Conditions: Advanced Solid Tumors Non-small Cell Lung Cancer
Keywords: BMS-986442 Nivolumab Chemotherapy
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 36
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate BMS-986442 in combination with nivolumab (with or without chemotherapy) for its antitumor efficacy and benefit to participants.

Detailed description:

Arms:
arm 1: None arm 2: Second line (2L) + Post-immuno-oncology (IO)/Platinum-Doublet Non-small cell lung cancer (NSCLC) arm 3: Post IO Gastric Cancer/Gastroesophageal Junction and Post-IO squamous cell carcinoma of the head and neck (SCCHN) arm 4: None arm 5: None arm 6: None

Interventions: intervention 1: BMS-986442 intervention 2: Nivolumab intervention 3: Docetaxel intervention 4: Carboplatin intervention 5: Pemexetred intervention 6: Paclitaxel
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days intervention 3: Specified dose on specified days intervention 4: Specified dose on specified days intervention 5: Specified dose on specified days intervention 6: Specified dose on specified days

Protocol document:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 1b/2 Study of BMS-986442 in Combination With Nivolumab or Nivolumab and 
Chemotherapies in Participants With Advanced Solid Tumors and Non-small Cell Lung Cancer 
 
NCT Number: NCT05543629 
Document Date (Date in which document was last revised): 12 January 2023 
 
 
 


Page:
1
Protocol Number:
CA115001
Date:
06-Jun-2022
Revised Date:
12-Jan-2023
CLINICAL PROTOCOL CA115001
A Phase 1b/2 Study of BMS-986442 in Combination with Nivolumab or Nivolumab and 
Chemotherapies in Participants with Advanced Solid Tumors and Non-small Cell Lung Cancer
Brief Title:
A Phase 1b/2 Study of BMS-986442 with Nivolumab with or without Chemotherapy in Solid 
Tumors and Non-small Cell Lung Cancer
Protocol Amendment 02
Incorporates Administrative Letter 01
Clinical Trial Physician-Medical Monitor
Bristol-Myers Squibb Company
Route 206 & Province Line Road
Lawrenceville, NJ 08543
Phone:
email: 
Clinical Scientist
Bristol-Myers Squibb Company
Route 206 & Province Line Road
Lawrenceville, NJ 08543
Phone:
email: 
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: 160891
EudraCT/EU Trial Number: 2022-501676-26-00
UTN: U1111-1283-1243
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Anti-TIGIT Bispecific Ab
Protocol Amendment No.: 02
Date: 12-Jan-2023
2
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS sponsored
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. References to BMS in this protocol may apply to partners to which BMS 
has transferred obligations (eg, a Contract Research Organization [CRO]).
© 2022 Bristol-Myers Squibb Company
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Protocol Amendment No.: 02
Date: 12-Jan-2023
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol Amendment 
02
12-Jan-2023
The main purpose of this amendment is to update the 
classification of the chemotherapies planned for 
administration from Non-Investigational Medicinal Product 
(Non-IMP) to IMP. Additional updates include providing 
regulatory agency identifier numbers, allowing both serum 
and plasma for blood-based clinical safety labs, and adding
clarity associated with palliative radiotherapy scenarios.
Administrative Letter 
01
08-Aug-2022
This letter aligns the primary objective presented in the 
Protocol Summary Objective and Endpoints table with the 
primary objective presented in Section 4, Objectives and 
Endpoints (Table 4-1) of the protocol.
Protocol Amendment 
01
27-Jul-2022
The main purpose of this amendment is to update the 
eligibility criteria to include all actionable mutations, adjust 
eligibility criteria for docetaxel, and adjust dosing 
modifications for nivolumab. In addition, staggered dosing 
for safety monitoring during dose escalation was utilized 
and stopping rules based on safety monitoring were 
specified
. 
Original Protocol
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OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02:
The purpose of this amendment is to update the classification of the chemotherapies (docetaxel, 
carboplatin, pemetrexed, and paclitaxel) planned for administration from Non-Investigational 
Medicinal Product (Non-IMP) to IMP. Distribution of the chemotherapies is unchanged and will 
be supplied by the Sponsor in regions where it is not available through insurance. The protocol 
was also updated to include additional regulatory agency identifier numbers on the title page, allow 
both serum and plasma for blood-based clinical safety laboratory evaluations, add clarity 
associated with palliative radiotherapy scenarios, and correct typographical errors/document 
formatting issues.
The protocol summary has been updated to align with the changes/edits reported in the table below.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section 
Number & 
Title
Description of Change
Brief Rationale
Title Page
Updated Clinical Scientist contact 
information.
Change in study personnel.
Added European Union Drug 
Regulating Authorities Clinical Trials 
Database/European Union 
(EudraCT/EU) Trial Number and 
Universal Trial Number (UTN).
Updated per regulatory agency identifier 
number availability.
Section 2: 
Schedule of 
Activities
Section 6.2: 
Exclusion 
Criteria
Section 7.1.3: 
Part D: 
Nivolumab, 
BMS-986442, 
Pemetrexed, and 
Carboplatin
Table 7.4.1-1: 
Adverse Event 
Criteria for 
Delay, Resume, 
and Discontinue 
of Nivolumab 
and BMS-986442
Section 9.2.7: 
Potential Drug-
induced Liver 
Injury
Table 9.4.4-1: 
Clinical 
Removed reference to serum 
chemistry procedures in Table 2-1: 
Screening Procedural Outline for All 
Parts (CA115001), Table 2-2: On-
Treatment Procedural Outline for All 
Parts (CA115001), and Table 2-3: 
Follow-Up Procedural Outline for All 
Study Parts (CA115001).
Updated mention of serum creatinine, 
alkaline phosphatase, and urea 
assessments to refer to 
“serum/plasma” assessments.
Updated to allow both serum and plasma 
samples when assessing study participant 
blood samples for safety purposes.
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section 
Number & 
Title
Description of Change
Brief Rationale
Laboratory 
Assessments
Section 3.2.4: 
BMS-986442 
Clinical Activity
Section 3.2.4.1: 
Preliminary 
Safety Data of 
BMS-986442 
Monotherapy
Section 3.3.1: 
Risk Assessment
Section 5.5: 
Justification for 
the BMS-986442 
Dose
Updated reports of preliminary data from 
BMS-986442 studies.
Data associated with BMS-986442/AGEN1777 
monotherapy study have been updated to align 
with Investigator Brochure v02 released on
21-Oct-2022.
Section 5.1.1: 
Screening
Information was added regarding 
reconsenting of participants who exceed 
the 28-day screening period due to study-
related procedures.
Information provided for extending the 
screening period.
Section 7.1: 
Study 
Interventions 
Administered
Updated Table 7.1-1: Study Interventions 
for Parts A to C; updated Table 7.1-2: 
Study Interventions for Parts D and E.
The chemotherapy (docetaxel, carboplatin, 
pemetrexed, and paclitaxel) classifications have 
been updated to Investigational Medicinal 
Product (IMP) based on current regulatory 
guidance.
Footnotes have been modified to reference 
chemotherapy subsection numbers.
Section 7.7.4: 
Palliative Local 
Therapy
Added new section.
Additional guidance for on-treatment palliative 
radiotherapy was added for clarity.
Table 9.4.4-1: 
Clinical 
Laboratory 
Assessments
Removed row indicating testing for 
drugs of abuse.
Correction of an inadvertent error.
All
Minor edits and formatting and 
typographical corrections.
Minor; therefore have not been summarized.
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 02: ............................ 
 
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02 ......................... 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.1.1 Research Hypothesis ................................................................................ 
 
3.2 Background ....................................................................................................... 
 
3.2.1 Indication Background ............................................................................. 
 
3.2.2 BMS-986442 Mechanism of Action ......................................................... 
 
3.2.3 Nivolumab Mechanism of Action ............................................................. 
 
3.2.4 BMS-986442 Clinical Activity ................................................................. 
 
3.2.4.1 Preliminary Safety Data of BMS-986442 Monotherapy ................. 
 
3.2.5 Nivolumab Clinical Activity ..................................................................... 
 
3.3 Benefit/Risk Assessment .................................................................................. 
 
3.3.1 Risk Assessment ....................................................................................... 
 
3.3.2 Benefit Assessment ................................................................................... 
 
3.3.3 Overall Benefit/Risk Conclusion .............................................................. 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Screening.................................................................................................. 
 
5.1.2 Treatment Period ..................................................................................... 
 
5.1.2.1 Part A: Dose Escalation of BMS-986442 with Nivolumab ............. 
 
5.1.2.2 Part B: Dose Expansions Evaluating the Combination of BMS-
986442 and Nivolumab ......................................................................... 
 
5.1.2.3 Parts C, D, and E: Dose Escalation of BMS-986442 in 
Combination with Nivolumab and Chemotherapy in NSCLC .............. 
 
5.1.2.4 Part F: Randomized Cohorts in NSCLC ......................................... 
 
5.1.3 Follow-up Period ..................................................................................... 
 
5.1.4 Data Monitoring Committee and Other Committees ............................... 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.4.1 Rationale for Combining BMS-986442 with Nivolumab ......................... 
 
5.4.2 Rationale for Combining BMS-986442 with Nivolumab and 
Chemotherapy ............................................................................................. 
 
5.4.3 Rationale for Two Year Duration of Treatment ....................................... 
 
5.4.4 Rationale for Treatment Beyond Progression ......................................... 
 
5.5 Justification for the BMS-986442 Dose ........................................................... 
 
5.5.1 Nivolumab ................................................................................................ 
 
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5.6 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 .................................................................... 
 
7.1.1 Part A and Part B: Nivolumab and BMS-986442 ................................... 
 
7.1.2 Part C: Nivolumab, BMS-986442, and Docetaxel ................................... 
 
7.1.3 Part D: Nivolumab, BMS-986442, Pemetrexed, and Carboplatin .......... 
 
7.1.4 Part E: Nivolumab, BMS-986442, Paclitaxel, and Carboplatin ............. 
 
7.1.5 Observation Time for All Study Parts ...................................................... 
 
7.2 Method of Study Intervention Assignment ....................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.4.1 Dose Modification Criteria for Nivolumab and BMS-986442 ................ 
 
7.4.2 Criteria to Resume Treatment of Nivolumab and BMS-986442 .............. 
 
7.4.3 Dose Modification Criteria for Docetaxel ............................................... 
 
7.4.4 Docetaxel Dose Reduction and Criteria to Resume Treatment ............... 
 
7.4.5 Dose Delay Criteria for Chemotherapies in Part D and Part E ............. 
 
7.4.6 Dose Reduction and Criteria to Resume Treatment for Chemotherapies in 
Part D and Part E ....................................................................................... 
 
7.4.6.1 Dose Reductions for Hematologic Toxicity for Chemotherapies in 
Part D and Part E ................................................................................. 
 
7.4.6.2 Dose Reductions for Non-hematologic Toxicities for 
Chemotherapies in Part D and Part E .................................................. 
 
7.4.6.3 Criteria to Resume Chemotherapy Treatment for Part D and Part E
............................................................................................................... 
 
7.4.7 Dose-limiting Toxicities ........................................................................... 
 
7.4.8 Management Algorithms for Immuno-oncology Agents .......................... 
 
7.4.9 Treatment of Related Infusion Reactions ................................................. 
 
7.4.10 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 Local Therapy .......................................................................... 
 
7.7.5 Surgery ..................................................................................................... 
 
7.7.5.1 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 ........................................................ 
 
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8.1.1 Nivolumab and BMS-986442 Treatment Beyond Disease Progression .. 
 
8.1.2 Post-study Intervention Study Follow-up................................................. 
 
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 and Clinical Assessment ................................................... 
 
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 ........................................................................... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.9 Additional Research .......................................................................................... 
 
9.10 Other Assessments .......................................................................................... 
 
9.11 Health Economics OR Medical Resource Utilization and Health Economics
........................................................................................................................... 
 
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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................................................................................... 
 
10.4.3 Secondary Endpoints ............................................................................. 
 
 
 
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 DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
 
APPENDIX 5 RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS ........................ 
 
APPENDIX 6 ECOG PERFORMANCE STATUS ..................................................... 
 
APPENDIX 7 MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 5 ............................................................................................................ 
 
APPENDIX 8 CYP3A4 STRONG INHIBITOR AND INDUCER GUIDANCE ....... 
 
APPENDIX 9 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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1
PROTOCOL SUMMARY
Protocol Title:
A Phase 1b/2 Study of BMS-986442 in Combination with Nivolumab or Nivolumab and 
Chemotherapies in Participants with Advanced Solid Tumors and Non-small Cell Lung Cancer
Brief Title: 
A Phase 1b/2 Study of BMS-986442 with Nivolumab with or without Chemotherapy in Solid 
Tumors and Non-small Cell Lung Cancer
Rationale:
BMS-986442
(AGEN1777)
is a fragment crystallizable-engineered bispecific human 
immunoglobulin gamma 1 antibody that selectively binds to 
 
and 
 
 on certain populations of T cells and natural killer (NK) cells. As a dual antagonist, BMS-
986442 is designed to block 
 binding to their shared ligand (
 
) and facilitate T-cell and NK cell activation by relieving inhibitory signals and enabling 
 to bind to the stimulatory receptor CD226.
Recent preclinical evidence supports that the programmed cell death protein 1 (PD-1) pathway 
may directly inhibit CD226 signaling and that the blockade of 
 PD-1 pathways
would be required for full restoration of CD226 co-stimulation and T-cell priming. Consistent with 
this, the combination of BMS-986442 with an anti-PD-1 antibody in human peripheral blood 
mononuclear cells stimulated with staphylococcal enterotoxin A peptide generated superior T-cell 
stimulation compared with BMS-986442, anti-PD-1, or the control antibodies alone. As 
chemotherapy increases tumor antigen delivery to antigen-presenting cells and subsequent T-cell 
priming, addition of chemotherapy to BMS-986442 and anti-PD-ligand(L)-1 treatment may 
further broaden the anti-tumor response and enhance therapeutic efficacy.
Taken together, these findings support the clinical rationale to combine BMS-986442 with a 
PD(L)-1 agent such as nivolumab (either alone or in combination with chemotherapy) to enhance 
anti-tumor efficacy in cancer patients.
Objectives and Endpoints: 
Objectives
Endpoints
Primary

To characterize the safety and tolerability, and to 
establish the MTD, MAD, and/or RP2D of 
BMS-986442 in combination with nivolumab or 
with nivolumab and the following chemotherapies: 
docetaxel; carboplatin and pemetrexed; carboplatin
and paclitaxel, in participants with advanced cancer 
including NSCLC.

Incidence of AEs, SAEs, AEs meeting protocol-
defined 
DLT 
criteria, 
AEs 
leading 
to 
discontinuation, and death (per CTCAE v5.0).
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Objectives
Endpoints
Secondary

To 
characterize 
the 
PK 
of 
BMS-986442 
administered in combination with nivolumab or in 
combination with nivolumab and chemotherapy.

Summary measures of BMS-986442 PK parameters 
such as, but not limited to, Cmax, Tmax, and AUC 
(0-T), from serum concentration-time data for 
BMS-986442 when administered in combination 
with nivolumab or in combination with nivolumab 
and chemotherapy.

To 
characterize 
the 
immunogenicity 
of 
BMS-986442 administered in combination with 
nivolumab or in combination with nivolumab and 
chemotherapy.

Incidence of ADAs
to BMS-986442 when 
BMS-986442 is administered in combination with 
nivolumab or in combination with nivolumab and 
chemotherapy.

To assess the preliminary anti-tumor activity of 
BMS-986442 administered in combination with 
nivolumab or nivolumab and chemotherapy.

ORR, DOR, DCR, and PFSR at 6 months and 12 
months per RECIST v1.1 by Investigator.
Abbreviations: ADA, anti-drug antibody; AE, adverse event; AUC (0-T), area under the serum concentration-time 
curve from time zero to the time of the last quantifiable concentration; Cmax, maximum observed concentration; 
CTCAE, Common Terminology Criteria for Adverse Events; DCR, disease control rate; DLT, dose-limiting toxicity; 
DOR, duration of response; MAD, maximum administered dose; MTD, maximum tolerated dose; NSCLC, non-small 
cell lung cancer; ORR, overall response rate; PFSR, progression-free survival rate; PK, pharmacokinetics; RP2D, 
recommended Phase 2 dose(s); SAE, serious adverse event; Tmax, time of maximum observed concentration; v, 
version.
Overall Design:
CA115001 is a Phase 1b/2 multi-center, open-label study of BMS-986442 administered in 
combination with nivolumab or nivolumab with 1 of 3 standard chemotherapy regimens used in 
the treatment of advanced solid tumors and advanced or metastatic non-small cell lung cancer
(NSCLC): docetaxel, carboplatin with pemetrexed, and carboplatin with paclitaxel. The study is 
composed of 6 parts. For all study parts nivolumab will be given at a fixed dose of 360 mg every 
3 weeks (Q3W).

Part A: Dose escalation of BMS-986442 in combination with nivolumab in participants with 
advanced solid tumors

Part B: Dose expansions for BMS-986442 in combination with nivolumab

Part B1: Randomized dose expansions in 2L+ post-immuno-oncology (IO)/platinum-
doublet NSCLC

Part B2: Dose expansions in post-IO gastric cancer/gastroesophageal junction and post-IO 
squamous cell carcinoma of the head and neck (SCCHN)

Part C: Dose escalation of BMS-986442 in combination with nivolumab and docetaxel in 2L+ 
post-IO/platinum-doublet NSCLC

Part D: Dose escalation of BMS-986442 in combination with nivolumab and carboplatin and 
pemetrexed in 1L non-squamous NSCLC

Part E: Dose escalation of BMS-986442 in combination with nivolumab and carboplatin and 
paclitaxel in 1L squamous NSCLC
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab

Part F may include randomized cohorts to evaluate whether BMS-986442 (either as 
monotherapy or in combination) can produce clinical benefit in participants with 
advanced/metastatic NSCLC. The design of Part F will be reported in a future amendment.
All participants will be centrally assigned to treatment (Parts A, B2, C, D, and E) or randomized 
(Part B1 and Part F) using Interactive Response Technology.
The study design schematic is presented in Figure 5.1-1.
Number of Participants:
The approximate total number of participants treated in Parts A to E will be 225.
Study Population:
Main Inclusion Criteria:

Participants in all parts of the study must have measurable disease per Response Evaluation 
Criteria in Solid Tumors (RECIST) v1.1.

Participants in Part A, advanced solid tumors, must meet all of the following:

Documented histologically or cytologically confirmed advanced unresectable/metastatic 
solid malignancy of any histology.

Have progressed on, are ineligible for, or intolerant of existing therapy(ies) known to 
provide clinical benefit for the condition of the participant.

Have experienced radiographically documented progressive disease on or after the most 
recent therapy.

Participants in Part B2 gastric cancer/gastroesophageal junction (GEJ) expansion must meet 
all of the following:

Advanced or metastatic gastric or GEJ cancer and have progressed during or after, or been 
intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting (or 
have progressed within 6 months of adjuvant therapy).

Disease progression while on or after prior PD-(ligand[L])1 treatment as monotherapy or 
in combination with other modalities.

Participants with known human epidermal growth factor receptor 2 (HER2)-positive 
gastric cancer and must have received prior treatment with a HER2 inhibitor (eg, 
trastuzumab).

Participants in Part B2 SCCHN expansion must meet all of the following:

Documented histologically confirmed, recurrent, or metastatic SCCHN (oral cavity, 
pharynx, larynx), and not amenable to local therapy with curative intent. Any other cancers 
of the head and neck, including nasopharyngeal cancer, salivary gland, and neuroendocrine 
tumors, are excluded.

Disease progression on or after, or been intolerant to, a platinum-containing regimen.

Prior focal palliative radiotherapy must have been completed at least 2 weeks before study 
drug administration.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab

Documented historical human papillomavirus (HPV) status for oropharyngeal cancers. 
HPV status should preferably be determined using p16 immunohistochemistry or HPV 
polymerase chain reaction (if available).

Disease progression while on or after prior PD-(L)1 treatment as monotherapy or in 
combination with other modalities, if available.

Participants in Parts B1 and C, NSCLC, must meet all of the following:

Documented histologically
or cytologically confirmed 
metastatic NSCLC of 
non-squamous or squamous histology with Stage IV A/B (as defined by the 8th 
International Association for the Study of Lung Cancer Classification) or recurrent disease 
following multi-modal therapy for locally advanced disease, measurable by RECIST v1.1

Recurrent or progressive disease during or after platinum-doublet chemotherapy (PDCT)
for advanced or metastatic disease, OR must have recurrent or progressive disease within 
6 months after completing PDCT for local disease.

Disease progression while on or after prior PD-(L)1 treatment as monotherapy or in 
combination with other modalities.

Prior definitive chemoradiation for locally advanced disease is permitted as long as the last 
administration of chemotherapy or radiotherapy (whichever was given last) occurred less 
than 6 months prior to enrollment.

Participants with disease having known actionable mutations in epidermal growth factor 
receptor (EGFR) including exon 20 insertion mutations, anaplastic lymphoma kinase 
(ALK), ROS proto-oncogene 1 (ROS1), rearranged during transfection
(RET), 
neurotrophic tropomyosin-receptor kinase (NTRK), Kirsten rat sarcoma (KRAS) (G12C),
MET exon 14 skipping mutations, or proto-oncogene B-Raf (BRAF) (V600E) must have 
progressed on, have been intolerant to, or not be a candidate for standard targeted therapy 
(as available per country/region standard-of-care practices).

Experienced radiographically documented progressive disease on or after the most recent 
therapy.

 
 
 
Participants in Parts D and E, NSCLC, must meet all of the following:

Documented histologically or cytologically confirmed 
metastatic NSCLC of 
non-squamous (Part D) or squamous (Part E) histology with Stage IVA/B (as defined by 
the 8th International Association for the Study of Lung Cancer Classification) or recurrent 
disease following multi-modal therapy for locally advanced disease, measurable by 
RECIST v1.1, who have not had systemic therapy for metastatic or recurrent disease.

Participants with disease having known genetic aberrations in EGFR including exon 20 
insertion mutations, ALK, ROS1, KRAS (G12C), RET, NTRK, MET exon 14 skipping 
mutations, or BRAF (V600E) that are sensitive to targeted therapy (as available per 
country/region standard-of-care practices) will be excluded.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab

Prior definitive chemoradiation for locally advanced disease is permitted as long as the last 
administration of chemotherapy or radiotherapy (whichever was given last) occurred at 
least 6 months prior to enrollment.

Prior adjuvant or neoadjuvant chemotherapy for early-stage lung cancer is permitted if 
completed at least 6 months prior to initiating study treatment.

Part F: Criteria for Part F will be similar to either Part C or Parts D/E, dependent on the 
population chosen (either post-PDCT and anti-PD-[L1] therapy or treatment-naive NSCLC),
and will be added via a future amendment.
Main Exclusion Criteria:

Untreated symptomatic central nervous system metastases or leptomeningeal metastases.

Concurrent malignancy (present during screening) requiring treatment, or history of prior 
malignancy active within 2 years prior to randomization in study Part B1 or treatment 
assignment in all other study parts.

Participants with an active, known, or suspected autoimmune disease.

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 randomization in study Part B1 or treatment assignment in all other study parts.

Previous severe acute respiratory syndrome coronavirus disease 2 infection within 10 days for 
mild or asymptomatic infections, or 20 days for severe/critical illness prior to C1D1.

Radiation therapy within 2 weeks prior to first study treatment.

Prior treatment with an anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated 
antigen 4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation 
or checkpoint pathways for Parts D and E.

Systemic anticancer therapies or biological therapies within 4 weeks or 5 half-lives (whichever 
is shorter) prior to the first administration of study treatment.

Prior therapy with an anti-
 or anti-
 antibody.

Part C: Prior docetaxel therapy is not permitted.

Parts D, and E: Prior systemic therapy for advanced or metastatic NSCLC is not permitted. 
Intervention Groups and Duration:

The screening period will be up to 28 days and begins by establishing the participant’s initial 
eligibility after signing the informed consent form. The treatment period will last a maximum 
of approximately 35 cycles (105 weeks) from the first dose of study treatment, even if the study 
is terminated and regardless of treatment delays. The follow-up period includes a safety 
follow-up and a survival follow-up that begin after the end of treatment visit or date of last 
dose (whichever occurs later). The safety follow-up period for all treatment groups is 100 days 
after the end-of-treatment visit or date of last dose (whichever occurs later), with visits to occur 
at 30, 60, and 100 (± 7) days. Survival follow-up for all parts will begin on the date of 
discontinuation of study treatment and last for a period of 2 years (approximately 105 weeks)
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
or until death, lost to follow-up, withdrawal of consent, conclusion of the study, or study 
termination, whichever comes first.

Dosing regimens are as follows, dependent on treatment assignment or randomization:

Nivolumab and BMS-986442: Participants will receive nivolumab at a dose of 360 mg 
Q3W over an approximately 30-minute infusion. Participants will receive BMS-986442 
(20 mg dose level up to and including 600 mg dose level) Q3W administered as a 60-minute 
infusion at the dose level indicated, dependent on treatment assignment or randomization. 
BMS-986442 at the 1200 mg dose level will be administered as an infusion over 90 minutes 
(Q3W). There will be no intra-subject dose escalations or reductions of BMS-986442 or 
nivolumab allowed. Doses of study drug(s) may be interrupted, delayed, or discontinued,
depending on how well the participant tolerates the treatment.

Docetaxel: Participants will receive Q3W docetaxel infusion at a dose based on body 
weight, using body surface area formula per institution practice. 

Pemetrexed: Participants will receive pemetrexed at a dose of 500 mg/m2 as a 10-minute 
intravenous (IV) infusion on Day 1 of each cycle. Pemetrexed will be administered on 
Cycle 1 through Cycle 4. Participants who have SD or response are permitted to receive 
pemetrexed 500 mg/m2 alone as maintenance therapy until disease progression or 
unacceptable toxicity.

Carboplatin: Carboplatin should be given following pemetrexed (Part D) or paclitaxel (Part 
E) on Day 1 of each cycle, and the carboplatin dose will be calculated using the Calvert 
formula. The dose of carboplatin may be capped per local standards. Carboplatin will be 
administered for up to 4 cycles.

Paclitaxel: Participants will receive paclitaxel 200 mg/m2 as a 180-minute IV infusion with 
carboplatin at a dose of area under the serum concentration-time curve (AUC) 5 or AUC 6
for Part D or AUC 6 for Part E as a 30-minute IV infusion on Day 1 of a 3-week cycle, or 
at doses per the local prescribing information. The infusion time can follow local 
institutional standards. Paclitaxel will be administered for up to 4 cycles. Paclitaxel dosing 
calculations should be based on body surface area.
Study Intervention: 
Study Intervention for CA115001
Medication
Potency
IMP/Non-IMP/AxMP
BMS-986442
 mg/vial
IMP
Nivolumab
100 mg/vial
IMP
Docetaxel
Various strengths
IMP
Carboplatin
450 mg/vial/various strengths
IMP
Pemetrexed
500 mg/vial/various strengths
IMP
Paclitaxel
100 mg/vial/various strengths
IMP
Abbreviations: AxMP, auxiliary medicinal product; IMP, investigational medicinal product.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Statistical Methods
In Parts A, C, D, and E of the study, at least 3 participants will be enrolled per dose level, and dose 
escalation decisions will be guided by Bayesian optimal interval (BOIN) design to identify the 
maximum tolerated dose (MTD). The final recommended MTD/maximum administered dose 
(MAD)/recommended Phase 2 dose (RP2D) will be based on recommendation from the BOIN and 
overall clinical assessment of all available safety, pharmacokinetic, pharmacodynamic, and 
efficacy data. A Bayesian continuous monitoring framework will be utilized for continuous 
monitoring of toxicity for a safety-evaluation period of 28 days of treatment and to detect safety 
signals that may lead to changes in study conduct.
Interim analyses may be performed for administrative purposes or publications. No formal 
inferences requiring any adjustment to statistical significance level will be performed.
Statistical methods for the randomized expansion in Part F will be introduced via amendment when 
the patient population is determined.
Data Monitoring Committee: 
A Data Monitoring Committee (DMC) will not be used in the study.
Other Committee: Yes
Although there is not a formal DMC for this study, 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, which will 
be employed in this study. To support safety oversight, BMS has established ongoing processes 
for collection, review, analysis, and submission of individual adverse event reports and their 
aggregate analyses. Signal detection will be performed at least monthly and ad hoc throughout the 
study. Because this is an open-label study, WWPS, the BMS Medical Monitor, and the 
Investigators will have access to all data necessary for safety evaluation.
 
