Item (FACIT GP5) is a single item 
from the Physical Well-being subscale of the Functional Assessment of Cancer Therapy - General 
(FACT-G).66 The single item “I am bothered by side effects of treatment” (GP5) is rated on a 
5-point Likert scale. Item responses are 1 - not at all to 5 - very much. This single item will be 
administered to assess the overall extent of perceived bother due to symptomatic adverse events. 
Evidence exists for the validity of this item and its usefulness as an overall summary measure of 
burden due to symptomatic treatment toxicities.67 
The FACIT GP5 will be collected for the first 12 weeks of treatment only. 
9.2 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, or a surrogate). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for following up 
on AEs that are serious, considered related to the study intervention or the study, or that caused 
the participant to discontinue before completing the study. 
Refer to Appendix 3 for SAE reporting. 
Use CTCAE v5 definitions and grading for safety reporting of all AE and SAEs on the case report 
form. 
Contacts for SAE reporting are also specified in Appendix 3. 
Immune-mediated adverse events (IMAEs) are AEs consistent with an immune-mediated 
mechanism or immune-medicated component for which non-inflammatory etiologies (eg, 
infection or tumor progression) have been ruled out. IMAEs can include events with an alternate 
etiology which were exacerbated by the 
. Information supporting the 
assessment will be collected on the participant’s case report form. 
9.2.1 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs must be collected from the time of signing the consent, including those thought to be 
associated with protocol-specified procedures, and within 100 days following discontinuation of 
dosing. 


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The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study intervention or protocol-specified procedure (eg, a follow-up skin biopsy, insert 
other appropriate example if needed.). 
• Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the appropriate section of the CRF module. 
• All SAEs will be recorded and reported to Sponsor or designee within 24 hours, as indicated 
in Appendix 3. 
• The investigator will submit any updated SAE data to the sponsor or designee within 24 hours 
of updated information being available. 
 
Investigators are not obligated to actively seek AEs or SAEs in former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
intervention 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. 
• The collection of non-serious AEs (with the exception of non-serious AEs related to 
SARS-CoV-2 infection) should begin at initiation of study treatment and collected 
continuously during the treatment period and for a minimum of 100 days following 
discontinuation of study treatment. 
• All SAEs, and all AEs (SAEs and non-serious AEs) associated with confirmed or suspected 
SARS-CoV-2 infection must be collected from the date of the participant’s written consent 
until 100 days following discontinuation of dosing. 
 
For participants randomized/assigned to treatment and never treated with study drug, collect SAEs 
for 30 days from the date of randomization/treatment assignment. 
Collect all nonserious adverse events (not only those deemed to be treatment-related) continuously 
during the treatment period and for a minimum of 100 days following discontinuation of study 
treatment. 
9.2.2 
Method of Detecting AEs and SAEs 
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
AEs, when appropriate for the program or protocol. 
Every adverse event must be assessed by the investigator with regards to whether it is considered 
immune-mediated. For events which are potentially immune-mediated, additional information will 
be collected on the participant’s case report form. 


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9.2.3 
Follow-up of AEs and SAEs 
• Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Appendix 3). 
• Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study intervention and for those present at the end of study intervention as appropriate. 
• All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study. 
• After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and AEs (SAEs and non-serious AEs) 
associated with confirmed or suspected SARS-CoV-2 infection will be followed until 
resolution, 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. 
 
All SAEs will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3). 
Further information on follow-up procedures is given in Appendix 3. 
9.2.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
product under clinical investigation are met. 
• An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the Investigator’s Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements. 
 
The Sponsor or designee must report AEs to regulatory authorities and ethics committees 
according to local applicable laws and regulations. A SUSAR (suspected, unexpected serious 
adverse reaction) is a subset of SAEs and must be reported to the appropriate regulatory authorities 
and investigators following local and global guidelines and requirements. 
9.2.5 
Pregnancy 
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
the Sponsor or designee. In order for the Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form. 
If any sexual activity involving penile intercourse (eg, vaginal, anal, oral) has occurred between a 
male participant and a pregnant partner(s) without the use of a condom during and at least for 


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3 months, after study product administration, the information should be reported to the Sponsor or 
designee, even if the male participant has undergone a successful vasectomy. 
9.2.6 
Laboratory Test Result Abnormalities 
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE eCRF, 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 intervention 
discontinued or interrupted 
• Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy 
 
It is expected that, wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia vs low hemoglobin value). 
9.2.7 
Potential Drug-induced Liver Injury 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs meeting 
the defined criteria must be reported as SAEs (see Section 9.2 and Appendix 3 for reporting 
details). 
Potential DILI is defined as: 
• AT (ALT or AST) elevation > 3 times upper limit of normal (ULN) 
AND 
• Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase not attributed to bone metastasis) 
AND 
• No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic. 
 
9.2.8 
Other Safety Considerations 
Any significant worsening of conditions noted during interim or final physical examinations, ECG, 
radiographic imaging, or any other potential safety assessment required or not required by the 
protocol should also be recorded as a nonserious AE or SAE, as appropriate, and reported 
accordingly. 


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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. Overdoses that meet the regulatory 
definition of SAE will be reported as an SAE (see Appendix 3). 
In the event of an overdose, the treating physician should: 
• Contact the Medical Monitor immediately 
• Closely monitor the participant for AEs/SAEs and laboratory abnormalities until at least 
5 times the projected elimination half-life of BMS-986218 (5× 15 days = 75 days), of 
nivolumab (5× 25 days = 125 days), and of docetaxel (5× 11 hours = 55 hours) 
• Obtain a plasma sample for PK analysis 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 
 
There are a few reports of docetaxel overdose. There is no known antidote for docetaxel overdose. 
In case of overdose, the participant should be kept in a specialized unit and vital functions closely 
monitored. Exacerbation of AEs may be expected. The primary anticipated complications of 
overdose would consist of bone marrow suppression, peripheral neurotoxicity, and mucositis. 
Participants should receive therapeutic G-CSF as soon as possible after discovery of overdose. 
Other appropriate symptomatic measures should be taken, as needed. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
9.4 
Safety 
Planned time points for all safety assessments are listed in the Schedule of Activities. 
9.4.1 
Physical Examinations 
Refer to Schedule of Activities (Section 2). 
9.4.2 
Vital signs 
Refer to Schedule of Activities (Section 2). 
9.4.3 
Electrocardiograms 
Refer to Schedule of Activities (Section 2). 
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. 


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Table 9.4.4-1: 
Clinical Laboratory Assessments 
 
Hematology 
Hemoglobin 
Hematocrit 
Total leukocyte count, including differential 
Platelet count 
Chemistry 
Aspartate aminotransferase (AST)a 
Alanine aminotransferase (ALT)a 
Total bilirubin, with reflex direct bilirubinb if > ULN 
Alkaline phosphatase (ALP) 
Lactate dehydrogenase (LDH) 
Creatinine 
Blood urea nitrogen (BUN) or serum UREA 
Glucose 
Total protein 
Albumin - screening only 
Sodium 
Potassium 
Chloride 
Calcium 
Phosphorus 
Creatine kinase 
TSH, free T3 and free T4 - screening 
TSH, with reflexive free T3 and free T4 if TSH is 
abnormal - on treatment 
Urinalysis 
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 
HIV-1 and -2 antibody (screening only, where mandated locally; refer to Appendix 7) 
Hepatitis B/C, (HBV sAG, HCV antibody or HCV RNA), - screening only 
Other Analyses 
Prostate Specific Antigen ([PSA]; PSA should be performed by the same lab throughout the treatment period to 
avoid variations in results between cycles) 
Testosterone (at screening only) 
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; 
BUN, blood urea nitrogen; HBV, hepatitis B virus; HBV sAG, hepatitis B surface antigen; HCV, hepatitis C virus; 
HIV, human immunodeficiency virus; INR, international normalized ratio; LDH, lactate dehydrogenase; 
PSA, prostate-specific  antigen;  RNA,  ribonucleic  acid;  T3,  triiodothyronine;  T4,  thyroxine; 
TSH, thyroid-stimulating hormone; ULN, upper limit of normal. 
a INR is optional to better evaluate elevated liver function tests 
b Direct bilirubin testing for all participants with Gilbert’s syndrome 
9.4.5 
Imaging Safety Assessment 
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the Study Investigator as per 
standard medical/clinical judgment. 


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9.5 
Pharmacokinetics 
Separate serum samples will be collected for PK and anti-drug antibody (ADA) assessments of 
BMS-986218, following the schedule presented in the following tables for participants treated with 
BMS-986218 and docetaxel (Table 9.5-1 for Part 1A and Part 2, Arm 2b) or BMS-986218, 
nivolumab, and docetaxel (Table 9.5-2 for Part 1B and Part 2, Arm 2c). Separate serum samples 
will be collected for PK and ADA assessments of nivolumab, following the schedule presented in 
the Table 9.5-2 for participants treated with BMS-986218, nivolumab, and docetaxel. 


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Table 9.5-1: 
Pharmacokinetic and Anti-Drug Antibody (ADA) Sampling 
Schedule for BMS-986218 Q3W when Co-administered with 
Docetaxel in Part 1A and Part 2 (Arm 2b) 


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Table 9.5-2: 
Pharmacokinetic and Anti-Drug Antibody (ADA) Sampling 
Schedule for BMS-986218 Q3W in Combination with Nivolumab 
and Docetaxel for Part 1B and Part 2 (Arm 2c) 


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Table 9.5-2: 
Pharmacokinetic and Anti-Drug Antibody (ADA) Sampling 
Schedule for BMS-986218 Q3W in Combination with Nivolumab 
and Docetaxel for Part 1B and Part 2 (Arm 2c) 
 
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. The following PK 
parameters for BMS-986218 and nivolumab will be reported: 
 
Ceoi 
End of infusion concentration 
Ctrough 
Trough-observed serum concentration 
 
BMS-986218 PK data may also be used in an integrated population PK or exposure-response 
analysis along with data from other BMS-986218 studies, which would be the subject of a separate 
report. 
Sparse nivolumab PK data will be collected and may be used in an integrated population PK or 
exposure-response analysis along with data from other nivolumab studies, which would be the 
subject of a separate report. 
All on-treatment timepoints are intended to align with days on which study intervention is 
administered. If it is known that a dose is going to be delayed, then the predose sample, if 
appropriate, should be collected just prior to the delayed dose. However, if a predose sample is 


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collected but the dose is subsequently delayed, an additional predose sample should not be 
collected. Blood samples should be drawn from a site other than the infusion site (ie, contralateral 
arm) on days of infusion. If the infusion was interrupted, the interruption details will also be 
documented on the CRF. Further details of sample collection, processing, and shipment will be 
provided in the laboratory/procedure manual. Treatment assignments will be released to the 
bioanalytical laboratory in order to minimize unnecessary analysis and/or reanalysis of PK/ADA 
samples. 
Concentration analyses for BMS-986218 and nivolumab will be performed by validated 
bioanalytical method(s). 
Bioanalytical samples designated for assessments (eg, immunogenicity, PK, or biomarker) from 
the same collection time point may be used interchangeably for analyses, if required (including, 
but not limited to, insufficient volume for complement assessment, to follow-up on suspected 
immunogenicity related AE, etc). 
Additionally, residual bioanalytical samples will be archived and may be used for potential 
exploratory bioanalysis (including, but not limited to, analysis of drug-ADA immune complexes, 
metabolite analyses, etc) and or for additional method purposes (including, but not limited to, 
cross-validation, ADA/PK selectivity, cutpoint, etc). 
9.6 
Immunogenicity Assessments 
Antibodies to BMS-986218 or nivolumab will be evaluated in serum samples collected from all 
participants according to the Table 9.5-1 and Table 9.5-2. Serum samples will be screened for 
antibodies binding to BMS-986218 or nivolumab, and the titer of confirmed positive samples will 
be reported. Other analyses may be performed to further characterize the immunogenicity of 
BMS-986218 and nivolumab. 
The detection and characterization of antibodies to BMS-986218 and nivolumab will be performed 
using validated method(s). Antibodies may be further characterized and/or evaluated for their 
ability to neutralize the activity of the study intervention(s). Samples may be stored for a maximum 
of 15 years (or according to local regulations) following the last participant’s last visit for the study 
at a facility selected by the Sponsor to enable further analysis of immune responses to 
BMS-986218 and nivolumab. Additionally, residual samples may be used for additional method 
purposes (including but not limited to cross-validation, ADA/PK selectivity, cut point, etc). 
9.7 
Genetics 
See Section 9.8.3 and Section 9.8.4 for relevant planned genomic analysis in blood and tumor 
samples from pre-treatment and on-treatment samples. 
9.8 
Biomarkers 
Biomarker measures of baseline and on-treatment peripheral blood, serum, and tumor samples will 
be used to identify pharmacodynamic markers associated with treatment. Additional biomarkers 
related to mechanism of action, safety biomarkers, and associations with response to docetaxel, 
BMS-986218 + docetaxel and BMS-986218 + nivolumab + docetaxel will be explored. 


