A Phase 1/2 Study of BMS-986408 Alone and in Combination With Nivolumab or With Nivolumab and Ipilimumab in Participants With Advanced Solid Tumors
Phase: PHASE1
Conditions: Advanced Solid Tumors
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Phase 1/2 Study of BMS-986408 Alone and in Combination with Nivolumab or with 
Nivolumab and Ipilimumab in Participants with Advanced Solid Tumors 
 
NCT Number: NCT05407675 
Document Date (Date in which document was last revised): December 11, 2023 
 
 
 

Page:
1
Protocol Number:
CA099003
Date:
18-Nov-2021
Revised Date:
11-Dec-2023
CLINICAL PROTOCOL CA099003
A Phase 1/2 Study of BMS-986408 Alone and in Combination with Nivolumab or with 
Nivolumab and Ipilimumab in Participants with Advanced Solid Tumors
Brief Title:
A Phase 1/2 Study of BMS-986408 with and without Nivolumab or Nivolumab and Ipilimumab 
in Participants with Solid Tumors
Protocol Amendment 04
Clinical Trial Physician-Medical Monitor
Bristol-Myers Squibb Company
3401 Princeton Pike 
Lawrenceville, NJ 08648
email:
Clinical Scientist
Bristol-Myers Squibb Company
86 Morris Avenue
Summit, NJ 07901
email: 
24-hr Emergency Telephone Number
USA: 1-866-470-2267
International: +1-248-844-7390
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: 156,177
EudraCT/EU Trial Number: 2022-500823-61-00
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Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Protocol Amendment No.: 04
Date: 11-Dec-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]).  
© 2023 Bristol-Myers Squibb Company
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CA099003
BMS-986408
DGKα/ζ Inhibitor
Protocol Amendment No.: 04
Date: 11-Dec-2023
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Protocol Amendment 
04
11-Dec-2023
The following key changes were made to this amendment:

Added 
 monotherapy cohort (Group B2).

Added a pH sub-study (Group G).

Added a dose expansion cohort of BMS-986408 in combination
with nivolumab (Group D2).

Added dose escalation (Group F) and dose expansion
(Group F2) cohorts to evaluate BMS-986408 in combination
with nivolumab and platinum-doublet chemotherapy in
non-small cell lung cancer.
Protocol Amendment 
03
21-Apr-2023
The following key changes were made in this amendment:

Added clarifications around 
 exclusionary
criteria.

Updated 
 exclusionary criteria.

Added guidance regarding 
management.
Updated the duration of contraception for males and females.
Protocol Amendment 
02
02-Dec-2022
The following key changes were made to this amendment:

Removed SARS-CoV-2 serology requirements.

Added 
clarification
regarding 
BMS-986408 

Added an exploratory biomarker for Groups C, D, and E.

Added 
 for BMS-986408 when
administered 
.

Administrative Letter 
01
03-Jun-2022

Change in clinical scientist.
Protocol Amendment 
01
25-Mar-2022
Dose-limiting toxicity criteria, discontinuation criteria for subjects 
with elevations in liver function laboratory values, and exclusion 
criteria for subjects with renal impairment or QT prolongation were 
modified 
Original Protocol
18-Nov-2021
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CA099003
BMS-986408
DGKα/ζ Inhibitor
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 04:
This protocol was amended to evaluate alternative dosing strategies, formulations, and 
combinations, and clinical efficacy in expansion cohorts. It includes the addition of the following 
groups:

Part 1, Group B2: An optional monotherapy
 cohort 
 to evaluate
alternative dosing strategies

Part 2, Group G: This cohort will assess the effect of proton pump inhibitor (PPI) use (pH
effect)
 BMS-986408.
After
participants
will be treated with daily dosing of BMS-986408 in combination with nivolumab every 4
weeks (Q4W).

Part 3, Group D2: Dose expansion of BMS-986408 in combination with nivolumab Q4W in
non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), and
microsatellite stable (MSS) colorectal cancer (CRC). 

Part 2, Group F and Part 3, Group F2: Dose escalation (Part 2, Group F) and dose expansion
(Part 3, Group F2) to evaluate BMS-986408 daily in combination with nivolumab and
platinum-doublet chemotherapy (PDCT) every 3 weeks (Q3W) in NSCLC without prior
systemic anti-cancer given as primary therapy in the advanced or metastatic setting.
Other changes include adding safety data from the first 25 treated participants, which aligns with 
the investigator’s brochure (IB). The preclinical sections were updated to align with the IB and 
provide rationale for the new combination of BMS-986408 with nivolumab plus PDCT.
 
 
. Biopsy samples will now 
be accepted if collected within the prior 3 months (previously 1 month). The inclusion criteria 
were updated 
 
 The text was updated throughout the protocol to include the additional 
cohorts and edited to remove redundant language.
Additional details of the changes are described in the table below.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 1: Protocol 
Summary
Updated to reflect changes made in the 
body of the protocol.
Transitioned the summary to a table 
format.
To align with protocol updates.
Simplification.
Table 2-1: Screening 
Procedural Outline 
(CA099003)
Table 2-3: On Treatment 
Procedural Outline 
(Parts 2 and 3, Groups D, 
D2, E, F, F2, and G)
Added the assessment of tumor 
programmed death ligand 1 (PD-L1)
status at screening, study treatments, and 
biopsy requirements (mandatory 
screening and on-treatment tumor 
biopsies for Group F and optional for 
Group F2, if tissue is available for PD-L1 
confirmatory testing). Added footnote “e” 
to Table 2-3.
Updated throughout protocol to include 
the dose escalation (Part 2, Group F) 
and dose expansion (Part 3, Group F2) 
cohorts evaluating BMS-986408 in 
combination with nivolumab and 
PDCT in participants with NSCLC. 
This included updating the schedule of 
activities, rationale, benefits/risks, 
objectives/endpoints, study design, 
sample sizes, eligibility criteria, 
contraception requirements, prohibited 
medications, and dose-limiting toxicity 
(DLT), PK, and biomarker assessments.
Section 3: Introduction
Section 3.3: Benefit/Risk 
Assessment
Section 3.3.1: Risk 
Assessment
Section 3.3.2: Benefit 
Assessment
Section 3.3.3: Overall 
Benefit/Risk Conclusion
Revised these sections to include 
rationale and benefit/risk assessment of 
BMS-986408 in combination with 
nivolumab and PDCT.
Table 4-1: Objectives and 
Endpoints
Updated objectives and endpoints to 
include BMS-986408 in combination of 
nivolumab and PDCT.
Section 5.1: Overall 
Design
 
Section 5.1.2: Part 2 
Combination Therapy 
Cohorts
Section 5.1.2.2: 
BMS-986408 in 
Combination with 
Nivolumab and PDCT 
(Group F)
Section 5.1.3: Part 3 
Expansion Cohorts
Section 5.1.5: Treatment 
Period
 
 
 
 
 
 
 