Brief Summary:
The purpose of this study is to characterize the safety and tolerability, and to establish the MTD, 
MAD, and/or RP2D of BMS-986442 in combination with nivolumab or with nivolumab and 
chemotherapy in participants with advanced cancer, including NSCLC. Study details include the 
following:
Study Duration: Maximum of 4 years (up to of 35 cycles [105 weeks] from first dose of study 
treatment and up to 2 years on follow-up).
Study Intervention Duration: Maximum of approximately 35 cycles (105 weeks) from the first 
dose of study treatment.
Study Visit Frequency: On-treatment monitoring will include planned clinic visits on Cycle 1 
Days 1, 2, 8, and 15; Cycle 2 Days 1, 2, and 8; and Day 1 of Cycles 3 and beyond. The safety 
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
follow-up visits will occur at 30, 60, and 100 (± 7) days after the end of treatment visit or date of 
last dose (whichever occurs later).
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
2
SCHEDULE OF ACTIVITIES
Table 2-1:
Screening Procedural Outline for All Parts (CA115001)
Procedure
Screening Visit
(Day -28 to -1)
Notes
Eligibility Assessments
Informed Consent
X
Must be obtained prior to performing any screening procedures. A participant is considered 
enrolled only when a protocol-specific informed consent is signed. 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. See Section 7.2 (Method 
of Study Intervention Assignment).
Inclusion/Exclusion Criteria
X
Must be confirmed prior to cohort assignment (Parts A, B2, C, D, and E) or cohort 
randomization (Part B1 and Part F) in IRT.
Medical History
X
All medical history relevant to disease under study, including tobacco history and any 
clinically significant toxicities or allergies related to previous treatments.
HPV Status for SCCHN
X
HPV status for oropharyngeal cancers, preferably using p16 IHC or HPV PCR, if available.
HER2 Status for Gastric/GEJ 
X
HER2-positive status, if available.
Mutation Status for NSCLC
X
EGFR (including exon 20 insertion mutations), ALK, ROS1, RET, NTRK, KRAS (G12C), 
MET exon 14 skipping mutations, and BRAF (V600E) status if available.
Prior Cancer Therapies
X
Includes all prior cancer treatment regimens including medications, surgery, and radiation.
Safety Assessments
Physical Examination (PE) and 
Physical Measurements
X
Includes height, weight, and BMI. If the screening PE is performed within 3 days prior to 
dosing on Day 1, then a single exam may count as both the screening and predose evaluation. 
ECOG PS
X
See Appendix 6. 
Vital Signs and Oxygen Saturation
X
Includes body temperature, respiratory rate, seated blood pressure, and seated heart rate.
Blood pressure and heart rate should be measured after the participant has been resting 
quietly for at least 5 minutes. Obtain Pulse oximetry at rest.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 2-1:
Screening Procedural Outline for All Parts (CA115001)
Procedure
Screening Visit
(Day -28 to -1)
Notes
ECG
X
Single ECG should be recorded after the participant has been supine for at least 5 minutes 
and prior to blood draws (see Section 9.4.3). 
Clinical Laboratory Assessments
(Hematology, Chemistry, and 
Urinalysis)
X
Includes blood and urine samples. Safety labs and urinalysis do not need to be repeated if 
performed within 3 days of C1D1. Refer to Section 9.4.4 and Table 9.4.4-1.
FSH
X
Women only, as needed to document postmenopausal status. See Appendix 4. 
Pregnancy Test (WOCBP only)
X
Serum or urine pregnancy test (minimum sensitivity equivalent units 25 IU/L or equivalent 
units of hCG) to be done at screening visit and repeated within 24 hours prior to first dose of 
study treatment. If the pregnancy test at screening is taken within 24 hours of dosing (C1D1), 
a repeat pregnancy test within 24 hours prior to first dose of study treatment is not required. 
WOCBP must have a negative pregnancy test within 24 hours prior to the start of study 
intervention and results also must be evaluated prior to study intervention administration. An 
extension up to 3 days prior to the start of study intervention administration is permissible in 
situations where results cannot be obtained within standard 24-hour window. 
Serology
X
See Section 9.4.4. For HIV: testing at sites where locally mandated. 
Assessment of Signs and Symptoms 
X
Collected from the date of participant's written consent until prior to C1D1.
AEs and SAE Assessment
X
All AEs (SAEs or non-serious AEs) associated with SARS-CoV-2 infection collected from 
time of consent. All SAEs must be collected from the date of participant's written consent and 
collection of AE should begin at initiation of study treatment. All AEs/SAEs must be graded 
using CTCAE v5.
Concomitant Medication Use 
X
Within 14 days prior to cohort assignment (Parts A, B2, C, D, and E) or cohort randomization 
(Part B1 and Part F) in IRT. Vaccine use (including COVID-19) must be collected within 30 
days prior to first dose of study drug See Section 6.2 (Exclusion Criteria). 
Tumor Assessments (Baseline)
Body Imaging
X
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected 
sites of disease. CT/MRI of the neck is required only for SCCHN participants. Refer to 
Imaging Assessment details in Section 9.1.1.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 2-1:
Screening Procedural Outline for All Parts (CA115001)
Procedure
Screening Visit
(Day -28 to -1)
Notes
Brain Imaging
X
MRI of the brain without and with contrast is required for participants with NSCLC and/or 
those without NSCLC that have known or suspected brain metastases, unless participant has 
completed an imaging study of the brain within 28 days prior to the date of first dose of study 
treatment. CT of the brain without and with contrast can be performed if MRI is 
contraindicated. See Section 9.1.1 for further details.
Abbreviations: AE; adverse event; ALK, anaplastic lymphoma kinase; BMI; body mass index; BRAF, proto-oncogene B-Raf; C, cycle; COVID-19, coronavirus 
disease 2019; CT; computed tomography; CTCAE, Common Terminology Criteria for Adverse Events; D, Day; ECG, electrocardiogram; ECOG PS, Eastern 
Cooperative Oncology Group Performance Status; EGFR, epidermal growth factor receptor; FSH, follicle-stimulating hormone; GEJ, gastroesophageal junction;
hCG, human chorionic gonadotropin; HER2, human epidermal growth factor receptor 2; HIV, human immunodeficiency virus; HPV, human papillomavirus; IHC, 
immunohistochemistry; IRT, Interactive Response Technology; IU, international units; KRAS, Kirsten rat sarcoma; MRI, magnetic resonance imaging; NSCLC, 
non-small cell lung cancer; NTRK, neurotrophic tropomyosin-receptor kinase; PCR, polymerase chain reaction; PE, physical examination; RET, rearranged during 
transfection; ROS1, ROS proto-oncogene 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus disease 2; SAE, serious adverse event; SCCHN, 
squamous cell carcinoma of the head and neck; v, version; WOCBP, women of child-bearing potential.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 2-2:
On-Treatment Procedural Outline for All Parts (CA115001)
Procedurea
(1 Cycle = 3 Weeks)
Cycle 1
Cycle 2
Cycle 3 
and 
Beyond
EOTb/Early 
Termination
Notesc
D1
D2
D8
D15
D1
D2
D8
D1
After C1D1, the visit window is ± 3 days.
Safety Assessments
Complete PE
X
X
If the screening PE is performed within 3 
days prior to dosing on Day 1, then a single 
exam may count as both screening and 
predose evaluation. 
Targeted Physical 
Examination (PE)
X
X
X
X
X
If there are any new or worsening clinically 
significant changes since the last 
examination, report changes on the 
appropriate non-serious or SAE CRF page.
ECOG PS
X
X
X
X
See Appendix 6.
Vital Signs, Physical 
Measurements, and 
Oxygen Saturation d
X
X
X
X
X
X
X
Includes body temperature, body weight
and BMI, respiratory rate, seated blood 
pressure, and seated heart rate. BP and heart 
rate should be measured after the participant 
has been resting quietly for at least 5 
minutes. Pulse oximetry at rest.
ECGs
X
X
X
X
ECGs should be recorded after the 
participant has been supine for at least 5 
minutes, and prior to blood draws. A single 
12-lead safety ECG to be done pre-dose on 
Day 1 of all treatment cycles (all study 
parts). See Section 9.4.3.
Protocol Amendment No.: 02
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 2-2:
On-Treatment Procedural Outline for All Parts (CA115001)
Procedurea
(1 Cycle = 3 Weeks)
Cycle 1
Cycle 2
Cycle 3 
and 
Beyond
EOTb/Early 
Termination
Notesc
D1
D2
D8
D15
D1
D2
D8
D1
After C1D1, the visit window is ± 3 days.
Clinical Laboratory 
Assessments
(Hematology and 
Chemistry)
X
X
X
X
X
X
X
Perform on site/local laboratory testing 
within 3 days prior to each dose. For the 
first treatment visit, labs need not be 
repeated if performed within 3 days and the 
results are available and have been 
reviewed for eligibility. If the participant 
has an IRR, draw additional blood for a 
cytokine panel to be performed on site/local 
laboratory. Refer to Section 9.4.4 for the list 
of laboratory tests to be conducted.
Thyroid Function Test 
(TSH)
X
X
X
X
If TSH is abnormal, reflexive fT3 and fT4 
should be collected. See Section 9.4.4 and 
Table 9.4.4-1.
Urinalysis
X
X
X
X
Refer to Section 9.4.4.
Pregnancy Test 
(WOCBP)
X
X
X
X
Serum or urine pregnancy test (minimum 
sensitivity equivalent units 25 IU/L or 
equivalent units of hCG) within 24 h prior 
to first dose and then every 3 weeks.
Sample should be drawn within 24 h of Day 
1 of each cycle, and results must be 
available and reviewed prior to 
administration of study treatment on Day 1 
of each cycle while on study treatment.
An extension up to 3 days to the start of 
study treatment or Day 1 of Cycle 2 and 
beyond is permissible in situations where 
results cannot be obtained within standard 
24-h window.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 2-2:
On-Treatment Procedural Outline for All Parts (CA115001)
Procedurea
(1 Cycle = 3 Weeks)
Cycle 1
Cycle 2
Cycle 3 
and 
Beyond
EOTb/Early 
Termination
Notesc
D1
D2
D8
D15
D1
D2
D8
D1
After C1D1, the visit window is ± 3 days.
Monitor for AEs and 
Serious Adverse Events 
(SAEs)
Record at each visit. All AEs (SAEs or nonserious AEs, including those associated with SARS-CoV-2 infection) must be collected
continuously during the treatment period until 100 days post discontinuation of dosing. All SAEs must be collected from the date
of participant’s written consent until 100 days post discontinuation of dosing or participation in the study, if the last scheduled visit 
occurs at a later time. All AEs/SAEs must be graded using CTCAE v5.
Concomitant Medication 
Use
Continuously; see notes
Record at each visit
PK and Immunogenicity Assessments
PK/Immunogenicity 
(IMG) Serial Blood 
Sampling
There is an additional PK draw on Cycle 1 Day 5. Refer to PK/IMG Collection Table 9.5-1 for timing of collections
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 2-2:
On-Treatment Procedural Outline for All Parts (CA115001)
Procedurea
(1 Cycle = 3 Weeks)
Cycle 1
Cycle 2
Cycle 3 
and 
Beyond
EOTb/Early 
Termination
Notesc
D1
D2
D8
D15
D1
D2
D8
D1
After C1D1, the visit window is ± 3 days.
Tumor Assessmentse
Body Imaging
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected sites of disease should occur every 6 
weeks starting from date of first dose (± 7 days) for the first 48 weeks, then every 12 weeks (± 7 days) until withdrawal of consent, 
death, or initiation of another anti-cancer treatment, whichever occurs first. For participants with SCCHN, a CT or MRI of the 
neck is also required. See Section 9.1.1 for further details. 
Brain Imaging
Participants with NSCLC and/or a history of brain metastasis or symptoms should have a surveillance MRI (without and with 
contrast) 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.
Study Interventionf
Nivolumab (All Parts)
X
X
X
Nivolumab 360 mg Q3W
BMS-986442 (All Parts)
X
X
X
BMS986442 Q3W
Docetaxel (Part C)
X
X
X
Docetaxel Q3W
Carboplatin (Parts D and
E)
X
X
X
Carboplatin will be administered Cycle 1 
through Cycle 4 (Q3W).
Pemetrexed (Part D)
X
X
X
Pemetrexed will be administered Cycle 1 
through Cycle 4 (Q3W). Participants who 
have SD or response are permitted to 
receive pemetrexed 500 mg/m2 as 
maintenance therapy until disease 
progression or unacceptable toxicity.
Paclitaxel (Part E)
X
X
X
Paclitaxel will be administered Cycle 1 
through Cycle 4 (Q3W).
Abbreviations: AE; adverse event; BMI, body mass index; BMS, Bristol-Myers Squibb; BP, blood pressure; CRF, Case Report Form; CT, computed tomography; 
CTCAE, Common Terminology Criteria for Adverse Events; C, cycle; D, Day; ECG, electrocardiogram; ECOG PS, Eastern Cooperative Oncology Group 
Performance Status; EOI, end of infusion; EOT, end of treatment; fT3, free triiodothyronine; fT4, free thyroxine; h, hour; hCG, human chorionic gonadotropin; 
IMG, immunogenicity; IRR, infusion-related reaction; IU, international units; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PE, physical 
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examination; PK, pharmacokinetic; Q3W, every 3 weeks; RECIST v1.1, response evaluation criteria in solid tumors version 1.1; SAE, serious adverse event; 
SARS-CoV-2, severe acute respiratory syndrome coronavirus disease 2; SCCHN, squamous cell carcinoma of the head and neck; SD, stable disease; TSH, thyroid-
stimulating hormone; v, version; WOCBP, women of childbearing potential.
a 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. 
b EOT is defined as the time point where the decision is made to discontinue the participant from treatment. Evaluations will be performed prior to study discharge. 
For participants who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit as the start 
of the safety follow-up period. For participants who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit 
(with all available safety and response data); it does not need to be repeated and will be considered the start of the safety follow-up period.
c Some of the assessments referred to in this section may not be captured as data in the CRF. They are intended to be used as safety monitoring by the treating 
physician. Additional testing or assessments may be performed as clinically necessary or where required by institutional or local regulations.
d Heart rate, BP, temperature, respiratory rate, and oxygen saturation will be obtained at the following timepoints (± 5 minutes for all timepoints): 

Nivolumab: At the start and EOI

BMS-986442: At infusion start and every 30 minutes throughout 60-minute infusion and every 30 minutes for the next hour following EOI.

Docetaxel: At infusion start and every 30 minutes throughout 60-minute infusion. 120-minute observation for first 2 cycles if participant does not 
experience any IRR, then they should be observed for at least 1 hour for all subsequent cycles (vitals every 30 minutes).

Carboplatin: At infusion start and end. 120-minute observation for first 2 cycles if participant does not experience any IRR, then they should be observed 
for at least 1 hour for all subsequent cycles (vitals every 30 minutes).

Pemetrexed: At infusion start.

Paclitaxel: At infusion start and every 15 minutes for the first 30 minutes of infusion, subsequently every 30 minutes throughout 180-minute infusion.

If any vital sign is abnormal (based upon clinical assessment) at the final check, the participant must be observed for an additional period of time, as 
clinically indicated. 
e The same imaging modality is to be used for all assessments, per RECIST v1.1 (Appendix 5). If dosing is delayed, tumor assessments should continue on this 
imaging schedule. If the participant discontinues treatment, see Table 2-3.
f See Section 7 for study intervention and administration details. Participant must receive the first dose of study treatment within 3 calendar days from vial 
allocation. 
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Table 2-3:
Follow-Up Procedural Outline for All Study Parts (CA115001)
Procedure
Follow-up Visit 1: 
30 Days From Last 
Dose of Study 
Intervention
(± 7 Days)a
Follow-up Visit 2: 
60 Days From Last 
Dose of Study 
Intervention
(± 7 Days)a
Follow-up Visit 3: 
100 Days From 
Last Dose of Study 
Intervention
(± 7 Days)a
Survival Follow-up 
(Assessed Every 12 
Weeks ± 14 Days 
for 2 Years From 
Last Dose of Study 
Intervention)b
Notesc
Safety Assessments
Targeted Physical 
Examination (PE) 
X
X
X
If there are any new or worsening 
clinically significant changes since the 
last examination, report changes on the 
appropriate non-serious or SAE CRF 
page.
Vital Signs and 
Physical 
Measurements
X
X
X
Weight, seated BP, seated heart rate, 
body temperature, and respiratory rate.
BP and heart rate should be measured 
after the participant has been resting 
quietly for at least 5 minutes.
ECOG PS
X
X
X
See Appendix 6.
Hematology,  
Chemistry, and 
Urinalysis
X
X
X
Refer to Section 9.4.4 Clinical Safety 
Laboratory Assessments for the list of 
laboratory tests and urinalysis.
Pregnancy Test 
(WOCBP)
X
X
X
Serum or urine (minimum sensitivity 
equivalent units 25 IU/L or equivalent 
units of hCG) pregnancy testing is 
required. If a urine test cannot be 
confirmed as negative (eg, an 
ambiguous result), a serum pregnancy 
test is required.
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Table 2-3:
Follow-Up Procedural Outline for All Study Parts (CA115001)
Procedure
Follow-up Visit 1: 
30 Days From Last 
Dose of Study 
Intervention
(± 7 Days)a
Follow-up Visit 2: 
60 Days From Last 
Dose of Study 
Intervention
(± 7 Days)a
Follow-up Visit 3: 
100 Days From 
Last Dose of Study 
Intervention
(± 7 Days)a
Survival Follow-up 
(Assessed Every 12 
Weeks ± 14 Days 
for 2 Years From 
Last Dose of Study 
Intervention)b
Notesc
Adverse Event (AE) 
and Serious Adverse 
Events (SAE) 
Assessment
X
X
X
See notes.
Record at each visit. Collect 
continuously throughout the treatment 
period and for a minimum of 100 days 
following discontinuation of dosing.
Beyond 100 days from the last dose of 
study therapy, participants will be 
followed for drug-related AEs/SAEs 
until resolution, returns to baseline, or 
is deemed irreversible, or until the 
participant is lost to follow-up or 
withdraws study consent. Participants 
will be followed for all AEs (SAEs and 
non-serious AEs) associated with 
confirmed or suspected SARS-CoV-2 
infection (as defined in Section 9.2.3).
All AEs/SAEs must be graded using 
CTCAE v5.
Concomitant 
Medications Review
X
X
X
Record at each visit.
Tumor Assessments
Body Imaging
Participants without progressive disease at EOT will have contrast-enhanced CT of the chest, CT/MRI of the abdomen, pelvis, and all 
other known and/or suspected sites of disease every 6 weeks (± 7 days) starting from first dose up until Week 48, and then every 12 
weeks (± 7 days) until withdrawal of consent, death, or initiation of another anti-cancer treatment, whichever occurs first. For 
participants with cancer of the head and neck, a CT or MRI of the neck is required.
Brain Imaging
Participants with NSCLC and/or a history of brain metastasis or symptoms without progressive disease at EOT should have a 
surveillance MRI (without and with contrast) 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.
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Table 2-3:
Follow-Up Procedural Outline for All Study Parts (CA115001)
Procedure
Follow-up Visit 1: 
30 Days From Last 
Dose of Study 
Intervention
(± 7 Days)a
Follow-up Visit 2: 
60 Days From Last 
Dose of Study 
Intervention
(± 7 Days)a
Follow-up Visit 3: 
100 Days From 
Last Dose of Study 
Intervention
(± 7 Days)a
Survival Follow-up 
(Assessed Every 12 
Weeks ± 14 Days 
for 2 Years From 
Last Dose of Study 
Intervention)b
Notesc
Pharmacokinetic (PK) and Immunogenicity Assessments
PK/Immunogenicity 
(IMG) Serial Blood 
Sampling
Refer to Table 9.5-1 for timing of collections.
Participant Status
Assessment of 
Survival Status and 
Subsequent Cancer 
Therapy
X
X
X
X
During Safety Follow-Up and every 3 
months (clinic visit or by telephone) 
during Survival Follow-up. Include 
documentation of subsequent cancer 
therapy (ie, systemic therapy, tumor-
directed surgery, or radiation therapy).
Abbreviations: AE; adverse event; BMS, Bristol-Myers Squibb; BP, blood pressure; CRF, case report form; CT, computed tomography; CTCAE, Common 
Terminology Criteria for Adverse Events; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EOT, end of treatment; hCG, human chorionic 
gonadotropin; IMG, immunogenicity; IU, international units; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PE, physical examination; 
PK, pharmacokinetic; SAE, serious adverse event; SARS-CoV-2, severe acute respiratory syndrome coronavirus disease 2; v, version; WOCBP, women of 
childbearing potential.
a Participants must be followed for at least 100 days after last dose of study intervention. 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) from 
last dose of study intervention. Follow-up Visit 3 occurs approximately 100 days (± 7) from last dose of study intervention.
b Survival Follow-up visits to occur every 12 weeks (± 14 days) from Follow-Up Visit 3. Survival visit 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 or is lost to follow-up.
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 lowest
priority:

Pharmacokinetic sampling

Safety (electrocardiogram)

Safety (clinical labs)
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3
INTRODUCTION
CA115001 is a Phase 1b/2 study of BMS-986442 (AGEN1777), a fragment crystallizable (Fc)-
engineered bispecific human immunoglobulin gamma 1 (IgG1) antibody that selectively blocks  
 
 and may enhance T and natural killer (NK) cell activation in combination with 
nivolumab or with nivolumab and chemotherapy.
The main goals of the study are to characterize the safety profile of BMS-986442 in combination 
with nivolumab or with nivolumab and chemotherapy, and to establish the recommended Phase 2 
dose(s) (RP2D) for these combinations.
Additional goals include the 
 
characterization of the pharmacokinetics (PK) for BMS-986442 and nivolumab, evaluation of the 
pharmacodynamic (PD) effects through analyses of several 
 aimed at establishing proof
of mechanism, and evaluation of the preliminary anti-tumor activity.
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
The development of immune checkpoint therapies has improved outcomes in patients with 
advanced malignancies.1 However, despite the clinical success of agents targeting programmed 
cell death protein 1 (PD-1) or its ligand PD-L1, most patients fail to respond or experience a limited 
duration of response.2
 and 
 are expressed by subsets of T and NK cells where they function as suppressive 
co-inhibitory receptors, including within the tumor microenvironment (TME).3
 and 
 
bind to 
which is expressed on myeloid cells such as antigen-presenting cells (APCs) and 
is overexpressed on tumor cells across several tumor indications.4
 expression has also been 
associated with poor response to anti-PD-1 antibody therapy, suggesting that 
 
blockade combined with PD(L)-1 pathway inhibition may help to overcome immune checkpoint-
mediated immune suppression within the TME.4 In preclinical models, blockade of 
 and 
 through a combination of monospecific antibodies has been shown to enhance anti-tumor 
efficacy compared with single agent treatments, and further enhanced efficacy has been observed 
with triple combination treatment including anti-PD-1. 5 Further supporting the rationale to 
combine BMS-986442 with PD-1 blockade, recent preclinical data support that the PD(L)-1 
pathway may also inhibit CD226 signaling directly via phosphatase recruitment by the PD-1 
intracellular domain.6
There is emerging evidence that Fcγ receptor (FcγR) co-engagement may contribute to anti-tumor 
efficacy in pre-clinical mouse models of immune checkpoint therapies, including 
 
antagonists.7 FcγRIIIA (CD16) co-engagement was shown to be required for optimal APC-
mediated T-cell priming by a 
 antibody in human immune cell assays. Based on these 
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findings, BMS-986442 is engineered with increased affinity to FcγRIIIA to further enhance APC-
mediated T-cell priming in the context of 
 and 
 inhibition. 
Taken together, these findings support the rationale to evaluate BMS-986442 in combination with 
nivolumab (with or without chemotherapy) for its antitumor efficacy and benefit to patients.
3.1.1
Research Hypothesis
Blockade of 
 and 
using BMS-986442 will enhance T and NK cell anti-tumor activity 
in the TME, broadening the therapeutic efficacy of anti-PD-1 based immunotherapy.
3.2
Background
3.2.1
Indication Background
Within the TME, the expression of co-inhibitory receptors such as 
 and 
 on immune 
cells correlates with a chronically exhausted, dysfunctional phenotype and is associated with 
limited response to immunotherapy.8
The Cancer Genome Atlas (TCGA) (across 33 types of indications) supports that 
 and 
 
expression are correlated and highly expressed across a variety of cancer types as compared to 
healthy tissues. Non-small cell lung cancer (NSCLC) and gastric cancer show particularly high 
expression of 
 and 
 within the TCGA dataset. 
 the shared ligand of 
 and 
, is reportedly overexpressed across multiple tumor indications, including NSCLC, 
squamous cell carcinoma of the head and neck (SCCHN), melanoma, pancreatic cancer, colorectal 
carcinoma (CRC), and ovarian cancer.9 Notably, the expression of 
 has been correlated with 
poor overall survival (OS).10 Emerging clinical data support the rationale to target PD(L)-1 
pathway blockade in the context of CD226 co-stimulatory signaling to further enhance T-cell 
responses and drive clinical efficacy.11 The importance of the CD226 pathway has been explored 
in mouse preclinical models representing gastric cancers and SCCHN. Taken together, these 
observations support the evaluation of BMS-986442 in combination with nivolumab (with or 
without chemotherapy) in a range of solid tumors, NSCLC, gastric cancer, and SCCHN.12,13
3.2.2
BMS-986442 Mechanism of Action
BMS-986442 is a Fc-engineered bispecific human IgG1 antibody that selectively blocks 
 
and 
 ligand interactions and enhances T and NK cell activation. 
Selectivity of BMS-986442 for human 
 and 
 was evaluated by surface plasmon 
resonance (SPR) relative to monovalent and bivalent anti-
 and anti-
 control antibodies. 
Results demonstrated that BMS-986442 specifically binds to human 
 and 
, but not to
human CD226, 
 CD111, or CD112. Anti-
 and anti-
bivalent control antibodies 
bound to 
 and 
, respectively and uniquely, confirming the specific binding of 
BMS-986442 for 
 and 
.
BMS-986442 is designed to bind 
 and 
 with high affinity to block the interaction of 
these receptors and their cognate ligand 
 BMS-986442 binds to recombinant human 
 
and 
 in a dose-dependent manner with estimated average affinities (KD) of 0.14 nM and 22.9 
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nM, respectively, as measured by SPR. BMS-986442 binds cynomolgus monkey 
 with an 
estimated average KD of 2.4 nM but does not bind cynomolgus monkey 
 or rodent 
.
In competitive cell-based binding assays, BMS-986442 exhibited concentration-dependent 
blockade of 
 binding to 
 or 
-expressing cells. For BMS-986442, mean IC50
values of 0.07 µg/mL (
-
) and 1.77 µg/mL 
 were determined. In 
contrast, the bivalent isotype control did not disrupt 
 nor 
-
 interactions. 
The monovalent anti-
 control blocked 
-
 interactions but did not disrupt 
-
 interactions. Likewise, the monovalent anti-
 control blocked 
 