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Peripheral blood and tumor tissue will be collected prior to therapy and on treatment. A biopsy 
(block or slides) should also be performed if medically feasible at the time of progression for 
participants on treatment for more than 6 cycles, for all study parts. If biomarker samples are drawn 
but study treatment(s) is not administered, samples will be retained. A detailed description of each 
assay system is provided below and a schedule to evaluate biomarkers of response is provided in 
Table 9.8-1. Further details of blood and tumor collection and processing will be provided to the 
site in the procedure manual. 


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Table 9.8-1: 
Biomarker Sampling Schedule for Part 1 and Part 2 
 
Study Day of 
Sample Collection 
(1 cycle = 3 weeks) 
Event 
Tumor 
Biopsya 
Serum 
(Cytokines)a 
Whole Blood 
Plasma 
(ctDNA)a 
Whole Blood 
(germline 
and TCR)a 
Whole Blood 
(PAXgene)a 
Blood 
(Immuno- 
phenotyping)a 
Anti-SARS- 
CoV-2 
Serologya 
Screening 
X 
X 
X 
X 
Cycle 1 Day 1 
Predoseb 
X 
X 
X 
X 
X 
Cycle 1 Day 8 
X 
X 
Cycle 1 Day 15 
X 
X 
Cycle 2 Day 1 
Predoseb 
X 
X 
X 
Cycle 2 Day 15 
Xc 
Xd 
Xd 
Xd 
Xd 
Xd 
Cycle 3 Day 1 
Predoseb 
X 
Cycle 4 Day 1 
Predoseb 
X 
X 
Every fourth cycle 
starting with Cycle 9 
Day 1 until EOT 
(Cycle 13 Day 1, 
Cycle 17 Day 1, 
Cycle 21 Day 1, 
Cycle 25 Day 1, etc) 
Predoseb 
X 
Approximately every 
6 months during 
study treatment 
X 


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Table 9.8-1: 
Biomarker Sampling Schedule for Part 1 and Part 2 
 
Study Day of 
Sample Collection 
(1 cycle = 3 weeks) 
Event 
Tumor 
Biopsya 
Serum 
(Cytokines)a 
Whole Blood 
Plasma 
(ctDNA)a 
Whole Blood 
(germline 
and TCR)a 
Whole Blood 
(PAXgene)a 
Blood 
(Immuno- 
phenotyping)a 
Anti-SARS- 
CoV-2 
Serologya 
Approximately 
4 weeks after 
documented or 
suspected 
SARS-CoV-2 
infection 
X 
At progression 
X 
X 
X 
X 
X 
X 
Xe 
Abbreviations: ctDNA, circulating tumor deoxyribonucleic acid; EOT, end of treatment; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; 
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TCR, T-cell repertoire. 
a Instructions for the collection and processing of all samples will be provided in the laboratory manual. Crossover participants in Arm 2d will not have any 
biomarkers samples drawn or tumor biopsies performed with the exception of anti-SARS-CoV-2 serology, which should follow the above table. 
b All predose samples should be taken prior to infusion. 
c Tumor biopsies to be performed, if medically feasible, between Cycle 2 Day 15 and Cycle 3 Day 1 (prior to dosing; if there is a delay in dosing Cycle 3, biopsy 
can be taken up until Cycle 2 Day 28 as long as it is prior to the Cycle 3 dose). A biopsy should also be performed, if medically feasible, at the time of progression 
for participants on-treatment for more than 6 cycles, for all study parts (excluding crossover participants in Arm 2d). For participants who have toxicities related 
to study therapy (ie, cytopenia) that may put them at increased risk from the biopsy, the on-study biopsy is not required. If the only site amenable to biopsy is 
also the only site of measurable disease, the investigator should prioritize maintaining a measurable target lesion (by RECIST v1.1) if there is a concern that the 
biopsy might impact tumor assessment. Investigators can provide an additional tumor biopsy during the course of the study if the tumor samples are obtained as 
part of standard care. 
d For participants undergoing on-treatment tumor biopsies, collections to be aligned with tumor biopsies. 
e Will be collected during a 30-day window during the follow-up period. 


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9.8.1 
Peripheral Blood Biomarkers 
A variety of factors that may impact the immunomodulatory properties and efficacy of 
BMS-986218 will be investigated in peripheral blood specimens taken from all participants prior 
to or during treatment. Results from these investigations will be evaluated for associations with 
dose, response, survival, and/or safety (AE) data. Several analyses will be completed and are 
described briefly below. 
9.8.2 
Exploratory Serum and Plasma Biomarkers 
Blood samples for exploratory biomarker analyses will be drawn pre- and post-treatment at 
specified time points in Table 9.8-1, processed for serum and plasma, and retained in frozen 
storage. Serum and plasma samples may be assessed by enzyme-linked immunosorbent assay 
(ELISA), circulating tumor DNA (ctDNA) measurements, or metabolomics for prostate or 
immune-related factors that will predict for safety and efficacy of docetaxel, BMS-986218 + 
docetaxel and BMS-986218 + nivolumab + docetaxel. Serum/plasma-based analyses may include, 
but not necessarily be limited to, soluble CXCL9, CXCL10, CTLA-4, MIC-A, MIC-B, 
interleukin 6 (IL-6), cytochrome P450 enzymes, ICOS, anti-SARS-CoV-2 antibodies, and ctDNA. 
9.8.2.1 
Plasma ctDNA 
The presence of cell-free DNA in circulating blood is a well-documented phenomenon. Fragments 
of DNA are shed into the blood stream from dividing cells during cell proliferation or cell death. 
In subjects with cancer, a fraction of this DNA is tumor-derived and is termed circulating tumor 
DNA (ctDNA). Albeit small, fragments of DNA average between 180 to 200 base pairs and 
specific genomic regions can be amplified with polymerase chain reaction (PCR). Moreover, 
several studies have detected mutations in ctDNA that exactly correspond to mutations from the 
parent tumor. Using tissue and plasma, BEAMing or similar technology will be utilized to measure 
cell-free DNA and the presence/frequency of various mutations in the circulation. TMB will also 
be assessed in plasma. 
9.8.3 
Immunophenotyping 
The proportion of specific lymphocyte subsets and expression levels of T-cell co-stimulatory 
markers in peripheral blood mononuclear cell preparations will be quantified by flow cytometry. 
Analyses may include, but not necessarily be limited to, the proportion of T-, B-, and natural killer 
cells, granulocytes, the proportion of memory, effector, and Tregs subsets, as well as expression 
levels of CTLA-4, NKG2D, ICOS, and Ki67. 
9.8.3.1 
T-cell Repertoire Analysis 
The diversity of the peripheral T-cell compartment and changes over the course of treatment with 
immunotherapeutic agents may be related to the mechanism of action of BMS-986218. In order to 
explore whether a diverse T-cell repertoire (TCR) is associated with response to therapy, next- 
generation, high-throughput, deoxyribonucleic acid (DNA) sequencing will be performed on DNA 
isolated from peripheral blood and tumor tissue to quantitate the composition of the TCR prior to 
and during therapy. 


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9.8.3.2 
Germline DNA Variants 
Whole blood will be collected from all participants prior to treatment to generate genomic DNA 
for single nucleotide polymorphism (SNP) analyses and to serve as a reference for tumor genomic 
testing, including tumor mutational load assessment. These genomic analyses will include 
assessment of SNPs within genes associated with CTLA-4 and other immunoregulatory signaling 
pathways (eg, CD16) to determine if natural variation within those genes is associated with 
response to BMS-986218 and/or with AEs during treatment. 
9.8.3.3 
Gene Expression Profiling 
Whole blood collected in PAXgene tubes or equivalent fixative will be examined for messenger 
ribonucleic acid (mRNA) gene expression by RNA sequencing (RNAseq) or quantitative real-time 
polymerase chain reaction (qRT-PCR) to characterize gene expression profiles associated with 
immune modulation or outcome following treatment with BMS-986218. 
9.8.4 
Tumor Samples 
Fresh tumor biopsy specimens will be obtained at screening prior to treatment from participants 
who have soft tissue lesion that is suspected to represent metastatic disease based on local review 
of imaging and is considered accessible for biopsy by an interventional radiologist (or other 
appropriate specialist) to characterize immune cell populations and expression of selected tumor 
markers. Lymph nodes must measure at least 1 cm in diameter along the short axis in order to be 
considered for biopsy. Fresh biopsy specimens are mandatory for these participants. Tumor 
specimens may be collected between Cycle 2 Day 15 and Cycle 3 Day 1; if there is a delay in 
Cycle 3 dosing, biopsy can be taken up until Cycle 2 Day 28 as long as it is prior to the Cycle 3 
dose. Bone lesion biopsies are unacceptable for submission. See Table 9.8-1 for the tumor 
collection schedule. Tissue biopsies will also be performed on treatment to characterize 
pharmacodynamic changes, including CTLA-4-expressing immune cell populations, and tumor 
factors. Pharmacodynamic changes within biomarkers in the tumor biopsy collected at progression 
will be utilized to evaluate the underlying mechanism(s) of acquired resistance to study treatment. 
If available, correlative analyses via gene expression and immunohistochemistry (IHC) expression 
characterization can be performed with fresh formalin-fixed, paraffin-embedded (FFPE) tissue 
samples. Investigators can provide an additional tumor biopsy during the course of the study if the 
tumor samples are obtained as part of standard care. 
• Both the screening and on-treatment tumor biopsies should be preferentially collected from the 
same site, if feasible. At the time of progression, the biopsy should be performed using a 
progressive lesion or a new lesion, if feasible. 
• Tumor biopsy samples should be obtained from core biopsy, punch biopsy, excisional biopsy, 
or surgical specimen, as fine needle aspirates and other cytology specimens are insufficient for 
downstream biomarker analyses. Bone lesion biopsies are unacceptable for submission. 
• On-treatment and progressive disease (PD) biopsies are mandated at acceptable clinical risk 
(as determined by the investigator). Please notify the BMS Medical Monitor (or designee) if 
on-treatment biopsy may pose unacceptable clinical risk or if tumor at the time of on-treatment 
biopsy is not accessible for sampling. Institutional guidelines for the safe performance of 
biopsies should be followed. 


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• If the only site amenable to biopsy is also the only site of measurable disease, the investigator 
should prioritize maintaining a measurable target lesion (by RECIST v1.1) if there is a concern 
that the biopsy might impact tumor assessment. 
 
Note: For participants with bone-only disease, inaccessible soft tissue lesions, or if the biopsy 
procedure would pose an unacceptable clinical risk for the participant, submission of tumor tissue 
obtained from a fresh biopsy is not required. 
9.8.4.1 
Characterization of Tumor Immune Microenvironment 
Immunohistochemistry (IHC) will be used to assess the number and composition of immune 
infiltrates in order to define the immune cell subsets present within FFPE tumor tissue before and 
after exposure to therapy. These IHC analyses will include, but not necessarily be limited to, the 
following markers: FOXP3, CTLA-4, CD16, CD3, CD8, PD-L1, and Granzyme B. 
9.8.4.2 
Characterization of Tumor T-cell Repertoire 
As described above, DNA sequencing may be performed on pre- and post-treatment tumor tissue 
to assess the composition of the TCR. DNA will be isolated from either the FFPE tumor block or 
equivalent preparations. 
9.8.4.3 
Gene Expression Profiling 
Fresh tumor biopsies that are collected at screening will be examined for mRNA gene expression 
by RNAseq, quantitative polymerase chain reaction (qPCR), or other technologies to characterize 
gene expression profiles associated with outcome following treatment with BMS-986218 in 
combination with docetaxel and BMS-986218 in combination with docetaxel plus nivolumab. 
9.8.4.4 
Mutational and DNA Methylation Analyses 
DNA from tumor samples will be collected between Cycle 2 Day 15 and Cycle 3 Day 1 and 
analyzed using whole exome sequencing to determine the number and identity of mutations found 
within a tumor. 
9.9 
Additional Research 
All PK, biomarker, cytokine, and residual samples will be collected for additional research (AR). 
Sample retention for additional research is mandatory for all participants, except where prohibited 
by local laws or regulations. 
This protocol will include residual sample storage for AR. 
For All US sites: 
Additional research is required for all study participants, except where prohibited by IRBs/ethics 
committees, 
prohibited 
by 
local 
laws 
or 
regulations, 
or 
academic/institutional 
requirements. Where one or more of these exceptions occurs, participation in the additional 
research should be encouraged but will not be a condition of overall study participation. 