 
 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 5.4: Scientific 
Rationale for Study 
Design
Section 5.4.3: Rationale 
for BMS-986408 in 
Combination with 
Nivolumab and PDCT
Section 5.5.2: Nivolumab
Section 7.1.1: 
BMS-986408 Dosing
Section 7.1.3.1: Paclitaxel 
and Carboplatin
Section 7.1.3.2: 
Pemetrexed and Cisplatin
Section 7.1.3.3: 
Pemetrexed and 
Carboplatin
Section 7.1.3.4: Optional 
Continuation 
Maintenance
Section 7.2: Method of 
Study Intervention 
Assignment
Section 7.4.2: Dose 
Delays for Chemotherapy
Section 7.4.3: Dose 
Reduction for 
Chemotherapy
Table 7.4.3-1: Dose 
Reduction for 
Chemotherapy
Section 7.4.3.1: 
Chemotherapy: Dose 
Reductions for 
Hematologic Toxicity
Table 7.4.3.1-1: Dose 
Modification for 
Hematologic Toxicity 
(Based on Nadir Counts)
Section 7.4.3.2: 
Chemotherapy: Dose 
Reductions for 
Non-hematologic 
Toxicities
Table 7.4.3.2-1: Dose 
modification for 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Non-Hematologic 
Toxicity
Section 7.4.4.2: Criteria 
to Resume Treatment 
with Chemotherapy
Section 5.2: Number of 
Participants
Section 10.2: Sample Size 
Determination
Added the sample size for Groups F 
and F2.
Section 6.1: Inclusion 
Criteria
Section 6.2: Exclusion 
Criteria
Added inclusion criterion 2)i) and 
exclusion criterion 3)k).
Added inclusion criterion 4)a)v)2)b) and 
modified criteria 4)b)i), 4)b)ii), 4)b)iii), 
and 4)b)iv) (contraception requirements)
for participants receiving chemotherapy.
Table 7-1: Study 
Intervention(s) for 
CA099003
Table 7.1-1: Study 
Intervention(s) 
Administered
Section 7.1.3: 
BMS-986408 in 
Combination with 
Nivolumab and PDCT
Added study interventions to the tables.
Added a new section (Section 7.1.3).
Section 7.4: Dosage 
Modification
Added dose modification criteria, which 
includes adding new sections for dose 
reduction of chemotherapy and criteria to 
resume treatment with chemotherapy.
Section 7.7.1: Prohibited 
and/or Restricted 
Treatments
Added that the investigator must also 
adhere to the contraindications, 
precautions, and drug interactions found 
in the United States Prescribing 
Information (USPI) or local label for each 
of the chemotherapy agents.
Section 9.5: 
Pharmacokinetics
Added Groups F and F2 to PK 
assessments.
Table 9.8-1: Biomarker 
Sampling Schedule for all 
Participants
Added Groups F and F2 to biomarker 
assessments.
Protocol Amendment No.: 04
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 9.8.2: Tumor-
based Biomarkers
Table 2-1: Screening 
Procedural Outline 
(CA099003)
Table 2-3: On Treatment 
Procedural Outline 
(Parts 2 and 3, Groups D, 
D2, E, F, F2, and G)
Table 9.4.4-1: Clinical 
Laboratory Assessments
Added Group D2 to the tables. Added 
optional screening and on-treatment 
biopsies as well as clinical assessments.
Updated throughout protocol to add the 
dose expansion cohorts for 
BMS-986408 
 in 
combination with nivolumab Q4W 
(Part 3, Group D2) in NSCLC, RCC, 
melanoma, and MSS CRC. This
included updating the schedule of 
activities, study design, sample sizes, 
eligibility criteria, and PK and 
 
Section 5.1.3: Part 3 
Expansion Cohorts
Section 5.4: Scientific 
Rationale for Study 
Design
Section 5.5.2: Nivolumab
Section 7.2: Method of 
Study Intervention 
Assignment
 
 
 
 
 
 
Section 5.2: Number of 
Participants
Section 10.2: Sample Size 
Determination
Added the sample size for Group D2.
Section 6.1: Inclusion 
Criteria
Added new eligibility criteria, including 
inclusion criterion 2)h) and related 
subcriteria.
Table 7-1: Study 
Intervention(s) for
CA099003
Table 7.1-1: Study 
Intervention(s) 
Administered
Section 7.1.1: 
BMS-986408 Dosing
Added study interventions.
Section 9.5: 
Pharmacokinetics
Added Group D2 to PK assessments.
Table 9.8-1: Biomarker 
Sampling Schedule for all 
Participants
Section 9.8.2: Tumor-
based Biomarkers
Added Group D2 to biomarker 
assessments.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Table 2-1: Screening 
Procedural Outline 
(CA099003)
Table 2-3: On Treatment 
Procedural Outline 
(Parts 2 and 3, Groups D, 
D2, E, F, F2, and G)
Table 9.4.4-1: Clinical 
Laboratory Assessments
Added Cycle 0 to the scheduled activities 
and study treatments (rabeprazole and 
BMS-986408). Added 
screening and on-treatment tumor 
biopsies as well as clinical assessments.
Added footnotes “c” and “f” to Table 2-3.
Updated throughout the protocol to 
include the PK group to assess the pH 
effect of 
 
BMS-986408 (Part 2, Group G). This
included updates to the schedule of 
activities, objectives/endpoints, study 
design, sample size, study population,
study interventions, and PK and 
biomarker assessments.
Table 4-1: Objectives and 
Endpoints
Added the exploratory objective 
 
 
 
Added the exploratory objective 
 
 
 
 
Section 5.1.2: Part 2 
Combination Therapy 
Cohorts
 
Section 5.1.2.3: pH Effect 
PK Sub-study 
 
 
(Group G)
 
Section 5.5.2: Nivolumab 
Section 7.2: Method of 
Study Intervention 
Assignment 
 
 
 
Section 5.2: Number of 
Participants
Section 10.2: Sample Size 
Determination
Added sample size for Group G.
Section 6.1: Inclusion 
Criteria
Added eligibility criteria, including 
inclusion criterion 2)h) and related 
subcriteria.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Table 7-1: Study 
Intervention(s) for 
CA099003
Table 7.1-1: Study 
Intervention(s) 
Administered
Section 7.1.1: 
BMS-986408 Dosing
Section 7.7.1: Prohibited 
and/or Restricted 
Treatments
Added study interventions.
Section 9.5: 
Pharmacokinetics
Table 9.5-3: 
Pharmacokinetic and 
Immunogenicity 
Sampling Schedule for 
Part 2, Groups D 
(Combination Cohort 
with Nivolumab), F 
(Combination Cohort 
with Nivolumab and 
Chemotherapy), and G 
(Starting C1D1), and Part 
3 Combination Expansion
Table 9.5-5: 
Pharmacokinetic 
Sampling Schedule for 
Part 2, Group G (Cycle 0 
pH Effect)
Added Group G to PK assessments.
Section 9.8.2: Tumor-
based Biomarkers
Added Group G to biomarker 
assessments.
Table 2-2: On Treatment 
Procedural Outline 
(Part 1, Groups A, B, B2, 
and C)
Added 
 
. Added screening and 
on-treatment tumor biopsies.
Updated throughout the protocol to 
include an optional monotherapy cohort 
(Group B2)
 
 
. This
included updating the schedule of 
activities, study design, sample sizes, 
study population, eligibility criteria,
study intervention, DLT, and PK and 
biomarker assessments.
 
 
Section 5.1.1: Part 1 
Monotherapy Cohorts
Section 5.1.5: Treatment 
Period
 
 
 
 
Protocol Amendment No.: 04
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 5.2: Number of 
Participants
Section 10.2: Sample Size 
Determination
Added the sample size for Group B2.
Section 6.1: Inclusion 
Criteria
Added eligibility criteria. Modified 
inclusion criterion 2)a) to apply to 
Group B2.
Table 7-1: Study 
Intervention(s) for 
CA099003
Table 7.1-1: Study 
Intervention(s) 
Administered
Section 7.1.1: 
BMS-986408 Dosing
Added study interventions.
 