interactions but did not disrupt 
-
 interactions. Consistent with the mechanism of 
action, these data demonstrate BMS-986442 is a potent ligand-blocking antagonist of 
 and 
. 
The key biophysical and functional characteristics of BMS-986442 include a high affinity and 
selectivity for human 
 and 
, a capacity for simultaneous antigen binding, an ability to 
block 
 and 
 interactions to its shared ligand 
 enhanced T-cell responsiveness 
and NK cell activation, enhanced binding to FcγRIIA and FcγRIIIA receptors, activation of 
FcγRIIA and FcγRIIIA signaling, and enhanced T-cell effector function in combination with the
anti-PD-1 balstilimab.
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 PD-1-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, 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 (OPDIVOTM) is approved for the treatment of several types of cancer in multiple 
regions including the United States (US, Dec-2014), the European Union (EU, Jun-2015), and 
Japan (Jul-2014).
3.2.4
BMS-986442 Clinical Activity
BMS-986442 is currently being evaluated in Study C-1400-01 (NCT#05025085), which is a Phase 
1 study to evaluate the safety and tolerability, PK, immunogenicity (IMG), and PD of BMS-
986442 (AGEN1777) as a single agent and in combination with balstilimab in patients with 
advanced, metastatic, solid tumors. As of 24-Jun-2022, only the single-agent dose escalation 
component of the study has been initiated. Three participants were treated at each of the 2-, 6-, 
20-, and 60-mg dose levels and 4 participants were treated at the 200-mg dose level, for a total of 
16 patients. Overall, the safety profile of BMS-986442 has been manageable with no dose-limiting 
toxicities (DLTs) or treatment-related serious adverse events (SAEs) reported thus far. One patient 
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with ocular melanoma who received multiple prior lines of therapies, including immunotherapy, 
was treated at the 6-mg dose level and has received 10 cycles of study treatment and has stable 
disease, which is still ongoing. It is anticipated that the study will enroll up to approximately 75 
evaluable patients with measurable advanced/metastatic solid tumors.
3.2.4.1
Preliminary Safety Data of BMS-986442 Monotherapy
Overall, based on preliminary data as of 24-Jun-2022, from study C-1400-01, the safety profile of 
BMS-986442 as monotherapy (n = 16) was manageable at the doses tested (up to 200 mg Q3W).
There were no DLTs or adverse events (AEs) that led to treatment discontinuation. Thirteen of 
sixteen patients had treatment-related AEs (TRAEs), with the most frequently reported being chills 
(n = 5 each, 31.3%), rash (n = 5, 31.3%), nausea, fatigue, and pruritus (n = 2 each, 12.5%). All 
treatment-related AEs were Grade 1 to 2; no Grade 3 or higher TRAEs were reported. For all 
TRAEs, the dose of BMS-986442 was not changed.
Infusion-related treatment-emergent AEs (TEAEs) occurred in 7 (43.8%) patients. Before 
prophylaxis, 6 cases of infusion-related reactions (IRRs) from 8 infusions (75%) were reported. 
After prophylaxis implementation, 4 cases of IRRs from 73 infusions (5.5%) were reported as of 
13-Oct-2022. The most frequently reported infusion-related TEAEs were chills (31.3%), rash
(12.5%), IRRs (6.3%), and nausea (6.3%). On average, infusion-related TEAEs started 1 to 2 hours 
after the end of the infusion and resolved with symptomatic treatment (eg, diphenydramine, 
meperidine, ondansetron, hydromorphone). No infusion-related TEAEs were Grade ≥3 and no 
infusion-related TEAEs led to permanent drug withdrawal or resulted in death. The incidence of 
IRRs has been reduced since establishing an effective prophylactic regimen of diphenhydramine, 
acetaminophen, and extension of the infusion duration to 60 minutes.
3.2.5
Nivolumab Clinical Activity
Nivolumab has demonstrated durable responses exceeding 6 months as monotherapy in several 
tumor types, including NSCLC, melanoma, renal cell carcinoma (RCC), classical Hodgkin 
lymphoma (cHL), small-cell lung cancer (SCLC), gastric cancer, SCCHN, urothelial cancer, 
hepatocellular carcinoma (HCC), and CRC. In confirmatory trials, nivolumab as monotherapy 
demonstrated a statistically significant improvement in OS as compared with the current standard 
of care in patients with advanced or metastatic NSCLC, unresectable or metastatic melanoma, 
advanced RCC, or recurrent or metastatic SCCHN. Details of the clinical activity in these various 
malignancies are provided in the United States Prescribing Information (USPI) and Summary of 
Product Characteristics (SmPC).
3.3
Benefit/Risk Assessment
3.3.1
Risk Assessment
Study CA0115001 is designed to begin with a BMS-986442 and nivolumab safety dose escalation 
in Part A, before moving into the dose expansions in Part B and the dose escalations of BMS-
986442 in combination with nivolumab and the designated chemotherapies occurring in Parts C to 
E.
BMS-986442 Risk Assessment:
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Detailed information about the known and expected benefits, risks, and reasonably anticipated 
adverse events (AEs) of BMS-986442 may be found in the IB.
Consistent with its mechanism of action, BMS-986442 enhances T-cell responsiveness and 
interleukin (IL)-2 secretion in a primary T-cell stimulation assay in which peripheral blood 
mononuclear cells (PBMCs) from healthy human donors are stimulated with staphylococcal 
enterotoxin A (SEA) peptide and increasing concentrations of BMS-986442. However, 
BMS-986442 did not enhance cytokine secretion in the absence of SEA peptide and therefore does 
not pose a significant cytokine-mediated infusion reaction or cytokine release syndrome risk as 
assessed using whole blood or PBMCs from healthy volunteer donors in cytokine release assays.
BMS-986442 poses a low risk for immunogenicity (IMG) as assessed in an in vitro dendritic cell:T 
cell co-culture activation assay. Human PBMCs were obtained from healthy donors with HLA-
DR class II alleles closely reflecting world population frequencies. The frequency of a positive 
response was 12.8%, 15.4%, and 61.5% for BMS-986442, Avastin (low IMG control), and ATR-
107 (high IMG control), respectively.
In a tissue cross reactivity study, BMS-986442-positive staining was observed on hematopoietic 
cells, Kupffer cells, lymphocytes, and Hofbauer cells from human tissues. The staining is 
considered on-target binding since it was consistent with the distribution of 
 in the tissues. 
 binding could not be determined due to technical difficulties to develop appropriate 
immunohistochemistry (IHC) reagents.
Potential safety risks of BMS-986442 may be anticipated based on the clinical evaluation of other 
monospecific 
 antagonistic antibodies. Anti-
 is currently being studied but there is no 
clinical data available at this time. A Phase 1 evaluation of a fully human monoclonal IgG1 
 
antibody, tiragolumab, was well tolerated up to 1200 mg when administered intravenous (IV) Q3W 
in participants with advanced solid tumors. No significant safety concerns were reported in 
participants administered with tiragolumab in combination with the anti-PD-L1 atezolizumab. In 
both the monotherapy and combination cohorts, Grade 3 or greater AEs were only reported in 4% 
of participants.16 In the Phase 2 trial CITYSCAPE, tiragolumab in combination with atezolizumab 
in participants with advanced NSCLC demonstrated a safety profile similar to that of atezolizumab 
alone. Immune-related AEs were more frequent in participants treated with tiragolumab and 
atezolizumab combination but were primarily Grade 1 or 2 and manageable.11
BMS-986442 is currently being evaluated as monotherapy in advanced solid tumors (Protocol C-
1400-01; NCT#05025085). As of 24-Jun-2022, the safety profile of BMS-986442 was manageable 
in 16 participants; 3 participants were treated at each of the 2-, 6-, 20-, and 60-mg dose levels, and 
four participants were treated at the 200-mg dose level (see Section 3.2.4.1).
In whole blood or PBMC cytokine release assay, BMS-986442, both in soluble or dry format, did 
not induce a dose-dependent increase in cytokine levels for IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, 
or IFN-γ, relative to untreated conditions or the isotype control antibody. These data support the 
conclusion that BMS-986442 does not present a significant risk for cytokine release or IRR.
Nivolumab Risk Assessment: 
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Extensive details on the safety profile of nivolumab are available in the IB and will not be repeated 
herein.
Overall, the safety profile of nivolumab monotherapy is manageable and generally consistent 
across completed and ongoing clinical trials with no maximum tolerated dose (MTD) reached at 
any dose tested up to 10 mg/kg. Most AEs were low-grade (Grade 1 to 2) with relatively few 
related high-grade (Grade 3 to 4) AEs. There was no pattern in the incidence, severity, or causality 
of AEs with respect to nivolumab dose level.
A pattern of immune-related AE has been defined, for which management algorithms have been
developed; these are provided in Appendix 7. Most high-grade events were manageable with the 
use of corticosteroids or hormone replacement therapy (endocrinopathies) as instructed in these 
algorithms.
Additional details on the safety profile of nivolumab, including results from other clinical studies, 
are also available in the nivolumab IB.
The frequency of these immune-related AEs may increase for BMS-986442 and nivolumab 
combination therapy with/without chemotherapy.
Nivolumab in Combination with Chemotherapy Risk Assessment: 
Nivolumab in combination with chemotherapy has been assessed in a variety of studies and has 
demonstrated an acceptable safety profile. In part 2 of the Phase 3 Study CA209227,14 the overall 
safety profile of nivolumab plus histology-based platinum-doublet chemotherapy (PDCT) in all 
treated participants with chemotherapy-naive Stage IV or recurrent NSCLC was consistent with 
the established safety profile of each component of the regimen. No new safety signals or toxicities 
were identified relative to previous experience with nivolumab monotherapy or with 
chemotherapy. Grade 3-4 TRAEs were reported in 44.8% and 35.3% of all participants treated 
with nivolumab plus PDCT and PDCT, respectively. Any grade TRAEs were reported in 84.8% 
and 78.4% participants treated with nivolumab plus PDCT and PDCT, respectively. In addition, 
in the Phase 3 Study CA2099LA, the combination of 2 immunotherapy agents, nivolumab and 
ipilimumab plus chemotherapy in treatment-naive NSCLC also demonstrated an acceptable safety 
profile and is now an approved regimen in some countries. In both CA209227 and CA2099LA, 
across all AE categories (serious AEs [SAEs], AEs leading to discontinuation of study drug, AEs), 
all causality and drug-related AEs were higher with the immunotherapy plus chemotherapy 
treatment combination when compared to chemotherapy treatment alone.
Although safety data from nivolumab in combination with docetaxel in NSCLC is not available, a 
non-randomized, multicohort, global Phase II CheckMate 9KD trial of 84 patients with 
chemotherapy-naive metastatic castration-resistant prostate cancer and ongoing androgen 
deprivation therapy received nivolumab in combination with docetaxel and prednisone for up to 
10 cycles followed by nivolumab maintenance for up to 2 years. Overall, safety was consistent 
with the individual treatments. The most common any-grade TRAE reported was fatigue (39.3%) 
and the most common Grade 3-4 TRAE reported was neutropenia (16.7%). Three treatment-
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related deaths were reported (1 pneumonitis related to nivolumab and 2 pneumonias related to 
docetaxel).15
SARS-CoV-2 Infection Risk Assessment:
Immunocompromised patient populations such as those with advanced solid tumors may be more 
susceptible to infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-
2) infections. In addition, the potential impact of BMS-986442 or BMS-986442 in combination 
with nivolumab with/without chemotherapy administration on the frequency or severity of SARS-
CoV-2 infections in participants with advanced solid tumors are currently unknown. Participants 
with recent or acute infections will be excluded or delay the start of treatment as defined in Section
7.4. 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 7.4.2. 
3.3.2
Benefit Assessment
Functional blockade of the 
 and 
 pathways is anticipated to enhance T and NK cell 
effector function and provide increased anti-tumor immunity either alone or in combination with 
PD-1/PD-L1 blockade. BMS-986442 is a Fc-engineered bispecific human IgG1 antibody, 
designed to bind 
 and 
 with high affinity, block the interaction of these receptors and 
their cognate ligand 
and enhance NK cell activation and T-cell responsiveness. 
Furthermore, the BMS-986442 Fc region was engineered to enhance binding to FcγR to further 
improve its ability to enhance T-cell effector function and anti-tumor immunity, consistent with 
the requirement of Fc-FcγR co-engagement between T cells and APCs to promote optimal 
modulation of 
 antibodies.7 Approximately 40% of patients express a low affinity allele of 
FcγRIIIA due to genetic polymorphism. FcγRIIIA polymorphism has been demonstrated to 
contribute to clinical activity of anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)
therapy.4 BMS-986442 demonstrates improved binding to both the high- and low-affinity FcγR 
and hence has the potential for similar clinical activity in participants with both the low- and high-
affinity FcγR. 
The combination of BMS-986442 and the anti-PD-1 antibody balstilimab generated superior T-
cell stimulation, as measured by IL-2 cytokine secretion, in comparison with BMS-986442, 
balstilimab, or the bivalent isotype control antibodies alone, in healthy donor human PBMCs 
stimulated with SEA peptide. These data support the potential benefit of BMS-986442 with anti-
PD-1 antibody such as nivolumab compared to either therapy alone to further augment tumor 
antigen recognition and T-cell responsiveness.
The investigation of 
 antibodies in human subjects has revealed promising anti-cancer 
effects. Two 
 antibodies, tiragolumab (IgG1; Roche) and vibostolimab (IgG1; Merck), 
demonstrated acceptable safety and tolerability profiles alone and in combination with 
atezolizumab (anti-PD-L1 antibody) or pembrolizumab (anti-PD-1 antibody), respectively, in 
patients with advanced solid tumors.16,17 Notably, in the Phase 2 (CITYSCAPE) trial, tiragolumab 
in combination with atezolizumab in advanced NSCLC patients with high levels of PD-L1 (> 50% 
expression) showed an overall response rate (ORR) of 66%, as compared to 24% for atezolizumab 
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therapy alone.11 Similarly, vibostolimab in combination with pembrolizumab demonstrated 
promising clinical efficacy in patients with metastatic NSCLC.18
Nivolumab plus PDCT clinical activity in chemotherapy-naive NSCLC has been demonstrated in 
2 clinical studies. In CA209012, a multi-arm Phase 1 safety study of nivolumab in chemotherapy-
naive 
NSCLC, 
56 
subjects 
were 
administered 
nivolumab 
in 
combination 
with 
cisplatin/gemcitabine, cisplatin/pemetrexed, or carboplatin/paclitaxel. ORR with the different 
combinations ranged from 42% to 50%. Nivolumab in combination with histology-based PDCT
was studied in Part 2 of the Phase 3 trial CA209227.7 In this trial, due to the hierarchical nature of 
the statistical design and because the primary end point of OS in the non-squamous population 
was not statistically significant, additional endpoints were purely descriptive. However, it is 
important to note that ORR, progression-free survival (PFS), and OS all demonstrated trends
towards improved efficacy with the nivolumab plus chemotherapy combination versus 
chemotherapy alone after a minimum follow-up of 19.5 months for OS and 18.4 months for all 
other data. The OS hazard ratio (HR) in all randomized subjects was 0.81 (95.62% confidence 
interval [CI]: 0.67,0.97). The median PFS and OS were numerically higher in participants who 
received nivolumab plus chemotherapy, with a median OS of 18.27 months versus 14.72 months 
in the chemotherapy group, and a median PFS of 8.38 months with the nivolumab plus 
chemotherapy group versus 5.52 months in the chemotherapy group. In addition, ORR was higher 
with nivolumab plus chemotherapy when compared with chemotherapy alone in the all 
randomized population, as well as in the non-squamous (48.1% vs 25.7%) and the squamous 
(59.8% vs 32.4%) patient sub-groups. 
3.3.3
Overall Benefit/Risk Conclusion
Overall, treatment with BMS-986442 in combination with nivolumab with/without chemotherapy 
in participants with advanced solid tumors, including NSCLC, gastric/gastroesophageal junction 
(GEJ) cancer, and SCCHN, is expected to be tolerable, and toxicities of the treatments are expected 
to be manageable. Immune-mediated adverse event (IMAE)-related toxicities may require the use 
of immunosuppressive agents. For management algorithms of AEs related to immuno-oncology 
(IO) agents, refer to Appendix 7.
Taking into account the measures taken to minimize risk to participants in this study, the potential 
risks identified in association with BMS-986442 in combination with nivolumab with/without 
chemotherapy are justified by the anticipated benefits that may be afforded to participants with 
advanced solid tumors, including NSCLC, gastric/GEJ cancer, and SCCHN. In addition, first-line 
therapy of BMS-986442 in combination with nivolumab and PDCT has the potential to improve 
efficacy compared to PDCT in combination with anti-PD-1 therapy.
The Sponsor will evaluate the benefit/risk profile of the study on an ongoing basis. This evaluation 
will be based on all available data, with particular attention to (i) AEs or other safety trends in this 
or any other clinical study of BMS-986442 whose character, severity, and/or frequency suggest 
that participants would be exposed to an unreasonable and significant risk of illness or injury; (ii) 
new nonclinical data suggesting an unreasonable and significant risk of illness or injury.
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If such evaluation suggests that the benefit/risk profile of the study has become unfavorable, the 
Sponsor will pause enrollment and/or treatment until further evaluation of data and until interaction 
with the appropriate Health Authority(ies) can take place regarding potential actions. Such actions 
may include (but are not limited to) study continuation, substantial amendment, or termination of 
the study.
4
OBJECTIVES AND ENDPOINTS
Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Primary
Primary

To characterize the safety and tolerability, and 
to establish the MTD, MAD, and/or RP2D of 
BMS-986442 in combination with nivolumab 
or 
with nivolumab 
and 
the 
following 
chemotherapies: docetaxel; carboplatin and 
pemetrexed; carboplatin and paclitaxel, in 
participants with advanced cancer including 
NSCLC.

Incidence of AEs, SAEs, AEs meeting protocol-defined 
DLT criteria, AEs leading to discontinuation, and death 
(per CTCAE v5.0).
Secondary
Secondary

To
characterize the PK of BMS-986442 
administered in combination with nivolumab or 
in 
combination 
with 
nivolumab 
and 
chemotherapy.

Summary measures of BMS-986442 PK parameters, 
such as, but not limited to, Cmax, Tmax, and AUC (0-
T), from serum concentration-time data for BMS-
986442 when administered in combination with 
nivolumab or in combination with nivolumab and 
chemotherapy.

To 
characterize the immunogenicity 
of 
BMS-986442 administered in combination 
with nivolumab or in combination with 
nivolumab and chemotherapy.

Incidence of ADAs to BMS-986442 when BMS-986442 
is administered in combination with nivolumab or in 
combination with nivolumab and chemotherapy.

To assess the preliminary anti-tumor activity of 
BMS-986442 administered in combination 
with 
nivolumab 
or 
nivolumab 
and 
chemotherapy.

ORR, DOR, DCR, and PFSR at 6 months and 12 months 
per RECIST v1.1 by Investigator.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Abbreviations: ADA, anti-drug antibody; AE, adverse event; AUC (0-T), area under the serum concentration-time 
curve from time zero to the time of the last quantifiable concentration;
 
Cmax, maximum observed concentration; CTCAE, Common Terminology Criteria for Adverse Events; 
 
 DCR, disease control rate; DLT, dose-limiting toxicity; DOR, duration of 
response; 
 
 
 
 MAD, maximum administered dose; MTD, maximum tolerated dose; 
NSCLC, non-small cell lung cancer; ORR, overall response rate; 
 
 
PFSR, progression-free survival rate; PK, pharmacokinetics; 
 RECIST, Response 
Evaluation Criteria in Solid Tumors;
 RP2D, recommended Phase 2 dose(s); SAE, serious 
adverse event; 
 
 
 
Tmax, time of maximum observed concentration; v, version.
5
STUDY DESIGN
5.1
Overall Design
CA115001 is a Phase 1b/2, multi-center, open-label study of BMS-986442 administered in 
combination with nivolumab or nivolumab with 1 of 3 standard chemotherapy regimens used in 
the treatment of advanced solid tumors and advanced or metastatic NSCLC: docetaxel, carboplatin 
with pemetrexed, and carboplatin with paclitaxel. The primary objectives of the proposed study 
are to characterize the safety and tolerability and to establish the RP2Ds and MTDs or evaluate the 
maximum administered dose (MAD) for these combinations. Secondary objectives of the study 
are to characterize the PK and IMG profile and to assess the preliminary antitumor activity of 
BMS-986442 when administered in combination with nivolumab or in combination with 
nivolumab and the designated chemotherapy regimens.
The study is composed of 6 parts, with the dose escalation of BMS-986442 in combination with a 
fixed dose of nivolumab occurring in Part A, the dose expansions for BMS-986442 and nivolumab 
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occurring in Part B, and the dose escalations of BMS-986442 in combination with nivolumab and 
the designated chemotherapies occurring in Parts C to E: docetaxel (Part C), carboplatin and 
pemetrexed (Part D), and carboplatin and paclitaxel (Part E). Part F may include randomized 
cohorts to evaluate whether BMS-986442 (either as monotherapy or in combination) can produce
clinical benefit in participants with advanced/metastatic NSCLC. The design of Part F will be 
reported in a future amendment.
See Section 6.1 (Inclusion Criteria) 
 for specifications.
The study design schematic is presented in Figure 5.1-1.
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Figure 5.1-1:
Study Design Schema
Abbreviations: 1L, first line; 2L, second line; C, Cycle; D, Day; DLX, dose level X; DLY, dose level Y; IO, immuno-oncology; IV, intravenous; GEJ, 
gastroesophageal junction; NSCLC, non-small cell lung cancer; Q3W, every 3 weeks; SCCHN, squamous cell carcinoma of the head and neck.
1 BMS-986442 (IV Q3W) in combination with a fixed dose of nivolumab (360 mg IV Q3W). Intermediate dose levels may be added after discussion and agreement 
between the Sponsor and the Investigators.
2
 
3 Up to 2 tumor-specific expansion cohorts may evaluate one selected dose level that is in the range of tolerable dose levels evaluated in Part A.
4 Parts C, D, and E may be opened after the initial safety evaluation of the first 10 participants in each dose level of Part B1. Each cohort in Parts C, D, and E have 
an optional backfill up to a total of 15 participants per dose level.
5 Part F will be described in a future amendment.
Part A: Dose Escalation
BMS-986442 + Nivolumab 1
Advanced solid tumors
20mg
60mg
200mg
600mg
1200mg
n ≥3 per 
dose level
DL X 
DL Y
Part D: BMS-986442 + Nivolumab + 
Carboplatin + Pemetrexed escalation 1, 4 
1L non-squamous NSCLC
n ≥6 per 
dose level
DL X 
DL Y
Part E: BMS-986442 + Nivolumab + 
Carboplatin + Paclitaxel escalation 1, 4 
1L squamous NSCLC
DL X 
DL Y
Part C: BMS-986442 + Nivolumab + 
Docetaxel escalation  1,4
n ≥6 per 
dose level
n ≥6 per 
dose level
2L+ Post IO NSCLC
DL X
DL Y
n=25 per 
dose level
Part B1: BMS-986442 + 
Nivolumab Randomized 
Dose Expansions 1
2L+ Post IO NSCLC
Gastric/GEJ
n= 20 
Mandatory baseline and on-
treatment tumor biopsies2
Part B2: BMS-986442 + 
Nivolumab 
Dose Expansions Post IO 1,3
SCCHN
n= 20 
Part F: NSCLC 
Randomized 
Cohorts 5
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5.1.1
Screening
The screening period will be up to 28 days and begins by establishing the participant’s initial 
eligibility after signing the informed consent form (ICF). The informed consent may be obtained 
electronically using an electronic consent form where allowed by applicable laws, regulations, and 
Institutional Review Boards (IRBs)/Independent Ethics Committees (IECs). Participants are able 
to opt out of this use and consent on a paper consent if necessary. Participants will be enrolled 
using Interactive Response Technology (IRT). See the Schedule of Activities (Section 2) for study 
procedures conducted during screening.
If a participant exceeds the 28-day screening period due to a study-related procedure (eg,
scheduling of a tumor biopsy or waiting for a study-related laboratory value) or a SARS-CoV-2
infection, the participant must be reconsented, but does not require a new participant identification
number (see Section 6.4.1). In this situation, the Medical Monitor should be notified, and the
fewest number of procedures from the initial screening should be repeated to qualify the
participant, while maintaining participant safety and eligibility.
5.1.2
Treatment Period
The treatment period will last a maximum of approximately 35 cycles (105 weeks) from the first 
dose of study treatment, regardless of treatment delays. For all parts, the DLT evaluation period 
will be 4 weeks or 1 full cycle and 1 week into the second cycle. 
Treatment arms are illustrated in Figure 5.1-1. On-treatment monitoring will include planned clinic 
visits, physical examinations, vital sign measurements, 12-lead ECG, and clinical laboratory 
evaluations that will be performed at selected times throughout the dosing interval (see Section 2).
Imaging for tumor assessment will utilize Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 and will occur every 6 weeks during the first 48 months of treatment, followed by every 12 
weeks during the remainder of treatment. Participants will be closely monitored for AEs 
throughout the study. Samples will be collected before and after study drug administration for PK 
analysis and pharmacodynamic parameter measurements (see Section 9.5 for further details).
5.1.2.1
Part A: Dose Escalation of BMS-986442 with Nivolumab
Part A will evaluate increasing doses of BMS-986442 in combination with nivolumab (360 mg IV 
Q3W). Both agents will be administered IV on a Q3W schedule, and the Bayesian optimal interval 
(BOIN) method will be utilized to guide the dose escalation with approximately 3 to 9 DLT-
evaluable participants per dose level. Five dose levels of BMS-986442 are planned to be evaluated, 
with a starting dose level of 20 mg. The starting dose level of BMS-986442 in combination with 
nivolumab was selected based on results from the ongoing study (C-1400-01, NCT05025085)
sponsored by Agenus, evaluating BMS-986442 monotherapy that has declared all dose levels up 
to 60 mg safe and tolerable (see Section 5.5 for further information). The C-1400-01 study is 
evaluating dose levels of BMS-986442 of 2, 6, 20, 60, 200, and 1200 mg, given to participants 
with advanced solid tumors IV on a Q3W schedule. 
The proposed escalation will start at BMS-986442 20 mg Q3W and escalate up to, but not exceed,
the MTD from the monotherapy escalation in the C-1400-01 study, if the MTD is determined. For 
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the situation that the MTD is not determined in the C-1400-01 study, the highest dose of 
BMS-986442 that may be tested in the Part A escalation of the current study will not exceed the 
maximum dose of BMS-986442 that was evaluated in the C-1400-01 study and that passed DLT 
review. The planned dose levels to be evaluated in the Part A combination escalation may also be 
modified, or intermediate dose levels may be added after discussion and agreement between the 
Sponsor and the Investigators.
The Part A decisions for escalation, de-escalation, or continuing evaluation at the same dose level 
will be guided by the BOIN escalation design framework (Table 5.1.2.1-1) with a target DLT rate 
of 30% (24%, 36%). Up to 9 DLT-evaluable participants may be treated at each dose level, 
depending on the number of observed DLTs. The DLT evaluation period will be 28 days (4 weeks) 
from Cycle 1 Day 1 (C1D1). Dose escalation/de-escalation decisions or decisions 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 PD data.
A staggered dosing (sentinel participant) approach will be used. The first participant in each cohort 
will be observed for at least 7 days after their initial exposure to the combination of BMS-986422 
and nivolumab before additional participants in that cohort are dosed. Subsequently, the remaining 
participants in each dose cohort must be observed for at least 24 hours after their initial exposure 
to the combination regimen before additional participants are exposed.
Initially, the first 3 participants treated in Part A will be evaluated for DLTs. If no DLT is observed 
in the first 3 DLT-evaluable participants, the current dose level will be considered safe, and another 
3 participants will be enrolled at the higher BMS-986442 dose level. If 1 DLT is observed out of 
3 DLT-evaluable participants, an additional 3 to 4 participants will be enrolled at the same 
BMS-986442 dose level. If ≤1 DLTs are observed out of 6 DLT-evaluable participants, the dose 
level will be considered safe. 
Although the maximum number of DLT-evaluable participants at each dose level is 9, if 3 DLTs 
are observed out of 9 DLT-evaluable participants, the design recommends staying at the same dose 
level (Table 5.1.2.1-1). After considering the totality of available data, including safety and PK/PD
from all treated participants, the dose may be considered safe based on discussion between the 
Investigator and Sponsor/Medical Monitor (MM). De-escalation may be considered if the safety 
and tolerability profile for the selected BMS-986442 dose is evaluated as not acceptable, after 
discussion between the Investigator(s) and the Sponsor/MM. Once a tolerable dose level has been 
determined for BMS-986442 in combination with nivolumab in Part A, enrollment in Parts B1 and 
B2 may begin. 
Table 5.1.2.1-1:
Safety Evaluation Guidance for DLT-related Decisions by BOIN 
Design Framework
Actions Based on 
Number of DLTs
Number of DLT-evaluable Participants Treated at the Current Dose
3
4
5
6
7
8
9
10
11
12
Escalate if # of DLT 
≤
0
0
1
1
1
1
2
2
2
2
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Table 5.1.2.1-1:
Safety Evaluation Guidance for DLT-related Decisions by BOIN 
Design Framework
Actions Based on 
Number of DLTs
Number of DLT-evaluable Participants Treated at the Current Dose
3
4
5
6
7
8
9
10
11
12
Stay if # of DLT =
1
1
NA
2
2
2
3
3
3
3, 4
De-escalate if # of 
DLT ≥
2
2
2
3
3
3
4
4
4
5
Eliminate if # of 
DLT ≥
3
3
4
4
5
5
5
6
6
7
Abbreviations: BOIN, Bayesian optimal interval; DLT, dose-limiting toxicity; NA, not applicable.
5.1.2.2
Part B: Dose Expansions Evaluating the Combination of BMS-986442 
and Nivolumab
Part B will be made up of 2 subparts:

Part B1 will involve randomized dose expansions to compare 2 tolerable dose levels in 
participants with 2L+ post-IO/platinum doublet NSCLC.