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• If the IRB/ethics committees and site agree to the mandatory additional research retention 
and/or collection, then the study participant must agree to the mandatory additional research 
as a requirement for inclusion in the study. 
• If optional participation is permitted and approved, then the study participants may opt out of 
the additional research retention and/or collection. 
 
For non-US Sites: 
Additional research is optional for all study participants, except where retention and/or collection 
is prohibited by local laws or regulations, ethics committees, or institutional requirements. 
 
Additional research is intended to expand the R&D capability at Bristol-Myers Squibb, and will 
support as yet undefined research aims that will advance our understanding of disease and options 
for treatment. This may also include genetic/genomic exploration aimed at exploring disease 
pathways, progression, and response to treatment etc. 
All requests for access to samples or data for additional research will be vetted through a committee 
of the study Sponsor’s senior leaders in Research and Development to ensure the research supports 
appropriate and well-defined scientific research activities. 
Sample Collection and Storage 
• Residual blood, serum, plasma, and tumor biopsies from available biomarker collection 
timepoints (Table 9.9-1) will also be retained for additional research purposes 
 
Samples kept for future research will be stored at the BMS Biorepository in 
or 
an independent, BMS-approved storage vendor. 
The manager of these samples will ensure they are properly used throughout their usable life and 
will destroy the samples at the end of the scheduled storage period, no longer than fifteen (15) 
years after the end of the study or the maximum allowed by applicable law. 
Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures. 
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual. 
Further details of sample collection and processing will be provided to the site in the procedure 
manual. 


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Table 9.9-1: 
Residual Sample Retention for Additional Research Schedule 
 
Sample Type 
Timepoints for which residual samples will be retained 
Residual Serum and 
Plasma 
All biomarker collections and all PK collections 
Tumor Biopsy and 
Blood Collection 
Screening, on-treatment, and at disease progression (if available) 
Abbreviation: PK, pharmacokinetic. 
 
9.10 
Other Assessments 
Whole blood, serum and plasma samples will be collected at the times indicated in Table 9.8-1 for 
the measurement of DNA, RNA, and protein biomarkers. These measurements may include, but 
are not limited to, assessments of SARS-CoV-2 serologic status. Serum will be collected as 
indicated in Table 9.8-1 for possible measurements of SARS-CoV-2 serology (anti-SARS-CoV-2 
total or IgG antibody). 
9.11 
Health Economics OR Medical Resource Utilization and Health 
Economics 
Health economics/medical resource utilization and health economics parameters will not be 
evaluated in this study. 
10 
STATISTICAL CONSIDERATIONS 
10.1 
Statistical Hypotheses 
BMS-986218 or BMS-986218 plus nivolumab will be safe and tolerable in combination with 
docetaxel and will improve clinical activity in participants with mCRPC as measured by rPFS. 
10.2 
Sample Size Determination 
Sample Size Justification for Safety Lead-in Portion (Part 1): 
Escalation/de-escalation decisions will be guided by the BOIN design (refer to Appendix 9). 
Though the exact number treated at a dose level will depend on the number of participants with a 
DLT, approximately 12 DLT-evaluable participants may be treated in Part 1A to assess the 
tolerability of BMS-986218 in combination with docetaxel. Similarly, in Part 1B, approximately 
12 to 18 participants may be treated with BMS-986218 in combination with docetaxel and 
nivolumab. With a maximum of 12 DLT-evaluable participants at a dose level, there will be above 
80% probability to observe at least 1 occurrence of a safety event if the event rate in the population 
is 13%. Similarly, with 6 or 9 DLT-evaluable participants at a dose level, there will be above 80% 
probability to observe at least 1 occurrence of the safety event if the event rate in the population is 
24% or 17%, respectively. A minimum of 6 DLT-evaluable participants and no more than 
12 DLT-evaluable participants will be evaluated at a dose level in Part 1A or Part 1B to ensure 
tolerability prior to initiating enrollment in Part 2 at these dose levels. Therefore, a total of 
approximately 30 DLT-evaluable participants may be evaluated during the safety lead-in, 


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including at least 6 participants (with 0 or 1 DLT) at each of the BMS-986218 + docetaxel and 
BMS-986218 + nivolumab + docetaxel combination doses that will be evaluated in Part 2. 
Sample Size Justification for Randomized, Controlled Portion (Part 2): 
The sample size of the study is calculated to have sufficient power for the primary efficacy 
endpoint of rPFS to compare Arm 2c to Arm 2a and Arm 2b to Arm 2a. Assuming that Arm 2a 
median rPFS is 6 months and a constant HR of 0.55 for the Arm 2c to Arm 2a comparison (for 
target median rPFS = 10.9 months), a total of 78 rPFS events will need to be observed across these 
2 arms, in order to have 91.3% power to show a difference at the 20% 2-sided alpha level, in this 
population, based on 58 participants per arm. Based on hierarchical testing of Arm 2b vs Arm 2a, 
assuming there was statistical significance in the Arm 2c vs Arm 2a comparison, and a constant 
HR of 0.62 for the Arm 2b to Arm 2a comparison, a total of 79 rPFS events will need to be observed 
across these 2 arms, with 58 participants per arm in order to have 80% power to show a difference 
at the 20% 2-sided alpha level. These calculations assume 18 months for accrual and a minimum 
of 10 months follow up. A total of 174 participants will need to be randomized assuming about 
21% dropout rate across arms (5% in control arm, 9% in the BMS-986218 + docetaxel arm, and 
7% in the BMS-986218 + nivolumab + docetaxel arm). 
The actual time of the final analysis will be based on the number of events observed, which will 
be monitored separately among Arm 2c and Arm 2a and among Arm 2b and Arm 2a during the 
study conduct. 
10.3 
Analysis Sets 
For the purpose of analysis, the following populations are defined in Table 10.3-1: 
Table 10.3-1: 
Analysis Sets 
 
Population 
Description 
Enrolled 
All participants who sign informed consent and are registered in IRT 
Treated 
All participants who received any amount of study intervention 
Randomized 
All participants who were randomized using IRT in Part 2 
Response-evaluable 
All participants who received at least 1 dose of study intervention, have a 
baseline tumor assessment with measurable disease, and 1 of the following: 
1) At least 1 evaluable on-treatment tumor assessment, 
2) Clinical progression, or 
3) Death prior to the first on-treatment tumor evaluation 
PSA-response Evaluable 
Participants with PSA values ≥ 2 ng/mL at baseline and at least 1 post-baseline 
assessment 


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Table 10.3-1: 
Analysis Sets 
 
Population 
Description 
DLT-evaluable 
All treated participants in Part 1A or Part 1B who have received study 
intervention (all components) and have completed the DLT-evaluation period of 
6 weeks, or who discontinued any study intervention due to toxicity prior to 
completing the DLT-evaluation period 
Pharmacokinetic 
All treated participants who have evaluable concentration-time data 
Immunogenicity 
All treated participants who have baseline and at least 1 post-baseline 
pre-infusion immunogenicity assessment 
Biomarker 
All treated participants with available biomarker data 
Clinical Outcomes Assessments 
(COAs) 
All participants with baseline and at least 1 post-baseline COA assessment 
Abbreviations: COA, clinical outcomes assessment; DLT, dose-limiting toxicity; IRT, Interactive Response 
Technology; PSA, prostate-specific antigen. 
 
 
10.4 
Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before database lock and will 
describe the selection of participants to be included in the analyses and procedures for accounting 
for missing, unused, and spurious data. Below is a summary of planned statistical analyses of the 
primary and secondary endpoints. 
A description of the participant population will be included in the clinical study report, including 
subgroups of age, gender, race, and other study-specific populations and demographic 
characteristics. A description of participant disposition will also be included in the clinical study 
report. 
10.4.1 
General Considerations 
The analysis of safety (Part 1 and Part 2) will be based on All treated population. The efficacy 
analysis in Part 2 will be based on All randomized population. Part 1 efficacy results will be 
described separately for All treated population. 
Efficacy analysis in Part 2 will be performed with the family-wise error rate controlled at 20%. 
The primary endpoint of rPFS will be first compared between Arm 2a and Arm 2c at the 2-sided 
significance level of 20%. The rPFS difference between Arm 2b and Arm 2a will be statistically 
tested only if the Arm 2c vs Arm 2a comparison meets statistical significance. Otherwise, the 
Arm 2b vs Arm 2a results will be descriptive. 
Statistical analysis of participants in Arm 2a who receive crossover treatment upon progression 
will be presented separately, after the start of intervention in the crossover arm (Arm 2d). 


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10.4.2 
Primary Endpoint(s) 
The primary endpoint for Part 1 is to assess safety based on incidence of AEs, SAEs, AEs meeting 
protocol-defined DLT criteria, TRAEs, AEs leading to discontinuation, and deaths. In addition, 
the selected tolerable dose levels of BMS-986218 in combination with docetaxel (Part 1A) and 
BMS-986218 in combination with docetaxel and nivolumab (Part 1B) will be determined using 
the DLT rate within the 6-week DLT window among DLT-evaluable participants in Part 1A and 
in Part 1B. The incidence of DLTs will be calculated for DLT-evaluable participants and compared 
to the actions recommended by the BOIN design to guide the dose escalation/stay/de-escalation 
decision for the BMS-986218 + docetaxel treatment and for the BMS-986218 + nivolumab + 
docetaxel treatment. 
The primary endpoint for Part 2 is rPFS of BMS-986218 + docetaxel and BMS-986218 + 
nivolumab + docetaxel combination therapies compared to rPFS of docetaxel monotherapy 
control, in the randomized population. rPFS is defined as the time from randomization to the date 
of first documented radiographic progression per BICR using PCWG3 or death due to any cause, 
whichever occurs first. Participants who do not progress or die will be censored on the date of their 
last evaluable tumor assessment. Participants who did not have any evaluable on-study tumor 
assessments and did not die will be censored at randomization date. 
The primary endpoints and analyses are shown in Table 10.4.2-1. 


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Table 10.4.2-1: 
Primary Endpoints and Statistical Analyses 
 
Endpoint Description 
Analysis 
Timeframe 
Safety Lead-in (Part 1A and 
Part 1B): The primary safety 
endpoint is the incidence of AEs, 
SAEs, 
AEs 
meeting 
protocol- 
defined DLT criteria, TRAEs, AEs 
leading to discontinuation, and 
deaths 
AEs will be presented using NCI 
CTCAE v5. On-study incidence of 
AEs, SAEs, TRAEs, and AEs 
leading to discontinuation will be 
tabulated using worst grade per NCI 
CTCAE v5 criteria by System Organ 
Class and Preferred Term 
DLT observation period is up to 
6 weeks from start of treatment. 
All AEs up to 100 days after the last 
treatment of study drug, eg, 
28 months since start of treatment at 
time of final analysis, and up to the 
end 
of 
survival 
follow-up 
(approximately 4 years) 
Randomized, Controlled Portion 
(Part 2): rPFS for randomized 
participants is the time between 
randomization date and the first date 
of 
documented 
radiographic 
progression, or death due to any 
cause, whichever occurs first. The 
radiographic progression will be 
assessed by Blinded Independent 
Central Review (BICR) per PCWG3 
The rPFS curve will be estimated 
using 
the 
Kaplan-Meier 
product-limit method. A log-rank 
test 
stratified 
by 
presence 
of 
measurable disease (Y/N), will be 
used to compare rPFS between 
Arm 2c and Arm 2a. Hazard Ratio 
(HR) and corresponding 2-sided 
95% CI for rPFS primary endpoint 
analysis will be estimated using a 
Cox proportional hazard model, 
with treatment arm as a single 
covariate, stratified by presence of 
measurable disease to assist in 
interpretation of the rPFS analysis. 
A similar analysis will be performed 
to compare Arm 2b to 2a, with 
statistical testing only if Arm 2c to 
Arm 2a comparison met statistical 
significance 
Time from randomization until the 
number of needed events are met, 
expected  approximately  at 
28 
months 
since 
start 
of 
randomization 
Abbreviations: AE, adverse event; BICR, blinded independent central review; CI, confidence interval; 
DLT, dose-limiting toxicity; HR, hazard ratio; NCI CTCAE v5, National Cancer Institute Common Terminology 
Criteria for Adverse Events version 5; PCWG3, Prostate Cancer Working Group 3; rPFS, radiographic 
progression-free survival; SAE, serious adverse event; TRAE, treatment-related adverse event; Y/N, yes/no. 
 