 
 
 
.
Section 9.5: 
Pharmacokinetics
Table 9.5-2: 
Pharmacokinetic and 
Immunogenicity 
Sampling Schedule for 
Part 1 Groups A, B, B2, 
and C
Table 9.5-5: 
Pharmacokinetic
Sampling Schedule for 
Part 2, Group G (Cycle 0 
pH Effect)
Added Group B2 to PK assessments. 
Included Table 9.5-5 for the sampling 
schedule 
followed by the 
Table 9.5-3 schedule starting at C1D1.
Table 9.8-1: Biomarker 
Sampling Schedule for all 
Participants
Section 9.8.2: Tumor-
based Biomarkers
Added Group B2 to biomarker 
assessments.
Table 2-1: Screening 
Procedural Outline 
(CA099003)
Edited a note to the row “Brain Imaging.”
To clarify that MRI of the brain without 
and with contrast is required for all 
NSCLC and melanoma participants in 
Part 3, Groups D2 and F2.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Table 2-4: Follow-up 
Procedural Outline 
(CA099003)
The safety follow-up period was revised 
from “last dose of study treatment” to 
“end of treatment (EOT).”
To align with the study design.
Updated the note in the row 
“Concomitant Medication Use.”
To clarify the minimum period in 
which the use of concomitant 
medication should be recorded.
Section 3.2.1.2: 
BMS-986408 Nonclinical 
Pharmacology
 
 
Section 3.2.1.4: 
BMS-986408 Nonclinical 
Toxicology
Section 3.2.1.5: 
BMS-986408 Clinical 
Activity
 
 
 
 
Added Section 3.2.1.5 and preliminary 
clinical data from CA099003.
Updated to align with the IB. Removed 
preclinical data that can be found in IB. 
Added clinical data to align with
the IB.
Table 2-4: Follow-up 
Procedural Outline 
(CA099003)
Section 9.2.3: Follow-up 
of AEs and SAEs
Removed text related to serious adverse 
events (SAEs) and adverse events (AEs)
associated with confirmed or suspected 
severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infections.
Updated information and language 
regarding SARS-CoV-2. 
Section 3.3: Benefit/Risk 
Assessment
Section 9.2.1: Time 
Period and Frequency for 
Collecting AE and SAE 
Information
Removed language related to acute 
SARS-CoV-2 infections and vaccines.
Relocated text related to AEs associated 
with SARS-CoV-2 infection.
Section 5.1.2: Part 2 
Combination Therapy 
Cohorts
Section 5.1.2.3: pH Effect 
PK Sub-study 
 
 
)
Section 5.1.3: Part 3 
Expansion Cohorts
Updated all parts of the study to allow 
 may be assessed in the 
protocol.
Table 7-1: Study 
Intervention(s) for 
CA099003
Added BMS-986408 
 the 
list of study interventions.
Section 5.1.6: Follow-up 
Period
Changed the survival follow-up period 
start from the date of discontinuation of 
study treatment to the EOT visit.
Updated to align with the Schedule of 
Activities (Section 2).
Protocol Amendment No.: 04
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 6.1: Inclusion 
Criteria
Modified criterion 2)d) to apply to 
Groups F and G as well and to state “3 
months” instead of “1 month” before the
start of the screening period.
Biopsy samples will now be accepted if 
collected within the prior 3 months.
Section 6.2: Exclusion 
Criteria
Modified exclusion criterion 
To align with the definition of 
 
Added criterion 
To list an exclusion criterion pertaining 
to Part 2, Group F and Part 3, 
Group F2.
Modified criterion 
To clarify that the 
 
 
 
Modified criteria 
To clarify that 
 
 
 
Modified criterion 
Revised to align with the target 
participant population for enrollment 
purposes.
Modified criterion 
Only
 
 should be considered an 
exclusion criterion.
Added criterion 5)c).
Added to address the addition of 
chemotherapy.
Table 7-1: Study 
Intervention(s) for 
CA099003
Modified the potency of nivolumab from 
“100 mg or 40 mg” to “100 mg/vial.”
Updated to align with the pharmacy 
manual.
Section 7.4.5: 
Added guidance in case of suspected or 
confirmed
 
Included guidance on diagnosis and 
management of 
 
Section 8.1: 
Discontinuation From 
Study Intervention
Added instructions for discontinuation 
from study intervention for all groups in 
Parts 2 and 3. 
To align with the addition of new 
cohorts in Parts 2 and 3.
Table 9.4.4-1: Clinical 
Laboratory Assessments
Added 
 
assessment to the list of analyses required 
Updated the laboratory assessments 
based on the addition of 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 9.5: 
Pharmacokinetics
Removed “predose (within approximately 
2 hours prior to dosing; 
 
 and added 
“The 
 collected from 
the participant during each time interval 
should be recorded 
To update the guidance for 
 
collection and analyses.
Added that 
 
samples will also be collected from all 
participants treated with 
 
Update to align with new groups.
Modified the text to state that, after the 
scheduled analysis of PK samples are 
complete, 
.
Clarification.
Added that BMS-986408 PK parameters 
will be derived from plasma 
concentration-time data during 
combination with nivolumab and 
chemotherapy.
To clarify that these derivations will 
also be performed in cohorts with 
combination with nivolumab and 
chemotherapy.
Added “in the plasma” in the paragraph 
related to concentration analyses.
Clarification.
In Table 9.5-2, footnote “b,” added “and 
prior to blood collections.”
To clarify that all ECGs should be 
recorded prior to blood collections.
Table 9.5-3: 
Pharmacokinetic and 
Immunogenicity 
Sampling Schedule for 
Part 2, Groups D 
(Combination Cohort 
with Nivolumab), F 
(Combination Cohort 
with Nivolumab and 
Chemotherapy), and G 
(Starting C1D1), and 
Part 3 Combination 
Expansion
Table 9.5-4: 
Pharmacokinetic and 
Immunogenicity 
Sampling Schedule for 
Part 2, Group E 
(Combination Cohort 
with Nivolumab and 
Ipilimumab)
Added a pre-dose plasma sample 
collection for BMS-986408 PK analyses 
in C1D1.
Included to establish participant 
baseline.
Revised footnote “b.”
To clarify that flush is mandatory to 
ensure delivery of the entire drug dose.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Table 9.5-3: 
Pharmacokinetic and 
Immunogenicity 
Sampling Schedule for 
Part 2, Groups D 
(Combination Cohort 
with Nivolumab), F 
(Combination Cohort 
with Nivolumab and 
Chemotherapy), and G 
(Starting C1D1), and 
Part 3 Combination 
Expansion
Added footnote “d” to C1D22.
To clarify that this collection is not 
applicable for Group F.
Former Section 9.8.1.1: 
Former Section 9.8.1.4: 
 
Deleted these sections.
Characterization of 
 
will no longer be 
performed.
Table 2-1: Screening 
Procedural Outline 
(CA099003)
Table 2-2: On Treatment 
Procedural Outline 
(Part 1, Groups A, B, B2, 
and C)
Table 2-3: On Treatment 
Procedural Outline 
(Parts 2 and 3, Groups D, 
D2, E, F, F2, and G)
Clarified the schedule of activities by 
consolidating the rows 
 
 for NSCLC and 
melanoma participants, clarifying 
targeted physical examination (PE), 
separating single from triplicate ECGs, 
and referencing Section 9.10 for details 
To clarify and/or increase readability.
Section 6.1: Inclusion 
Criteria
Added criterion 2)b)v).
Criterion 2)c) is no longer applicable per 
Protocol Amendment 04.
Former criterion 2)c) is a subcriterion 
from 2)b).
Edited criterion 4)a)v)2)a).
Section 7.7.1: Prohibited 
and/or Restricted 
Treatments
Clarified the use of immunosuppressive 
doses of systemic corticosteroids.
Section 9.2: Adverse 
Events
Added a reference to the electronic case 
report form instructions.
Section 9.2.3: Follow-up 
of AEs and SAEs
Modified the text to limit SAE follow-up 
to 
 
 
 
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DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04
Section Number & 
Title
Description of Change
Brief Rationale
Section 9.4.3: 
Electrocardiograms
Removed “a single 12-lead ECG will be 
collected as outlined” and added a 
reference to Section 2.
Table 9.4.4-1: Clinical 
Laboratory Assessments
Added that the assessment of prothrombin 
time is needed at screening only.
Table 9.5-2: 
Pharmacokinetic 
Sampling Schedule for 
Part 1, Groups A, B, B2, 
and C
Removed the baseline sample collections 
and added a pre-dose collection in C1D1.
Table 9.8-1: Biomarker 
Sampling Schedule for all 
Participants
Former biomarker sampling schedule 
tables were merged into a single table for 
all participants in the study.
 