Part B2 will involve evaluation of 1 selected dose level in 2 additional tumor types: gastric 
cancer/GEJ and SCCHN.
Part B1: Randomized Dose Expansions in Post-IO/Platinum-Doublet NSCLC Participants
Part B1 is designed to further characterize 2 different dose levels of BMS-986442 in combination 
with nivolumab (360 mg IV Q3W) in participants with advanced or metastatic NSCLC who have 
been treated with a platinum-doublet standard of care chemotherapy and have also progressed 
while on a prior PD-(L)1 agent as a monotherapy or in combination. The 2 dose levels for Part B1
will be selected based on the totality of the available data from the Part A dose escalation, including 
safety, tolerability, PK, IMG,
 results. Participants will be randomized to 1 of 
the 2 dose levels and each dose level will treat up to 25 participants.
Participants in Part B1 will undergo mandatory attempted screening biopsy (see Section 9.8.2).
The goal of Part B1 is to evaluate 2 dose levels of BMS-986442 for evidence of PD modulation in 
the tumor, for additional safety and tolerability evaluation and to evaluate preliminary anti-tumor 
efficacy in participants with NSCLC who have progressed on prior PD-(L)1 treatment. The 
available data from Part B will be utilized to identify the RP2D for the doublet combination.
There will be a planned safety review after the first 10 participants in each of the 2 dose levels in 
Part B1 have completed the first 2 cycles of study treatment. The results of this safety review,
along with PK and PD data (as available), will be required to initiate Parts C, D, and E. Enrollment 
into Part B1 will not be paused for this safety review.
Part 
B2: 
BMS-986442 
+ 
Nivolumab, 
Dose 
Expansion
in 
post 
IO 
Gastric 
Cancer/Gastroesophageal Junction and Post-IO SCCHN
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Gastric cancer/GEJ and SCCHN are among the solid tumors with highest expression of 
 and 
 and therefore have the potential to benefit from treatment with BMS-986442 and 
nivolumab. Part B2 includes 2 expansion cohorts in post IO gastric cancer/GEJ and post IO 
SCCHN with approximately 20 response evaluable participants in each. The main objective of 
these expansion cohorts is to further evaluate the safety and preliminary efficacy at a tolerated 
dose level. Part B2 may start once Part A has completed enrollment and the available data are
reviewed for safety and tolerability. The dose of BMS-986442 selected will be based on the totality 
of the data available (eg, safety, PK, PD) and will not exceed the highest dose determined to be 
safe and tolerable in Part A.
5.1.2.3
Parts C, D, and E: Dose Escalation of BMS-986442 in Combination with 
Nivolumab and Chemotherapy in NSCLC
Parts C, D, and E are combination dose escalation cohorts that will evaluate BMS-986442 in 
combination with nivolumab and chemotherapy in NSCLC. They will open after the planned 
safety review of the first 10 participants in each dose level is completed in Part B1. For Parts C, 
D, and E, dose escalation will be guided by the BOIN method and approximately 6 to 12 DLT-
evaluable participants will be treated at each dose level to enable DLT review and dose escalation 
decisions. The subsequent decisions will be based on the BOIN design framework as shown in
Table 5.1.2.1-1. Additional participants (for a maximum of 15 per dose level) may be treated at or 
below the MTD for further evaluation of safety, PK, IMG, and PD parameters. Each part may treat
approximately 30 participants over 2 dose levels.
Part C: Dose Escalation for BMS-986442 in Combination with Nivolumab and Docetaxel
Part C will evaluate up to 2 different dose levels of BMS-986442 in combination with nivolumab
(360 mg IV Q3W) and docetaxel (75 mg/m2 IV Q3W) for this triplet combination in participants 
with advanced or metastatic NSCLC who have been treated with 2L+ platinum-doublet standard 
of care chemotherapy and progressed while on prior PD-(L)1 treatment.
Part D: Dose Escalation for BMS-986442 in Combination with Nivolumab, Carboplatin, and 
Pemetrexed
Part D will evaluate up to 2 different dose levels of BMS-986442 in combination with nivolumab, 
carboplatin, and pemetrexed in participants with advanced/metastatic non-squamous NSCLC who 
have not had systemic therapy for advanced/metastatic disease.
Part E: Dose Escalation for BMS-986442 in Combination with Nivolumab, Carboplatin, and 
Paclitaxel
Part E is designed to evaluate the safety of up to 2 different dose levels of BMS-986442 in 
combination with nivolumab, carboplatin, and paclitaxel in participants with advanced/metastatic 
squamous NSCLC who have not had systemic therapy for advanced/metastatic disease.
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5.1.2.4
Part F: Randomized Cohorts in NSCLC
Phase 2 randomized cohorts may be introduced following a substantial amendment that will fully 
define Part F. The intent of Part F, if proposed, would be to evaluate whether BMS-986442 either 
alone or in combination with nivolumab with/without chemotherapy may provide additional 
clinical benefit over standard-of-care treatment in participants with metastatic NSCLC for frontline 
treatment or subsequent to PDCT and anti-PD-(L)1 therapy. The rationale for the indication 
chosen, the randomized treatment arms, and the dose of BMS-986442 will be based on the 
safety/tolerability, PK/PD, and preliminary efficacy data from Parts A, B1, C, D, and E.
5.1.3
Follow-up Period
The follow-up period includes a safety follow-up and a survival follow-up, which begin after the 
end of treatment visit or date of last dose (whichever occurs later). The safety follow-up period for 
all treatment groups, even if the study is terminated, is 100 days after the end-of-treatment visit or 
date of last dose (whichever occurs later), with visits to occur at 30, 60, and 100 (± 7) days. Survival 
follow-up for all parts will occur every 12 weeks (± 14 days) from Follow-up Visit 3 and last for 
a period of 2 years from the date of discontinuation of study treatment or until death, lost to follow-
up, withdrawal of consent, conclusion of the study, or study termination, whichever comes first.
5.1.4
Data Monitoring Committee and Other Committees
A Data Monitoring Committee (DMC) will not be used in the study.
Although there is not a formal DMC for this study, 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), 
which will be employed in this study. To support safety oversight, BMS has established ongoing 
processes for collection, review, analysis, and submission of individual AE reports and their 
aggregate analyses. Because this is an open-label study, WWPS, the BMS MM, and the 
Investigators will have access to all data necessary for safety evaluation.
BMS WWPS is an internal group that operates independently from the clinical team to monitor
safety across all BMS protocols and to analyze all data in an unblinded fashion. Within BMS, an
SMT is established for investigational therapies under clinical development, and a member of
WWPS chairs this team. In addition, signal detection is performed at least monthly and ad hoc
throughout the study by the SMT composed, at a minimum, of the WWPS medical safety
assessment physician (Chair of the SMT), MM, Global Regulatory lead, and Pharmacovigilance 
Scientist; all of whom analyze the data in an unblinded fashion. Furthermore, the SMT routinely 
monitors for actual or potential issues related to participant safety that could result in a change in 
the medical benefit/risk balance associated with the use of study treatment(s).
If there is any treatment-related Grade ≥ 4 toxicity or death as assessed by the Sponsor, enrollment 
in that arm will be placed on hold and an ad-hoc SMT meeting will be convened. Additionally, a 
Bayesian continuous monitoring framework will be utilized for continuous monitoring of toxicity 
in the study. If at any time during the study, the posterior probability of the DLT rate exceeding 
33% is greater than 0.85, that will also trigger enrollment in that arm being placed on hold and an 
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ad-hoc SMT meeting being convened. The SMT will re-evaluate the benefit-risk profile of the 
drug combination in context of the totality of the data, and assess whether termination or
resumption of the cohort/study is appropriate.
5.2
Number of Participants
The approximate total number of participants treated in Parts A to E will be 225.

Part A: Approximately 45 participants for the dose escalation.

Part B: Approximately 90 participants total, across both subparts B1 and B2.

Part B1: Approximately 50 participants, 25 per dose level.

Part B2: Approximately 40 participants, 20 per tumor type.

Parts C, D, and E: Approximately 30 participants for each part, or 15 participants per dose 
level for up to 2 dose levels, for a total of approximately 90 participants.

Part F: Varies depending on whether randomized participants are in post-IO or 1L NSCLC; 
will be clarified via a future amendment.
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-986442 is being investigated in participants with advanced solid tumors or NSCLC in 
combination with nivolumab or nivolumab and chemotherapy. The study design includes the 
following:

A 28-day screening period

A treatment period that can last up to 2 calendar years (approximately 105 weeks) for
BMS-986442 (Q3W) and/or nivolumab (Q3W)

Dose escalation portion (Part A), advanced solid tumors

Randomized dose expansion (Part B1)

Tumor-specific expansion in gastric and SCCHN (Part B2)

Combinations with chemotherapy (Parts C, D, and E)

Safety follow-up (100 days over 3 visits)

Survival follow-up (up to 2 years after last dose)
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5.4.1
Rationale for Combining BMS-986442 with Nivolumab
 and 
 are expressed on subsets of T and NK cells and function as negative regulators 
of T and NK cell effector function in the TME.3
 and 
 bind to a shared ligand, 
 
which is expressed on APCs and overexpressed on some tumor cells and functions to suppress 
anti-tumor T-cell and NK cell function. 
 expression has been associated with poor response 
to anti-PD-1 therapy, suggesting that blockade of both 
 and 
 are needed to achieve full 
reversal of checkpoint suppression.4 In preclinical models, blockade of 
 and 
 through 
a combination of monospecific antibodies has been shown to enhance anti-tumor efficacy 
compared with single agent treatments, and triple combination with anti-PD-1 to further enhance 
efficacy.5 Further supporting the rationale to combine 
 and 
 blockade with PD-1 
blockade, recent preclinical data support that the PD(L)-1 pathway may also inhibit CD226 
signaling directly.6 Retrospective expression analysis showed that high levels of 
 were
associated with limited response to antibodies targeting the PD(L)-1 pathway, particularly in 
patients with high PD-L1-expressing tumors.19
Taken together, these findings support the rationale to evaluate BMS-986442 in combination with 
nivolumab (with or without chemotherapy) to increase antitumor efficacy and provide clinical 
benefit to patients.
5.4.2
Rationale for Combining BMS-986442 with Nivolumab and 
Chemotherapy
The interaction of a tumor with the immune system is complex. Tumors and the TME are known 
to express a variety of factors that impede a robust immune response from eliminating the tumor. 
Soluble and membrane-bound factors have been shown to inhibit the cytolytic activity of tumor 
infiltrating T cells (eg, PD-L1, transforming growth factor [TGF]-beta). In addition, some tumor-
derived factors are able to enhance immune system counter-regulatory systems, such as increased 
T-regulatory cells. Finally, suboptimal tumor antigen delivery and presentation has been postulated 
as another mechanism by which tumors can successfully evade immune system recognition. 
Cancer therapeutics such as chemotherapy may modulate tumor/immune system interactions in 
favor of the immune system. Chemotherapy can result in tumor cell death with a resultant increase 
in tumor antigen delivery to antigen-presenting cells, and tumor cell death may also lead to a 
reduction in soluble and membrane-bound factors inhibiting tumor-infiltrating T cells. 
Chemotherapy may also disrupt immune system regulatory networks by decreasing numbers of T-
regulatory cells. 
Despite recent innovations in cancer treatment, alternative therapies are needed for participants 
with advanced NSCLC. The recent Food and Drug Administration approvals of pembrolizumab 
in combination with PDCT and nivolumab in combination with ipilimumab and PDCT in first-line 
NSCLC increase the armamentarium of immunotherapy combinations and have improved the 
prognosis in this population. However, less than 50% of patients are expected to benefit from anti-
PD-1/PD-L1 combination therapy, highlighting the need for further investigation into other 
strategies such as simultaneous inhibition of multiple immune checkpoints in combination with 
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chemotherapy. The rationale for combining BMS-986442 and nivolumab (Section 5.4.1) and the 
clinical data from trials studying nivolumab in combination with chemotherapy suggest a potential 
for increasing benefit by combining these agents and targeting their non-overlapping mechanisms 
of action (see Section 3.2.2 and Section 3.2.3). The safety profile of nivolumab in combination 
with chemotherapy has been manageable. Therefore, it is expected that once the safety profile of 
BMS-986442 and nivolumab is evaluated in Part A and is on-going in Part B1 in this study, 
addition of BMS-986442 to nivolumab and chemotherapy will provide an acceptable benefit/risk 
ratio for further evaluation in Parts C, D, and E.
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 2-4 months, and 
emerging data suggests that benefit can be maintained in the absence of continued treatment. A 
retrospective pooled analysis of 2 melanoma studies suggests that the majority of patients who 
discontinue nivolumab and/or ipilimumab for toxicity maintain disease control in the absence of 
further treatment.20
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 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.21 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).22
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; HR = 0.42 (95% CI, 0.25 to 0.71). 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. 
Collectively, these data suggest that there is minimal if any benefit derived from continuing IO 
treatment beyond 2 years in advanced tumors. Even though immunotherapy is well tolerated, 
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patients will be at risk for additional toxicity with longer-term treatment. Therefore, in this study, 
treatment 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 atypicalclinical 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 a BMS Phase 2 study 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 target lesions and as newly visible small 
non-target 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.
5.5
Justification for the BMS-986442 Dose
CA115001 is the first study combining BMS-986442 plus nivolumab with and without
chemotherapy. The BMS-986442 starting dose of 20 mg IV Q3W was selected based on the totality 
of available preclinical and clinical data from the ongoing Agenus C-1400-01 Phase 1 study. 
Based on preclinical data, a Q3W-dosing interval for BMS-986442 is supported by estimated
human PK parameters. The serum terminal half-life of BMS-986442 was calculated to be 
 
days in a single-dose non-Good Laboratory Practice cynomolgus monkey toxicokinetic study. The 
predicted serum BMS-986442 terminal half-life in humans was estimated to be ~  days.
Agenus C-1400-01 is an ongoing Phase 1 study that is evaluating the safety, tolerability, PK, IMG, 
and PD of BMS-986442 (AGEN1777) as a single agent in participants with advanced, metastatic 
solid tumors. As of 24-Jun-2022, 16 participants have been treated Q3W with 2 mg (n = 3), 6 mg
(n = 3), 20 mg (n = 3), 60 mg (n = 3), and 200 mg (n = 4) BMS-986442. There have been no 
reported DLTs, all dose levels tested were declared tolerable, and the monotherapy MTD/MAD
has not yet been determined (Section 3.2.4.1).
The starting dose of BMS-986442 (20 mg IV Q3W) in study CA115001 is below the 60-mg dose
of BMS-986442 that has cleared the DLT evaluation in the ongoing C-1400-01 study.
5.5.1
Nivolumab
The nivolumab dose of 360 mg IV Q3W was selected based on clinical data and modeling and 
simulation approaches using population PK (PPK) and exposure-response (E-R) analyses of data 
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from studies in multiple tumor types (melanoma, NSCLC, and RCC) where body weight 
normalized dosing (mg/kg) was used.
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 up to 10 mg/kg IV Q2W. Nivolumab monotherapy was originally approved as a body-
weight based dose of 3 mg/kg IV Q2W, and was updated to 240 mg IV Q2W or 480 mg IV Q4W 
in multiple indications.23,24 Nivolumab 360 mg IV Q3W is also under evaluation in monotherapy 
and in combination therapy studies. Less frequent 360 mg IV Q3W and 480 mg IV Q4W dosing 
regimens can reduce the burden to patients of frequent, lengthy IV treatments and allow 
combination of nivolumab with other agents using alternative dosing regimens. 
The benefit/risk profiles of nivolumab 240 mg IV Q2W, 360 mg IV Q3W, and 480 mg IV Q4W 
are predicted to be comparable to 3 mg/kg IV Q2W. This assessment is based on a comprehensive 
characterization of nivolumab PK, safety, efficacy, and E-R relationships across indications. PPK 
analyses have shown that the PK of nivolumab is linear with proportional exposures over a dose 
range of 0.1 to 10 mg/kg; no clinically meaningful differences in PK across ethnicities and tumor 
types were observed. Using the PPK model, the exposures following administration of several 
dosing regimens of nivolumab administered as a flat dose were simulated, including 240 mg IV 
Q2W, 360 mg IV Q3W, and 480 mg IV Q4W. The simulated average serum concentration at 
steady state (Cavgss) following administration of nivolumab 360 mg IV Q3W and 480 mg IV 
Q4W are predicted to be similar to those following administration of nivolumab 240 mg IV Q2W 
and nivolumab 3 mg/kg IV Q2W administered to patients over a wide body weight range (34-180 
kg) across tumor types. 
Extensive E-R analyses of multiple PK measures (maximum serum concentration [Cmax] at Day 
1, average serum concentration [Cavg] at Day 28, and trough serum concentration [Cmin] at Day 
28) and efficacy and safety endpoints indicated that the efficacy of the flat-dose 480 mg IV Q4W 
regimen is similar to that of the 3 mg/kg IV Q2W regimen. In E-R efficacy analyses for OS and 
ORR conducted in melanoma, RCC, and NSCLC using Cavgd28 as the exposure measure, 
probabilities of achieving a response and survival probabilities at 1 year and 2 years for 480 mg 
IV Q4W were similar to those of 3 mg/kg IV Q2W. In E-R safety analyses, it was demonstrated 
that the exposure margins for safety are maintained following nivolumab 480 mg IV Q4W, and 
that the predicted risks of discontinuations due to AEs or death, AE Grade 3+, and IMAEs Grade 
2+ are similar following nivolumab 480 mg IV Q4W relative to nivolumab 3 mg/kg IV Q2W 
across tumor types. In addition, nivolumab exposures with 240 mg IV Q2W, 360 mg IV Q3W, 
and 480 mg IV Q4W flat-dose regimens across tumor types are maintained well below the 
corresponding exposures observed with the well-tolerated 10 mg/kg IV Q2W regimen.
Additional details on nivolumab posologies and benefit/risk can be found in the IB.
5.6
Clinical Pharmacology Summary of Nivolumab
Nivolumab PK was assessed using a PPK approach for single-agent nivolumab.
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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 as 
a 60-minute IV infusion 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. 
Nivolumab CL does not decrease over time in patients with completely resected melanoma, as the 
geometric mean population CL is 24% lower in this patient population compared with patients 
with metastatic melanoma at steady state. 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 IV 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 IV every 2 
weeks. The predicted exposure (Cavg and Cmax) of nivolumab after a 30-minute infusion is 
comparable to that observed with a 60-minute infusion.
Specific Populations: The PPK analysis suggested that the following factors had no clinically 
important effect on the CL of nivolumab: age (29 to 87 years), weight (35 to 160 kg), gender, race, 
baseline lactate dehydrogenase (LDH), PD-L1 expression, solid tumor type, tumor size, renal 
impairment, and mild hepatic impairment. 
Renal Impairment: The effect of renal impairment on the CL of nivolumab was evaluated by a 
PPK 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 CL of nivolumab 
were found between patients with renal impairment and patients with normal renal function.
Hepatic Impairment: The effect of hepatic impairment on the CL of nivolumab was evaluated by 
PPK analyses in patients with HCC and in patients with other tumors with mild hepatic impairment 
(total bilirubin [T. bili] less than or equal to the upper limit of normal [ULN] and aspartate 
aminotransferase [AST] greater than ULN or T. bili greater than 1 to 1.5 times ULN and any AST)
and in HCC patients with moderate hepatic impairment (T. bili greater than 1.5 to 3 times ULN 
and any AST). No clinically important differences in the CL 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 IB and product 
label.
Nivolumab 360 mg IV Q3W is approved in combination with ipilimumab 1 mg/kg IV Q6W in 
patients with malignant pleural mesothelioma, in combination with ipilimumab 1 mg/kg Q6W and 
2 cycles of platinum-doublet chemotherapy in patients with metastatic NSCLC, and in combination 
with fluoropyrimidine- and platinum-containing chemotherapy in patients with gastric cancer, GEJ 
cancer, and esophageal adenocarcinoma. Nivolumab 360 mg IV Q3W will be the dosing regimen
used in combination with BMS-986442 with or without chemotherapy in this study.
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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 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.
2) Type of Participant and Target Disease Characteristics
a) Participants in all parts of the study must have measurable disease per RECIST v1.1 
(Appendix 5).
b) Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 
or 1 (Appendix 6).
c) Participants must have a life expectancy of at least 3 months at the time of first dose.
d) Participants in Part A advanced solid tumors must meet all of the following:
i)
Documented 
histologically 
or 
cytologically 
confirmed 
advanced 
unresectable/metastatic solid malignancy of any histology.
ii) Have progressed on, are ineligible for, or intolerant of existing therapy(ies) known to 
provide clinical benefit for the condition of the participant.
iii) Have experienced radiographically documented progressive disease on or after the 
most recent therapy.
e) Participants in Part B2 gastric cancer/GEJ expansion must meet all of the following:
i)
Advanced or metastatic gastric or GEJ cancer and have progressed during or after, or 
been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic 
setting (or have progressed within 6 months of adjuvant therapy).
ii) Disease progression while on or after prior PD-(L)1 treatment as monotherapy or in 
combination with other modalities.
iii) Participants with known human epidermal growth factor receptor 2 (HER2)-positive 
gastric cancer must have received prior treatment with a HER2 inhibitor (eg, 
trastuzumab).
f)
Participants in Part B2 SCCHN expansion must meet all of the following:
i)
Documented histologically confirmed, recurrent, or metastatic SCCHN (oral cavity, 
pharynx, larynx), and not amenable to local therapy with curative intent. Any other 
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cancers of the head and neck, including nasopharyngeal cancer, salivary gland, and 
neuroendocrine tumors are excluded.
ii) Disease progression on or after, or been intolerant to, a platinum-containing regimen.
iii) Prior focal palliative radiotherapy must have been completed at least 2 weeks before 
study drug administration.
iv) Documented historical human papillomavirus (HPV) status for oropharyngeal cancers. 
HPV status should preferably be determined using p16 IHC or HPV polymerase chain 
reaction (PCR) (if available).
v) Disease progression while on or after prior PD-(L)1 treatment as monotherapy or in 
combination with other modalities, if available.
g) Participants in Parts B1 and C, NSCLC, must meet all of the following:
i)
Documented histologically or cytologically confirmed metastatic NSCLC of non-
squamous or squamous histology with Stage IV A/B (as defined by the 8th International 
Association for the Study of Lung Cancer Classification) or recurrent disease following 
multi-modal therapy for locally advanced disease, measurable by RECIST v1.1.
ii) Recurrent or progressive disease during or after PDCT for advanced or metastatic 
disease OR must have recurrent or progressive disease within 6 months after 
completing PDCT for local disease.
iii) Disease progression while on or after prior PD-(L)1 treatment as monotherapy or in 
combination with other modalities.
iv) Prior definitive chemoradiation for locally advanced disease is permitted as long as the 
last administration of chemotherapy or radiotherapy (whichever was given last) 
occurred less than 6 months prior to enrollment.
v) Participants with disease having known actionable mutations in epidermal growth 
factor receptor (EGFR) including exon 20 insertion mutations, anaplastic lymphoma 
kinase (ALK), ROS proto-oncogene 1 (ROS1), rearranged during transfection (RET), 
neurotrophic tropomyosin-receptor kinase (NTRK), Kirsten rat sarcoma (KRAS)
(G12C), MET exon 14 skipping mutations, or proto-oncogene B-Raf (BRAF) (V600E) 
must have progressed on, have been intolerant to, or not be a candidate for standard 
targeted therapy (as available per country/region standard-of-care practices).
vi) Experienced radiographically documented progressive disease on or after the most 
recent therapy.
h)
 
 
 
 
i)
Participants in Parts D and E, NSCLC, must meet all of the following:
i)
Documented histologically or cytologically confirmed metastatic NSCLC of non-
squamous (Part D) or squamous (Part E) histology with Stage IV A/B (as defined by 
the 8th International Association for the Study of Lung Cancer Classification) or 
recurrent disease following multi-modal therapy for locally advanced disease, 
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measurable by RECIST v1.1, who have not had systemic therapy for metastatic or 
recurrent disease.
ii) Participants with disease having known genetic aberrations in EGFR including exon 
20 insertion mutations, ALK, ROS1, KRAS (G12C), RET, NTRK, MET exon 14 
skipping mutations or BRAF (V600E) that are sensitive to targeted therapy (as 
available per country/region standard-of-care practices) will be excluded.
iii) Prior definitive chemoradiation for locally advanced disease is permitted as long as the 
last administration of chemotherapy or radiotherapy (whichever was given last) 
occurred at least 6 months prior to enrollment.
iv) Prior adjuvant or neoadjuvant chemotherapy for early-stage lung cancer is permitted if 
completed at least 6 months prior to initiating study treatment.
j)
Part F: Criteria for Part F will be similar to either Part C or Parts D/E, dependent on the 
population chosen (either post-PDCT and anti-PD-[L1] therapy or treatment-naive 
NSCLC), and will be added via a future amendment.
3) Age of Participant
Participant must be ≥ 18 years of age or local age of majority at the time of signing the informed 
consent.
4) Reproductive Status
Investigators shall counsel women of childbearing potential (WOCBP), and male participants 
who are sexually active with WOCBP, on the importance of pregnancy prevention, the 
implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to 
transmission of study intervention, present in seminal fluid, to a developing fetus, even if the 
participant has undergone a successful vasectomy or if the partner is pregnant.

The Investigator shall evaluate the effectiveness of the contraceptive method in relationship 
to the first dose of study intervention.

Local laws and regulations may require the use of alternative and/or additional 
contraception methods.
a) Female Participants:
i)
Females ages 18 years, or age of majority, or older at time of consent.
ii) Female participants who are not of childbearing potential must have documented proof 
that they are not of childbearing potential.
iii) Women who are not of childbearing potential are exempt from contraceptive 
requirements.
iv) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 
IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior 
to the start of study treatment. An extension up to 72 hours prior to the start of study 
treatment is permissible in situations where results cannot be obtained within the 
standard 24 hour window.

If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy 
test is required. In such cases, the participant must be excluded from participation if the serum 
pregnancy result is positive.
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
Additional requirements for pregnancy testing during and after study intervention are located 
in Section 2, Schedule of Activities.

The Investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
v) WOCBP must agree to follow instructions for method(s) of contraception defined in 
Appendix 4 and as described below and included in the ICF.