 
Efficacy analysis will be performed with the family-wise error rate controlled at 20%. The 
BMS-986218 + nivolumab + docetaxel treatment will be first compared vs the docetaxel 
monotherapy control. rPFS will be compared between the BMS-986218 + nivolumab + docetaxel 
treatment group and the docetaxel monotherapy control, using stratified log-rank test (presence of 
measurable disease). If this comparison meets statistical significance, then the BMS-986128 + 
docetaxel treatment group will be tested similarly versus the docetaxel monotherapy control. 
The stratified hazard ratio (stratified by presence of measurable disease) from Cox regression 
model comparing each combination treatment arm to the control will be presented along with 
95% CI. 
Median rPFS will be estimated using Kaplan-Meier approach for each arm. A two-sided 95% CI 
(log-log transformation) for median rPFS will also be computed. rPFS rates at specified time points 
(ie, 6 months, 12 months, etc) will be computed along with 95% CI using log-log transformation. 


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10.4.3 
Secondary Endpoint(s) 
The secondary endpoints (Part 2) and statistical analysis methods are described in Table 10.4.3-1. 
There is no adjustment for multiplicity for secondary endpoints. 
The effect of each treatment will be estimated based on the additional efficacy endpoints using 
point estimates and 95% CI. Details of censoring rules for the time-to-event endpoints will be 
provided in the study SAP. All efficacy endpoints analysis will use all randomized population for 
primary analysis, unless otherwise specified. 
Table 10.4.3-1: 
Secondary Endpoints (Part 2) and Statistical Analyses 
 
Endpoint Description 
Analysis 
Timeframe 
Objective 
Response 
Rate 
per 
PCWG3  (ORR-PCWG3)  is  the 
proportion of participants who have 
a confirmed complete or partial best 
overall response (BOR) per PCWG3 
among randomized participants who 
have measurable disease at baseline. 
The BOR is defined as the best 
response designation, as determined 
by the BICR, recorded between the 
date of randomization and the date 
of 
objectively 
documented 
radiographic progression, or last 
tumor 
measurement, 
whichever 
occurs first 
Summary statistics of BOR will be 
tabulated by treatment arm. The 
ORR estimates and 95% CI will be 
tabulated by cohort and calculated 
based 
on 
the 
Clopper-Pearson 
method the ORR difference between 
Arm 2b vs Arm 2a and Arm 2c vs 
Arm 2a will also be tabulated with 
point estimates and 95% CI 
Approximately 28 months since the 
start of randomization (based on the 
number of needed rPFS events) 
Time to Response per PCWG3 
(TTR-PCWG3) is the time from 
randomization date to the date of the 
first documented CR or PR per 
PCWG3, as determined by BICR 
TTR-PCWG3 will be tabulated for 
the responders by treatment arm 
using summary statistics 
Approximately 28 months since the 
start of randomization (based on the 
number of rPFS events for primary 
analysis) 
Duration of Response per PCWG3 
(DOR-PCWG3) is the time between 
the date of first response (CR/PR per 
PCWG3) to the date of first 
documented 
radiographic 
progression 
per 
PCWG3 
as 
determined by BICR, or death due to 
any cause 
DOR-PCWG3 will be tabulated by 
Kaplan-Meier 
estimates 
and 
95% CI. Participants who neither 
progress nor die will be censored at 
the last tumor assessment 
Approximately 28 months since the 
start of randomization (based on the 
number of rPFS events for primary 
analysis) 
PSA Response Rate (PSA-RR) is the 
proportion 
of 
randomized 
participants with a 50% or greater 
decrease in PSA from baseline 
(defined as Cycle 1 Day 1 
pre-treatment) to any post-baseline 
PSA result. A second consecutive 
value obtained 3 or more weeks later 
is required to confirm the PSA 
response 
PSA-RR will be calculated for all 
participants who are PSA-response 
evaluable. Summary statistics of 
PSA-RR will be tabulated by cohort 
by point estimates and 95% CI based 
on the Clopper-Pearson method; 
The PSA-RR difference between 
Arm 2b vs Arm 2a and Arm 2c vs 
Arm 2a will also be tabulated with 
point estimates and 95% CI 
Approximately 28 months since the 
start of randomization (based on the 
number of rPFS events for primary 
analysis) 


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Table 10.4.3-1: 
Secondary Endpoints (Part 2) and Statistical Analyses 
 
Endpoint Description 
Analysis 
Timeframe 
Time 
to 
PSA 
Progression 
(TTP-PSA) is the time between 
randomization date to the date of 
PSA progression per PCWG3 in 
randomized participants. 
TTP-PSA will be tabulated by 
Kaplan-Meier 
estimates 
and 
95% CI. TTP-PSA for participants 
without a PSA progression, will be 
censored at the date of last PSA 
evaluation. For participants with no 
post-baseline PSA evaluation, the 
time will be censored at the date of 
randomization 
Approximately 28 months since the 
start of randomization (based on the 
number of rPFS events for primary 
analysis) 
Overall Survival (OS) for all 
randomized participants is the time 
between randomization date and the 
date of death from any cause 
The OS curve will be estimated for 
each treatment arm using the 
Kaplan-Meier product-limit method. 
Hazard Ratio of Arm 2c: Arm 2a and 
Arm 2b: Arm 2a and corresponding 
2-sided 95% CI for OS will be 
estimated using a Cox proportional 
hazard model, with treatment arm as 
a single covariate, stratified by 
presence of measurable disease to 
assist in interpretation of the 
analysis 
4 years since randomization 
Overall safety and tolerability will 
be measured by the incidence of 
AEs, TRAEs, SAEs, AEs leading to 
discontinuation, and deaths 
AEs will be presented using NCI 
CTCAE v5. On-study incidence of 
AEs, SAEs, TRAEs, and AEs 
leading to discontinuation will be 
tabulated using worst grade per NCI 
CTCAE v5 criteria by System Organ 
Class and Preferred Term 
28 months at the primary endpoint 
analysis time; in addition, up to 
100 days after the last treatment of 
study drug, or end of survival 
follow-up eg, at 4 years 
Abbreviations: AE, adverse event; BICR, blinded independent central review; BOR, best overall response; CI, 
confidence interval; CR, complete response; DOR, duration of response; NCI CTCAE v5, National Cancer Institute 
Common Terminology Criteria for Adverse Events version 5; ORR, objective response rate; OS, overall survival; 
PCWG3, Prostate Cancer Working Group 3; PSA, prostate-specific antigen; PR, partial response; PSA-RR, PSA 
response rate; rPFS, radiographic progression-free survival; SAE, serious adverse event; TRAE, treatment-related 
adverse event; TTP-PSA, time to PSA progression; TTR, time to response. 
 
It may be noted that for the time to PSA progression (TTP-PSA) endpoint, in participants with an 
initial PSA decline from baseline, the date of PSA progression is the date that an increase of 25% 
or more and an absolute increase of 2 ng/mL or more from the nadir are documented and confirmed 
by a second consecutive PSA value at least 3 weeks later. For participants with no PSA decline 
from baseline, the date of PSA progression is the date that an increase of 25% or more and an 
absolute increase of 2 ng/mL or more from baseline are documented beyond Week 12. 


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10.4.4 
Exploratory Endpoint(s) 
10.4.4.1 
Pharmacokinetic Analysis for BMS-986218 and Nivolumab 
Statistical analyses for exploratory PK endpoints are summarized in Table 10.4.4.1-1. 
Table 10.4.4.1-1: 
Pharmacokinetic ‑ Statistical Analyses 
Endpoint 
Statistical Analysis Methods 
Ceoi, Ctrough 
Summary statistics of PK parameter: geometric means and coefficients of 
variation, by treatment and by day 
Abbreviations: Ceoi, end of infusion concentration; Ctrough, trough-observed serum concentration (this includes 
predose concentrations [C0] and Ctau); PK, pharmacokinetic. 
 
 
PK serum concentration-time data for BMS-986218, and nivolumab may be pooled with data from 
other studies for integrated population PK and ER analyses, which will be presented in a separate 
report. 
10.4.4.2 
Immunogenicity Analysis 
Statistical analyses for endpoints related to the immunogenicity of BMS-986218 and nivolumab 
are summarized in Table 10.4.4.2-1 and Table 10.4.4.2-2, respectively. 
Table 10.4.4.2-1: 
Immunogenicity of BMS-986218 - Statistical Analyses 
 
Endpoint 
Statistical Analysis Methods 
Incidence of ADA to BMS-986218 
Baseline ADA-positive participant is defined as a participant who has an 
ADA-detected sample at baseline.a,b ADA-positive participant is a 
participant with at least 1 ADA-positive sample relative to baseline after 
initiation of the treatment 
Frequency distribution of 
baseline ADA-positive 
participants and ADA-positive 
participants after initiation of the 
treatment 
Abbreviations: ADA, anti-drug antibody; SAP, statistical analysis plan. 
a Baseline sample is the last sample before initiation of the treatment. 
b Details of the immunogenicity data analysis, including ADA titers, will be provided in the SAP. 
 
 
Table 10.4.4.2-2: 
Immunogenicity of Nivolumab - Statistical Analyses 
 
Endpoint 
Statistical Analysis Methods 
Incidence of ADA to nivolumab 
Baseline ADA-positive participant is defined as a participant who has an 
ADA-detected sample at baseline.a,b ADA-positive participant is a 
participant with at least 1 ADA-positive sample relative to baseline after 
initiation of the treatment 
Frequency distribution of 
baseline ADA-positive 
participants and ADA-positive 
participants after initiation of the 
treatment 
Abbreviations: ADA, anti-drug antibody; SAP, statistical analysis plan. 
a Baseline sample is the last sample before initiation of the treatment. 
b Details of the immunogenicity data analysis, including ADA titers, will be provided in the SAP. 


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10.4.4.3 
Biomarker Analysis 
Statistical analyses related to biomarkers endpoints are summarized in Table 10.4.4.3-1. 
Table 10.4.4.3-1: 
Biomarkers - Statistical Analyses 
 
Endpoint 
Statistical Analysis Methods 
Summary measures of change (or % change) from baseline in various 
biomarkers in the tumor and peripheral blood 
Association measures of biomarker at baseline or of biomarker changes with 
tumor response measures 
• 
Summary statistics/plots of 
biomarkers by planned study 
day and dose in each arm 
• 
Plots and summaries of 
select baseline biomarkers or 
biomarker changes by tumor 
response outcome 
 
10.4.4.4 
Clinical Outcomes Assessments 
As exploratory endpoints, analyses of EORTC QLQ-C30 and FACIT GP5 data will be described 
in the clinical trial statistical analyses plan. COA analyses will be performed by cohort and total 
in all treated participants who have had an assessment at baseline (Day 1, assessment prior to 
administration of drug on day of first dose) and at least 1 subsequent assessment while on 
treatment. Questionnaire completion rate, defined as the proportion of questionnaires actually 
received out of the expected number, will be calculated and summarized at each assessment point. 
10.4.5 
Other Safety Analysis 
10.4.5.1 
Continuous Safety Monitoring 
A Bayesian continuous monitoring framework will be utilized in the randomized part of the study 
to monitor for toxicity for a safety-evaluation period of 6 weeks of treatment and detect safety 
signals that may lead to changes in study conduct.68 In addition to the study DMC, the ongoing 
evaluation of the accumulating safety data by the Sponsor will include quantitative safety 
monitoring based on pre-specified criteria and will be applied to Arm 2b or Arm 2c (see Table 
10.4.5.1-1). If the specified safety boundary (number of AEs) is exceeded, the DMC may be 
contacted for additional evaluations of the safety and risk-benefit as needed. 
For this type of monitoring, the proportion of DLT is used to provide formal monitoring 
boundaries. These boundaries were established using a prior distribution of Beta (0.67, 1.33), 
which is a weak informative prior reflecting the target DLT % used in escalation). The posterior 
distribution at any time point is Beta(0.67 + n, 1.33 + [m-n]), where n is the number of participants 
observed with DLT, and m is the total number of safety-evaluable participants. 
The monitoring function for toxicity is defined as the posterior probability of DLT rate > 33% 
cumulative data) > 0.85. This criterion implies that there is a greater than 85% predictive 
probability that the toxicity rate is larger than 33%. It will be applied after at least 18 randomized 
participants across arms are safety-evaluable and can be performed on a continuous basis 
afterwards. The resulting boundaries are presented below. 