 
Section 10.3: Analysis 
Sets
Updated the description of the biomarker 
population.
Clarification.
Appendix 2: Study 
Governance 
Considerations
Removed requirement to adhere to the 
European Union (EU) Directive 
2001/20/EC.
To align with new EU regulations.
All
Updated references to groups (eg, 
“Groups D and E” may be updated to 
“Part 2” to account for the new Groups F 
and G). Updated the tables and text 
throughout the protocol to include the 
new groups and study interventions.
The protocol was updated throughout to 
align with the addition of new groups 
Minor 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 04: ............................ 
 
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 04 ......................... 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.2.1 BMS-986408 ............................................................................................ 
 
3.2.1.1 BMS-986408 Mechanism of Action ................................................ 
 
3.2.1.2 BMS-986408 Nonclinical Pharmacology ....................................... 
 
 
 
3.2.1.4 BMS-986408 Nonclinical Toxicology ............................................. 
 
3.2.1.5 BMS-986408 Clinical Activity ........................................................ 
 
3.2.2 Nivolumab ................................................................................................ 
 
3.2.2.1 Nivolumab Mechanism of Action .................................................... 
 
3.2.2.2 Nivolumab Clinical Activity ............................................................ 
 
3.2.3 Ipilimumab Mechanism of Action ............................................................ 
 
3.2.4 Nivolumab Combined with Ipilimumab Clinical Activity ........................ 
 
3.2.5 Nivolumab Combined with Ipilimumab Clinical Pharmacology ............. 
 
3.2.6 Nivolumab plus PDCT 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 Part 1 Monotherapy Cohorts ................................................................... 
 
5.1.2 Part 2 Combination Therapy Cohorts ..................................................... 
 
5.1.2.1 BMS-986408 in Combination with Nivolumab with or without 
Ipilimumab (Groups D and E) .............................................................. 
 
5.1.2.2 BMS-986408 in Combination with Nivolumab and PDCT (Group F)
............................................................................................................... 
 
5.1.2.3 pH Effect PK Sub-study 
 (Group G)..... 
 
5.1.3 Part 3 Expansion Cohorts ........................................................................ 
 
5.1.4 Screening.................................................................................................. 
 
5.1.5 Treatment Period ..................................................................................... 
 
5.1.6 Follow-up Period ..................................................................................... 
 
5.1.7 Data Monitoring Committee and Other Committees ............................... 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
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5.4 Scientific Rationale for Study Design .............................................................. 
 
 
 
5.4.2 Rationale for 2-Year Duration of Treatment ........................................... 
 
5.4.3 Rationale for BMS-986408 in Combination with Nivolumab and PDCT
..................................................................................................................... 
 
5.5 Justification for Dose ........................................................................................ 
 
 
 
5.5.2 Nivolumab ................................................................................................ 
 
5.5.3 Ipilimumab ............................................................................................... 
 
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 
 Period ....................................... 
 
7 STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ....................... 
 
7.1 Study Interventions Administered .................................................................... 
 
7.1.1 BMS-986408 Dosing ................................................................................ 
 
7.1.2 BMS-986408 in Combination with Nivolumab or with Nivolumab and 
Ipilimumab .................................................................................................. 
 
7.1.3 BMS-986408 in Combination with Nivolumab and PDCT ...................... 
 
7.1.3.1 Paclitaxel and Carboplatin ............................................................. 
 
7.1.3.2 Pemetrexed and Cisplatin ............................................................... 
 
7.1.3.3 Pemetrexed and Carboplatin .......................................................... 
 
7.1.3.4 Optional Continuation Maintenance .............................................. 
 
7.2 Method of Study Intervention Assignment ....................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.4.1 Dose Delay and Discontinuation Criteria for BMS-986408, Nivolumab 
and Ipilimumab ........................................................................................... 
 
7.4.2 Dose Delays for Chemotherapy ............................................................... 
 
7.4.3 Dose Reduction for Chemotherapy .......................................................... 
 
7.4.3.1 Chemotherapy: Dose Reductions for Hematologic Toxicity .......... 
 
7.4.3.2 Chemotherapy: Dose Reductions for Non-hematologic Toxicities . 
 
7.4.4 Criteria to Resume Treatment .................................................................. 
 
7.4.4.1 Criteria to Resume Treatment with BMS-986408, Nivolumab, or 
Ipilimumab ............................................................................................ 
 
7.4.4.2 Criteria to Resume Treatment with Chemotherapy ........................ 
 
7.4.5 
..................................................................................................................... 
 
 
 
7.4.7 Treatment of Immunotherapy Infusion-related Reactions ....................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
 
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7.7.2 Other Restrictions and Precautions ......................................................... 
 
7.7.2.1 Imaging Restriction and Precautions ............................................. 
 
7.7.2.2 Palliative Local Therapy................................................................. 
 
7.8 Continued Access to Study Intervention After the End of the Study ............... 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation From Study Intervention ........................................................ 
 
8.1.1 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 .............................................................................................. 
 
8.4 Study Stopping Criteria..................................................................................... 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
9.1.1 Efficacy Assessment for the Study ............................................................ 
 
9.1.1.1 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 ........................................................................... 
 
9.7 Genetics............................................................................................................. 
 
9.8 Biomarkers ........................................................................................................ 
 
9.8.1 Peripheral Biomarkers ............................................................................. 
 
9.8.1.1 Immunophenotyping ........................................................................ 
 
9.8.1.2 Peripheral Blood Gene Expression Profiling and TCR Sequencing
............................................................................................................... 
 
9.8.1.3 Measurement of Soluble Analytes ................................................... 
 
9.8.2 Tumor-based Biomarkers ......................................................................... 
 
9.8.2.1 Tumor Mutational Burden Assessment ........................................... 
 
9.8.2.2 Characterization of Tumor Immune Microenvironment ................. 
 
9.8.2.3 Tumor Gene Expression Profiling and TCR Sequencing ............... 
 
9.9 Additional Research .......................................................................................... 
 
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9.10 Other Assessments .......................................................................................... 
 
9.11 Health Economics OR Medical Resource Utilization and Health Economics
........................................................................................................................... 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Statistical Hypotheses ..................................................................................... 
 
10.2 Sample Size Determination ............................................................................. 
 
10.3 Analysis Sets ................................................................................................... 
 
10.4 Statistical Analyses ......................................................................................... 
 
10.4.1 General Considerations ......................................................................... 
 
10.4.2 Primary Endpoint(s) .............................................................................. 
 
10.4.3 Secondary Endpoint(s) ........................................................................... 
 
10.4.4 Exploratory Endpoint(s) ........................................................................ 
 
10.4.5 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 EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMACE 
STATUS ................................................................................................................. 
 
APPENDIX 7 MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 5.0 ......................................................................................................... 
 
 
 
 
 
 
 
 
 
 
 
APPENDIX 13 COUNTRY- AND REGION-SPECIFIC REQUIRMENTS .............. 
 