WOCBP are permitted to use hormonal contraception methods (as described in Appendix 4).
vi) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least 1 of the following conditions applies:
(a) Is not a WOCBP 
OR
(b) Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of < 1% per year), preferably with low user dependency, as 
described in Appendix 4 during the intervention period and for the duration 
described below, and agrees not to donate eggs (ova, oocytes) for the purpose 
of reproduction for the same time period:
(i) All participants: 6 months after last dose.
b) Male Participants:

Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception as defined in Appendix 4 and as described below.
i)
Azoospermic male participants enrolled in Parts A, B1, or B2 are exempt from 
contraceptive requirements. However, azoospermic male participants enrolled in Parts 
C, D, or E 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 enrolled in Parts C, D, or E are required 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 enrolled in Parts C, D, or E in the study should be advised to 
use highly effective methods of contraception during the study intervention period and 
for at least 3 months after the last dose of the male participant’s study intervention.
iv) Male participants enrolled in Parts C, D, or E with a pregnant or breastfeeding partner 
must agree to remain abstinent from penile-vaginal intercourse or use a male condom 
during each episode of penile penetration during the intervention period and for at least 
3 months after the last dose of study intervention.
v) Male participants enrolled in Parts C, D, or E must refrain from donating sperm during 
the intervention period and for at least 3 months after the last dose of study intervention.
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.
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vii)No additional contraceptive measures are required to be used for male participants 
enrolled in Parts A, B1, or B2.
6.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1) Medical Conditions
a) Untreated symptomatic 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 randomization in 
study Part B1, or treatment assignment in all other study parts. Imaging performed within 
28 days prior to first study treatment in study Part B1 or treatment assignment in all other 
study parts must document radiographic stability of CNS lesions and be performed after 
completion of any CNS directed therapy.
b) Leptomeningeal metastases.
c) Concurrent malignancy (present during screening) requiring treatment or history of prior 
malignancy active within 2 years prior to randomization in study Part B1 or treatment 
assignment in all other study parts (ie, participants with a history of prior malignancy are 
eligible if treatment was completed at least 2 years before randomization/ treatment 
assignment and the patient has no evidence of disease). Participants with history of prior 
early-stage basal/squamous cell skin cancer or non-invasive or in situ cancers that have 
undergone definitive treatment at any time are also eligible.
d) Participants with an active, known, or suspected autoimmune disease. Participants with 
type 1 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.
e) 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 randomization in study Part B1 or treatment assignment in all other study 
parts. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily 
prednisone equivalent, are permitted in the absence of active autoimmune disease. 
f)
Prior organ or tissue allograft.
g) Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless 
the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
h) History of life-threatening toxicity related to prior T-cell agonist or checkpoint inhibitor 
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 other immune checkpoint pathways), except 
those that are unlikely to re-occur with standard countermeasures (eg, hormone 
replacement after adrenal crisis).
i)
History of or with active interstitial lung disease or pulmonary fibrosis.
j)
Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal 
therapy ≤ 7 days prior to the first dose of study treatment.
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k) Known human immunodeficiency virus (HIV) positive with an acquired immune 
deficiency syndrome (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 for at least 4 weeks prior to randomization in 
study Part B1 or Part F or treatment assignment in all other study parts, as clinically 
indicated, while enrolled on study.
ii) They have a documented HIV viral load of less than 400 copies/mL within 4 weeks 
prior to the first dose of study treatment.
iii) They continue on antiretroviral therapy as clinically indicated while enrolled on study.
iv) 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.
l)
Participants with serious or uncontrolled medical disorders.
m) Subject has any condition, including active or uncontrolled infection, or the presence of 
laboratory abnormalities, which places the subject at unacceptable risk if he/she were to 
participate in the study.
n) Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections, or 
20 days for severe/critical illness, prior to C1D1. 
i)
Acute symptoms must have resolved and based on Investigator assessment in 
consultation with the MM, there are no sequelae that would place the participant at a 
higher risk of receiving study treatment.
o) Uncontrolled or significant cardiovascular disease including, but not limited to, any of the 
following:
i)
Myocardial infarction or stroke/transient ischemic attack within the past 12 months.
ii) Uncontrolled angina within the past 3 months.
iii) History of aortic aneurysm.
iv) Any history of clinically significant arrhythmias (such as ventricular tachycardia, 
ventricular fibrillation, or Torsades de Pointes).
v) History of other clinically significant heart disease (eg, cardiomyopathy, congestive 
heart failure with New York Heart Association functional classification III to IV, 
pericarditis, or significant pericardial effusion).
vi) Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
vii)QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation > 
480 msec, except for right bundle branch block.
viii)
History of myocarditis, regardless of etiology.
2) Reproductive Status
a) Woman who are pregnant.
b) Women who are breastfeeding.
3) Prior/Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7
Concomitant Therapy.
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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.
c) Radiation therapy within 2 weeks prior to first study treatment. Participants must have 
recovered (ie, Grade ≤1 or at baseline) from radiation-related toxicities prior to first study 
treatment.
d) Prior treatment with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, or any other 
antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways for 
Parts D and E.
e) Systemic anticancer therapies or biological therapies within 4 weeks or 5 half-lives 
(whichever is shorter) prior to the first administration of study treatment.
f)
Participation in a study of an investigational agent and received study therapy or used an 
investigational device within 28 days or 5 half-lives (whichever is shorter).
g) Treatment with any live/attenuated vaccine within 30 days of first study treatment.
h) Previous SARS-CoV-2 vaccine within 7 days of C1D1. For vaccines requiring more than 
1 dose, the full series (eg, both doses of a 2-dose series) should be completed prior to C1D1
when feasible and when a delay in C1D1 would not put the study participant at risk.
i)
Part C: Prior docetaxel therapy is not permitted.
j)
Parts D and E: Prior systemic therapy for advanced or metastatic NSCLC is not permitted.
k) Prior therapy with an anti-
 or anti-
 antibody.
4) Allergies and Adverse Drug Reaction
a) History of allergy or hypersensitivity to study drug components.
b) Part C: History of hypersensitivity to docetaxel or polysorbate 80.
c) Part D: Hypersensitivity to pemetrexed, carboplatin, or any of the excipients.
d) Part E: Hypersensitivity to paclitaxel, carboplatin, or any of the excipients.
5) Physical and Laboratory Test Findings
a) White blood cells < 2000/μL.
b) Neutrophils < 1500/μL (stable off any growth factor within 4 weeks of first study treatment 
administration).
c) Platelets < 100 x 103/μL (transfusion to achieve this level is not permitted within 2 weeks 
of first study treatment administration).
d) Hemoglobin < 9.0 g/dL (transfusion to achieve this level is not permitted within 2 weeks 
of first study treatment administration).
e) Serum/plasma creatinine > 1.5 x ULN, unless creatinine clearance (CrCl) ≥ 40 mL/min 
(measured or calculated using the Cockroft-Gault formula).
f)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): > 3.0 x ULN.
Participants in Part C only: AST and/or ALT > 1.5 x ULN concomitant with alkaline 
phosphatase > 2.5 x ULN.
g) All participants, except Part C: Total bilirubin > 1.5 x ULN (except participants with 
Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN).
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Participants in Part C only: Total bilirubin > ULN. 
h) Any positive test result for hepatitis B virus (HBV) indicating presence of virus, eg,
Hepatitis B surface antigen (sAG, Australia antigen) positive.
i)
Any positive test result for hepatitis C virus (HCV) indicating presence of active viral 
replication (detectable HCV-ribonucleic acid [RNA]). Note: Participants with positive 
HCV antibody and an undetectable HCV RNA are eligible to enroll.
j)
Participants with ≥Grade 2 peripheral neuropathy for Parts C, D, and E.
6) 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 for participants in Part C.
d) Any major surgery within 4 weeks of study drug administration. Participants must have 
recovered from the effects of major surgery or significant traumatic injury at least 14 days 
before the first dose of study treatment.
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 SAEs.
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).
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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 Table 2-1, Screening Procedural 
Outline, may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the MM may be needed to identify whether repeat testing of any particular parameter is 
clinically relevant.
Some participants may develop suspected or confirmed symptomatic SARS-CoV-2 infection, or 
be discovered to have asymptomatic SARS-CoV-2 infection during the screening period. In such 
cases, participants may be considered eligible for the study after meeting all inclusion/exclusion 
criteria related to active infection, and after meeting the following criteria: 

At least 10 days (20 days for severe/critical illness) have passed since symptoms first appeared 
or positive RT-PCR or viral antigen test result, and

At least 24 hours have passed since last fever without the use of fever-reducing medications, 
and

Acute symptoms (eg, cough, shortness of breath) have resolved and 

In the opinion of the Investigator, there are no SARS-CoV-2 infection sequelae that may place 
the participant at a higher risk of receiving investigational treatment

In the instance of a SARS-CoV-2 infection during screening, the screening period may be 
extended beyond the protocol-specified timeframe with MM approval.

Any screening tests already performed which could potentially be affected by the SARS-CoV-
2 infection or its complications on an individual basis and agreed upon with the MM (eg, safety 
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.
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7.1
Study Interventions Administered
The selection and timing of dose for each participant is as follows:
Table 7.1-1:
Study Interventions for Parts A to C
Part
Part A
Part B1 & B2
Part C
Intervention 
Name
BMS-986442 + nivolumab
BMS-986442 + nivolumab 
BMS-986442 + nivolumab + 
docetaxela
Type 
Biologic + Biologic
Biologic + Biologic
Biologic + Biologic + Drug
Dose Formulation
Solutions in a single-use 
vial
Solutions in a single-use vial
Solutions in a single-use vial
Unit Dose 
Strength(s)
mg/vial + 100 mg/vial
or
 mg/vial + 100 mg/vial
mg/vial + 100 mg/vial
or
 mg/vial + 100 mg/vial
 mg/vial + 100 mg/vial + 
various strengths
or
 mg/vial + 100 mg/vial + 
various strengths
Dosage Level(s)
BMS-986442: 20, 60, 200, 
600, 1200 mg Q3W
Nivolumab 360 mg Q3W
BMS-986442: Doses Q3W 
TBD
Nivolumab 360 mg Q3W
BMS-986442: Doses Q3W 
TBD
Nivolumab 360 mg Q3W
Docetaxel 75 mg/m2 Q3W
Route of 
Administration
IV infusions
IV infusions
IV infusions
Use
Experimental
Experimental
Experimental + SOC
IMP and Non-
IMP/AxMP
IMP + IMP
IMP + IMP
IMP + IMP + IMP
Sourcing
Provided centrally by the 
Sponsor
Provided centrally by the 
Sponsor
Provided locally by the trial 
site (docetaxel)b + provided 
centrally by the Sponsor 
(BMS-986442 + 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)
TIGIT bispecific antibody 
(BMS-986442)
Anti-PD-1 (nivolumab) or 
BMS-936558 or MDX1106 
or Ono-4538
TIGIT bispecific antibody 
(BMS-986442)
Anti-PD-1 (nivolumab) or 
BMS-936558 or MDX1106 
or Ono-4538
TIGIT bispecific antibody 
(BMS-986442)
Anti-PD-1 (nivolumab) or 
BMS-936558 or MDX1106 
or Ono-4538
Taxane/Taxotere
chemotherapy (docetaxel)
Abbreviations: AxMP, auxiliary medicinal product; BID, twice daily; IMP, investigational medicinal product; IV, 
intravenous; PD-1, programmed cell death protein 1; Q3W, every 3 weeks; SmPC, Summary of Product 
Characteristics; SOC, standard of care; TBD, to be determined; TIGIT, T cell immunoreceptor with Ig and ITIM 
domains.
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a Premedication consists of an oral corticosteroid, such as dexamethasone 16 mg per day (eg, 8 mg BID) for 3 days 
starting 1 day prior to docetaxel administration (see Section 7.1.2).
b 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 for Parts D and E
ARM Name
Part D
Part E
Intervention Name
4 cycles of BMS-986442 + nivolumab + 
carboplatin + pemetrexed,a followed by 
BMS-986442 + nivolumab + pemetrexed 
maintenance
4 cycles of BMS-986442 + nivolumab + 
carboplatin + paclitaxel,b followed by 
BMS-986442 + nivolumab maintenance
Type 
Biologic + Biologic + Drug + Drug
Biologic + Biologic + Drug + Drug
Dose Formulation
Solutions in a single-use vial
Solutions in a single-use vial
Unit Dose Strength(s)
 mg/vial or 
 mg/vial + 100 mg/vial + 
450 mg/vial /various strengths + 500 
mg/vial/various strengths
 mg/vial or 
 mg/vial + 100 mg/vial 
+ 450 mg/vial /various strengths + 100 
mg/vial/various strengths
Dosage Level(s)
BMS-986442: Dose TBD Q3W
Nivolumab 360 mg Q3W
Carboplatin AUC 5 or AUC 6 Q3Wc
Pemetrexed 500 mg/m2 Q3W 
BMS-986442: Dose TBD Q3W
Nivolumab 360 mg Q3W
Carboplatin AUC 6 Q3W 
Paclitaxel 200 mg/m2 Q3W 
Route of 
Administration
IV Infusions
IV Infusions
Use
Experimental (BMS-986442 + nivolumab) 
+ SOC
Experimental (BMS-986442 +
nivolumab) + SOC
IMP and Non-
IMP/AxMP
IMP + IMP + IMP + IMP
IMP + IMP + IMP + IMP
Sourcing
Provided locally by the trial site
(carboplatin, pemetrexed, and paclitaxel)d
+ provided centrally by the Sponsor 
(BMS-986442 + Nivolumab)
Provided locally by the trial site
(carboplatin, pemetrexed, and paclitaxel)d
+ provided centrally by the Sponsor 
(BMS-986442 + 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)
TIGIT bispecific antibody (BMS-986442)
Anti-PD-1 (nivolumab) or BMS-936558 or 
MDX1106 or Ono-4538
Platinum chemotherapy (carboplatin)
Folate analog metabolic inhibitor 
(pemetrexed)
TIGIT bispecific antibody (BMS-986442)
Anti-PD-1 (nivolumab) or BMS-936558 
or MDX1106 or Ono-4538
Platinum chemotherapy (carboplatin)
Taxane chemotherapy (paclitaxel)
Abbreviations: AUC, area under the serum concentration-time curve; AxMP, auxiliary medicinal product; IMP, 
investigational medicinal product; IV, intravenous; PD-1, programmed cell death protein 1; Q3W, every 3 weeks; 
SOC, standard of care; TBD, to be determined; TIGIT, T cell immunoreceptor with Ig and ITIM domains.
a Premedications for use with pemetrexed include corticosteroids, folic acid, vitamin B12, and antiemetic treatments 
(see Section 7.1.3).
b Premedications for use with paclitaxel include corticosteroids and histamine H2-receptor blockers (see Section 
7.1.4).
c Dose selected per local SOC.
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d Sponsor may provide carboplatin, pemetrexed, and paclitaxel in regions where it is not available through insurance
or as part of SOC.
During the treatment phase, participants will receive 1 of the treatment regimens by arm described 
in Table 7.1-1 and Table 7.1-2.
7.1.1
Part A and Part B: Nivolumab and BMS-986442
Nivolumab will be administered as the first infusion. Participants will receive nivolumab at a dose 
of 360 mg over an approximately 30-minute infusion each treatment cycle followed by an
observation period of at least 30 minutes. If needed, flush the IV line with an appropriate amount 
of diluent (eg, 0.9% Sodium Chloride or 5% Dextrose in water) to ensure that the complete dose 
is administered over approximately 30 minutes. Begin study treatment within 3 calendar days of 
randomization in study Part B1 or treatment assignment in all other study parts.
Participants will receive BMS-986442 at the dose level indicated dependent on treatment 
assignment or randomization. BMS-986442 (20 mg dose level up to and including 600 mg dose 
level) will be administered as an infusion over 60 minutes (Q3W) followed by a 60-minute 
observation period. BMS-986442 at the 1200 mg dose level will be administered as an infusion 
over 90 minutes (Q3W), followed by a 60-minute observation period.
There will be no intra-subject dose escalations or reductions of BMS-986442 or nivolumab 
allowed. For Q3W dosing cycles, participants may be dosed no less than 19 days from the previous 
dose. Premedications are not recommended for the first dose of nivolumab. Participants should 
receive prophylaxis with IV diphenhydramine 25 mg (or equivalent) 30 minutes prior to dosing of 
BMS-986442 with or without acetaminophen 325 to 1000 mg administered 30 to 60 minutes 
before the first 3 study drug administrations of BMS-986442. If pre-dosed premedicated 
participants experience no infusion-related reactions (IRRs), potential cessation of premedication 
beyond dose 3 may be discussed with the MM. 
Monitor participants carefully for infusion reactions during nivolumab and BMS-986442 
administration. If an acute infusion reaction is noted, manage participants according to Section 
7.4.
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 IB and/or Pharmacy Manual for further details regarding storage, 
preparation, and administration of nivolumab and BMS-986442.
Care must be taken to assure sterility of the prepared solution, as the product does not contain any 
antimicrobial preservative or bacteriostatic agent.
Use separate infusion bags and filters when administering nivolumab and BMS-986442 and/or 
chemotherapies mentioned in Table 7.1-1 on the same day.
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Parts A and B: BMS-986442 and nivolumab study treatment will continue until progression, 
unacceptable toxicity, withdrawal of consent, completion of 2 years of treatment (approximately 
105 weeks), or the study ends, whichever occurs first. 
7.1.2
Part C: Nivolumab, BMS-986442, and Docetaxel
Follow the instructions in Part A and Part B above for administration of nivolumab and 
BMS-986442. After the BMS-986442 infusion, there is a 60-minute delay before the start of the 
docetaxel infusion to monitor the participant for signs of possible infusion reactions and to 
differentiate any such reaction from one related to the subsequent docetaxel infusion. Dosing of 
nivolumab, BMS-986442, and docetaxel will be continued for a maximum of 24 months Q3W (± 
3 days), until progression, unacceptable toxicity, withdrawal of consent, or the study ends, 
whichever occurs first. For docetaxel, the recommended premedication regimen is oral 
dexamethasone 16 mg per day (eg, 8 mg twice daily) (or equivalent dose of another corticosteroid) 
for 3 days starting 1 day prior to docetaxel administration; 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.
Dosing calculations of docetaxel should be based on the body weight assessed at baseline using 
body surface area formula per institution practice. Docetaxel should be infused over 60 minutes. 
The dose may remain the same if the participant’s weight is within 10% of the baseline weight or 
prior dose weight. All doses should be rounded up or to the nearest milligram per institutional 
standard.
Participants who experience an event related to docetaxel necessitating discontinuation of 
chemotherapy may continue to receive other study treatments (Section 7.4.4). Study treatment can
continue for up to 2 years (approximately 105 weeks), or until treatment discontinuation criteria 
are met. 
7.1.3
Part D: Nivolumab, BMS-986442, Pemetrexed, and Carboplatin
Follow the instructions in Part A and Part B above for administration of nivolumab and 
BMS-986442. After the BMS-986442 infusion, there is a 60-minute delay before the start of the 
pemetrexed infusion to monitor the participant for signs of possible infusion reactions and to 
differentiate any such reaction from one related to the subsequent chemotherapy infusion.
Pemetrexed dosing calculations should be based on the body surface area calculation. The dose
may remain the same if the participant’s weight is within 10% of the weight used to calculate the
previous dose.
Premedications for use with pemetrexed include the following:

Oral or IV corticosteroid should be given according to local standards at a dose equivalent to 
dexamethasone 4 mg twice daily on the day prior to, the day of, and the day after the 
administration of pemetrexed.

Oral folic acid 350 to 1000 μg daily (dosed in accordance with local prescribing information)
should be given starting 1 week prior to the first dose of pemetrexed, with at least 5 doses of 
folic acid administered in the 7 days prior to the first dose. Oral folic acid should be continued 
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daily throughout the treatment with pemetrexed and for 21 days after the last dose of 
pemetrexed. 

Intramuscular injection of vitamin B12 1000 μg should be given approximately 1 week prior 
to the first dose of pemetrexed and repeated every 3 cycles thereafter during pemetrexed 
treatment. Subsequent injections of vitamin B12 may be given on the same day as pemetrexed 
(participant with non-squamous histology may begin folic acid and vitamin B12 prior to 
treatment assignment, in anticipation of pemetrexed).

Antiemetic premedication will be administered according to local standards. Recommended 
antiemetic treatments are dexamethasone (dosing according to local standards; an equivalent 
dose of another corticosteroid may be substituted) and a 5-HT3 receptor antagonist (type per 
Investigator discretion and local standards of care). Additional use of antiemetic premedication 
may be employed at the discretion of the Investigator.
Participants will receive pemetrexed at a dose of 500 mg/m2 as a 10-minute IV infusion on Day 1
of each cycle. 
Carboplatin should be given following pemetrexed on Day 1 of each cycle, and the carboplatin 
dose (area under the serum concentration-time curve [AUC] 5 or 6) will be calculated using the 
Calvert formula as follows: 
Carboplatin dose (mg) = target area under the serum concentration-time curve 
(AUC) × (CrCl [mL/min] + 25)
CrCl calculation is based on the Cockcroft-Gault formula and should include the most recent 
serum/plasma creatinine and most recent weight. NOTE: If calculation of the CrCl by the 
Cockcroft-Gault formula yields a result of > 125 mL/min, then a CrCl should be calculated by an 
alternative formula per institutional standards or capped at 125 mL/min. 
The dose of carboplatin may be capped per local standards and should be administered 
intravenously for 15 minutes or longer. 
After Cycle 4 of carboplatin and pemetrexed, participants in Part D who have SD or response are 
permitted to receive pemetrexed 500 mg/m2 alone as maintenance therapy until treatment 
discontinuation criteria are met or approximately 2 years (approximately 105 weeks) of total 
treatment have been received.
7.1.4
Part E: Nivolumab, BMS-986442, Paclitaxel, and Carboplatin
Follow the instructions in Part A and Part B above for administration of nivolumab and 
BMS-986442. After the BMS-986442 infusion, there is a 60-minute delay before the start of the 
paclitaxel infusion to monitor the participant for signs of possible infusion reactions and to 
differentiate any such reaction from one related to the subsequent chemotherapy infusion.
Participants will receive paclitaxel 200 mg/m2 as a 180-minute IV infusion with carboplatin at a 
dose of AUC 5 or AUC 6 for Part D and AUC 6 for Part E as a 30-minute IV infusion on Day 1 
of a 3-week cycle, or at doses per the local prescribing information. The infusion time can follow 
local institutional standards.
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Paclitaxel dosing calculations should be based on the body surface area calculation. The dose may 
remain the same if the participant’s weight is within 10% of the baseline weight or prior dose 
weight.
Premedications for use with paclitaxel include the following: 

Oral or IV corticosteroid should be given according to local standard at a dose equivalent to 
dexamethasone 20 mg, 12 hours and 6 hours prior to paclitaxel administration. 

Histamine H2-receptor blocker (per local standard of care) should be administered 30 to 60 
minutes prior to paclitaxel infusion.

Doses of paclitaxel and/or carboplatin may be interrupted, delayed, reduced, or discontinued 
depending on how well the participant tolerates the treatment.
Follow the instructions in Part D for administering carboplatin following paclitaxel. 
Participants who complete the first 4 cycles of study treatment without evidence of disease 
progression will continue with maintenance treatment of BMS-986442 and nivolumab.
7.1.5
Observation Time for All Study Parts
Participants should be observed for 2 hours after all infusions are completed for the first 2 cycles,
and if they do not experience any IRR, then they should be observed for at least 1 hour after 
completion of all infusions for all subsequent cycles.
7.2
Method of Study Intervention Assignment
Study using IRT: All participants will be centrally assigned to treatment (Parts A, B2, C, D, and 
E) or randomized (Parts B1 and F) 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 the Schedule of Activities 
(Section 2). 
Participants in Part B1 will be randomized to receive 1 of 2 interventions (Q3W). Randomization
will be done according to a computer-generated randomization scheme prepared by a 
Randomization coordinator within the Drug Supply Management Department of BMS Research 
and Development.
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 treatment (Parts A, B2, C, D, and E) or randomize the 
participant into the open dose panel (Part B1). 
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7.3
Blinding
This is an open-label study; participants in Parts A, B2, C, D, and E will be assigned to treatment 
and participants in Parts B1 and F 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.
7.4
Dosage Modification
Dosing for all study treatment drugs should initially be delayed if any criteria in Table 7.4.1-1 (for 
BMS-986442 and/or nivolumab) or Table 7.4.3-1 (for docetaxel) or Section 7.4.5 (chemotherapy 
for Parts D and E) are met. That is, immunotherapy should also be delayed if criteria for delay of
chemotherapy are met, and chemotherapy should also be delayed if criteria for immunotherapy are 
met.
Intra-subject dose escalation or dose reductions will not be permitted for BMS-986442 or 
nivolumab, in order to allow better evaluation of the safety and efficacy at individual dose levels 
and schedules, except as described for cohort level dose de-escalations for BMS-986442. 
Assessments of study interventions will be used in considering criteria for dose delay, resumption, 
and discontinuation (see Section 7.4.1, Section 7.4.2, and Section 8.2.1).
Parts C to E: Dose reductions for chemotherapy may be required and will be performed according 
to the following guidance (see Section 7.4.3 through Section 7.4.6.3). In Parts D and E, the dose 
reductions for each agent in the chemotherapy regimen are not linked and may be adjusted 
independently. If criteria for discontinuation of the chemotherapy regimen are met, 
immunotherapy (BMS-986442 and nivolumab) may continue until the criteria for treatment 
discontinuation are met. If criteria for discontinuation of BMS-986442 and nivolumab are met, 
chemotherapy may continue if the participant meets the criteria to continue chemotherapy 
treatment.
7.4.1
Dose Modification Criteria for Nivolumab and BMS-986442
Dose delay criteria apply for all drug-related AEs. Delay administration of nivolumab and 
BMS-986442 if any of the delay criteria in Table 7.4.1-1 are met. Delay nivolumab and 
BMS-986442 dosing 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 nivolumab and BMS-986442, re-evaluate weekly, or more 
frequently if clinically indicated, and resume dosing when criteria to resume treatment are met (see 
Section 7.4.2). Continue tumor assessments per protocol even if dosing is delayed. See Section 8.2
for further information regarding permanent discontinuation of study interventions.
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Table 7.4.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986442
Drug-Related Adverse 
Event (AE) per CTCAE V5
Severity 
Action Taken
Clarifications, Exceptions, and Resume Criteria
Gastrointestinal
Colitis or Diarrhea
Grade 2 
Delay dose
Dosing may resume when AE resolves to baseline.
Grade 3 
Nivolumab monotherapy: Delay 
dose
Dosing may resume when AE resolves to baseline.
Grade 4 
Permanently discontinue
Renal
Serum/Plasma 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.bili increased
AST or ALT > 3x and ≤5x 
ULN or T.bili > 1.5x and 
≤3x ULN, regardless of 
baseline value
Delay dose
Dosing may resume when laboratory values return to 
baseline.
AST or ALT > 5 x ULN, 
regardless of baseline value
Delay dose or permanently 
discontinue 
In most cases of AST or ALT > 5 x ULN, study 
treatment will be permanently discontinued. If the 
Investigator determines a possible favorable 
benefit/risk ratio that warrants continuation of study 
treatment, a discussion between the Investigator and 
the MM/designee must occur and approval from the 
MM be received prior to resuming therapy.
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Table 7.4.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986442
Drug-Related Adverse 
Event (AE) per CTCAE V5
Severity 
Action Taken
Clarifications, Exceptions, and Resume Criteria
Concurrent AST or ALT > 3 
x ULN and T.bili > 2 x ULN, 
regardless of baseline value, 
or
T. bili > 3 x ULN, or 
AST or ALT > 8 x ULN with 
no tumor involvement of the 
liver, 
or 
AST or ALT > 10 x ULN 
with tumor involvement of 
the liver 
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 
MM 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 
MM needed prior to resuming therapy. If 
hyperglycemia resolves, or is adequately controlled 
with glucose-controlling agents, participant may not 
require discontinuation of study drug.
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BMS-986442
Anti-TIGIT Bispecific Ab
Table 7.4.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986442
Drug-Related Adverse 
Event (AE) per CTCAE V5
Severity 
Action Taken
Clarifications, Exceptions, and Resume Criteria
Hypophysitis/Hypopituitarism 
Symptomatic Grade 1-3 that 
is also associated with 
corresponding abnormal lab 
and/or pituitary scan
Delay dose 
Dosing may resume if endocrinopathy resolves to be 
asymptomatic or is adequately controlled with only 
physiologic hormone replacement.
Grade 4
Delay dose or permanently 
discontinue
Mandatory discussion with and approval from the 
MM 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 
MM needed prior to resuming therapy. If 
endocrinopathy resolves or is adequately controlled 
with physiologic hormone replacement or other 
medical management, participant may not require 
discontinuation of study drug.
Skin
Rash
Grade 2 rash covering > 30% 
body surface area or Grade 3 
rash 
Delay dose 
Dosing may resume when rash reduces to ≤10% 
body surface area 
Suspected Stevens-Johnson 
syndrome (SJS), toxic 
epidermal necrolysis (TEN),
or drug reaction with 
eosinophilia and systemic 
symptoms (DRESS)
Delay dose
Dosing may resume if SJS, TEN, or DRESS is ruled 
out and rash reduces to ≤10% body surface area.
Grade 4 rash or confirmed 
SJS,TEN, or DRESS
Permanently discontinue
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Table 7.4.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986442
Drug-Related Adverse 
Event (AE) per CTCAE V5
Severity 
Action Taken
Clarifications, Exceptions, and Resume Criteria
Neurological
Guillain-Barre Syndrome 
(GBS)
Any Grade
Permanently discontinue
Myasthenia Gravis (MG)
Any Grade
Permanently discontinue
Encephalitis
Any Grade encephalitis
Delay dose 
After workup for differential diagnosis, (ie, infection, 
tumor-related), if encephalitis is not drug-related, 
then dosing may resume when AE resolves.
Any Grade drug-related 
encephalitis 
Permanently discontinue
Myelitis
Any Grade myelitis
Delay dose
After workup for differential diagnosis, (ie, infection, 
tumor-related), if myelitis is not drug-related, then 
dosing may resume when AE resolves.
Any Grade drug-related 
myelitis
Permanently discontinue
Neurological (other than 
GBS, MG, encephalitis, or 
myelitis)
Grade 2
Delay dose
Dosing may resume when AE resolves to baseline.
Grade 3 or 4
Permanently discontinue
Myocarditis
Myocarditis
Symptoms induced from 
mild to moderate activity or 
exertion
Delay dose
Dosing may resume after myocarditis has resolved.
Severe or life-threatening, 
with symptoms at rest or 
with minimal activity or 
exertion, and/or where 
intervention indicated.
Permanently discontinue
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BMS-986442
Anti-TIGIT Bispecific Ab
Table 7.4.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986442
Drug-Related Adverse 
Event (AE) per CTCAE V5
Severity 
Action Taken
Clarifications, Exceptions, and Resume Criteria
Other Clinical AE
Pancreatitis: 
Amylase or Lipase increased
Grade 3 with symptoms
Delay dose
Note: Grade 3 increased amylase or lipase without 
signs or symptoms 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)
Grade 2 non-skin AE, except 
fatigue
Delay dose
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value.
Grade 3 AE - first occurrence 
lasting ≤ 7 days
Delay dose
Dosing may resume when AE resolves to Grade ≤ 1 
or baseline value.
Grade 3 AE - first occurrence 
lasting > 7 days
Permanently discontinue
Recurrence of Grade 3 AE of 
any duration
Permanently discontinue
Grade 4 or life-threatening 
adverse reaction
Permanently discontinue
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BMS-986442
Anti-TIGIT Bispecific Ab
Table 7.4.1-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Nivolumab and BMS-986442
Drug-Related Adverse 
Event (AE) per CTCAE V5
Severity 
Action Taken
Clarifications, Exceptions, and Resume Criteria
Other Lab abnormalities 
Other Drug-Related lab 
abnormality (not listed 
above)
Grade 3
Delay dose
Exceptions:
No delay required for: Grade 3 lymphopenia 
Permanent discontinuation for: Grade 3 
thrombocytopenia > 7 days or associated with 
bleeding. 
Grade 4
Permanently discontinue
Exceptions: The following events do not require 
discontinuation of study drug: 
Grade 4 neutropenia ≤ 7 days.
Grade 4 lymphopenia or leukopenia.
Grade 4 isolated electrolyte 
imbalances/abnormalities that are not associated with 
clinical sequelae and are responding to 
supplementation/appropriate management within 72 
hours of their onset.
Infusion Reactions (manifested by fever, chills, rigors, headache, rash, pruritus, arthralgia, hypotension, hypertension, bronchospasm, or other 
allergic-like reactions.)
Hypersensitivity reaction or 
infusion reaction
Grade 3 or 4
Permanently discontinue
Refer to Section 7.4.9 on Treatment of Related 
Infusion Reactions.
Abbreviations: AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; 
DRESS, drug reaction with eosinophilia and systemic symptoms; GBS, Guillain-Barre syndrome; MG, myasthenia gravis; MM, medical monitor; SJS, Stevens-
Johnson syndrome; T.bili, total bilirubin; TEN, toxic epidermal necrolysis; ULN, upper limit of normal; V, version.
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7.4.2
Criteria to Resume Treatment of Nivolumab and BMS-986442
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 MM (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.
Dose delay is required for participants with confirmed SARS-CoV-2 infection. Participants with 
confirmed SARS-CoV-2 infection may resume treatment after 1) at least 10 days (20 days for 
severe/critical illness) have passed since symptoms first appeared, positive RT-PCR test result, or 
positive viral antigen test result, 2) resolution of acute symptoms (including at least 24 hours has 
passed since last fever without fever reducing medications), 3) evaluation by the Investigator with 
confirmation that there are no sequelae that would place the participant at a higher risk of receiving 
investigational treatment, and 4) consultation by the MM. 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 or 
greater due to SARS-CoV-2 infection, the MM/designee must be consulted.
7.4.3
Dose Modification Criteria for Docetaxel
The criteria for dose delay, resumption, and discontinuation in Table 7.4.3-1 apply to docetaxel. 
In addition, delay docetaxel for any AE, laboratory abnormality, or intercurrent illness that 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 7.4.4).
Continue tumor assessments per protocol even if dosing is delayed. Dose modifications of 
docetaxel are permissible.
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BMS-986442
Anti-TIGIT Bispecific Ab
Table 7.4.3-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel
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 
count ≥ 1.5 × 109/L.
1st episode: No dose reduction is required. 
2nd episode: Consider dose reduction by 1 dose level.a
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 count ≥ 1.5 × 109/L.
No dose reduction if isolated and duration ≤ 7 days and recovered by Day 22 to ≤ 
Grade 1.
If duration > 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 count ≥ 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.
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CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
Table 7.4.3-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel
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
Grade 3 or 4
Permanently 
discontinue
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BMS-986442
Anti-TIGIT Bispecific Ab
Table 7.4.3-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel
Drug-related AE per 
CTCAE V5
Severity
Action Taken for 
Docetaxel
Clarifications, Exceptions, and Resume Criteria
Hepatic
AST, ALT, or T.bilib
increased with or without 
alkaline phosphatase increase
AST or ALT > 3× 
and ≤ 5× 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
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 7.4.10.
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Table 7.4.3-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel
Drug-related AE per 
CTCAE V5
Severity
Action Taken for 
Docetaxel
Clarifications, Exceptions, and Resume Criteria
Other Clinical AE
CME diagnosed by 
ophthalmologic examination
Any grade
Permanently 
discontinue
CME has been reported in participants treated with docetaxel. Participants with 
impaired vision should undergo a prompt and complete ophthalmologic 
examination. In case CME 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.
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 
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Table 7.4.3-1:
Adverse Event Criteria for Delay, Resume, and Discontinue of Docetaxel
Drug-related AE per 
CTCAE V5
Severity
Action Taken for 
Docetaxel
Clarifications, Exceptions, and Resume Criteria
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 MM.
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; CME, cystoid macular edema; 
CTCAE, Common Terminology Criteria for Adverse Events; G-CSF, granulocyte colony-stimulating factor; INR, international normalized ratio; MM, medical 
monitor; 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; V, version.
a See Section 7.4.4 for instructions on docetaxel dose reduction.
b For participants with Gilbert’s syndrome, direct bilirubin should be monitored and utilized in place of T.bili for toxicity assessments.
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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 that
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 Table 7.4.3-1 for criteria on resuming docetaxel treatment after a dose delay.
Table 7.4.4-1:
Dose Reductions for Docetaxel
Dose Level
Docetaxel
Starting dose
75 mg/m2
First dose reduction
60 mg/m2
Second dose reduction
Discontinue docetaxel
7.4.5
Dose Delay Criteria for Chemotherapies in Part D and Part E
Chemotherapy drugs in Parts D and E should be delayed for any of the following on Day 1 of each 
cycle:

Absolute neutrophil count (ANC) < 1500/µL (SI units: < 1.5 × 109/L)

Platelets < 100 x 103/μL (SI units: < 0.1 × 109/L)

Any Grade ≥2 non-skin, non-hematologic, drug-related AE (excluding Grade 2 alopecia, 
Grade 2 fatigue, and Grade 2 laboratory abnormalities)

Any Grade ≥3 skin, drug-related AE

Any Grade ≥3 drug-related laboratory abnormality, with the following exceptions for 
lymphopenia, AST, ALT, or T. bili:

Grade 3 lymphopenia does not require dose delay.

If a participant has a baseline AST, ALT, or T. bili that is within normal limits, delay dosing
for drug-related Grade ≥2 toxicity.

If a participant has baseline AST, ALT, or T. bili within the Grade 1 toxicity range, delay
dosing for drug-related Grade ≥3 toxicity.

Any AE, laboratory abnormality, or intercurrent illness that, in the judgment of the 
investigator, warrants delaying the dose of study medication. Investigators should consult local 
labeling for the chemotherapy drugs being administered to any given participant for additional 
guidance on dose delays.
Participants should be re-evaluated weekly or more frequently if clinically indicated until re-
treatment criteria are met (as per Section 7.4.6.3).
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7.4.6
Dose Reduction and Criteria to Resume Treatment for Chemotherapies 
in Part D and Part E
Dose reductions for chemotherapy may be required and will be performed according to Table 
7.4.6-1 or per institutional guidelines. Chemotherapy dose reductions are permanent; once the dose 
of any chemotherapy agent is reduced, it may not be re-escalated in subsequent cycles, except as 
noted when starting pemetrexed maintenance therapy. The dose reductions for each agent in the 
PDCT regimen are not linked and may be adjusted independently as summarized below.
Table 7.4.6-1:
Dose Reductions for Chemotherapy (Parts D and E)
Dose Level
Carboplatin
Pemetrexed
Paclitaxel
Starting Dose
AUC6 or AUC5
500 mg/m2
200 mg/m2
1st dose reduction
AUC5 (if starting dose 
was AUC6) or AUC4 (if 
starting dose was AUC5)
375 mg/m2
150 mg/m2
2nd dose reduction
AUC4 (if starting dose 
was AUC6) or AUC3 (if 
starting dose was AUC5)
250 mg/m2
100 mg/m2
3rd dose reduction
Discontinue
Discontinue
Discontinue
Abbreviation: AUC, area under the serum concentration-time curve.
Dose modifications listed are specific to USPI. Variations may apply per local label.
Any participants with 2 prior dose reductions for 1 agent who experience a toxicity that would
cause a third dose reduction must be discontinued from that agent.
7.4.6.1
Dose Reductions for Hematologic Toxicity for Chemotherapies in Part D 
and Part E
Dose modifications for hematologic toxicities (according to Common Terminology Criteria for 
Adverse Events [CTCAE] v5) are summarized in Table 7.4.6.1-1. Dose adjustments are based on 
nadir blood counts (assessed as per local standards) since the preceding drug administration. Dose
level adjustments for PDCT are relative to that of the preceding administration. Generally, both 
chemotherapy agents in the PDCT regimen should be dose-reduced together for hematologic 
toxicity. Participants receiving chemotherapy may receive growth factors (including granulocyte 
colony-stimulating factor [G-CSF] and erythropoietin) after completion of the first cycle at the 
discretion of the Investigator and following local guidelines. Additionally, prophylactic antibiotics 
may be used according to local standards of care. Please report any antibiotic or growth factor use 
on the electronic case report form (eCRF). Dose modifications listed are specific to USPI. 
Variations may apply per local label.
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Table 7.4.6.1-1:
Dose Modifications for Hematologic Toxicity (Based on Nadir 
Counts)
Toxicity
Carboplatin
Paclitaxel
Pemetrexed
Neutrophil Count Decrease
Grade 4 (< 500/mm3 or < 0.5 × 109/L)
Reduce 1 dose level
Reduce 1 dose level
Reduce 1 dose level
Platelet Count Decrease
Grade 3 (25,000 < 50,000/mm3;
25.0 < 50.0 × 109/L)
Reduce 1 dose level
Reduce 1 dose level
Reduce 1 dose level
Grade 4 (< 25,000/mm3; < 25.0 × 109/L)
Reduce 1 dose level
Reduce 1 dose level
Reduce 1 dose level
7.4.6.2
Dose Reductions for Non-hematologic Toxicities for Chemotherapies in 
Part D and Part E
Chemotherapy dosing guidelines use CTCAE v5. All dose reductions should be made based on 
the worst-grade toxicity. Participants experiencing any of the toxicities during the previous cycle 
should have their chemotherapy delayed until retreatment criteria are met and then reduced for all 
subsequent cycles by 1 dose level or discontinued as appropriate. Dose levels for the 2 drugs in 
the PDCT regimen are not linked and may be reduced independently, as summarized in Table 
7.4.6.2-1.
Table 7.4.6.2-1:
Dose Modifications for Non-Hematologic Toxicity for 
Chemotherapies (Parts D and E)
Toxicity
Carboplatin
Paclitaxel
Pemetrexed
Febrile neutropenia
Grade ≥ 3
Reduce 1 dose level
Reduce 1 dose level
Reduce 1 dose level
Diarrhea
Grade ≥ 3
No change
Reduce 1 dose level
Reduce 1 dose level
Allergic reactiona
Grade ≥ 3
Discontinue
Discontinue
Discontinue
Neuropathy
Grade 2
Reduce 1 dose level
No change
No change
Neuropathy
Grade 3-4
Discontinue
Discontinue
Discontinue
CrCl < 50 mL/min
No change
Discontinue if CrCl
< 20 mL/ min
No change
Other Grade ≥ 3 toxicity
(except for fatigue and transient
arthralgia and myalgia)
Adjust as medically 
indicated
Adjust as medically 
indicated
Adjust as medically 
indicated
Abbreviations: CrCl, creatinine clearance.
a Only the drug(s) causing the hypersensitivity reaction or acute infusion reaction (Grade ≥3) require(s) 
discontinuation. All other drugs may be continued.
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7.4.6.3
Criteria to Resume Chemotherapy Treatment for Part D and Part E
Participants may resume treatment with chemotherapy when the absolute neutrophil count returns 
to 1500/μL (SI units: < 1.5 × 109/L), the platelet count returns to <100 × 103/μL (SI units: < 0.1 × 
109/L), and all other drug-related toxicities have returned to baseline or Grade 1 (or Grade 2 for 
alopecia and fatigue). If a participant fails to meet criteria for re-treatment, then re-treatment should 
be delayed, and the participant should be re-evaluated weekly or more frequently as clinically 
indicated. Any participant who fails to recover from toxicity attributable to chemotherapy to 
baseline or Grade 1 (except Grade 2 alopecia and fatigue) within 6 weeks from the last dose given 
should discontinue the drug(s) that caused the delay. When resuming chemotherapy treatment, 
please follow the dose-reduction recommendations in Section 7.4.5.
7.4.7
Dose-limiting Toxicities
The DLT evaluation period is 28 days for Parts A, B, C, D, and E. Participants in all parts will be 
considered DLT evaluable if they receive all specified study treatments (Cycle 1 and Cycle 2) and 
did not have a DLT event occur at any time before completion of the DLT period. In addition, 
participants who experienced a DLT after receiving a minimum of a partial dose of BMS-986442 
will be DLT evaluable. Participants who receive a partial or full dose of BMS-986442 but do not 
meet DLT evaluable criteria will be included in the overall safety evaluation. 
For the purpose of guiding decisions regarding dose escalation in Parts A, C, D, and E, DLTs will 
be defined based on the incidence, intensity, and duration of the AEs for which no clear alternative
cause is identified and will exclude events clearly related to disease progression or intercurrent
illness. The DLT evaluation period will begin on the first day of Cycle 1 and end on Day 28 (ie, 4
weeks). Any toxicities that occur beyond the DLT period will be accounted for in making final 
dose level decisions. Participants who have discontinued due to a DLT or received all specified 
study treatments during the 4-week DLT period will be considered as DLT evaluable. Participants 
who withdraw from the study during the DLT evaluation period, or have received less than the 
specified number of study treatments for reasons other than a DLT during the DLT evaluation 
period, will not be considered as DLT-evaluable participants and may be replaced with a new 
participant at the same dose level. Participants who are dose delayed during the DLT evaluation 
period for reasons other than a DLT will be considered as DLT-evaluable participants if they 
received at least 1 cycle of study treatment.
Any AE that is not clearly due to disease progression or extraneous causes that occurs within the 
28-day DLT evaluation window and meets criteria for permanent discontinuation as listed in Table 
7.4.1-1, Table 7.4.3-1 and Table 7.4.6.2-1, will be considered a DLT. In addition, the following 
AEs will be DLTs, except for those that are clearly due to disease progression or extraneous causes.

Any death that is not clearly due to the underlying disease or extraneous causes within the 28-
day DLT period.
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Non-hematological toxicity:

Any Grade ≥ 3 non-hematological toxicity. Exceptions will be made for:

Grade 3 nausea, diarrhea, or vomiting that resolves to baseline within 72 hours after 
holding study treatment and implementing optimal medical management. 

Grade 3 fatigue that resolves to ≤ Grade 2 within 7 days.

Grade 3 increases in amylase or lipase that are not associated with symptoms or clinical 
manifestations of pancreatitis.

Grade 3 rash that reduces to ≤ Grade 1 within 14 days.

Grade 3 or 4 isolated electrolyte imbalances/abnormalities that are not associated with 
clinical sequelae and are responding to supplementation/appropriate management within 
72 hours.

AST/ALT > 3× and ≤ 5× ULN or T.bili > 1.5× and ≤ 3× ULN that is associated with new 
clinical signs/symptoms of liver inflammation or any case that meets Hy’s Law criteria.

Any AST/ALT > 5× ULN or T.bili > 3× ULN, irrespective of baseline values.

Any Grade myocarditis.

Any Grade myelitis, encephalitis, myasthenia gravis, or Guillain-Barre syndrome.

Grade ≥ 2 uveitis, episcleritis, iritis eye pain, or blurred vision.

Any Grade confirmed Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or 
drug reaction with eosinophilia and systemic symptoms (DRESS).
Hematological toxicity:

Grade 4 neutropenia of > 7 days duration.

Grade 4 thrombocytopenia.

Grade 3 thrombocytopenia with clinically significant bleeding.

Febrile neutropenia.
Toxicity for Parts C to E Only :

Any AE resulting in a > 2-week delay in the cycle of chemotherapy during the first 2 cycles 
(Parts C-E only) will be a DLT. 
DLT Exception:

Infusion reactions attributed to chemotherapy will not be considered DLTs.
Note: For participants who experience a DLT, further treatment will be based on Table 7.4.3-1, and
the criteria to resume treatment in Section 7.4.2 and Section 7.4.6.
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7.4.8
Management Algorithms for Immuno-oncology Agents
IO agents are associated with AEs that can differ in severity and duration from AEs caused by 
other therapeutic classes. Nivolumab and BMS-986442 are considered IO agents and the 
management algorithms in Appendix 7 provide guidance on assessing and managing the following 
groups of AEs:

Gastrointestinal

Renal

Pulmonary

Hepatic

Endocrinopathy

Skin

Neurological

Myocarditis
7.4.9
Treatment of Related Infusion Reactions
Since nivolumab contains only human immunoglobulin protein sequences, it is 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 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):

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.
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
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 ipilimumab 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).
7.4.10
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 a hypersensitivity reaction to docetaxel, including a more severe hypersensitivity 
reaction. These participants should be closely monitored during initiation of docetaxel therapy.
7.5
Preparation/Handling/Storage/Accountability
The IMP/Non-IMP/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 IMP/Non-
IMP/AxMP is only dispensed to study participants. The IMP/Non-IMP/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 
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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.
IMP/Non-IMP/AxMP documentation (whether supplied by BMS or not) must be maintained and 
must include 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.

The Investigator, institution, or head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition of 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 AE):

Immunosuppressive agents.

Immunosuppressive doses of systemic corticosteroids. Participants are permitted the use of 
topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal 
systemic absorption). Adrenal replacement steroid doses > 10 mg daily prednisone are 
permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (eg, contrast 
dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity 
reaction caused by a contact allergen) is permitted.

Any concurrent systemic anti-neoplastic therapy (ie, chemotherapy, hormonal therapy, 
immunotherapy, or standard or investigational agents for treatment of NSCLC, SCCHN, 
gastric cancer)

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. 
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
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. 
7.7.2
Other Restrictions and Precautions
Strong cytochrome P450 3A4 (CYP3A4) inhibitors and inducers should be avoided during the 
treatment with docetaxel (Part C). Please refer to Appendix 8 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 chemotherapy may receive growth factors (including granulocyte 
colony-stimulating factor [G-CSF] and erythropoietin) after completion of the first cycle at the 
discretion of the Investigator and following local guidelines.

Prior palliative radiotherapy must have been completed at least 2 weeks prior to treatment.

Participants may receive authorized or approved SARS-CoV-2 vaccines while continuing on 
study treatment at the discretion of the Investigator. 

Treatment of active SARS-CoV-2 infections or high-risk exposures, including use of 
investigational therapies, is allowed and should be discussed with the MM.

Participants may receive authorized or approved non-vaccine pre-exposure prophylaxis against 
SARS-CoV-2 infection, such as the combination tixagevimab co-packaged with cilgavimab. 
Washout periods for monoclonal antibodies and experimental agents do not apply to said 
prophylactic medications. If SARS-CoV-2 pre-exposure prophylaxis is being used, the site 
should consistently document its use in the Prior and Concomitant Medication CRF (especially 
the date of administration). It may be unclear how non-vaccine pre-exposure prophylactic 
agents against SARS-CoV-2 infection affects central lab assessment of SARS-CoV-2 
serology. Certain agents in this class may have long elimination half-lives (and durations of 
effect), which may impact subsequent plans for vaccination against SARS-CoV-2.
7.7.4
Palliative Local Therapy
Palliative local therapy, including palliative radiation therapy and palliative surgical resection, to 
symptomatic non-target bone lesions, skin lesions, or CNS lesions is permitted prior to 
discontinuation of study intervention for participants who do not have evidence of overall clinical 
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or radiographic progression per RECIST v1.1. Palliative local therapy to lesions causing 
hemoptysis may also be permitted prior to discontinuation of study intervention in participants 
who do not have evidence of overall clinical or radiographic progression per RECIST v1.1, 
provided that the lesions undergoing palliative local therapy are not the only sites of measurable 
disease and the case is discussed with and approved by the Sponsor/Medical Monitor (or designee). 
Participants requiring palliative local therapy should be evaluated 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 start of local therapy. If progression per RECIST v1.1 is 
identified on any tumor assessments prior to the initiation of palliative local therapy, then 
participants must either discontinue study intervention or they must meet criteria to continue 
treatment beyond progression (Section 8.1.1) in order to resume immunotherapy after palliative 
local therapy. The potential for overlapping toxicities with radiotherapy and immunotherapy 
currently is not known; however, anecdotal data suggest that it is tolerable. As concurrent 
radiotherapy and the immunotherapy regimens evaluated in this study have not been formally 
evaluated, whenever palliative radiotherapy is required for a tumor lesion, then immunotherapy 
should be withheld for at least 1 week before, during, and 1 week after radiation. Participants 
should be closely monitored for any potential toxicity during and after receiving radiotherapy and 
AEs should resolve to Grade ≤ 1 prior to resuming immunotherapy.
7.7.5
Surgery
Participants undergoing major surgery for any reason while on study should have BMS-986442, 
nivolumab, and/or chemotherapy held for at least 3 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 MM (or designee) in discussion with the Investigator.
7.7.5.1
Imaging Restriction and Precautions
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history, and renal status), the appropriate imaging modality and 
contrast regimen 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 magnetic resonance imaging (MRI), participants with severe renal insufficiency (ie, eGFR 
< 30 mL/min/1.73 m2) are at increased risk of nephrogenic systemic fibrosis, therefore MRI 
contrast is contraindicated. In addition, participants may be excluded from MRI if they have 
tattoos, metallic implants, pacemakers, etc. This will be outlined in the image 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.
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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-986442 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 
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.)

Pregnancy (refer to Section 9.2.5).

Significant noncompliance with protocol (eg, procedures, assessments, medications, etc). The 
Investigator should discuss such issues with the MM.

Investigators may consider the discontinuation of investigational treatment for participants,
after discussion with the MM, for the following:

Radiographic progression of disease per RECIST 1.1 criteria; however, participants who 
meet criteria for treatment beyond progression may continue to receive study intervention.

Clinical deterioration attributed to disease progression, without radiographic progression 
per RECIST 1.1, that in the judgment of the Investigator makes it unsafe for the participant 
to continue with study intervention.
Nivolumab and BMS-986442 treatment must be permanently discontinued per criteria in Table 
7.4.1-1 in Section 7.4.1. Discontinue nivolumab and BMS-986442 for any AE, laboratory 
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abnormality, or intercurrent illness which, in the judgment of the Investigator, presents a 
substantial clinical risk to the participant with continued nivolumab dosing.
Any event that leads to a 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 AEs are allowed. 

Dosing delays lasting > 8 weeks from the previous dose that occur for non-drug-related reasons 
may be allowed if approved by the MM (or designee). 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 eCRF.
8.1.1
Nivolumab and BMS-986442 Treatment Beyond Disease Progression
Accumulating evidence indicates a minority of participants treated with immunotherapy may 
derive clinical benefit despite initial evidence of PD.25
Participants treated with BMS-986442 and nivolumab will be permitted to continue with their 
assigned treatment beyond initial RECIST 1.1-defined PD, 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.

Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, CNS metastases).

Participant provides written informed consent prior to receiving additional nivolumab 
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).
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Radiographic assessment/scan(s) should continue in accordance with the Section 2 Schedule of 
Activities for the duration of the treatment beyond progression and should be submitted to the 
central imaging vendor. Balance the assessment of clinical benefit with clinical judgment as to 
whether the participant is clinically deteriorating and unlikely to receive any benefit from 
continued treatment with nivolumab and BMS-986442.
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 disease progression. 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 disease progression. 
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. 
New lesions are considered measurable at the time of initial progression if the longest diameter is 
at least 10 mm (except for pathological lymph nodes which must have a short axis of at least 15 
mm). Any new lesion considered non-measurable at the time of initial progression may become 
measurable and therefore be 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.
8.1.2
Post-study Intervention Study Follow-up
In this study, 
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), even if the study is terminated. All participants who received 
study interventions will also be followed for survival data.
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 
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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.

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 
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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.
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 (Parts A, B2, C, D, and E) 
and randomization (Parts B1 and F). 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.
 

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.
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9.1
Efficacy Assessments
9.1.1
Imaging Assessment for 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 Imaging 
Manual provided by the central imaging vendor. Participants in Parts A, B2, C, D and E will be 
assessed locally by the investigator or designee using the RECIST 1.1 criteria (see Appendix 5).
Collect any additional imaging that may demonstrate tumor response or progression (including 
scans performed at unscheduled time points and/or at an outside institution) for RECIST 1.1 tumor 
assessment. X-rays and bone scans that clearly demonstrate interval progression of disease, for 
example most commonly as unequivocal lesions that are unmistakably new since the prior 
CT/MRI, should be submitted to the central imaging vendor. Otherwise, they do not need to be 
submitted centrally.
9.1.1.1
Methods of Measurement
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected sites 
of disease should be performed for tumor assessments. For participants with SCCHN, CT or MRI 
of the neck is also required. Images should be acquired with slice thickness of 5 mm or less with 
no intervening gap (contiguous). Every attempt should be made to image each participant using an 
identical acquisition protocol on the same scanner for all imaging time points. Tumor 
measurements should be made by the same Investigator or radiologist for each assessment, 
whenever possible. Changes in tumor measurements and tumor response to guide ongoing study 
treatment decisions will be assessed by the Investigator using RECIST 1.1 criteria (refer to 
Appendix 5).
If a participant has a contraindication for CT IV contrast, then a non-contrast CT of the chest and 
a contrast-enhanced MRI of the neck (required for SCCHN participants), abdomen, pelvis, and 
other known/suspected sites of disease should be obtained.
If a participant has a contraindication for both MRI and CT IV contrasts, then a non-contrast CT 
of the chest and a non-contrast MRI of the neck (required for SCCHN participants), 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 IV contrast, then a non-contrast CT of the neck (required for SCCHN 
participants), chest, abdomen, pelvis, and other known/suspected sites of disease is acceptable.
Use of CT component of a PET-CT scanner: Combined modality scanning such as with PET-
CT is increasingly used in clinical care and is a modality/technology that is in rapid evolution; 
therefore, the recommendations outlined here may change rather quickly with time. At present, 
low-dose or attenuation correction CT portions of a combined PET-CT are of limited use in 
anatomically based efficacy assessments and it is therefore suggested that they should not be 
substituted for dedicated diagnostic contrast-enhanced CT scans for anatomically based RECIST 
1.1 measurements. However, if a site can document that the CT performed as part of a PET-CT is 
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of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then the CT portion 
of the PET-CT can be used for RECIST 1.1 measurements. Note, however, that the PET portion 
of the CT introduces additional data that may bias an Investigator if it is not routinely or serially 
performed.
Bone scan or PET scan are not adequate for assessment of RECIST 1.1 response in target lesions. 
In selected circumstances where such modalities are the sole modality used to assess certain non-
target organs, those non-target organs may be evaluated less frequently. For example, bone scans 
may need to be repeated only when complete response (CR) is identified in target disease or when 
progression in bone is suspected.
Bone scans may be collected per local standards, as clinically indicated.
MRI of the brain (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. MRI of the brain without and with contrast is required at screening for participants 
with NSCLC and/or those without NSCLC that have known or suspected brain metastases, unless 
participant has completed an imaging study of the brain within 28 days prior to the date of first 
dose of study treatment. Participants with NSCLC and/or a history of brain metastasis or symptoms 
without progressive disease at EOT should have a surveillance MRI (without and with contrast) 
per standard of care (approximately every 12 weeks), or sooner if clinically indicated.
9.1.1.2
Imaging and Clinical Assessment
Tumor assessments should continue on the protocol-defined imaging schedule, regardless if dosing 
is delayed or discontinued. Changes in tumor measurements and tumor responses will be assessed 
by the same Investigator or designee (ie, radiologist or sub-investigator), using RECIST 1.1 
criteria. Investigators will report the number and size of new lesions that appear while on study. 
The time point of tumor assessments will be reported on the eCRF based on the Investigator’s 
assessment using RECIST 1.1 criteria (see Appendix 5 for specifics of RECIST 1.1 criteria to be 
used in this study). Assessments of partial response (PR) and complete response (CR) must be 
confirmed at least 4 weeks (28 days) after initial response. A best overall response of SD requires 
a minimum of 35 days on study from date of first dose to the date of the first imaging assessment.
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 AEs and SAEs on the CRF.
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IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component 
for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. 
IMAEs can include events with an alternate etiology which were exacerbated by the induction of 
autoimmunity. Information supporting the assessment will be collected on the participant’s CRF.
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.
The Investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study intervention or a protocol-specified procedure (eg, a follow-up skin biopsy).

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 the 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.
For participants randomized (Parts B1 and Part F) or assigned (Parts A, B2, C, D, and E) to 
treatment and never treated with study drug, collect SAEs for 30 days from the date of 
randomization or treatment assignment. 
Collect all non-serious AEs (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.
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.
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.
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.
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Every AE must be assessed by the Investigator with regard to whether it is considered immune-
mediated. For events which are potentially immune-mediated, additional information will be 
collected on the participant’s CRF.
9.2.3
Follow-up of AEs and SAEs

Non-serious 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 non-serious AEs that cause interruption or discontinuation of 
study intervention and for those present at the end of study intervention, as appropriate.

All identified non-serious AEs must be recorded and described on the non-serious AE page of 
the CRF (paper or electronic). Completion of supplemental CRFs may be requested for AEs 
and/or laboratory abnormalities that are reported/identified during the course of the study.

After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and nonserious AEs of special interest (as 
defined in Section 9.2) will be followed until resolution, until the condition stabilizes, until the 
event is otherwise explained, or until the participant is lost to follow-up (as defined in Section 
8.3). 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 IB 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
If, following initiation of the study intervention, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least 6
months after study treatment administration, the Investigator must immediately notify the BMS 
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MM/Designee of this event and complete and forward a Pregnancy Surveillance Form to the BMS 
designee within 24 hours of awareness of the event and in accordance with SAE reporting 
procedures described in Appendix 3.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome, and where applicable offspring information, must be reported on the Pregnancy 
Surveillance Form. Protocol-required procedures for study discontinuation and follow-up must be 
performed on the participant.
Any pregnancy that occurs in a female partner of a male study participant during and at least for 3 
months after study treatment administration, enrolled in Parts C, D, or E 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.
Any pregnancy that occurs in a female partner of a male study participant enrolled in Parts A, B1, 
or B2 is not required to be reported to the Sponsor or designee.
If any sexual activity involving penile intercourse (eg, vaginal, anal, oral) has occurred between a 
male participant enrolled in Parts C, D, or E and a pregnant partner(s) without the use of a condom 
during and at least for 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. Reporting is not required for any sexual activity involving penile intercourse (eg, 
vaginal, anal, oral) that has occurred between a male participant enrolled in Parts A, B1, or B2 and 
a pregnant partner(s) without the use of a condom.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the non-serious 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
Specific criteria for identifying a potential drug-induced liver injury (DILI) have not been 
identified for this protocol. Standard medical practice in identifying and monitoring hepatic issues 
should be followed.
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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 ULN
AND

Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum/plasma
alkaline phosphatase)
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, 
x-ray filming, or any other potential safety assessment required or not required by the protocol 
should also be recorded as a non-serious AE or SAE, as appropriate, and reported accordingly.
9.3
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. 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 do the following:

Contact the MM immediately.