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If anytime during the randomized phase (first 60 participants in Arm 2b and Arm 2c), this DLT 
proportion reaches the pre-specified threshold for toxicity in Arm 2b or Arm 2c, then, taking into 
account all available safety information, additional evaluation will be conducted including 
triggering adhoc DMC meeting to allow a complete by treatment arm safety assessment and risk 
benefit evaluation. Therefore, this criterion implies that the study may terminate enrollment toward 
an arm when there is greater than 85% probability that the toxicity rate is over 33%, corresponding 
to a final boundary of 13 participants with DLT out of 30 evaluable participants in an arm. 
 
Table 10.4.5.1-1: 
Safety Continuous Monitoring Boundary for Arm 2b or Arm 2c 
 
Number of Safety-evaluable 
Participants (per Arm)a 
Toxicity Boundary (# Evaluable Participants with Event) for > 85% 
Probability of DLT > 33% 
5-7 
4 
8-9 
5 
10-12 
6 
13-15 
7 
16-17 
8 
18-20 
9 
21-23 
10 
24-25 
11 
26-28 
12 
29-31 
13 
Abbreviation: DLT, dose-limiting toxicity. 
a Additional thresholds for the monitoring of > 30 participants per arm if needed will be calculated by the statistician. 
 
10.4.6 
Other Analyses 
Other analyses may include analyses of assessments, which are not defined as endpoints, that need 
to be prespecified and not necessarily be reported in the clinical study report, such as, but not 
limited to additional biomarkers, population PK, and health technology assessment-related 
endpoints. 
PK and biomarker exploratory analyses will be described in the SAP finalized before database 
lock. The population PK analysis and pharmacodynamic analyses will be presented separately 
from the main clinical study report. 
Analysis related to the impact of SARS-CoV-2 serologic status on participants receiving study 
intervention will be described in the SAP. 


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10.5 
Interim Analyses 
There is no plan for an official interim analysis of efficacy in Part 2 with any adjustment of the 
type 1 error rate. 


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11 
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31 Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD- 
1 antibody in cancer. N Engl J Med 2012;366:2443-54. 
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metastatic castration-resistant prostate cancer: multicohort, open-label Phase II KEYNOTE- 
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34 Fizazi K, Gonzalez Mella P, Castellan D, et al. CheckMate 9KD arm B final analysis: efficacy 
and safety of nivolumab plus docetaxel for chemotherapy-naive metastatic castration-resistant 
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increased after ipilimumab therapy in patients with prostate cancer. Nat Med 2017;23:551-5. 
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castration-resistant prostate cancer: preliminary analysis of patients in the CheckMate 650 trial. 
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38 Selby MJ, Engelhardt JJ, Quigley M, et al. Anti-CTLA-4 antibodies of IgG2a isotype enhance 
antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res 
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39 Simpson TR, Li F, Montalvo-Ortiz W, et al. Fc-dependent depletion of tumor-infiltrating 
regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp 
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40 Waight JD, Chand D, Dietrich S, et al. Selective FcγR co-engagement on APCs modulates the 
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43 BMS-986218: Investigator brochure version 05. Bristol-Myers Squibb Company; 2021. 
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45 Nivolumab (BMS-936558): Investigator brochure version 20. Bristol-Myers Squibb 
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2008;26:242-5. 
47 Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus placebo plus 
prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer 
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controlled phase 3 study. Lancet Oncol 2015;16:152-60. 
48 Westgeest HM, Kuppen MCP, van den Eertwegh AJM, et al. The effects of new life- 
prolonging drugs for metastatic castration-resistant prostate cancer (mCRPC) patients in a real- 
world population. Prostate Cancer Prostatic Dis. In press 2021. 
49 Mezynski J, Pezaro C, Bianchini D, et al. Antitumour activity of docetaxel following treatment 
with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Ann Oncol 
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50 Azad AA, Leibowitz-Amit R, Eigl BJ, et al. A retrospective, Canadian multi-center study 
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51 Yuan Y, Hess KR, Hilsenbeck SG, et al. Bayesian optimal interval design: a simple and well- 
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52 National Comprehensive Cancer Network. NCCN Guidelines. Prostate Cancer Version 
2.2021. 
53 Schadendorf D, Wolchok JD, Hodi FS, et al. Efficacy and safety outcomes in patients with 
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54 Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase 
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55 Brahmer J, Horn L, Jackman D, et al. Five-year follow-up from the CA209-003 study of 
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57 Spigel DR, McLeod M, Hussein MA, et al. Randomized results of continuous vs 1-year fixed- 
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58  Opdivo. US Prescribing Information. Bristol-Myers Squibb; 2020. 
59 Opdivo. Annex I Summary of Product Characteristics. Bristol-Myers Squibb Company; 2020. 
60 Shen YC, Chiang PH, Luo HL, et al. Determine of the optimal number of cycles of docetaxel 
in the treatment of metastatic castration-resistant prostate cancer. Kaohsiung J Med Sci 
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61 Pond GR, Armstrong AJ, Wood BA, et al. Evaluating the value of number of cycles of 
docetaxel and prednisone in men with metastatic castration-resistant prostate cancer. Eur Urol 
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62 Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: 
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12 
APPENDICES 


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APPENDIX 1 
ABBREVIATIONS AND TRADEMARKS 
 
Term 
Definition 
1L 
first line 
Ab 
antibody 
ADA 
anti-drug antibody 
ADT 
androgen deprivation therapy 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
AJCC 
American Joint Committee on Cancer 
ALK 
anaplastic lymphoma kinase 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
APC 
antigen-presenting cell 
AR 
androgen receptor 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase 
AUC(TAU) 
area under the concentration-time curve in 1 dosing interval 
AxMP 
auxiliary medicinal product 
BICR 
blinded independent central review 
BLRM 
basic linear ranking model 
BMI 
body mass index 
BMS 
Bristol-Myers Squibb 
BOIN 
Bayesian Optimal Interval 
BOR 
best overall response 
BP 
blood pressure 
BUN 
blood urea nitrogen 
Cavgss 
average serum concentration at steady state 
CD 
cluster of differentiation 
Ceoi 
end of infusion concentration 
cHL 
classical Hodgkin lymphoma 
CHO 
Chinese hamster ovary 
CI 
confidence interval 
CL 
clearance 


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Term 
Definition 
CLss 
geometric mean steady-state clearance 
cm 
centimeter 
Cmax 
maximum observed concentration 
CMO 
cystoid macular oedema 
CNS 
central nervous system 
COA 
clinical outcomes assessment 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CR 
complete response 
CRC 
colorectal cancer 
CRF 
case report form, paper or electronic 
CRPC 
castration-resistant prostate cancer 
CT 
computed tomography 
CTCAE v5 
Common Terminology Criteria for Adverse Events version 5 
ctDNA 
circulating tumor deoxyribonucleic acid 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
CTLA-4-NF 
cytotoxic T-lymphocyte-associated protein 4 non-fucosylated 
Ctrough 
trough-observed serum concentration 
CV 
coefficient of variation 
DCR 
disease control rate 
DDR 
DNA damage repair 
DILI 
drug-induced liver injury 
DLT 
dose-limiting toxicity 
DM 
Data Management 
DMC 
Data Monitoring Committee 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
DOR-PCWG3 
DOR per PCWG3 
DOR-PSA 
duration of PSA response 
DRESS 
drug reaction with eosinophilia and systemic symptoms 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 


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Term 
Definition 
eGFR 
estimated glomerular filtration rate 
EGFR 
epidermal growth factor receptor 
ELISA 
enzyme-linked immunosorbent assay 
EOI 
end of infusion 
EOT 
end of treatment 
EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer Quality of 
Life Questionnaire 
FACIT GP5 
Functional Assessment of Chronic Illness Therapy General Physical 
Item 5 
FACT-G 
Functional Assessment of Cancer Therapy - General 
Fc 
fragment crystallizable 
FcγR 
Fcγ receptor 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
FIH 
first-in-human 
fT3 
free T3 
fT4 
free T4 
g 
gram 
GBS 
Guillain-Barre Syndrome 
G-CSF 
granulocyte colony-stimulating factor 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GM-CSF 
granulocyte-macrophage colony-stimulating factor 
GnRH 
gonadotropin-releasing hormone 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCC 
hepatocellular carcinoma 
HCV 
hepatitis C virus 
hIgG1 
human immunoglobulin G1 
HIV 
human immunodeficiency virus 
hr 
hour 
HR 
hazard ratio 
HRD 
homologous recombination deficiency 
HRPC 
hormone-refractory prostate cancer 


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Term 
Definition 
HRR 
homologous recombination repair 
HuMAb 
human monoclonal antibody 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IgG 
immunoglobulin G 
IHC 
immunohistochemistry 
IL-6 
interleukin 6 
IMAE 
immune-mediated adverse events 
IMG 
immunogenicity 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
I-O 
immuno-oncology 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IV 
intravenous 
kg 
kilogram 
L 
liter 
LAM 
lactation amenorrhea method 
LDH 
lactate dehydrogenase 
mAb 
monoclonal antibody 
MAD 
maximum administered dose 
mCRPC 
metastatic castration-resistant prostate cancer 
mCSPC 
metastatic castration-sensitive prostate cancer 
mg 
milligram 
MG 
myasthenia gravis 
MID 
minimally important difference 
min 
minute 
mL 
milliliter 
MMR 
measles, mumps, rubella 
mOS 
median overall survival 


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Term 
Definition 
MRI 
magnetic resonance imaging 
mRNA 
messenger ribonucleic acid 
MTD 
maximum tolerated dose 
µg 
microgram 
N 
number of participants or observations 
NA 
not applicable 
NAT 
novel antiandrogen therapy 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NF 
non-fucosylated 
ng 
nanogram 
nmCRPC 
non-metastatic castration-resistance prostate cancer 
NSAID 
nonsteroidal anti-inflammatory drug 
NSCLC 
non-small cell lung cancer 
ORR 
objective response rate 
ORR-PCWG3 
ORR per PCWG3 
OS 
overall survival 
PARP 
poly ADP ribose polymerase 
PC 
prostate cancer 
PCR 
polymerase chain reaction 
PCWG3 
Prostate Cancer Working Group 3 
PD 
progressive disease 
PD-1 
programmed death-1 
PD-L1 
programmed death-ligand 1 
PD-L2 
programmed death-ligand 2 
PE 
physical examination 
PFS 
progression-free survival 
PID 
patient identification number 
PK 
pharmacokinetic 
PPK 
population PK 
PR 
partial response 
PSA 
prostate-specific antigen 
PSA-RR 
PSA response rate 


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Term 
Definition 
PSMA 
prostate-specific membrane antigen 
Q2W 
every 2 weeks 
Q3W 
every 3 weeks 
Q4W 
every 4 weeks 
qPCR 
quantitative polymerase chain reaction 
QW 
every week 
R&D 
Research and Development 
RANKL 
receptor activator of nuclear factor kappa-B ligand 
RCC 
renal cell carcinoma 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RNA 
ribonucleic acid 
RNAseq 
RNA sequencing 
rPD 
radiographic progressive disease 
rPFS 
radiographic PFS 
RT-PCR 
reverse transcriptase polymerase chain reaction 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SCCHN 
squamous cell carcinoma of the head and neck 
SCLC 
small cell lung cancer 
SD 
stable disease 
SJS 
Stevens-Johnson syndrome 
SmPC 
Summary of Product Characteristics 
SMT 
Safety Management Team 
SNP 
single nucleotide polymorphism 
SOC 
standard of care 
SUSAR 
suspected, unexpected serious adverse reaction 
t1/2 
geometric mean elimination half-life 
T3 
triiodothyronine 
T4 
thyroxine 
TB/T.bili 
total bilirubin 
TCR 
T-cell repertoire 
TEN 
toxic epidermal necrolysis 


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Term 
Definition 
TMB 
tumor mutational burden 
TRAE 
treatment-related adverse event 
Treg 
regulatory T-cell 
TSH 
thyroid-stimulating hormone 
TT-SSE 
time to first symptomatic skeletal event 
TT-SST 
time to initiation of subsequent systemic therapy 
TTP-PSA 
time to PSA progression 
TTR 
time to response 
TTR-PCWG3 
TTR per PCWG3 
TTR-PSA 
time to PSA response 
ULN 
upper limit of normal 
US 
United States 
USPI 
US Prescribing Information 
Vss 
geometric mean volume of distribution at steady state 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 
WWPS 
Worldwide Patient Safety 
Y/N 
yes/no 


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APPENDIX 2 
STUDY GOVERNANCE CONSIDERATIONS 
The terms “participant” and “subject” refer to a person who has consented to participate in the 
clinical research study. Typically, the term “participant” is used in the protocol and the term 
“subject” is used in the Case Report Form (CRF). 
REGULATORY AND ETHICAL CONSIDERATIONS 
This study will be conducted in accordance with: 
• Consensus ethical principles derived from international guidelines, including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines 
• Applicable laws, regulations, and requirements 
 
The study will be conducted in compliance with the protocol. The protocol, any 
revisions/amendments, and the participant informed consent form (ICF) will receive 
approval/favorable  opinion  by  Institutional  Review  Board/Independent  Ethics 
Committee (IRB/IEC), and regulatory authorities according to applicable regulations prior to 
initiation of the study. 
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation) that is likely to affect, 
to a significant degree, one or more of the following: (1) the rights, physical safety or mental 
integrity of one or more participants; (2) the scientific value of the clinical trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP regulation(s) or 
trial protocol(s). 
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks. 
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE 
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, Investigator’s Brochure, product labeling information, ICF, 
participant recruitment materials (eg, advertisements), and any other written information to be 
provided to participants. 
The investigator, Sponsor, or designee should provide the IRB/IEC with reports, updates, and other 
information (eg, expedited safety reports, amendments, administrative letters) annually, or more 
frequently, in accordance with regulatory requirements or institution procedures. 