APPENDIX 14 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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CA099003
BMS-986408
DGKα/ζ Inhibitor
1
PROTOCOL SUMMARY
Protocol Title 
A Phase 1/2 Study of BMS-986408 Alone and in Combination with Nivolumab or with 
Nivolumab and Ipilimumab in Participants with Advanced Solid Tumors
Brief Title
A Phase 1/2 Study of BMS-986408 with and without Nivolumab or Nivolumab and 
Ipilimumab in Participants with Solid Tumors
Background and 
Rationale
BMS-986408 is a novel small-molecule dual inhibitor
 
 
 
 
.
Objectives and 
Endpoints
Objectives 
Endpoints
Primary

To characterize the safety and tolerability,
and to establish the MTD, maximum
administered dose, and/or RP2D(s), and
optimal schedule of oral BMS-986408
administered as monotherapy and in
combination 
with 
nivolumab
± ipilimumab
or 
chemotherapy
to 
participants with advanced cancer.

Incidence of DLTs, AEs, SAEs, AEs
leading to discontinuation, and deaths.
Secondary

To characterize the PK profile of
BMS-986408 
following 
oral 
administration as monotherapy and in 
combination 
with 
nivolumab
± ipilimumab
or 
chemotherapy
to 
participants with advanced solid tumors.

Summary measures of BMS-986408
PK parameters in plasma, such as, but
not limited to, Cmax, Tmax, and
AUC(0-T), from concentration-time
data during BMS-986408 monotherapy
and in combination with nivolumab
± ipilimumab or chemotherapy.

To evaluate the preliminary anti-tumor
activity of BMS-986408 as monotherapy
and in combination with nivolumab
± ipilimumab 
or 
chemotherapy 
in
participants with advanced cancer.

ORR and DOR per RECIST v1.1.
Overall Design
CA099003 is a Phase 1/2, first-in-human, multi-center, open-label study of oral BMS-986408 
administered as a single agent or in combination with nivolumab, nivolumab and ipilimumab, 
or nivolumab and PDCT in participants with solid tumors. 
The study is composed of 3 parts, with monotherapy dose escalation evaluated in Part 1 and 
combination therapy of escalating doses of BMS-986408 with nivolumab, nivolumab and 
ipilimumab, or nivolumab and PDCT evaluated in Part 2. Part 3 will include expansion 
cohorts to evaluate the combination of BMS-986408 with nivolumab or nivolumab and 
PDCT. 
All participants will complete 3 study periods: screening 
 treatment 
(approximately 104 weeks), and follow-up (up to 2 years following the end of treatment visit). 
The duration of study participation by individual participants will be approximately 4 years.
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BMS-986408
DGKα/ζ Inhibitor
Number of 
Participants 
The approximate total number of participants treated will be 402 for Parts 1, 2, and 3:
 
Study Population

Males or females ≥ 18 years of age or local age of majority at the time of consent. 

Part 1, Groups A, B, and B2: Advanced, unresectable/metastatic, solid malignancy of 
any histology that is measurable by RECIST v1.1, and have received, be refractory to, 
ineligible for, or intolerant of existing therapy(ies) known to provide clinical benefit for 
the condition of the participant. 

Part 1, Group C and Part 2, Groups D and E: Advanced, unresectable/metastatic 
malignancy measurable by RECIST v1.1, with the following histologies: HNSCC, 
NSCLC, melanoma, or RCC, have previously received therapy containing anti-PD-L1 or 
anti-CTLA-4 agents, and have received, be refractory to, ineligible for, or intolerant of 
existing therapy(ies) known to provide clinical benefit for the condition of the participant.

Part 1, Group C and Part 2, Groups D, E, F, and G: Tumor lesions that can be biopsied 
at acceptable risk (pretreatment and on treatment).

Part 2, Group G and Part 3, Group D2: Measurable disease by RECIST v1.1 and received 
and then progressed or been intolerant to anti-PD-1 or anti-PD-L1 (anti-PD-1/PD-L1 not 
required for MSS CRC) in the advanced or metastatic setting as the most recent therapy
with the following histologies: NSCLC, melanoma, RCC, or MSS CRC.

Part 2, Group F and Part 3, Group F2: Metastatic Stage IV A/B NSCLC of non-squamous 
or squamous histology that have not had prior exposure to IO and no prior systemic 
anti-cancer given as primary therapy for advanced or metastatic NSCLC.
Study 
Intervention 
Administration 
and Duration
For Part 1, Groups A and B2 (if evaluated), participants will take oral BMS-986408 once 
daily.
For Part 1, Group B (if evaluated), participants will take oral BMS-986408 twice daily 
(approximately once every 12 hours).
The planned cohorts in Parts 1, Group C, Part 2, and Part 3 will take BMS-986408 utilizing 
the schedule described for Groups A, B, or B2. Participants receiving combination with 
nivolumab (Groups D, D2, E, and G) will receive BMS-986408 daily and nivolumab 480 mg 
Q4W. Participants receiving ipilimumab (Group E) will receive ipilimumab 1 mg/kg Q8W 
after nivolumab as above. Participants receiving PDCT (Groups F and F2) will be treated 
with BMS-986408 in combination with nivolumab 360 mg and PDCT Q3W. 
For Group G, PK sub-study, participants will receive a single dose of BMS-986408 (1 of 
3 formulations). Some participants will be treated with rabeprazole starting 4 days prior to 
BMS-986408 for a total of 5 days. After the PK sub-study, participants will be treated with 
BMS-986408 daily in combination with nivolumab 480 mg Q4W.
Statistical 
Methods
There is no formal research hypothesis for this study to be statistically tested. The dose 
escalation decisions in Parts 1 and 2 will be guided 
.
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DGKα/ζ Inhibitor
Data Monitoring 
or Other 
Committee
A data monitoring committee will not be used in the study.
Abbreviations: AE, adverse event; AUC(0-T), area under the concentration-time curve from time 0 to time of last 
quantifiable concentration; Cmax, maximum concentration;
CRC,
colorectal cancer; CTLA-4, cytotoxic 
T lymphocyte-associated protein 4; DGK, diacylglycerol kinase; DLT, dose-limiting toxicity; DOR, duration of 
response; HNSCC, squamous cell carcinoma of the head and neck; IO, immuno-oncology; ipi, ipilimumab;
MSS, microsatellite stable; MTD, maximum tolerated dose; nivo, nivolumab; NSCLC, non-small cell lung cancer; 
ORR, objective response rate; PD-L1, programmed death ligand 1; PDCT, platinum-doublet chemotherapy; 
PK, pharmacokinetics; Q3W, every 3 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; RCC, renal cell carcinoma; 
RECIST, Response Evaluation Criteria in Solid Tumors; RP2D, recommended Phase 2 dose; SAE, serious adverse 
event; Tmax, time of maximum observed concentration;
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2
SCHEDULE OF ACTIVITIES
Abbreviations used in this protocol are listed in Appendix 1.
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Table 2-1:
Screening Procedural Outline (CA099003)
Procedure
Screening Visit
(Days -28 to -1)
Notes
Eligibility Assessments
Informed Consent
X
A participant is considered enrolled only when a protocol-specific informed consent form is signed. 
Must be obtained prior to performing any screening procedures. If a participant is re-enrolled, the 
participant must be reconsented. 
IRT Participant Assignment
X
Register in IRT system to obtain participant number prior to starting any screening procedures. 
After completing all screening procedures, utilize IRT to either screen fail or obtain treatment 
assignment information, as applicable. Treatment assignment can occur up to 3 days prior to first 
dose. See Section 7.2.
Inclusion/Exclusion Criteria
X
Must be confirmed prior to first dose. See Section 6.
Medical History
X
All medical history relevant to disease under study, including tobacco history. Include any clinically
significant toxicities or allergies related to previous treatments.
Prior Cancer Therapies
X
Including all prior cancer treatment regimens and medications administered.
Safety Assessments
Physical Examination (PE)
X
If the screening PE is performed within 72 hours prior to dosing on Day 1, then a single exam may 
count as both the screening and pre-dose evaluation.
Physical Measurements
X
Includes height, weight, and BMI.
Vital Signs and Oxygen 
Saturation
X
Includes body temperature, respiratory rate, and seated blood pressure and heart rate. Blood pressure 
and heart rate should be measured after the participant has been resting quietly for at least 5 
minutes. Obtain oxygen saturation by pulse oximetry at rest.
ECOG Performance Status
X
See Appendix 6.
Concomitant Medication Use
X
Within 14 days prior to dosing on Day 1. Vaccine use must be collected within 
days prior to first 
dose. See Section 6.2.
Electrocardiogram (ECG)
X
ECGs should be recorded after the participant has been supine for at least 5 minutes. Screening ECG 
is to be collected as a single reading on the site’s local ECG machine.
Laboratory Tests
Clinical Laboratory Assessments
X
Includes blood and urine samples. See Section 9.4.4.
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CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-1:
Screening Procedural Outline (CA099003)
Procedure
Screening Visit
(Days -28 to -1)
Notes
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. WOCBP must have a negative pregnancy test within 24 hours prior to the start of study 
therapy and results also must be evaluated prior to study therapy administration. If pregnancy test is 
taken within 24 hours of dosing (C1D1), a further pregnancy test is not required.
An extension up to 72 hours prior to the start of study treatment is permissible in situations where 
results cannot be obtained within standard 24-hour window.
Follicle-stimulating Hormone
X
Women only, as needed to document postmenopausal status. Refer to Appendix 4.
Serology
X
See Section 9.4.4 for list of laboratory tests to conduct.
HPV Status of Tumor for HNSCC 
of the Oropharynx
X
Historical HPV status for oropharyngeal cancers should be documented if available, but it is not 
required. HPV status should have been determined using p16 IHC or HPV PCR, if available.
 