Closely monitor the participant for AEs/SAEs and laboratory abnormalities until at least
5 times the projected elimination half-life of BMS-986442 (5 × 9.01 days ~ 46 days), of
nivolumab (5 × 25 days = 125 days), of docetaxel (5 × 11.1 hours ~ 2.5 days), of carboplatin 
(5 × 5.9 hours ~ 1.5 days), paclitaxel (5 × 27 hours ~ 6 days), and pemetrexed (5 × 3.5 hours
~ 18 hours).

Obtain a plasma sample for PK analysis if requested by the MM (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.
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Participants should receive therapeutic G-CSF as soon as possible after discovery of overdose.
Other appropriate symptomatic measures should be taken, as needed.
There is no known antidote for paclitaxel overdosage. The primary anticipated complications of 
overdosage would consist of bone marrow suppression, peripheral neurotoxicity, and mucositis.
There is no known antidote for carboplatin overdosage. The anticipated complications of 
overdosage would be secondary to bone marrow suppression and/or hepatic toxicity.
No drugs are approved for the treatment of pemetrexed overdose. Based on animal studies, 
administration of leucovorin may mitigate the toxicities of pemetrexed overdosage. It is not known 
whether pemetrexed is dialyzable.
Decisions regarding dose interruptions or modifications will be made by the Investigator in
consultation with the MM 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.
9.4.2
Vital Signs
Refer to Schedule of Activities.
9.4.3
Electrocardiograms
Refer to the Schedule of Activities for timing of assessments in Table 2-1 and Table 2-2.
To monitor participant safety throughout the study, the Investigators will review the 12-lead ECGs 
collected using their site’s standard ECG machines. In both scenarios, Fridericia’s Correction 
Formula (QTcF) will be the QT interval correction method applied to each ECG reading.
9.4.4
Clinical Safety Laboratory Assessments

Investigators must document their review of each laboratory safety report.

A local laboratory will perform the analyses and will provide reference ranges for these tests.

Results of clinical laboratory tests performed on Day -1 must be available prior to dosing.
Table 9.4.4-1:
Clinical Laboratory Assessments
Hematology - Complete Blood Count
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Prothrombin time, activated partial thromboplastin time, and international normalized ratio - screening only
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Table 9.4.4-1:
Clinical Laboratory Assessments
Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Direct bilirubin (reflex if total bilirubin is abnormal)
Gamma-glutamyl transferase (reflex if liver
function is abnormal)
Alkaline phosphatase (ALP)
Lactate dehydrogenase (LDH)
Creatinine
Blood urea nitrogen (BUN) or serum/plasma urea
Uric acid 
Glucose (fasting glucose at screening)
Amylase
Lipase
Troponin
C-reactive protein
Total protein
Albumin - screening only
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatine kinase/Creatine phosphokinase
Creatinine clearance - screening only
TSH, free T3 and free T4 - screening (total T3 may be 
allowed if collection of fT3 is not feasible.
TSH, with reflexive fT3 and fT4 if TSH is abnormal -
on treatment (total T3 may be allowed if collection
of fT3 is not feasible)
Cytokine panel: if the participant has an IRR, draw 
additional blood and preform analysis locally
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
Hepatitis B/C, (HBV sAG, HCV antibody or HCV RNA) - screening only
HIV-1 and -2 antibody (HIV RNA if HIV-positive) - screening only, and as mandated by local requirement
Other Analyses
Pregnancy test (WOCBP only: minimum sensitivity 25 IU/L or equivalent units of hCG).
FSH screening - only required to confirm menopause in women < age 55
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, 
blood urea nitrogen; FSH, follicle-stimulating hormone; fT3, free triiodothyronine; fT4, free thyroxine; HBV, hepatitis 
B virus; hCG, human chorionic gonadotropin; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IRR, 
infusion-related reaction; IU, international units; LDH, lactate dehydrogenase; RNA, ribonucleic acid; sAG, surface 
antigen; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; WOCBP, women of childbearing 
potential.
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
The PK of BMS-986442 will be derived from serum concentration versus time data when 
appropriate. The PK parameters to be assessed following intensive PK collections include the 
following:
Cmax
Maximum observed serum concentration
Tmax
Time of maximum observed serum concentration
AUC(0-T)
Area under the serum concentration-time curve from time zero to time of last 
quantifiable concentration
AUC(TAU)
Area under the serum concentration-time curve in 1 dosing interval
Parameters that may potentially be assessed following dose administration in Cycle 4
Ctau
Serum concentration observed at the end of a dosing interval
CLT
Total body clearance
Css-avg
Average concentration over a dosing interval (AUC[TAU]/tau)
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady-state to AUC(TAU) after the 
first dose
T-HALFeff
Effective elimination half-life that explains the degree of accumulation observed for a 
specific exposure measure (exposure measure includes AUC[TAU])
Parameter to be reported separately
Individual participant PK parameter values will be derived by noncompartmental methods using a 
validated PK analysis program. Actual times will be used for the analyses.
Table 9.5-1 lists the sampling schedule to be followed for the assessment of PK and IMG. Further 
details of blood collection and processing will be provided to the site in the Laboratory Manual.
All predose samples should preferably be taken within 30 minutes before the start of any dose 
infusion. Predose serum nivolumab concentrations will be collected for the assessment of 
 
 when administered in combination with 
BMS-986442.
End-of-infusion (EOI) PK samples for BMS-986442 and nivolumab should be taken immediately 
following the last drug infusion (preferably within 5 minutes after the end of the infusion) on the 
contralateral arm (ie, the arm not used for the infusion). Because the EOI PK sample is drawn with 
the intent of accurately estimating the Cmax of the drug, draw the EOI PK sample after all the 
study drug has been infused. If the site infuses the drug without a flush, then collect the EOI PK 
sample within approximately 5 minutes after the end of the infusion. If a flush is administered to 
clear the IV lines of the drug and to ensure delivery of the entire drug dose, then draw the EOI 
sample within approximately 5 minutes after end of the flush. Do not draw EOI samples from the 
same IV access that the drug was administered. On-treatment PK samples are intended to be drawn 
relative to actual dosing days. For Parts A to F, EOI PK samples should be taken following the 
instructions noted in Table 9.5-1.
If a dose occurs on a different day within the cycle due to delays or minor schedule adjustments, 
PK and ADA samples should be adjusted accordingly. If it is known that a dose is going to be
delayed, then the predose sample should be collected just prior to the delayed dose. However, if a 
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predose sample is collected but the dose is subsequently delayed, an additional predose sample 
should not be collected. Further details of sample collection, processing, and shipment will be 
provided in the Laboratory Manual.
Table 9.5-1:
Pharmacokinetic and Immunogenicity Sampling Schedule for Parts 
A-E (All participants)
Study Day of 
Sample Collection
(1 Cycle = 3 weeks)
Event
Time 
(Relative to 
Start of 
Infusion) 
(hr:min)
BMS-986442 
PK Serum 
Sample
BMS-986442 
ADA Serum
Sample
Cycle 1 Day 1
Predosea
0:00
X
X
EOIb
See noteb
X
4:00
X
Cycle 1 Day 2
24:00
X
Cycle 1 Day 5
96:00c
X
Cycle 1 Day 8
168:00d
X
Cycle 1 Day 15
336:00
X
Cycle 2 Day 1
Predosea
0:00
X
X
EOIb
See noteb
X
Cycle 3 Day 1
Predosea
0:00
X
X
EOIb
See noteb
X
Cycle 4 Day 1
Predosea
0:00
X
X
EOIb
See noteb
X
4:00
X
24:00
X
96:00c
X
168:00d
X
336:00
X
Cycle 5 Day 1
Predosea
0:00
X
X
Cycle 9 Day 1 and 
every 5 cycles 
thereafter until EOT
Predosea
0:00
X
X
EOT
X
X
Follow-up Period
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Table 9.5-1:
Pharmacokinetic and Immunogenicity Sampling Schedule for Parts 
A-E (All participants)
Study Day of 
Sample Collection
(1 Cycle = 3 weeks)
Event
Time 
(Relative to 
Start of 
Infusion) 
(hr:min)
BMS-986442 
PK Serum 
Sample
BMS-986442 
ADA Serum
Sample
Follow-up 30 Day
X
X
Follow-up 100 Day
X
X
Abbreviations: ADA, anti-drug antibody; Cmax, maximum observed concentration; EOI, end of infusion; EOT, end 
of treatment; PK, pharmacokinetics.
a Predose: All predose samples should be taken within 30 minutes before the start of the study drug infusion.
b Since the end of infusion PK (EOI) sample is drawn with the intent of accurately estimating the maximum 
concentration (Cmax) of the drug, draw the EOI when all the study drug has been infused. If the site infuses drug 
without a flush, then collect the EOI sample within approximately 5 minutes after end of infusion. If a flush is 
administered to clear the IV lines of the drug and to ensure delivery of the entire drug dose, then draw the EOI 
sample within approximately 5 minutes after end of the flush. Do not draw EOI samples from the same IV access 
that the drug was administered.
c The 96:00 hour sample may be taken between 72:00 and 120:00 hours post dose.
d The 168:00 hour sample may be taken between 144:00 and 192:00 hours post dose.
Treatment assignments will be released to the bioanalytical laboratory in order to minimize 
unnecessary analysis and/or reanalysis of PK/ADA samples.
Serum concentration analyses for BMS-986442 and nivolumab will be performed by validated 
bioanalytical method(s).
Bioanalytical samples designated for assessments (eg, IMG, PK, 
) 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 IMG-related 
AE, etc).
Additionally, residual bioanalytical samples will be archived and may be used for potential 
 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-986442 and nivolumab will be evaluated in serum samples collected from all 
participants according to the collection schedule in Table 9.5-1. Additionally, serum samples 
should also be collected at the final visit from participants who discontinued study intervention or 
were withdrawn from the study. These samples will be tested by the Sponsor/designee.
Serum samples will be screened for antibodies binding to BMS-986442 and nivolumab, and the 
titer of confirmed positive samples will be reported. Other analyses may be performed to further 
characterize the IMG of BMS-986442 and nivolumab.
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The detection and characterization of antibodies to BMS-986442 and nivolumab will be performed 
using validated method(s) by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to study intervention will also be evaluated for serum concentration to 
enable interpretation of the antibody data. 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-986442 and nivolumab.
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9.9
Additional Research
This protocol will include residual sample storage for additional research.
For All sites:
Additional research is required for all study participants, except where prohibited by IRBs/ethics 
committees, local laws or regulations, or academic/institutional requirements. Where 1 or more of 
these exceptions occurs, participation in the additional research should be encouraged but will not 
be a condition of overall study participation. 

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.
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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.
Sample Collection and Storage
Residual samples (see 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 the 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 laboratory 
procedure manual.
Table 9.9-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time points for Which Residual Samples Will be Retained
Serum/Plasma
All
PBMC
All
Tumor Biopsy
All
Abbreviation: PBMC, peripheral blood mononuclear cell.
9.10
Other Assessments
Whole blood, serum and plasma samples will be collected at the times indicated in 
for 
the measurement of DNA, RNA, 
.
9.11
Health Economics OR Medical Resource Utilization and Health 
Economics
Not applicable.
10
STATISTICAL CONSIDERATIONS
10.1
Statistical Hypotheses
There is no formal primary research hypothesis for this study to be statistically tested.
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10.2
Sample Size Determination 
Sample Size Justification for Dose Escalation (Parts A and C to E)
It is expected that at least 3 DLT-evaluable participants will be treated in Part A of the study in 
each dose level. Though the exact number will depend on the number of participants with a DLT, 
up to approximately 9 DLT-evaluable participants may be treated to enable DLT review. 
Assuming a DLT target of 30% (24%, 36%), the BOIN design framework will be used to guide 
decisions in this setting, including potential de-escalation to a lower dose of BMS-986442 in 
combination with nivolumab.
Similarly, in Parts C, D, and E, approximately 6 to 12 DLT-evaluable participants will be treated 
at each dose level to enable DLT review and dose escalation decisions guided by the BOIN 
method. Additional participants (for a maximum of 15 per dose level) may be treated at any dose 
level at or below the estimated MTD for further evaluation of safety, PK, IMG, and PD parameters,
as required.
Sample Size Justification for Indication-specific Cohorts (Part B)
Parts B1 and B2 will be indication-specific cohorts of BMS-986442 in combination with 
nivolumab. Part B1 will involve randomized dose expansions to compare 2 tolerable dose levels 
in participants with 2L+ post-IO/platinum doublet NSCLC, and Part B2 will involve evaluation of 
1 selected dose level in 2 additional tumor types: gastric cancer/GEJ and SCCHN.
The sample sizes for Parts B1 and B2 are based on assessing an initial anti-tumor activity signal 
as estimated by the ORR following treatment of BMS-986442 in combination with nivolumab and 
to provide additional information for the safety profile in the NSCLC and gastric cancer/GEJ and 
SCCHN populations, respectively.
Approximately 50 participants will be treated with BMS-986442 in combination with nivolumab 
in Part B1 and an additional 40 participants may be treated with the same treatment in Part B2.
In addition to the above, Table 10.2-1 summarizes the 80% exact CI for various ORRs for 
combination therapy with sample sizes of 20, 25, and 30. For example, 4 responders will need to 
be observed in 25 evaluable participants (an observed ORR = 16%) for the lower bound of the 
80% CI to exclude a 5% ORR. Similarly, 6 responders will need to be observed in 20 evaluable 
participants (an observed ORR = 30%) for the lower bound of the 80% CI to exclude a 15% ORR.
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Table 10.2-1:
Potential ORR and Exact 80% CI
Sample Size
Number of Responders
ORR
80% Exact CI
20
2
0.10
[0.027, 0.245]
3
0.15
[0.056, 0.304]
5
0.25
[0.127, 0.415]
6
0.30
[0.166, 0.467]
25
3
0.12
[0.045, 0.248]
4
0.16
[0.072, 0.295]
6
0.24
[0.131, 0.383]
8
0.32
[0.196, 0.467]
30
3
0.10
[0.037, 0.209]
5
0.17
[0.083, 0.287]
7
0.23
[0.135, 0.361]
10
0.33
[0.218, 0.466]
Abbreviations: CI, confidence interval; ORR, overall response rate.
10.3
Analysis Sets
For the purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who signed informed consent (and are registered into the IRT,
if applicable)
Treated
All participants who received at least 1 dose of study intervention
Randomized (Part B1 only)
All participants who were randomized using IRT
Response- Evaluable
All participants who received at least 1 dose of study intervention, had 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
PK
All treated participants who have evaluable concentration-time data
PK Evaluable
All participants who have adequate PK profiles or have at least 1 evaluable PK 
parameter.
IMG
All participants who received BMS-986442 or nivolumab who have baseline 
and at least 1 post-baseline measurement
Abbreviations: IMG, immunogenicity; IRT, Interactive Response Technology; PK, pharmacokinetics.
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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. 
10.4.1
General Considerations
In Parts A, C, D, and E of the study, at least 3 participants will be enrolled per dose level and dose 
escalation decisions will be guided by BOIN design to identify the MTD. The BOIN design takes 
a very simple form, rendering it easy to implement in practice. The dose escalation and de-
escalation in the BOIN design is determined by comparing the observed DLT rate at the current 
dose with a pair of fixed dose escalation and de-escalation boundaries, which allows generation of 
a decision table that guides dose selection depending on the number of participants treated and 
observed DLTs. A BOIN dose-escalation decision table with a selected target DLT rate of 30%, 
an escalation boundary of 24%, and de-escalation boundary of 36% will be used in this study.
Dose escalation may be stopped prior to reaching an MTD based on review of available safety, 
PK, and PD data, and on discussions between the sponsor and Investigators. While the BOIN will 
use DLT and safety information only, clinical assessment will take into consideration the totality 
of available data including PK/PD from all treated participants, in assigning the next dose level. 
The final recommended MTD/MAD/RP2D will be based on the recommendation from the BOIN 
and overall clinical assessment of all available safety, PK, PD, and efficacy data.
10.4.2
Primary Endpoint
Table 10.4.2-1:
Primary Endpoint
Primary Endpoint
Statistical Analysis Methods
Incidence of AEs, SAEs, AEs meeting protocol-
defined DLT criteria, AEs leading to 
discontinuation, and death.
DLT rate by dose level, frequency distribution of treated 
participants with AEs using the worst CTCAE grade. 
Participants will only be counted (1) once at the preferred 
term level, (2) once at the system organ class level, and (3) 
once in the “total participant” row at their worst CTCAE
grade, regardless of system organ class or preferred term.
Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; DLT, dose-limiting 
toxicity; SAE, serious adverse event.
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10.4.3
Secondary Endpoints
Table 10.4.3-1:
Secondary Endpoints
Secondary Endpoint
Statistical Analysis Methods
Summary measures of BMS-986442 PK parameters, 
such as but not limited to, Cmax, Tmax, AUC(0-T) 
from serum concentration-time data during 
BMS-986442 when administered in combination with 
nivolumab or in combination with nivolumab and 
chemotherapy.
Summary statistics tabulations by dose: geometric means 
and CVs (medians and ranges for Tmax).
Scatter plots vs dose for each cycle measured; dose 
proportionality based on a power model and a CI around 
the power coefficient.
Incidence of ADAs to BMS-986442 when 
BMS-986442 is administered in combination with 
nivolumab or in combination with nivolumab and 
chemotherapy.
Frequency distribution of baseline ADA-positive 
participants and ADA-positive participants after initiation 
of the treatment for each of BMS-986442 and nivolumab.
ORR, DOR, DCR, PFSR at 6 and 12 months.
The ORR and its corresponding 95% exact CI will be 
calculated by Clopper-Pearson method. Median DOR and 
its corresponding 95% CI will be estimated using KM
product-limit method. The DCR and its corresponding 
95% exact CI will be calculated by Clopper-Pearson 
method. The PFSR at 6 and 12 months will be estimated 
by the KM method and corresponding 95% CI will be 
derived based on the Greenwood formula by treatment for 
each tumor type.
Abbreviations: ADA, anti-drug antibody; AUC(0-T), area under the serum concentration-time curve from time zero 
to the time of the last quantifiable concentration; CI, confidence interval; Cmax, maximum observed concentration; 
DCR, disease control rate; DOR, duration of response; KM, Kaplan-Meier; ORR, overall response rate; PFSR,
progression-free survival rate; PK, pharmacokinetic; Tmax, time of maximum observed concentration.
10.4.5
Other Safety Analysis
10.4.5.1
Continuous Safety Monitoring
A Bayesian continuous monitoring framework will be utilized for continuous monitoring of 
toxicity in the study to detect safety signals that may lead to changes in study conduct.26
For this type of monitoring, the proportion of DLTs is used to provide formal monitoring 
boundaries. These boundaries were established using a non-informative prior, Beta (0.5, 0.5). The 
posterior distribution is Beta (0.5+n, 0.5+(m-n)), where n is the number of participants observed 
with DLT, and m is the total number of treated 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% posterior probability 
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that the aggregate DLT rate across arms is larger than 33%. It will be applied after at least 3
participants per arm in the study are treated and can be performed on a continuous basis afterwards. 
The resulting boundaries are presented in Table 10.4.5.1-1. 
If any time during the study, this DLT rate reaches the pre-specified threshold for toxicity in any 
treatment arm, then, taking into account all available safety information, the dose level may be re-
evaluated and, based on the totality of data, an additional lower dose level may be administered to 
the remaining participants. Therefore, this criterion implies that the study may terminate 
enrollment toward an arm when there is greater than 85% probability that the DLT rate is over 
33%.
Table 10.4.5.1-1:
Safety Continuous Monitoring Boundary
Number of Safety-evaluable Participants (per 
Arm)a
Aggregate Toxicity Boundary (# Evaluable 
Participants with Event) for > 85% Probability of 
DLT > 33%
3
2
4-5
3
6-7
4
8-10
5
11-12
6
13-15
7
16-17
8
18-20
9
21-23
10
24-25
11
Abbreviation: DLT, dose-limiting toxicity.
a Additional thresholds for the monitoring of > 25 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, 
 PPK, health care utilization endpoints, and health technology assessment-
related endpoints.
 will be described in the SAP finalized before database lock. PPK 
analysis and E-R analyses, if conducted, would be reported in a separate pharmacometrics report. 
Pharmacodynamic analyses will be presented separately from the main clinical study report. 
10.5
Interim Analyses 
Interim analyses may be performed for administrative purposes or publications. No formal 
inferences requiring any adjustment to statistical significance level will be performed.
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11
REFERENCES
1
Pitt JM, Marabelle A, Eggermont A, et al. Targeting the tumor microenvironment: removing 
obstruction to anticancer immune responses and immunotherapy. Ann Oncology 
2016;27:1482-92.
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Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, adaptive, and acquired resistance to 
cancer immunotherapy. Cell 2017;168:707-23.
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4
 
5
6
Banta KL, Xu X, Chitre AS, et al. Mechanistic convergence of the 
 and PD-1 inhibitory 
pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. Immunity 
2022;55:512-26.
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Waight JD, Chand D, Dietrich S, et al. Selective FcγR co-engagement on APCs modulates the 
activity of therapeutic antibodies targeting T cell antigens. Cancer Cell 2018;33:1033-47.
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Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic 
science to clinical practice. Nat Rev Immunol 2020;20:651-68.
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10 Murakami D, Matsuda K, Iwamoto H, et al. Prognostic value of 
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patients with colorectal cancer. PloS One 2022;17:e0265908.
11 Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a randomized, 
double-blind, phase II study of the anti-
 antibody tiragolumab (tira) plus atezolizumab 
(atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected 
NSCLC (CITYSCAPE). J Clin Oncol 2020;38:9503.
12 He W, Zhang H, Han F, et al. 
/
 signaling regulates CD8+ T-cell metabolism 
and promotes tumor progression in human gastric cancer. Cancer Res 2017;77:6375-88.
13 Wu L, Mao L, Liu JF, et al. Blockade of 
/
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and enhances antitumor capability in head and neck squamous cell carcinoma. Cancer 
Immunol Res 2019;7:1700-13.
14 Paz-Ares L, Ciuleanu TE, Yu X, et al. Nivolumab (NIVO) + platinum-doublet chemotherapy 
(chemo) vs chemo as first-line (1L) treatment (tx) for advanced non-small cell lung cancer 
(aNSCLC): CheckMate 227 - part 2 final analysis. Ann Oncol 2019;30:xi67-8.
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15 Fizazi K, Mella PG, Castellano D, et al. Nivolumab plus docetaxel in patients with 
chemotherapy-naïve metastatic castration-resistant prostate cancer: results from the phase II 
CheckMate 9KD trial. Eur J Cancer 2022;160:61-71.
16 Bendell JC, Bedard P, Bang Y-J, et al. Phase Ia/Ib dose-escalation study of the anti-
 
antibody tiragolumab as a single agent and in combination with atezolizumab in patients with 
advanced solid tumors. Presented at: American Association for Cancer Research 2020 Annual 
Meeting; June 22-24, 2020. Abstract CT302.
17 Golan T, Bauer T, Jimeno A, et al. Phase 1 dose-finding study of the anti-
 antibody MK-
7684 as monotherapy and in combination with pembrolizumab in patients with advanced solid 
tumors. Presented at: 33rd Annual Meeting of the Society for the Immunotherapy of Cancer; 
November 7-11, 2018; Washington, DC.
18 Niu J, Maurice-Dror C, Lee DH, et al. First-in-human phase 1 study of the anti-
 antibody 
vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including 
non-small-cell lung cancer. Ann Oncol. 2022;33(2):169-80.
19 Lee SE, Kim YJ, Sung M, et al. Association with PD-L1 expression and clinicopathological 
features in 1000 lung cancers: a large single-institution study of surgically resected lung 
cancers with a high prevalence of EGFR mutation. Int J Mol Sci 2019;20: 4794.
20 Schadendorf D, Wolchok JD, Hodi FS, et al. Efficacy and safety outcomes in patients with 
advanced melanoma who discontinued treatment with nivolumab and ipilimumab because of 
adverse events: a pooled analysis of randomized phase II and III trials. J Clin Oncol 
2017;35:3807-14.
21 Brahmer J, Horn L, Jackman D, et al. Five-year follow-up from the CA209-003 study of 
nivolumab in previously treated advanced non-small cell lung cancer (NSCLC): clinical 
characteristics of long-term survivors. Cancer Res 2017;77:CT077.
22 Font EF, Gettinger SN, Burgio MA, et al. Three-year follow-up from CheckMate 017/057: 
nivolumab versus docetaxel in patients with previously treated advanced non-small cell lung 
cancer (NSCLC). Annals Oncol 2017;28:V462.
23 OPDIVO (nivolumab) US Prescribing Information. Bristol-Myers Squibb, Princeton, NJ. 
March 2020.
24 Opdivo® Annex I Summary of Product Characteristics. Bristol-Myers Squibb Company. 2020.
25 Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity 
in solid tumors: immune-related response criteria. Clin Cancer Res 2009;15:7412-20.
26 Thall PF, Simon R. Practical Bayesian guidelines for phase IIB clinical trials. Biometrics 
1994;50:337-49.
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
ADA
anti-drug antibody
AE
adverse event
AIDS
acquired immune deficiency syndrome
ALK
anaplastic lymphoma kinase
ALP
alkaline phosphatase
ALT
alanine aminotransferase
APC
antigen-presenting cell
AST
aspartate aminotransferase
AUC
area under the serum concentration-time curve
AUC(0-T)
area under the serum concentration-time curve from time zero to the time 
of the last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in 1 dosing interval
AxMP
auxiliary medicinal product
BMI
body mass index
BMS
Bristol-Myers Squibb
BOIN
Bayesian optimal interval
BP
blood pressure
BRAF
proto-oncogene B-Raf
BUN
blood urea nitrogen
Cavg
average serum concentration
Cavg28
average serum concentration at Day 28
Cavgss
average serum concentration at steady state
CD
cluster of differentiation
cHL
classical Hodgkin lymphoma
CI
confidence interval
CL
clearance
CLss
steady-state clearance
CLT
total body clearance
Cmax
maximum observed concentration
Cmin
minimum observed concentration
CME
cystoid macular edema
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Term
Definition
CNS
central nervous system
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CR
complete response
CRC
colorectal carcinoma
CrCl
creatinine clearance
CRF
case report form, paper or electronic
CRO
contract research organization
CSR
clinical study report
Css-avg
average concentration over a dosing interval
CT
computed tomography
CTAg
clinical trial agreement
Ctau
serum concentration observed at the end of a dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
CTLA-4
cytotoxic T-lymphocyte-associated antigen 4
CV
coefficient of variation
CYP3A4
cytochrome P450 3A4
DCR
disease control rate
DILI
drug-induced liver injury
dL
deciliter
DLT
dose-limiting toxicity
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
DOR
duration of response
DRESS
drug reaction with eosinophilia and systemic symptoms
ECG
electrocardiogram
eCRF
electronic Case Report Form
ECOG PS
Eastern Cooperative Oncology Group Performance Status
EDC
electronic data capture
eGFR
estimated glomerular filtration rate
EGFR
epidermal growth factor receptor
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Term
Definition
EOI
end-of-infusion
EOT
end of treatment
E-R
exposure-response
EU
European Union
Fc
fragment crystallizable
FcγR
Fcγ receptor
FSH
follicle-stimulating hormone
fT4
free thyroxine
GBS
Guillain-Barre syndrome
G-CSF
granulocyte colony stimulating factor
GEJ
gastroesophageal junction
h
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCC
hepatocellular carcinoma
hCG
human chorionic gonadotropin
HCV
hepatitis C virus
HER2
human epidermal growth factor receptor 2
HIV
human immunodeficiency virus
HPV
human papillomavirus
HR
hazard ratio
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICF
informed consent form
ICMJE
International Committee of Medical Journal Editors
IEC
Independent Ethics Committee
IFN-γ
interferon-γ
IgG1
immunoglobulin gamma 1
IHC
immunohistochemistry
IL
interleukin
IMAE
immune-mediated adverse event
IMG
immunogenicity
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Term
Definition
IMP
Investigational Medicinal Product
INR
international normalized ratio
IO
immuno-oncology
IP
Investigational Product
IRB
Institutional Review Board
IRR
infusion-related reactions
IRT
Interactive Response Technology
ITIM
immunoreceptor tyrosine-based inhibitory motif
IU
international unit
IV
intravenous
KRAS
Kirsten rat sarcoma
LAM
lactational amenorrhea method
LDH
lactate dehydrogenase
MAD
maximum administered dose
MG
Myasthenia Gravis
min
minute
mL
milliliter
MM
Medical Monitor
MMR
measles, mumps, rubella
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
g
microgram
N
number of participants or observations
N/A
not applicable
NK
natural killer
Non-IMP
non-investigational medicinal product
NRAS
N-ras oncogene
NSAID
non-steroidal anti-inflammatory drug
NSCLC
non-small cell lung cancer
NTRK
neurotrophic tropomyosin-receptor kinase
ORR
overall response rate
OS
overall survival
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Term
Definition
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
pharmacodynamic
PD-1
programmed cell death protein 1
PD-L1
programmed cell death ligand 1
PDCT
platinum-doublet chemotherapy
PE
physical examination
PFS
progression-free survival
PFSR
progression-free survival rate
PID
patient identification number
PK
pharmacokinetic
PPK
population pharmacokinetics
PR
partial response
QTcF
QT interval corrected for heart rate using Fridericia’s formula
Q2W
every 2 weeks
Q3W
every 3 weeks
Q4W
every 4 weeks
Q6W
every 6 weeks
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors
RET
rearranged during transfection
RNA
ribonucleic acid
ROS1
ROS proto-oncogene 1
RP2D
recommended Phase 2 dose(s)
RT-PCR
reverse transcriptase polymerase chain reaction
SAE
serious adverse event
SAP
Statistical Analysis Plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus disease 2
SCCHN
squamous cell carcinoma of the head and neck
SCLC
small-cell lung cancer
SD
stable disease
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Term
Definition
SEA
staphylococcal enterotoxin A
SI
international system of units
SJS
Stevens-Johnson syndrome
SmPC
Summary of Product Characteristics
SMT
Safety Management Team
SOC
standard of care
SPR
surface plasmon resonance
SUSAR
suspected, unexpected serious adverse reaction
T. bili
total bilirubin
TBD
to be determined
TCGA
The Cancer Genome Atlas
TEN
toxic epidermal necrolysis
TGF
transforming growth factor
T-HALFeff
effective elimination half-life that explains the degree of accumulation 
observed for a specific exposure measure
TIGIT
T-cell immunoreceptor with Ig and ITIM domains
Tmax
time of maximum observed concentration
TME
tumor microenvironment
TNF-α
tumor necrosis factor α
TRAE
treatment-related adverse event
Treg
regulatory T cell
TSH
thyroid-stimulating hormone
ULN
upper limit of normal
USPI
United States Prescribing Information
v
version
Vss
geometric mean volume of distribution at steady state
WNOCBP
women not of childbearing potential
WOCBP
women of childbearing potential
WWPS
Worldwide Patient Safety
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The terms “participant” and “subject” refer to a person who has consented to participate in the 
clinical research study. Typically, the term “participant” is used in the protocol and the term
“subject” is used in the Case Report Form (CRF).
REGULATORY AND ETHICAL CONSIDERATIONS
This study will be conducted in accordance with:

Consensus ethical principles derived from international guidelines, including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
International Ethical Guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP)
Guidelines

Applicable laws, regulations, and requirements
The study will be conducted in compliance with the protocol. The protocol, any 
revisions/amendments, and the participant informed consent form (ICF) will receive 
approval/favorable opinion by the 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, 1 or more of the following: (1) the rights, physical safety, or 
mental integrity of 1 or more participants; (2) the scientific value of the clinical trial (eg, 
reliability and robustness of generated data). Items (1) or (2) can be associated with either GCP 
regulation(s) or trial protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, Investigator’s Brochure, product labeling information, ICF, 
participant recruitment materials (eg, advertisements), and any other written information to be 
provided to participants.
The investigator, Sponsor, or designee should provide the IRB/IEC with reports, updates, and 
other information (eg, expedited safety reports, amendments, administrative letters) annually, or 
more frequently, in accordance with regulatory requirements or institution procedures.
The investigator is responsible for providing oversight of the conduct of the study at the site and 
adherence to requirements of the following where applicable:
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ICH guidelines 
United States (US) Code of Federal Regulations, Title 21, Part 50 (21CFR50)
European Union (EU) Directive 2001/20/EC
European Regulation 536/2014 for clinical studies (if applicable) 
European Medical Device Regulation 2017/745 for clinical device research (if applicable)
the IRB/IEC
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, 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 the following:

IRB/IEC

Regulatory authority(ies), if applicable according to 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, by the local Health Authority, must be sent to Bristol-Myers 
Squibb Company (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 study and 
for 1 year after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that participants are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which they volunteer to 
participate. 
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The Sponsor or designee will provide the investigator with an appropriate sample ICF, which 
will include all elements required by the ICH GCP, and applicable regulatory requirements. The 
sample ICF will adhere to the ethical principles that have their origin in the Declaration of 
Helsinki.
The investigator or his/her representative must:

Obtain IRB/IEC written approval/favorable opinion of the written ICF and any other 
information to be provided to the participant prior to the beginning of the study and after any 
revisions are completed for new information.

Provide a copy of the ICF and written information about the study in the language in which 
the participant is proficient prior to clinical study participation. The language must be 
nontechnical and easily understood. 

Explain the nature of the study to the participant and answer all questions regarding the 
study.

Inform the participant that his/her participation is voluntary. The participant will be required 
to sign a statement of informed consent that meets the requirements of 21 CFR Part 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 the 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 the participant’s medical record that written informed consent was 
obtained before the 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 the participant to the most current version of the ICF(s) during his/her
participation.
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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BMS COMMITMENT TO DIVERSITY IN CLINICAL TRIALS 
The mission of BMS is to transform patients’ lives through science by discovering, developing, 
and delivering innovative medicines that help them prevail over serious diseases. 
BMS is committed to doing its part to ensure that patients have a fair and just opportunity to 
achieve optimal health outcomes. 
BMS is working to improve the recruitment of a diverse participant population with the goal that 
the clinical trial becomes more reflective of the real-world population and the people impacted 
by the diseases studied.
DATA PROTECTION, DATA PRIVACY, AND DATA SECURITY 
BMS collects and processes personal data of study participants, patients, health care providers, 
and researchers for biopharmaceutical research and development to advance innovative, high-
quality medicines that address the medical needs of patients. BMS ensures the privacy, 
protection, and confidentiality of such personal data to comply with applicable laws. To achieve 
these goals, BMS has internal policies that indicate measures and controls for processing 
personal data. BMS adheres to these standards to ensure that collection and processing of 
personal data are limited and proportionate to the purpose for which BMS collects such personal 
data. This purpose is clearly and unambiguously notified to the individual at the time of 
collection of personal data. In the true spirit of science, BMS is dedicated to sharing clinical trial 
information and data with participants, medical/research communities, the media, policy makers, 
and the general public. This is done in a manner that safeguards participant privacy and informed 
consent while respecting the integrity of national regulatory systems. Clinical trial data, health-
related research, and pharmacovigilance activities on key-coded health data transferred by BMS 
across national borders is done in compliance with the relevant data protection laws in the 
country and GCP requirements. 
BMS protects Personal Information with adequate and appropriate security controls as indicated 
under the data protection laws. To align with the recommended security standards, BMS has 
adopted internal security standards and policies to protect personal data at every stage of its 
processing.
To supplement these standards, BMS enters into Clinical Trial Agreements (CTAgs) with 
confidentiality obligations to ensure proper handling and protection of personal data by third 
parties accessing and handling personal data. BMS takes unauthorized access and disclosure of 
Personal Information very seriously. BMS has adopted the security standards that include 
National Institute of Standards and Technology Cybersecurity Framework for studies in the US. 
BMS aligns with these standards to continuously assess and improve its ability to protect, detect, 
and respond to cyber attacks and other unauthorized attempts to access personal data. These 
standards also aid in mitigating possible adverse effects. Furthermore, BMS Information 
Technology has defined 6 principles to protect our digital resources and information: 
1) Responsibilities of IT Personnel
2) Securing the BMS Digital Infrastructure
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3) Identity and Access Management
4) External Partner Connections
5) Cyber Threat Detection and Response
6) Internal Cyber Incident Investigation
SOURCE DOCUMENTS
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the electronic Case Report Form (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.

Definition of what constitutes source data and its origin can be found in the source data 
location list/map or equivalent document.
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 the 
following:

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

non-study 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 per the Delegation of 
Authority Form
Sourced by site and not supplied by 
BMS or its vendors (examples include 
Investigational Product sourced from 
the site’s stock or commercial supply or 
a specialty pharmacy)
The investigator or designee accepts responsibility 
for documenting traceability and study intervention 
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 test result 
abnormalities that are reported or identified during the study.
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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 serious adverse events (SAEs)
and pregnancy, which will be reported on the electronic SAE form and Pregnancy Surveillance 
Form, respectively. If the electronic SAE form is not available, a paper SAE form can be used. 
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. 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 non-compliance 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 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. 
The investigator (or head of the study site in Japan) must contact BMS prior to destroying any 
records associated with the study.
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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 INTERVENTION
For this study, study interventions (those supplied by BMS or a vendor or sourced by the 
investigator), such as partially used study intervention containers, vials, and syringes, may be 
destroyed on site. 
If
Then
Study interventions 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 intervention 
containers must be immediately destroyed as 
required for safety or to meet local regulations 
(eg, cytotoxic or biologic agents).
Partially used study interventions and/or 
empty containers may be destroyed after 
proper reconciliation and documentation.
However, unused Investigational Medicinal 
Product must be reconciled by the site 
monitor/Clinical Research Associate prior to 
destruction.
If study interventions will be returned, the 
return will be arranged by the responsible 
Study Monitor.
Study interventions sourced by site, not 
supplied by BMS (or its vendors; eg, study 
interventions 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.
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.
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
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 interventions provided by BMS (or its vendors). Destruction of 
non-study interventions sourced by the site, not supplied by BMS, is solely the responsibility of 
the investigator or designee.
STUDY AND SITE 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 the following:
For study termination
Discontinuation of further study intervention development
For site termination:

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 or no recruitment (evaluated after a reasonable amount of time) of participants by 
the investigator
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 
ensure appropriate participant therapy and/or follow-up.
DISSEMINATION OF CLINICAL STUDY DATA
To benefit potential study participants, patients, health care 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 per regulatory and 
BMS requirements. BMS will post study information on local, national, or regional databases in 
compliance with national and international standards for disclosure. BMS may also voluntarily 
disclose information to applicable databases.
In the European Union (EU), the summary of results and summary for laypersons will be 
submitted within 1 year of the end of trial in the EU/European Economic Area and third 
countries.
CLINICAL STUDY REPORT
A Signatory Investigator must be selected to sign the Clinical Study Report (CSR). 
For each CSR related to this protocol, the following criteria will be used to select the Signatory 
Investigator:
Participant recruitment (eg, among the top quartile of enrollers)
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 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 the Sponsor is aligned with the criteria of the International 
Committee of Medical Journal Editors (ICMJE; www.icmje.org). Authorship selection is based 
on 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)
2) Drafting the work or revising it critically for important intellectual content
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3) Final approval of the version to be published
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 the 
Sponsor 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 DEFINITIONS AND 
METHODS OF CONTRACEPTION
Appendix 4 provides general information and definitions related to Woman of Childbearing 
Potential and methods of contraception that can be applied to most clinical trials. For information 
specific to this study regarding acceptable contraception requirements for female and male 
participants, refer to Section 6.1 of the protocol. Only the contraception methods as described in 
Section 6.1 are acceptable for this study.
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP:

Premenarchal

Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Postmenopausal female

A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle-stimulating hormone (FSH) level 
> 40 mIU/mL to confirm menopause.
Note: Females treated with hormone replacement therapy (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. Suggested 
guidelines for the duration of the washout periods for HRT types are presented below. 
Investigators should use their judgement in checking serum FSH levels. 

1-week minimum for vaginal hormonal products (rings, creams, gels)

4-week minimum for transdermal products

8-week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
End of Relevant Systemic Exposure
End of relevant systemic exposure is the timepoint where the Investigational Medicinal Product 
(IMP) or any active major metabolites have decreased to a concentration that is no longer 
considered to be relevant for human teratogenicity or fetotoxicity. This should be evaluated in 
context of safety margins from the no-observed-adverse-effect level or the time required for 5 
half-lives of the IMP to pass.
METHODS OF CONTRACEPTION
Local laws and regulations may require use of alternative and/or additional contraception 
methods.
Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of < 1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation. (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol.)b

Oral (birth control pills)

Intravaginal (rings)

Transdermal

Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy.

Progestogen-only hormonal contraception associated with inhibition of ovulation. (This
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol.)b

Oral

Injectable

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy.
Highly Effective Methods That Are User Independent

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation. (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol.)b

Intrauterine device.
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
Intrauterine hormone-releasing system (IUS). (This method of contraception can only be 
used by WOCBP participants in studies where hormonal contraception is permitted by the 
study protocol.)b,c

Bilateral tubal occlusion.

Vasectomized partner 
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.
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.

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 
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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.
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
RESPONSE EVALUATION CRITERIA IN SOLID TUMORS 
GUIDELINES (VERSION 1.1) WITH BMS MODIFICATIONS
1
EVALUATION OF LESIONS
Solid tumors will be evaluated using Response Evaluation Criteria In Solid Tumors version 1.1 
(RECIST 1.1) guideline with BMS modifications.1
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows:
1.1
Measurable
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of:
10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ൒2x slice thickness if 
greater than 5mm.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥15 mm in short axis when assessed by CT/MRI scan (scan slice thickness 
recommended to be no greater than 5 mm).
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 
20 mm and qualifies as a malignant, measurable node. In this example, 20 mm should be 
recorded as the node measurement. All other pathological nodes (those with short axis ≥10 mm 
but < 15 mm) should be considered non-target lesions. Nodes that have a short axis < 10 mm are 
considered non-pathological and should not be recorded or followed.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
1.2
Non-Measurable
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10 mm or pathological lymph nodes with ≥10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: 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.
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Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
1.3
Special considerations regarding lesion measurability
1.3.1
Bone lesions
Bone scan, PET scan and plain films are not considered adequate imaging techniques to measure 
bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.
Blastic bone lesions are non-measurable.
1.4
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs 
should be identified as target lesions and will be recorded and measured at baseline (this means 
in instances where patients have only one or two organ sites involved a maximum of two and 
four lesions respectively will be recorded).
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum 
of two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph 
nodes’ or ‘multiple liver metastases’).
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2
RESPONSE CRITERIA
2.1
Evaluation of Target Lesions
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking 
as reference the baseline sum diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is 
also considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed as 
either fully resolved or too small to measure (due to missing or poor quality images), and the 
sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above. 
2.1.1
Special Notes on the Assessment of Target Lesions
2.1.1.1
Lymph nodes
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target 
lesions, the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a 
normal lymph node is defined as having a short axis of < 10 mm. Case report forms or other data 
collection methods may therefore be designed to have target nodal lesions recorded in a separate 
section where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, 
SD and PD, the actual short axis measurement of the nodes is to be included in the sum of target 
lesions.
2.1.1.2
Target lesions that become ‘too small to measure’
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the 
lesion has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is 
believed to be present and is faintly seen but too small to measure, a default value of 5 mm 
should be assigned as the reference diameter. (Note: It is less likely that this rule will be used for 
lymph nodes since they usually have a definable size when normal and are frequently surrounded 
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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’.
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 (< 10 mm short axis). 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s)
Progressive Disease (PD): Unequivocal progression of existing non-target lesions.
2.2.1
Special Notes on Assessment of Progression of Non-Target Disease
The concept of progression of non-target disease requires additional explanation as follows:
2.2.1.1
When the patient also has measurable disease
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in 
presence of SD or PR in target disease, the overall tumor burden has increased sufficiently to 
merit discontinuation of therapy A modest ‘increase’ in the size of one or more non-target 
lesions is usually not sufficient to qualify for unequivocal progression status. Pleural effusions, 
pericardial effusions and ascites will not be followed as target or non-target lesions and will not 
contribute to response or progression. The designation of overall progression solely on the basis 
of change in non-target disease in the face of SD or PR of target disease will therefore be 
extremely rare.
2.2.1.2
When the patient has only non-measurable disease
This circumstance arises in some trials when it is not a criterion of study entry to have 
measurable disease. The same general concepts apply here as noted above, however, in this 
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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: ie, an increase in tumor 
burden representing an additional 73% increase in ‘volume’ (which is equivalent to a 20% 
increase diameter in a measurable lesion). Examples include, an increase in lymphangitic disease 
from localized to widespread, or may be described as ‘sufficient to require a change in therapy’. 
If ‘unequivocal progression’ is seen, the patient should be considered to have had overall PD at 
that point. While it would be ideal to have objective criteria to apply to non-measurable disease, 
the very nature of that disease makes it impossible to do so; therefore the increase must be 
substantial.
2.2.2
New Lesions
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of new lesions are important. There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a new lesion should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging 
modality or findings thought to represent something other than tumor (for example, some ‘new’ 
bone lesions may be simply healing or flare of pre-existing lesions). This is particularly 
important when the patient’s baseline lesions show partial or complete response. For example, 
necrosis of a liver lesion may be reported on a CT scan report as a ‘new’ cystic lesion, which it is 
not.
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new 
fluid collection is seen on a post-baseline imaging exam, a comment may be made, but the 
appearance of a new fluid collection alone should not result in an assessment of Progressive 
Disease (PD). A lesion identified on a follow-up study in an anatomical location that was not 
scanned at baseline is considered a new lesion and will indicate disease progression. An example 
of this is the patient who has visceral disease at baseline and while on study has a CT or MRI 
brain ordered which reveals metastases. The patient’s brain metastases are considered to be 
evidence of PD even if he/she did not have brain imaging at baseline. A lesion identified on 
Chest X-Ray that was not present in prior CT can be considered a new lesion and will result in 
Progressive Disease (PD).
If a new lesion is equivocal, for example because of its small size, continued follow-up 
evaluation will clarify if it represents truly new disease. If repeat scans confirm there is definitely 
a new lesion, then progression should be declared using the date of the initial scan. While FDG-
PET response assessments need additional study, it is sometimes reasonable to incorporate the 
use of FDG-PET scanning to complement CT scanning in assessment of progression 
(particularly possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be 
identified according to the following algorithm:
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1) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion.
2) No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 
CT scans are needed to determine if there is truly progression occurring at that site (if so, the 
date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET 
at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD.
2.3
Response Assessment
2.3.1
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
disease progression or the last response recorded, taking into account any requirement for 
confirmation and censoring rules regarding subsequent therapy. The patient’s best overall 
response assignment will depend on the findings of both target and non-target disease and will 
also take into consideration the appearance of new lesions. Furthermore, depending on the nature 
of the study and the protocol requirements, it may also require confirmatory measurement.
2.3.2
Time Point Response
At each protocol specified time point, a response assessment occurs. Table 2.3.2-1 provides a 
summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline. When patients have non-measurable (therefore non-target) 
disease only, Table 2.3.2-2 is to be used. 
Table 2.3.2-1:
Time Point Response
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; NE, not evaluable.
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Table 2.3.2-2:
Time Point Response: Patients with Non-target Disease Only
Non-Target Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR, complete response; PD, progressive disease; NE, not evaluable.
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.
2.3.3
Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point 
of 4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as 
in Table 2.3.3-1. When SD is believed to be best response, it must meet the protocol specified 
minimum time from the date of first treatment 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 and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
CR
CR
CR
PR
SD, PD OR PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, 
PD
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Table 2.3.3-1:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
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; NE, not evaluable.
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). 
Best response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be 
claimed when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not 
CR at the first time point. Under these circumstances, the original CR should be changed to PR and the best 
response is PR.
2.3.4
Confirmation Scans
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a 
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation.
Verification of Progression: Progression of disease should be verified in cases where 
progression is equivocal. If repeat scans confirm PD, then progression should be declared using 
the date of the initial scan. If repeat scans do not confirm PD, then the subject is considered to 
not have progressive disease.
REFERENCES
1 Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumors: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47.
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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
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.
Protocol Amendment No.: 02
Date: 12-Jan-2023
157
3.0
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3.0
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
158
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
159
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
160
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
161
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
162
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
163
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
164
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
28-Sep-2020
Protocol Amendment No.: 02
Date: 12-Jan-2023
165
3.0
Approved
930186980
3.0
v
Approved
1.0
v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
APPENDIX 8
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.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
APPENDIX 9
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for Protocol Amendment 01, 27-Jun-2022:
The purpose of this amendment is
 
 to update the eligibility criteria to include all actionable mutations, adjust 
eligibility criteria for docetaxel, and adjust dosing modifications for nivolumab. In addition, the 
protocol was updated to utilize staggered dosing for safety monitoring during dose escalation and 
specify stopping rules for the study based on safety monitoring
 
. In addition 
 the dosing instructions were 
updated and additional information provided regarding the 
 plan.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 2:
Schedule of 
Activities
Table 2-1:
Screening 
Procedural 
Outline for All 
Parts 
(CA115001)
MET exon 14 skipping mutation 
status and EGFR exon 20 
insertion mutation status were 
added to the eligibility 
assessments.
To align with updated eligibility criteria 
.
Section 
5.1.2.1:
Part A: Dose 
Escalation of 
BMS-986442 
with 
Nivolumab
The following language was 
added to this section:
“A staggered dosing (sentinel 
participant) approach will be used. 
The first participant in each cohort 
will be observed for at least 7 
days after their initial exposure to 
the combination of BMS-986422 
and nivolumab before additional 
participants in that cohort are 
dosed. Subsequently, the 
remaining participants in each 
dose cohort must be observed for 
at least 24 hours after their initial 
exposure to the combination 
Added additional enrollment guidelines 
and safety monitoring for dose 
escalation (Part A) 
 
.
Protocol Amendment No.: 02
Date: 12-Jan-2023
167
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PI
PI
PI
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
regimen before additional 
participants are exposed.
Section 5.1.3:
Follow-up 
Period
A clarification was added that is 
applicable to the safety follow-up 
period. The words “even if the 
study is terminated” were added 
to the following language in this 
section:
“The safety follow-up period for 
all treatment groups, even if the 
study is terminated, is 100 days 
after the end-of-treatment visit or 
date of last dose (whichever 
occurs later), with visits to occur 
at 30, 60, and 100 (± 7) days.
Updated for clarification 
 
. 
Section 5.1.4:
Data 
Monitoring 
Committee 
and Other 
Committees
The following language was 
added to this section:
“If there is any treatment-related 
Grade ≥ 4 toxicity or death as 
assessed by the Sponsor, 
enrollment in that arm will be 
placed on hold and an ad-hoc 
SMT meeting will be convened. 
Additionally, a Bayesian 
continuous monitoring framework 
will be utilized for continuous 
monitoring of toxicity in the 
study. If at any time during the 
study, the posterior probability of 
the DLT rate exceeding 33% is 
greater than 0.85, that will also 
trigger enrollment in that arm 
being placed on hold and an ad-
hoc SMT meeting being 
convened. The SMT will re-
evaluate the benefit-risk profile of 
the drug combination in context of 
the totality of the data, and assess 
whether termination or 
Specified stopping rules based on safety 
.
Protocol Amendment No.: 02
Date: 12-Jan-2023
168
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
resumption of the cohort/study is 
appropriate.”
Section 6.1:
Inclusion 
Criteria 
Inclusion criterion 2-g-v was 
updated to specify epidermal 
growth factor receptor (EGFR) 
mutations include exon 20 
insertion mutations, as well as 
updated to add MET exon 14 
skipping mutations, and include 
abbreviations for rearranged 
during transfection and 
neurotrophic tropomyosin-
receptor kinase. The updated 
criterion is as follows:
“Participants with disease having 
known actionable mutations in 
epidermal growth factor receptor 
(EGFR) including exon 20 
insertion mutations, anaplastic 
lymphoma kinase (ALK), ROS 
proto-oncogene 1 (ROS1), 
rearranged during transfection 
(RET), neurotrophic tropomyosin-
receptor kinase (NTRK), Kirsten 
rat sarcoma (KRAS) (G12C), 
MET exon 14 skipping mutations, 
or proto-oncogene B-Raf (BRAF) 
(V600E) must have progressed 
on, have been intolerant to, or not 
be a candidate for standard 
targeted therapy (as available per 
country/region standard-of-care 
practices).”
Inclusion criterion 2-i-ii was 
updated to specify EGFR 
mutations include exon 20 
insertion mutations, as well as 
updated to add MET exon 14 
Updated and clarified eligibility criteria 
to include known actionable mutations 
(as per regional standard of care) 
 
.
Protocol Amendment No.: 02
Date: 12-Jan-2023
169
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3.0
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v


Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
skipping mutations, RET, and 
NTRK. The updated criterion is as 
follows:
“Participants with disease having 
known genetic aberrations in 
EGFR including exon 20 insertion 
mutations, ALK, ROS1, KRAS 
(G12C), RET, NTRK, MET exon 
14 skipping mutations, or BRAF 
(V600E) that are sensitive to 
targeted therapy (as available per 
country/region standard-of-care 
practices) will be excluded.”
Section 6.2: 
Exclusion 
Criteria 
Exclusion criterion 5-f was 
updated to add specific 
requirements for participants in 
study Part C. The additional 
criterion that was added and 
applicable to study Part C is as 
follows:
“Participants in Part C only: AST 
and/or ALT > 1.5 x ULN 
concomitant with alkaline 
phosphatase > 2.5 x ULN.”
Exclusion criterion 5-g was 
updated to add specific 
requirements for participants in 
study Part C. The additional 
criterion that was added and 
applicable to study Part C is as 
follows:
“All participants, except Part C: 
Total bilirubin > 1.5 x ULN 
(except participants with Gilbert 
Syndrome who must have a total 
bilirubin level of < 3.0 x ULN). 
Participants in Part C only: Total 
bilirubin > ULN.”
To implement more stringent exclusion 
criteria and align with the docetaxel US 
Prescribing Information (USPI) 
 
. 
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 7.1.1:
Part A and 
Part B: 
Nivolumab 
and BMS-
986442
This section was updated to 
include separate infusion time 
guidance (90 minutes) for the 
BMS-986442 dose level of 1200 
mg. The updated BMS-986442 
infusion time guidance displayed 
in this section is as follows:
“BMS-986442 (20 mg dose level 
up to and including 600 mg dose 
level) will be administered as an 
infusion over 60 minutes (Q3W) 
followed by a 60-minute 
observation period. BMS-986442 
at the 1200 mg dose level will be 
administered as an infusion over 
90 minutes (Q3W), followed by a 
60-minute observation period.”
To align with dosing recommendations 
based on endotoxin exposure at 1200 mg 
dose.
Section 7.1.3:
Part D: 
Nivolumab, 
BMS-986442, 
Pemetrexed, 
and 
Carboplatin
This section was updated to 
include “dosed in accordance with 
local prescribing information,” 
which was added to the guidance 
for oral folic acid administration. 
The updated language is as 
follows:
“Oral folic acid 350 to 1000 μg 
daily (dosed in accordance with 
local prescribing information)
should be given starting 1 week 
prior to the first dose of 
pemetrexed, with at least 5 doses 
of folic acid administered in the 7 
days prior to the first dose.”
To align with regional dosing variations 
of folic acid in conjunction with 
pemetrexed 
.
Section 7.4.1:
Dose 
Modification 
Criteria for 
Nivolumab 
and BMS-
986442
The hepatic severity criterion 
within table 7.4.1-1 was updated 
to include the following additional 
criteria for permanent 
discontinuation of nivolumab and 
BMS-986442 (additional criteria 
in underline):
Updated dose modification guidelines 
for hepatic adverse events to align with 
the current USPI for nivolumab 
 
.
Protocol Amendment No.: 02
Date: 12-Jan-2023
171
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Table 7.4.1-1:
Adverse Event 
Criteria for 
Delay, 
Resume, and 
Discontinue of 
Nivolumab 
and BMS-
986442
“Concurrent AST or ALT > 3 x
ULN and T.bili > 2 x ULN, 
regardless of baseline value, or
T. bili > 3 x ULN, or 
AST or ALT > 8 x ULN with no 
tumor involvement of the liver, or 
AST or ALT > 10 x ULN with 
tumor involvement of the liver”
Protocol Amendment No.: 02
Date: 12-Jan-2023
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Clinical Protocol
CA115001
BMS-986442
Anti-TIGIT Bispecific Ab
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 
10.4.5.1:
Continuous 
Safety 
Monitoring 
Table 
10.4.5.1-1: 
Safety 
Continuous 
Monitoring
Boundary
This section and table content 
were updated in order to expand 
the participant population to all 
treated participants. Part B 
specifics were replaced with 
treated participants in all study 
parts. The previously specified 
time period of 28 days was 
removed, as the safety monitoring 
time period will be expanded and 
encompass the full study length 
(through all participants’ safety 
follow-up).
This section and table were updated in 
parallel with the updates made within 
Section 5.1.4 (specified stopping rules 
based on safety 
 
).
All
Minor formatting and 
typographical corrections.
Because these errors are minor, they 
have not been summarized.
Protocol Amendment No.: 02
Date: 12-Jan-2023
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