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The investigator is responsible for providing oversight of the conduct of the study at the site and 
adherence to requirements of the following where applicable: 
• ICH guidelines, 
• United States Code of Federal Regulations, Title 21, Part 50 (21CFR50) 
• European Union Directive 2001/20/EC; or 
• European Regulation 536/2014 for clinical studies (if applicable), 
• European Medical Device Regulation 2017/745 for clinical device research (if applicable), 
• the IRB/IEC 
• and all other applicable local regulations. 
 
COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS 
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and, if 
applicable, also by the local Health Authority), except where necessary to eliminate an immediate 
hazard(s) to study participants. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s), the deviation or change will be submitted as soon 
as possible to: 
• IRB/IEC 
• Regulatory authority(ies), if applicable by local regulations (per national requirements) 
 
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and, if applicable, also by the local Health Authority, must be sent to Bristol-Myers 
Squibb (BMS). 
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the ICF must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from participants 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new participants prior to enrollment. 
FINANCIAL DISCLOSURE 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information, in accordance with regulations, to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate Health Authorities. Investigators 
are responsible for providing information on financial interests during the course of the study and 
for 1 year after completion of the study. 


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INFORMED CONSENT PROCESS 
Investigators must ensure that participants are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which they volunteer to 
participate. 
The Sponsor or designee will provide the investigator with an appropriate sample ICF, which will 
include all elements required by the ICH GCP, and applicable regulatory requirements. The sample 
ICF will adhere to the ethical principles that have their origin in the Declaration of Helsinki. 
The investigator or his/her representative must: 
• Obtain IRB/IEC written approval/favorable opinion of the written ICF and any other 
information to be provided to the participant prior to the beginning of the study and after any 
revisions are completed for new information. 
• Provide a copy of the ICF and written information about the study in the language in which 
the participant is proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 
• Explain the nature of the study to the participant and answer all questions regarding the study. 
• Inform participant that his/her participation is voluntary. Participant will be required to sign a 
statement of informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, 
where applicable, and the IRB/IEC or study center. 
• Allow time necessary for participant to inquire about the details of the study. 
 
Obtain an ICF signed and personally dated by participant and by the person who conducted the 
informed consent discussion. 
• Include a statement in participant’s medical record that written informed consent was obtained 
before participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
• Re-consent participant to the most current version of the ICF(s) during his/her participation in 
the study, as applicable. 
 
Revise the ICF whenever important new information becomes available that is relevant to the 
participant’s consent. The investigator, or a person designated by the investigator, should fully 
inform the participant of all pertinent aspects of the study and of any new information relevant to 
the participant’s willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules applicable to regulatory requirements, the participant’s signed 
ICF, and, in the US, the participant’s signed HIPAA Authorization. 
The ICF must also include a statement that BMS and local and foreign regulatory authorities have 
direct access to participant records. 


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The rights, safety, and well-being of the study participants are the most important considerations 
and should prevail over interests of science and society. 
SOURCE DOCUMENTS 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be explained. 
• The investigator may need to request previous medical records or transfer records, depending 
on the study. Also, current medical records must be available. 
• Definitions of what constitutes source data can be found in local site guidelines. 
 
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are handwritten on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical records/electronic health 
records, adverse event (AE) tracking/reporting, protocol-required assessments, and/or drug 
accountability records. 
When paper records from such systems are used in place of an electronic format to perform 
regulated activities, such paper records should be certified copies. A certified copy consists of a 
copy of original information that has been verified, as indicated by a dated signature, as an exact 
copy having all of the same attributes and information as the original. 
STUDY INTERVENTION RECORDS 
Records for study intervention (whether supplied by BMS, its vendors, or the site) must 
substantiate study intervention integrity and traceability from receipt, preparation, administration, 
and through destruction or return. Records must be made available for review at the request of 
BMS/designee or a Health Authority. 


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If 
Then 
Supplied by BMS (or its vendors): 
Records or logs must comply with applicable 
regulations and guidelines and should include: 
• amount received and placed in storage area 
• amount currently in storage area 
• label identification number or batch number 
• amount dispensed to and returned by each 
participant, including unique participant 
identifiers 
• amount transferred to another area/site for 
dispensing or storage 
• nonstudy disposition (eg, lost, wasted) 
• amount destroyed at study site, if applicable 
• amount returned to BMS 
• retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 
• dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form 
Sourced by site and not supplied by BMS 
or its vendors (examples include IP 
sourced from 
the 
sites stock 
or 
commercial supply or a specialty 
pharmacy) 
The investigator or designee accepts responsibility 
for documenting traceability and study treatment 
integrity in accordance with requirements applicable 
under 
law 
and 
the 
standard 
operating 
procedures/standards of the sourcing pharmacy 
BMS or its designee will provide forms to facilitate inventory control if the investigational site 
does not have an established system that meets these requirements. 
 
CASE REPORT FORMS 
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents, or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study. 
For sites using the Sponsor or designee electronic data capture (EDC) tool, eCRFs will be prepared 
for all data collection fields except for fields specific to SAEs and pregnancy, which will be 


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reported on the electronic SAE form and Pregnancy Surveillance Form, respectively. If the 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left blank 
only in those circumstances permitted by study-specific CRF completion guidelines provided by 
the Sponsor or designee. 
The confidentiality of records that could identify participants must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). 
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF and SAE/pregnancy CRFs must be promptly reviewed, signed, and dated by 
the investigator or qualified physician who is a sub-investigator and who is delegated this task on 
the Delegation of Authority Form. Sub-investigators in Japan may not be delegated the CRF 
approval task. For eCRFs, review and approval/signature is completed electronically through the 
BMS EDC tool. The investigator must retain a copy of the CRFs, including records of the changes 
and corrections. 
Each individual electronically signing eCRFs must meet Sponsor or designee training 
requirements and must only access the BMS EDC tool using the unique user account provided by 
the Sponsor or designee. User accounts are not to be shared or reassigned to other individuals. 
MONITORING 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site, they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. 
Certain CRF pages and/or electronic files may serve as the source documents. 
In addition, the study may be evaluated by the Sponsor or designee internal auditors and 
government inspectors who must be allowed access to CRFs, source documents, other study files, 
and study facilities. BMS audit reports will be kept confidential. 
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities 
and promptly forward copies of inspection reports to the Sponsor or designee. 
RECORDS RETENTION 
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or its designee, whichever is longer. 


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The investigator (or head of the study site in Japan) must contact BMS prior to destroying any 
records associated with the study. 
BMS or its designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed. 
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed-upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or its designee. 
RETURN OF STUDY TREATMENT 
For this study, study treatments (those supplied by BMS or a vendor or sourced by the 
investigator), such as partially used study treatment containers, vials, and syringes, may be 
destroyed on site. 
 
If 
Then 
Study treatments supplied by BMS (including 
its vendors) 
Any unused study interventions supplied by 
BMS can only be destroyed after being 
inspected and reconciled by the responsible 
Study Monitor, unless study treatments 
containers must be immediately destroyed as 
required for safety, or to meet local regulations 
(eg, cytotoxics or biologics). 
Partially used study interventions and/or 
empty containers may be destroyed after 
proper reconciliation and documentation. But 
unused IMP must be reconciled by site 
monitor/Clinical Research Associate prior to 
destruction. 
If study treatments will be returned, the return 
will be arranged by the responsible Study 
Monitor. 
Study treatments sourced by site, not supplied 
by BMS (or its vendors; eg, study treatments 
sourced from the site’s stock or commercial 
supply or a specialty pharmacy) 
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures. 


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It is the investigator’s or designee’s responsibility to arrange for disposal of study interventions, 
provided that procedures for proper disposal have been established according to applicable federal, 
state, local, and institutional guidelines and procedures, and provided that appropriate records of 
disposal are kept. The following minimal standards must be met: 
• On-site disposal practices must not expose humans to risks from the drug. 
• On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances. 
• Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s standard operating procedures and a copy provided to BMS upon request. 
• Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal (eg, incinerator, licensed sanitary landfill, or licensed waste-disposal 
vendor) must be documented. 
• Accountability and disposal records are complete, up-to-date, and available for the Study 
Monitor to review throughout the clinical trial period. 
 
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers. 
If conditions for destruction cannot be met, the responsible Study Monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of non-study 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee. 
STUDY AND SITE START AND CLOSURE 
The Sponsor/designee reserves the right to close the study site or to terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies have 
been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include, but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local Health Authorities, the Sponsor’s procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study intervention development 
 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 


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regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
DISSEMINATION OF CLINICAL STUDY DATA 
In order to benefit potential study participants, patients, healthcare providers and researchers, and 
to help BMS honor its commitments to study participants, BMS will make information about 
clinical research studies and a summary of their results available to the public as per regulatory 
and BMS requirements. BMS will post study information on local, national or regional databases 
in compliance with national and international standards for disclosure. BMS may also voluntarily 
disclose information to applicable databases. 
CLINICAL STUDY REPORT 
A Signatory Investigator must be selected to sign the Clinical Study Report (CSR). 
For each CSR related to this protocol, the following criteria will be used to select the Signatory 
Investigator: 
• Participant recruitment 
• Involvement in trial design and interpretation 
 
SCIENTIFIC PUBLICATIONS 
The data collected during this study are confidential and proprietary to the Sponsor or designee. 
Any publications or abstracts arising from this study must adhere to the publication requirements 
set forth in the Clinical Trial Agreement (CTAg) governing [study site or investigator] 
participation in the study. These requirements include, but are not limited to, submitting proposed 
publications to the Sponsor or designee at the earliest practicable time prior to submission or 
presentation and otherwise within the time period set forth in the CTAg. 
Scientific publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
Principal Investigator, sub-investigator, or any other member of the study staff without the prior 
written consent of the Sponsor. 
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE, www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship: 
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable participants with quality data), analysis, or interpretation of data for the 
work (eg, problem solving, advice, evaluation, insights and conclusion); AND 
2) Drafting the work or revising it critically for important intellectual content; AND 
3) Final approval of the version to be published; AND 


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4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved. 
 
Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Sub-investigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered. 
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work. 
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions. 


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APPENDIX 3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING 
ADVERSE EVENTS 
 
Adverse Event Definition: 
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a 
pre-existing medical condition in a clinical investigation participant administered study 
treatment that does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study treatment, whether or 
not considered related to the study treatment. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, electrocardiograms, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically significant 
in the medical and scientific judgment of the investigator. Note that abnormal lab tests or 
other safety assessments should only be reported as AEs if the final diagnosis is not 
available. Once the final diagnosis is known, the reported term should be updated to be the 
diagnosis. 
• Exacerbation of a chronic or intermittent pre-existing condition, including either an increase 
in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration, even though 
it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose, as a verbatim term (as reported by the investigator), 
should not be reported as an AE/serious adverse event (SAE) unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae and should specify “intentional overdose” as the verbatim 
term. 
Events NOT Meeting the AE Definition 
• Medical or surgical procedure (eg, endoscopy, appendectomy); the condition that leads to 
the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
DEFINITION OF SAE 
If an event is not an AE per definition above, then it cannot be an SAE, even if serious conditions 
are met. 