 
 
X
See Section 6.1.
Tumor PD-L1 Expression
X
See Section 6.1.
Biomarker Assessments
Collection of Fresh Biopsy
X
Biopsies are optional at the discretion of the Investigator and/or Participant for Part 1, Groups A, B, 
and B2 and Part 3, Groups D2 and F2.
Part 1, Group C and Part 2, Groups D, E, F, and G: A fresh pre-treatment biopsy from a single, 
appropriately accessible lesion (obtained from a core biopsy, excisional biopsy, incisional, or 
surgical specimen), is required during the screening period or within 3 months before the start of the 
screening period, with no intervening systemic anti-cancer treatment between time of acquisition 
and enrollment, must be sent to the central laboratory. Participants must have a lesion that can be 
biopsied at an acceptable clinical risk as judged by the Investigator to be eligible for the study. Fine 
needle aspirates and other cytology specimens are not allowed. A repeat biopsy at screening from 
the same or an alternative site will be required if clinically feasible (at the discretion of the 
Investigator), and the initial attempt was unsuccessful in obtaining adequate tissue for biomarker 
analysis. Only 1 repeat attempt may be performed, if clinically feasible. An unsuccessful fresh 
tumor biopsy at screening will not exclude participants from receiving or continuing study 
treatment. The biopsy sample should be submitted to central laboratory prior to treatment 
assignment except if biopsy was attempted but was not completed due to safety concerns. 
 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-1:
Screening Procedural Outline (CA099003)
Procedure
Screening Visit
(Days -28 to -1)
Notes
 
Bone lesions are unacceptable sites for biopsy. See Section 9.8 and Table 9.8-1. Instructions for the 
collection and processing of all samples will be provided in the laboratory manual.
Collection of Archival Tumor 
Tissue
X
OPTIONAL at the discretion of the Investigator and/or participant for all parts of the study, 
EXCEPT for participants in Group F2, for whom it is mandatory unless FFPE material is provided. 
Archived tumor specimens, in the form of blocks or sectioned slides, are optional and can be
submitted prior to study treatment administration, if available.
Instructions for the collection and processing of all samples will be provided in the laboratory 
manual.
An archival sample cannot be substituted for a required fresh biopsy.
AE Reporting
Assessment of Signs and 
Symptoms
X
Within 14 days prior to dosing.
Monitor for non-serious AEs and 
SAEs
X
Part 1: All non-serious AEs associated with SARS-CoV-2 and SAEs must be collected from the date 
of participant’s written consent until 
 post discontinuation of study treatment or participation 
in the study, if the last scheduled visit occurs at a later time. 
Parts 2 and 3: All non-serious AEs associated with SARS-CoV-2 and SAEs must be collected from 
the date of participant’s written consent until 
 post discontinuation of study treatment or 
participation in the study, if the last scheduled visit occurs at a later time. 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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1.0
v
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1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-1:
Screening Procedural Outline (CA099003)
Procedure
Screening Visit
(Days -28 to -1)
Notes
Tumor Assessments
Body Imaging
X
Contrast-enhanced CT of the chest, abdomen, pelvis, and all other known and/or suspected sites of 
disease, within 28 days prior to first dose. CT/MRI of the neck is required only for HNSCC 
participants. Refer to Imaging Assessment details in Section 9.1.1.
Brain Imaging
X
MRI of the brain without and with contrast is required for all NSCLC and melanoma participants in 
Groups D2 and F2 and participants with known or suspected brain metastases, unless participant has 
completed an imaging study of the brain within 28 days prior to date of first dose. 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; 
 BMI, body mass index; 
 C, cycle; CT, computed 
tomography; D, day; ECG, electrocardiogram; ECOG, Eastern Cooperative Oncology Group; 
; FFPE, formalin-fixed 
paraffin-embedded; h, hour; hCG, human chorionic gonadotrophin; HNSCC, squamous cell carcinoma of the head and neck; 
 IHC, 
immunohistochemistry; IRT, interactive response technology; 
; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; 
 PCR, polymerase chain reaction; PD-L1, programmed death ligand 1; PE, physical examination; 
 
; SAE, serious adverse event; SARS-CoV-2, severe acute respiratory syndrome-coronavirus 2; WOCBP, women of childbearing potential.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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v
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1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 0
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
Safety Assessments
Physical 
Examination (PE)
X
X
X
X
X
If the screening PE is performed 
within 72 hours prior to dosing on 
Day 1 then a single exam may count 
as both the screening and pre-dose 
evaluation.
If there are any new or worsening 
clinically significant changes since 
the last examination, report changes 
on the appropriate nonserious or 
serious AE CRF page. 
Targeted PE
X
X
X
X
X
X
X
Symptom directed as clinically 
indicated.
Vital Signs 
(including oxygen 
saturation)
X
X
X
X
X
X
X
X
X
X
X
X
Includes body temperature, 
respiratory rate, seated blood 
pressure, and heart rate. Blood 
pressure and heart rate should be 
measured after the participant has 
been resting quietly for at least 5 
minutes. Obtain oxygen saturation by 
pulse oximetry at rest. 
Vital signs must be collected 
immediately prior to the start of 
treatment at each visit.
Extended monitoring of vital signs 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
on 
 
 post 
administration of BMS-986408.
Blood Pressure 
X
X
Participants will be supplied with an 
 
 
 