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


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Pregnancy and DILI must follow the same transmission timing and processes to BMS as used for 
SAEs. (See Section 9.2.5 for reporting pregnancies.) 
EVALUATING AES AND SAES 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration, 
will be considered and investigated. 
• The investigator will also consult the Investigator’s Brochure and/or product information for 
marketed products in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that 
the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor. 
• The investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
• Assessment of Intensity 
For the reporting of all AEs, including intensity or severity, on case report forms, please follow 
the definitions in National Cancer Institute Common Terminology Criteria for Adverse Events 
version 5 (NCI CTCAE v5). 
 
Follow-up of AEs and SAEs 
If only limited information is initially available, follow-up reports are required. 
(Note: Follow-up SAE reports must include the same investigator term[s] initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study treatment or if new 
information becomes available, the SAE report must be updated and submitted within 24 hours 
to BMS (or designee) using the same procedure used for transmitting the initial SAE report. 
All SAEs must be followed to resolution or stabilization. 


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REPORTING OF SAES TO SPONSOR OR DESIGNEE 
 
• SAEs, whether related or not related to study treatment, and pregnancies must be reported 
to BMS (or designee) immediately within 24 hours of awareness of the event. 
• SAEs must be recorded on the SAE Report Form. 
− The required method for SAE data reporting is through the electronic case report 
form (eCRF). 
− The paper SAE Report Form is intended only as a back-up option when the electronic 
data capture system is unavailable/not functioning for transmission of the eCRF to BMS 
(or designee). 
♦ In this case, the paper form is transmitted via email or confirmed facsimile 
transmission. 
♦ When paper forms are used, the original paper forms are to remain on site. 
• Pregnancies must be recorded on paper Pregnancy Surveillance Forms and transmitted via 
email or confirmed facsimile transmission. 
SAE Email Address: 
SAE Facsimile Number: Will be provided by local site monitor. 
SAE Telephone Contact (required for SAE and pregnancy reporting): Will be provided by local 
site monitor. 


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APPENDIX 4 
WOMEN OF CHILDBEARING POTENTIAL OF MALE 
PARTNERS 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 
One of the highly effective methods of contraception listed below is required during study duration 
and until the end of relevant systemic exposure, defined as 3 months after the end of study 
treatment. Less than highly effective contraception methods are not acceptable. 
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 


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• Intrauterine device. 
• Intrauterine hormone-releasing system (IUS). (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol.)b,c 
• Bilateral tubal occlusion. 
• Vasectomized partner 
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
• Sexual abstinence. 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
• Continuous abstinence must begin at least 30 days prior to initiation of study therapy. 
• It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
• WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 
• Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participant chooses to forego complete abstinence. 
• 
Periodic abstinence (including, but not limited to, calendar, symptothermal, postovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea 
method (LAM) are not acceptable methods of contraception for this study. 
NOTES: 
a Typical use failure rates may differ from failure rates when contraceptive methods are used consistently and 
correctly. Use should be consistent with local regulations regarding the use of contraceptive methods for 
participants in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the 
efficacy of the contraceptive method. Hormonal contraception is permissible only when there is sufficient 
evidence that the IMP and other study medications will not alter hormonal exposures such that contraception 
would be ineffective or result in increased exposures that could be potentially hazardous. In this case, alternative 
methods of contraception should be utilized. For information specific to this study regarding permissibility of 
hormonal contraception, refer to Sections 6.1 INCLUSION CRITERIA and 7.7.1 PROHIBITED AND/OR 
RESTRICTED TREATMENTS of the protocol. 
c IUSs are acceptable methods of contraception in the absence of definitive drug interaction studies when hormone 
exposures from intrauterine devices do not alter contraception effectiveness. For information specific to this 
study regarding permissibility of hormonal contraception, refer to Sections 6.1 INCLUSION CRITERIA and 
7.7.1 PROHIBITED AND/OR RESTRICTED TREATMENTS of the protocol. 


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Less Than Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of > 1% per year when used consistently and correctly. 
• Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously. 
• Diaphragm with spermicide. 
• Cervical cap with spermicide. 
• Vaginal sponge with spermicide. 
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action. (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited.) 
Unacceptable Methods of Contraception 
• Periodic abstinence (calendar, symptothermal, postovulation methods). 
• Withdrawal (coitus interruptus). 
• Spermicide only. 
• LAM. 
 
COLLECTION OF PREGNANCY INFORMATION 
Guidance for collection of pregnancy information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and Appendix 3. 


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APPENDIX 5 
PROSTATE CANCER WORKING GROUP 3 (PCWG3) 
GUIDELINES 
1 
EVALUATION OF LESIONS 
Bone lesions should be evaluated with Technetium-99m based radionuclide bone scan as per 
PCWG3.1 
At baseline, soft tissue lesions/lymph nodes will be categorized as measurable or non-measurable 
as follows. 
1.1 
Measurable 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ≥ 2x slice thickness if 
greater than 5mm. 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be ≥ 15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm). 
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis ≥ 10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed. 
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions. 
1.2 
Non-Measurable 
All other soft tissue lesions are considered non-measurable, including small lesions (longest 
diameter < 10mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques. 
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions. 


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1.3 
Special considerations regarding bone lesions 
• Bone lesions will be assessed with Technetium-99m based radionuclide bone scans as per 
PCWG3. 
1.4 
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions 
When more than one measurable lesion is present at baseline all lesions up to a maximum of 
20 lesions total (and a maximum of 5 lesions per organ system) representative of all involved 
organs should be identified as target lesions and will be recorded and measured at baseline. 
Note: A maximum of 5 lesions can be selected per organ system. For example, a maximum of 
5 lung lesions can be selected. A maximum of 5 lymph nodes can be selected at baseline, as the 
lymphatic system is considered one organ. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Pelvic lymph nodes and extrapelvic 
lymph nodes (retroperitoneal, mediastinal, thoracic and other) may be reported separately, per 
PCWG3. Measurements are not required and these lesions should be followed as ‘present’, 
‘absent’, or in rare cases ‘unequivocal progression’ (more details to follow). In addition, it is 
possible to record multiple non-target lesions involving the same organ as a single item on the case 
record form (e.g., ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver metastases’). 
2 
RESPONSE CRITERIA 
2.1 
Evaluation of Target Lesions 
• Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm. 
• Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters. 
• Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression). 
• Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 


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• Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed 
as either fully resolved or too small to measure (due to missing or poor quality images), and 
the sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above. 
 
2.1.1 
Special Notes on the Assessment of Target Lesions 
2.1.1.1 
Lymph nodes 
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target lesions, 
the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a normal 
lymph node is defined as having a short axis of < 10 mm. Case report forms or other data collection 
methods may therefore be designed to have target nodal lesions recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions. 
2.1.1.2 
Target lesions that become ‘too small to measure’ 
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (e.g., 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned 
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 
default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm. 
2.1.1.3 
Lesions that split or coalesce on treatment 
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’. 


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2.2 
Evaluation of Non-Target Lesions 
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need 
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol. 
• Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10mm short axis). 
• Non-CR/Non-PD: Persistence of one or more non-target lesion(s) 
• Progressive Disease (PD): Unequivocal progression (see below) of existing non-target 
lesions. 
 
2.2.1 
Special Notes on Assessment of Progression of Non-Target Disease 
The concept of progression of non-target disease requires additional explanation as follows: 
2.2.1.1 
When the patient also has measurable disease 
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy (see examples in Appendix 2 and further details below). A modest 
‘increase’ in the size of one or more non-target lesions is usually not sufficient to qualify for 
unequivocal progression status. Pleural effusions, pericardial effusions and ascites will not be 
followed as target or non-target lesions and will not contribute to response or progression. The 
designation of overall progression solely on the basis of change in non-target disease in the face 
of SD or PR of target disease will therefore be extremely rare. 
2.2.1.2 
When the patient has only non-measurable disease 
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
disease burden. Because worsening in non-target disease cannot be easily quantified (by definition: 
if all lesions are truly non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on the change 
in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: i.e., an increase in tumor burden representing an additional 
73% increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in lymphangitic disease from localized to widespread, or may be 
described as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the 
patient should be considered to have had overall PD at that point. While it would be ideal to have 
objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore the increase must be substantial. 


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2.2.2 
New Lesions 
New bone lesions 
New bone lesions should be evaluated as per PCWG3 criteria. Bone lesions will be assessed by 
radionuclide bone scan only. Radiographic progression on bone scan is defined by the following 
criteria: 
• At least 2 new lesions on the first post-treatment bone scan, confirmed on the next scan 
(performed at least 6 weeks later) AND with at least two additional lesions as compared to the 
first post-treatment bone scan. Date of progression is then the date of first post-treatment scan, 
• For scans after the first post-treatment scan, at least 2 new lesions relative to the first post- 
treatment scan AND confirmed on a subsequent scan (performed at least 6 weeks later). Date 
of progression is the date of the scan that first documents at least 2 new lesions relative to the 
first post-treatment scan. 
 
New soft tissue lesions 
The appearance of new malignant soft tissue lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging modality 
or findings thought to represent something other than tumor. This is particularly important when 
the patient’s baseline lesions show partial or complete response. For example, necrosis of a liver 
lesion may be reported on a CT scan report as a ‘new’ cystic lesion, which it is not. 
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new fluid 
collection is seen on a post-baseline imaging exam, a comment may be made, but the appearance 
of a new fluid collection alone should not result in an assessment of Progressive Disease (PD). A 
lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD). 
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. 
2.3 
Response Assessment 
2.3.1 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the study treatment until 
disease progression per PCWG3 criteria, or the last response recorded, taking into account any 
requirement for confirmation and censoring rules regarding subsequent therapy. The patient’s best 


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overall response assignment will depend on the findings of both target and non-target disease and 
will also take into consideration the appearance of new lesions. Furthermore, depending on the 
nature of the study and the protocol requirements, it may also require confirmatory measurement. 
2.3.2 
Time Point Response 
At each protocol specified time point, a response assessment occurs. Table 2.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) disease 
only, Table 2.3.2-2 is to be used. 
 
Table 2.3.2-1: 
Time Point Response: Patients With Target (± Non-Target) Disease 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable 
 
 
Table 2.3.2-2: 
Time Point Response: Patients with Non-target Disease Only 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PDa 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response, PD = progressive disease and NE = inevaluable 
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised. 


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2.3.3 
Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point of 
≥ 4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as in 
Table 2.3.3-1. When SD is believed to be best response, it must meet the protocol specified 
minimum time from the date of first treatment or randomization date. 
For example, if the first scheduled follow-up imaging visit is Week 6 (± 7 days) for a particular 
protocol, a Best Response of SD can only be made after the subject is on-study for a minimum of 
6 weeks (42 days) minus 7 days, for an absolute minimum time on-study of 35 days from the 
reference start date (reference date is considered Day 1 on study). If the subject is not on-study 
for at least this amount of time, any tumor assessment indicating stable disease before this time 
period will have a Best Response of NE unless PD is identified. 
Special note on response assessment: When nodal disease is included in the sum of target lesions 
and the nodes decrease to ‘normal’ size (< 10 mm), they may still have a measurement reported 
on scans. This measurement should be recorded even though the nodes are normal in order not to 
overstate progression should it be based on increase in size of the nodes. As noted earlier, this 
means that patients with CR may not have a total sum of ‘zero’ on the case report form (CRF). 
 
Table 2.3.3-1: 
Best Overall Response (Confirmation of CR&PR Required) 
Overall Response 
First Time Point 
Overall Response 
Subsequent Time Point 
BEST Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD OR PRa 
CR 
SD 
SD provided minimum criteria for SD duration met, otherwise, 
PD 
CR 
PD 
SD provided minimum criteria for SD duration met, otherwise, 
PD 
CR 
NE 
SD provided minimum criteria for SD duration met, otherwise, 
NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration met, otherwise, 
PD 
PR 
NE 
SD provided minimum criteria for SD duration met, otherwise, 
NE 
NE 
NE 
NE 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and 
NE = inevaluable 


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a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR. 
 
 
2.3.4 
Confirmation Scans 
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR 
(eg, CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of 
a previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation. 
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease. 
REFERENCES 
1 Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated 
Recommendations From the Prostate Cancer Clinical Trials Working Group 3. Scher et al. J 
Clin Oncol 2016, 34(12):1402-1418. 


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APPENDIX 6 
ECOG PERFORMANCE STATUS 
 
ECOG PERFORMANCE STATUSa 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
a Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, and Carbone PP. Toxicity and Response 
Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649-655 


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APPENDIX 7 
COUNTRY SPECIFIC REQUIREMENTS/DIFFERENCES 
 
 
Original Language 
Country-specific Language or Differences 
Mexico, Greece 
Section 9.4.4 Clinical Safety Laboratory 
Assessments, Table 9.4.4-1: Clinical 
Laboratory Assessments 
Add “HIV” to the list of laboratory tests 
 
 
*HIV testing for entry into clinical trials is not a requirement in 
France, Spain, Italy, UK, NL, Finland, Denmark, Sweden, USA 
Mexico, Greece 
Section 6.2 Exclusion Criteria, 
Exclusion criterion: 1) l 
“Known human immunodeficiency virus (HIV) positive with an AIDS 
defining opportunistic infection within the last year, or a current CD4 
count < 350 cells/μL. Participants with HIV are eligible if: 
i) 
They have received antiretroviral therapy (ART) for at least 
4 weeks prior to randomization/treatment assignment as clinical 
indicated while enrolled on study (see Section 7.7.2 for CYP3A4 
restriction) 
ii) They continue on ART as clinically indicated while enrolled on 
study 
iii) CD4 counts and viral load are monitored per standard of care by a 
local health care provider” 
NOTE: Testing for HIV must be performed at sites where mandated 
locally. HIV positive participants must be excluded where mandated 
locally (see Appendix 7).” 
 
To be replaced with “Positive test for HIV.” 


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APPENDIX 8 
MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 5 
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. Noninflammatory etiologies should be considered and appropriately 
treated. 
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The oral 
equivalent of the recommended IV doses may be considered for ambulatory patients with 
low-grade toxicity. The lower bioavailability of oral corticosteroids should be taken into account 
when switching to the equivalent dose of oral corticosteroids. 
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
procedure, is recommended. 
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used. 


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APPENDIX 9 
BOIN DESIGN DETAILS AND OPERATING CHARACTERISTICS 
The Bayesian optimal interval (BOIN) design will be used to guide decisions on safety evaluation 
(including escalation or de-escalation) of BMS-986218 in combination with docetaxel and 
docetaxel and nivolumab in Parts 1A and Part 1B of the study.1,2 The BOIN design is implemented 
in a simple way similar to the traditional 3+3 design, but is more flexible and possesses superior 
operating characteristics that are comparable to those of the more complex model-based designs. 
The target toxicity rate for the selected tolerable dose (or maximum tolerated dose [MTD] per the 
standard escalation) is ϕ = 0.30 based on clinical rationale and known toxicity for docetaxel and 
of BMS-986218 in combination with nivolumab. The maximum sample size expected is 
12 participants (Part 1A) or 12 to 18 participants (Part 1B) assuming at least 2 dose levels. Treating 
patients in cohorts of approximate size 3, the BOIN design uses the following rule, optimized to 
minimize the probability of incorrect dose assignment, to guide decisions related to dose 
escalation/de-escalation: 
• if the observed DLT rate at the current dose is ≤ 0.236, it is considered safe to escalate the dose 
to the next higher dose level; 
• if the observed DLT rate at the current dose is > 0.359, it is recommended to de-escalate the 
dose to the next lower dose level; 
• otherwise, stay at the current dose and evaluate additional participants. 
 
In addition, if the current dose is the lowest dose and the rule indicates dose de-escalation, treat 
the new participants at the lowest dose unless the number of DLTs reaches the elimination 
boundary, at which point terminate the trial for safety. 
If the current dose is the highest dose and the rule indicates dose escalation, treat the new 
participants at the highest dose. 
 
For the purpose of overdose control, doses j and higher levels will be eliminated from further 
examination if Pr(pj> 0.30 | data) > 0.95 and at least 3 evaluable patients have been treated at dose 
level j, where pj is the true DLT rate of dose level j,j= 1,⋯, 3. This posterior probability is evaluated 
based on the beta-binomial model yj∣pj ∼ binomial(pj) with pj∼uniform(0,1), where yj is the 
number of patients experienced DLT at dose level j. When the lowest dose is eliminated, stop the 
trial for safety. The probability cutoff 0.95 is chosen to be consistent with the common practice 
that when the target DLT rate ≤ 1/6, a dose with 2/3 patients experienced DLT is eliminated. The 
above dose escalation/de-escalation and elimination rule can be equivalently presented in Table 1, 
which will be used to conduct the trial. 
Operating characteristics of the BOIN design are evaluated for three scenarios, assuming that up 
to 3 dose levels may be evaluated, and starting at Dose level 2 with the option to escalate to a 
higher dose, de-escalate to a lower dose level, or select current dose level as tolerable . These 
results are based on 1000 simulations using the BOIN software, with the added restriction to select 


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a dose with DLT rate below the upper limit (0.334) of the specified target DLT interval as selected 
tolerable dose.3 
Table 1: 
BOIN Design Operating Characteristics, with n <= 12 at a dose 
 
Scenario 
Dose 1 
Dose 2 
Dose 3 
N of Patients 
% Early Stop 
Scenario 1 
DLT Rate 
0.3 
0.40 
0.50 
% Selection 
39.1 
32.1 
10.8 
18 
% Pts treated 
29.4 
53.9 
16.7 
11.9 
Scenario 2 
DLT Rate 
0.13 
0.3 
0.45 
% Selection 
26.6 
47.6 
20.8 
5 
% Pts treated 
14.8 
59 
26.2 
12 
Scenario 3 
DLT Rate 
0.2 
0.25 
0.3 
% Selection 
15.6 
34.4 
46.9 
3.1 
% Pts treated 
10.2 
50.8 
39 
12 
The target DLT rate = 0.30 (0.236,0.359); assuming 3 dose levels, starting at dose level 2, and treating cohort of size 
3, total up to n=12, and ≤ 12 participants per dose level. Note: “% Early Stopping”" refers to early stopping due to 
excessive DLT 
 
 
Results of the simulations, presenting scenarios with the target DLT rate at the lower dose level, 
starting (middle) dose level, or higher dose level, show that the dose with the target DLT rate is 
selected as the tolerable dose most often. 
References: 
1 Liu S, Yuan Y. Bayesian optimal interval designs for Phase I clinical trials. J R Stat Soc: Ser C, 
2015;64:507-23. 
2 Yuan Y, Hess KR, Hilsenbeck SG, et al. Bayesian optimal interval design: a simple and well- 
performing design for Phase I oncology trials. Clin Cancer Res 2016; 22:4291-301. 
3 https://www.trialdesign.org/one-page-shell.html#BOIN 


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APPENDIX 10 
CYP3A4 STRONG INHIBITOR AND INDUCER GUIDANCE 
The lists below are not meant to be all inclusive. Please consult individual drug labels for further 
information. Additional information is also available at: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio 
nsLabeling/ucm093664.htm 
Representative Examples of Drugs that are Strong CYP3A4 Inhibitors or Inducers 
 
CYP Enzyme 
Strong Inhibitorsa 
≥ 5 fold Increase in AUC 
Or > 80% Decrease in CL 
Strong Inducers 
≥ 80% Decrease in AUC 
CYP3A 
Boceprevir, clarithromycin, conivaptan, 
grapefruit juiceb, indinavir, itraconazole, 
ketoconazole, lopinavir/ritonavir, 
mibefradilc, nefazodone, nelfinavir, 
posaconazole, ritonavir, saquinavir, 
telaprevir, telithromycin, voriconazole 
Avasimibed, carbamazepine, phenytoin, 
rifampin, St. Johns Worte 
Abbreviations: AUC = area under the concentration time curve; CL = clearance; CYP = cytochrome P450. 
a A strong inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a substrate for that CYP 
by equal or more than 5-fold 
b The effect of grapefruit juice varies widely among brands and is concentration, dose, and preparation dependent. 
Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used 
(eg, high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (eg, low 
dose, single strength) 
c Withdrawn from the United States market because of safety reasons 
d Not a marketed Drug 
e The effect of St John’s Wort varies widely and is preparation dependent 


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APPENDIX 11    PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY 
Overall Rationale for Protocol Amendment 01, 24-Nov-2021 
The overall purpose for Protocol Amendment 01 is to provide updates to increase participant safety 
(ie, dose-limiting toxicities [DLTs] and adverse events [AEs] for delay, resume, and discontinue 
of study treatments). Clarification was added to indicate that participants who discontinue study 
treatment prior to radiographic progression will stay on the same imaging schedule as participants 
on treatment. Updates were made to clarify that prior radium 223 and 177Lu-prostate-specific 
membrane antigen(PSMA)-617 treatment for prostate cancer is allowed and to exclude participants 
whose Technetium-99m bone scan is interpreted as a “superscan,” which would preclude 
assessment of radiographic progression in bone. Updates were made to the hepatic AE criteria for 
delay, resume, and discontinue of study treatments. Additional language was added to clarify DLT 
criteria and DLT exceptions. The progression-free survival (PFS) primary endpoint was changed 
to radiographic progression-free survival (rPFS) throughout the protocol to better articulate how 
progression will be assessed. 
The protocol summary has been revised as applicable to align with the protocol changes. 
This protocol amendment applies to all participants. 
Summary of Key Changes for Protocol Amendment 01 
Section Number & Title 
Description of Change 
Brief Rationale 
All 
Updated all references to the 
PFS endpoint to rPFS 
Updated for clarification, as 
PFS will be determined using 
Prostate Cancer Working 
Group 3 (PCWG3) criteria 
for radiographic progression 
Table 2-2: On Study 
Treatment Procedural Outline 
(CA022009) 
Table 2-3: Long-term 
Follow-up Procedural Outline 
(CA022009) 
Under Efficacy Assessments - 
Body Imaging/Bone Scan, 
updated timing of tumor 
assessments for the first 
24 weeks and if progression 
is not documented prior to 
discontinuation of study 
treatment 
Updated for clarity; 
participants who discontinue 
prior to radiographic 
progression will stay on the 
same assessment schedule as 
participants on study 
treatment 
Section 6.1: Inclusion Criteria 
Updated inclusion criterion 
2) f) to specify that prior 
radium 223 and 
177Lu-PSMA-617 treatment 
for prostate cancer is allowed 
Updated to clarify acceptable 
prior treatments 


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Summary of Key Changes for Protocol Amendment 01 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 6.2: Exclusion 
Criteria 
Added criterion 1) q) 
specifying that participants 
with superscan on 
Technetium-99m 
radionuclide bone scans are 
not eligible 
Updated to exclude 
superscan, which would 
impact the ability to assess 
efficacy 
Section 7.1: Study 
Interventions Administered 
Added flush language 
following BMS-986218 
administration and removed 
5% dextrose in water diluent 
Updated for clarity and 
accuracy; BMS-986218 is not 
compatible with dextrose 
Section 7.1: Study 
Interventions Administered 
Added Mosteller formula to 
calculate body surface area for 
docetaxel dosing 
Added to ensure consistency 
across all sites 
Table 7.4.1-1: Adverse Event 
Criteria for Delay, Resume, 
and Discontinue of 
Nivolumab and BMS-986218 
• To Hepatic AEs - AST, 
ALT or T. bili Increased: 
Updated notes for the first 
severity; symptoms of 
liver inflammation were 
modified to remove 
jaundice and pruritus and 
include fatigue, nausea, 
vomiting, fever, rash, 
and/or eosinophilia 
• Added international 
normalized ratio (INR) 
> 1.5 to the third severity 
Updated for clarity and 
completeness 
Table 7.4.2-1: Adverse Event 
Criteria for Delay, Resume, 
and Discontinue of Docetaxel 
To Hepatic AEs - AST, ALT, 
or T. bili increased with or 
without alkaline phosphatase 
increase: 
modified the second severity 
to “AST or ALT > 5× ULN 
or T. bili > 3× ULN, 
regardless of baseline value 
or concurrent AST or ALT 
> 3× ULN and T. bili > 2× 
ULN or INR > 1.5, regardless 
of baseline value” 
Updated and added INR for 
clarity and completeness 


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Summary of Key Changes for Protocol Amendment 01 
Section Number & Title 
Description of Change 
Brief Rationale 
Section 7.4.5: Dose-limiting 
Toxicities 
Updated the definition of 
DLTs to include details on 
neutropenic fever, Grade 3 or 
higher non-hematologic 
toxicity (with exceptions), 
and all AEs except those that 
are clearly and 
incontrovertibly due to 
disease progression or 
extraneous causes 
Additional language has been 
added to increase participant 
safety and to clarify what 
defines a DLT, including 
adding DLT exceptions for 
non-hematologic AEs 
Table 9.4.4-1: Clinical 
Laboratory Assessments 
Added a footnote specifying 
INR is optional to better 
evaluate elevated liver 
function tests 
Updated for clarity and 
completeness