.
See Section 5.1.2.
Body Weight
X
X
X
X
Triplicate 12-lead 
Electrocardiogram 
(ECG)
X
X
X
Triplicate 12-lead ECGs 5 minutes 
apart to be performed per Table 9.5-
2. 
All triplicate ECGs should be 
recorded on the Sponsor-provided 
ECG machine and results should be 
transmitted electronically to the 
central laboratory.
Electrocardiogram 
(ECGs)
X
X
X
X
X
X
X
All single 12-lead ECGs should be 
recorded on the site’s ECG machine 
(locally) predose after the participant 
has been supine for at least 5 minutes 
and prior to blood draws.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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v
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Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
Concomitant 
Medication Use
X
X
X
X
X
X
X
X
X
X
X
X
ECOG 
Performance 
Status
X
X
X
X
X
X
AE Reporting
Monitor for 
Non-serious AEs 
and SAEs
Continuously
All AEs (including non-serious AEs 
and SAEs) must be collected 
continuously during the treatment 
period. 
Laboratory Tests
Clinical 
Laboratory 
Assessments
X
X
X
X
X
X
X
X
X
Perform onsite/local laboratory 
testing within 72 hours prior to each 
dose. For the first treatment visit, 
labs need not be repeated if they 
were performed within 72 hours and 
the results are available and have 
been reviewed for eligibility.
See Section 9.4.4 and Table 9.4.4-1. 
Thyroid Function 
Test (TSH)
X
X
X
X
X
If TSH is abnormal, free T3 and free 
T4 should be collected.
See Section 9.4.4 and Table 9.4.4-1.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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v
Approved
1.0
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Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
Urinalysis
X
X
X
X
X
X
See Section 9.4.4 and Table 9.4.4-1.
Pregnancy Test
(WOCBP only) 
X
X
X
X
X
Serum or urine pregnancy test 
(minimum sensitivity equivalent 
units 25 IU/L or equivalent units of 
hCG). 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 72 h prior to the start 
of study treatment or Day 1 of Cycles 
2 and beyond is permissible in 
situations where results cannot be 
obtained within standard 24 h 
window.
PK Assessments
PK Collections
See Table 9.5-2
Includes plasma and urine samples.
Refer to Section 9.5 for timing of 
collections
Protocol Amendment No.: 04
Date: 11-Dec-2023
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1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
Biomarker Assessments
Biomarker 
Sample 
Collections
See Table 9.8-1.
Refer to biomarker collection table in 
Section 9.8 for timing of collections.
Tumor Biopsy
X
X
Biopsies are optional at the discretion 
of the Investigator and/or Participant 
for Part 1, Groups A, B, and B2 (if 
evaluated). 
Part 1, Group C only: Mandatory 
on-treatment biopsy should be 
performed on C2D15 (± 7 days) 
only. EOT biopsy is optional at the 
discretion of the Investigator and/or 
Participant. An on-treatment biopsy 
does not need to be performed if a 
fresh biopsy was not collected at 
screening or the screening biopsy or 
biopsies did not contain adequate 
tumor tissue for biomarker analysis. 
The screening and on-treatment 
tumor biopsies should be 
preferentially collected from the 
same site, if feasible. 
See Section 9.8 and Table 9.8-1. 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
Imaging Assessments
Body Imaging
Contrast-enhanced CT of the chest, CT/MRI of the neck (required only for HNSCC participants), abdomen, pelvis, and 
all other known and/or suspected sites of disease should occur every 8 weeks (± 7 days) starting from C1D1 for the first 
48 weeks, then every 12 weeks (± 7 days) until disease progression or discontinuation of all study treatment, whichever 
occurs later. See Section 9.1.1 for further details.
Brain Imaging
Participants with a history of brain metastasis or symptoms should have a surveillance MRI performed per standard of 
care (approximately every 12 weeks ± 7 days), 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.
Other Assessments
BMS-986408 
X
X
(Cycle 
3 only)
Only for participants administered 
BMS-986408 
 
 See Section 9.10 and 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-2:
On Treatment Procedural Outline (Part 1, Groups A, B, B2, and C)
Procedurea,b
Cycle 
Cycle 1
Cycles 2 and 3
Cycle 
4+
EOTd
Notes
1 Cycle = 4 Weeks 
Exception: Group B2 
(Cycle 0 = 2 Weeks)
D1
D8
D1
D2
D8
D15
D16
D22
D1
D15
D1
Visit Window 
(days)
±2
±2
± 2
± 2
± 2
±2
± 2
± 2
The C1D15 and C1D16 visits must 
occur within the visit window 
stated and must be 24 h apart.
Study Intervention
Dispense 
BMS-986408 
Q4W
X
X
X
X
BMS-986408 to be supplied by BMS 
and issued to the participant at the 
beginning of every cycle (see 
Section 7.1). 
Abbreviations: AE, adverse event; C, cycle; CRF, case report form; CT, computed tomography; D, day; ECG, electrocardiogram; ECOG, Eastern Cooperative 
Oncology Group; eCRF, electronic case report form; EOT, end of treatment; h, hour; hCG, human chorionic gonadotrophin; HNSCC, squamous cell carcinoma of 
the head and neck; min, minute; MRI, magnetic resonance imaging; PE, physical examination; PK, pharmacokinetics; Q4W, every 4 weeks; SAE, serious adverse 
event; T3, triiodothyronine; T4, thyroxine; TSH, thyroid stimulating hormone; WOCBP, women of childbearing potential
a If all components of study treatment are delayed, the procedures scheduled for that same time point should be delayed to coincide with when the time point’s 
dosing actually occurs (except radiographic tumor assessments).
b 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.
 
d EOT is defined as the visit where the decision is made to discontinue the participant from treatment. Evaluations will be performed prior to study discharge, or 
for participants who are prematurely discontinued. For participants who complete all scheduled cycles of therapy, the EOT visit will be the same as the last 
scheduled and completed on-treatment visit (eg, C26D1) and the start of the safety follow-up period. For participants who do not complete all scheduled cycles 
of therapy, the EOT visit will be the most recent on treatment visit (with all available safety and response data); it does not need to be repeated and will be 
considered as the start of the safety follow-up period.
Protocol Amendment No.: 04
Date: 11-Dec-2023
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5.0
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1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 0
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
Safety Assessments
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 
nonserious or serious AE 
CRF page.
Targeted PE
X
X
X
X
X
X
X
Symptom directed as 
clinically indicated.
Vital Signs 
(including oxygen 
saturation)
X
X
X
X
X
X
X
X
X
X
Includes body temperature, 
respiratory rate, seated blood 
pressure, and heart rate. 
Blood pressure and heart rate 
should be measured after the 
participant has been resting 
quietly for at least 5 minutes. 
Obtain oxygen saturation by 
pulse oximetry at rest. 
Vital signs must be collected 
immediately prior to the start 
of treatment at each visit.
Body Weight
X
X
X
X
X
Protocol Amendment No.: 04
Date: 11-Dec-2023
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1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
Triplicate 12-lead 
Electrocardiogram 
(ECG)
X
X 
(Group 
G only)
Triplicate 12-lead ECGs 
5 minutes apart to be 
performed per Table 9.5-5.
All triplicate ECGs from C0 
and C1 should be recorded 
on the Sponsor-provided 
ECG machine and results 
should be transmitted 
electronically to the central 
laboratory.
Electrocardiogram 
(ECGs)
Xf
X
X
X
X
X
All single 12-lead ECGs 
should be recorded on the 
site’s ECG machine (locally) 
predose after the participant
has been supine for at least 5 
minutes and prior to blood 
draws. On Cycle 1 Day 1, a 
single safety ECG to be done 
predose and at 6 hours after 
dosing BMS-986408. Only a 
pre-dose ECG is required at 
all other timepoints.
Concomitant 
Medication Use
X
X
X
X
X
X
X
X
X
X
X
X
X
Protocol Amendment No.: 04
Date: 11-Dec-2023
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930176449
5.0
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1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
ECOG Performance 
Status
X
X
X
X
X
X
AE Reporting
Monitor for non-
serious AEs and 
SAEs
Continuously
All AEs (including 
non-serious AEs and SAEs) 
must be collected 
continuously during the 
treatment period.  
Laboratory Tests
Clinical Laboratory 
Assessments
X
X
X
X
X
X
X
X
X
Perform onsite/local 
laboratory testing within 72 
hours prior to each dose. For 
the first treatment visit, 
laboratory assessments need 
not be repeated if they were 
performed within 72 hours 
and the results are available 
and have been reviewed for 
eligibility.
See Section 9.4.4 and Table 
9.4.4-1.
Thyroid Function 
Test (TSH)
X
X
X
X
If TSH is abnormal, free T3 
and free T4 should be 
Protocol Amendment No.: 04
Date: 11-Dec-2023
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930176449
5.0
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Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
collected. See Section 9.4.4
and Table 9.4.4-1.
Urinalysis
X
X
X
X
See Section 9.4.4 and Table 
9.4.4-1.
Pregnancy Test 
(WOCBP only)
X
X
X
X
X
Serum or urine pregnancy 
test (minimum sensitivity 
equivalent units 25 IU/L or 
equivalent units of hCG). 
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 
72 h prior to the start of study 
treatment or Day 1 of Cycles 
2 and beyond is permissible 
in situations where results 
cannot be obtained within 
standard 24 h window.
Protocol Amendment No.: 04
Date: 11-Dec-2023
39
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Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
PK and Immunogenicity Assessments
PK sample 
Collection
See Table 9.5-3, Table 9.5-4, and Table 9.5-5.
Refer to Section 9.5 for 
timing of collections.
Biomarker Assessments
Biomarker Sample 
Collection
See Table 9.8-1.
Refer to Section 9.8 for 
timing of collections
Tumor Biopsy
X 
(Cycle 2 
only)
X
Biopsies are optional at the 
discretion of the investigator 
and/or participant for Part 3, 
Groups D2 and F2. 
Mandatory on-treatment 
biopsy should be performed 
on C2D15 (± 7 days) for 
Part 2, Groups D, E, F, 
and G. EOT biopsy is 
optional at the discretion of 
the Investigator and/or 
participant. An on-treatment 
biopsy does not need to be 
performed if a fresh biopsy 
was not collected at 
screening or the screening 
biopsy or biopsies did not 
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Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
contain adequate tumor tissue 
for biomarker analysis. The 
screening and on-treatment 
tumor biopsies should be 
preferentially collected from 
the same site, if feasible. 
Refer to Table 9.8-1for 
timing of collections.
Efficacy Assessments
Body Imaging
Contrast-enhanced CT of the chest, CT/MRI of the neck (required only for HNSCC participants), abdomen, 
pelvis, and all other known and/or suspected sites of disease should occur every 8 weeks (± 7 days) starting 
from C1D1 for the first 48 weeks, then every 12 weeks (± 7 days) until disease progression or 
discontinuation of all study treatment, whichever occurs later. See Section 9.1.1 and Section 5.1.2 for further 
details.
Brain Imaging
Participants with a history of brain metastasis or symptoms should have a surveillance MRI performed per 
standard of care (approximately every 12 weeks ± 7 days), 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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DGKα/ζ Inhibitor
Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
Other Assessments 
BMS-986408
 
X
X 
(Cycle 3 
only)
Only for participants 
administered BMS-986408 
. See 
Section 9.10 and 
 
Study Intervention
Dispense 
BMS-986408 Q4W
(Groups D, D2, E, 
and G) 
X 
 
)
X
X
X
BMS-986408 to be supplied 
by BMS and issued to the 
participant at the beginning 
of every cycle. See 
Section 7.1. 
Nivolumab Infusion 
Q4W (Groups D, 
D2, E, and G)
X
X
X
Nivolumab will be supplied 
by BMS.
Ipilimumab infusion 
Q8W (Group E)
X
X 
(Cycle 3 
only)
X 
(Cycle 5 and 
every 2 
cycles 
thereafter)
Ipilimumab will be supplied 
by BMS. Ipilimumab 
infusions on Day 1 of every 
second cycle; therefore, on 
Day 1 of Cycles 1, 3, 5, 7, 9, 
11, 13, 15, 17, 19, 21, 23, 
and 25.
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Table 2-3:
On Treatment Procedural Outline (Parts 2 and 3, Groups D, D2, E, F, F2, and G)
Procedurea,b
Cycle 
Cycle 1
Cycle 2 and
Cycle 3
Cycle 4+
EOTd
Notes
Groups D, D2, E, and G: 
1 Cycle = 4 Weeks
Groups F and F2: 
1 Cycle = 3 Weeks 
(Exception: Group G 
Cycle 0 = 11 Days)
D-4
D1
D2
D3-
D5
D1
D2
D8
D
15
D
22e
D1
D15
D1
Visit Window 
(± days)
± 2
± 2
± 2
± 2
± 2
± 2
Dispense 
BMS-986408 Q3W 
+ Nivolumab 
Infusion Q3W + 
4 Cycles of PDCT 
Infusion Q3W 
(Groups F and F2)
X
X
X
BMS-986408 to be supplied 
by the Sponsor and issued to 
the participant at the 
beginning of every cycle. 
Nivolumab will be supplied 
by the Sponsor. See 
Section 7.1 for details on 
PDCT sourcing and 
administration. 
Dispense 
Rabeprazole (Group
G)
X
 
 
 
Abbreviations: AE, adverse event; C, cycle; CRF, case report form; CT, computed tomography; D, day; ECG, electrocardiogram; ECOG, Eastern Cooperative 
Oncology Group; eCRF, electronic case report form; EOT, end of treatment; h, hour; hCG, human chorionic gonadotrophin; MRI, magnetic resonance imaging; 
PDCT, platinum-doublet chemotherapy; PE, physical examination; PK, pharmacokinetics; Q3W, every 3 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; SAE, 
serious adverse event; T3, triiodothyronine; T4, thyroxine; TSH, thyroid stimulating hormone; WOCBP, women of childbearing potential.
a If all components of study treatment are delayed, the procedures scheduled for that same time point should be delayed to coincide with when the time point’s 
dosing actually occur (except radiographic tumor assessments).
b 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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d EOT is defined as the visit where the decision is made to discontinue the participant from treatment. Evaluations will be performed prior to study discharge, or 
for participants who are prematurely discontinued. For participants who complete all scheduled cycles of therapy, the EOT visit will be the same as the last 
scheduled and completed on-treatment visit (eg, C26D1) and the start of the safety follow-up period. For participants who do not complete all scheduled cycles 
of therapy, the EOT visit will be the most recent on treatment visit (with all available safety and response data); it does not need to be repeated and will be 
considered as the start of the safety follow-up period. 
e Cycle 1 Day 22 visit is not applicable to Groups F and F2.
f Single 12-lead ECG on Cycle 1 Day 1 is not applicable to Group G.
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DGKα/ζ Inhibitor
Table 2-4:
Follow-up Procedural Outline (CA099003) 
Procedure
Follow-up 
1
 days
(±7 Days)
Follow-up 
2a
60 days
(±7 Days)
Follow-up 
3a
100 days
(±7 Days)
Survival 
Follow-up
Notes
Part 1 has a safety follow-up period of 
 with 1 
follow-up visit at 30 days after EOT.
 
 
Follow-up visits should be conducted in person and occur 
relative to the last dose of study treatment or EOT visit, 
whichever is later.
Safety Assessments
Targeted PE, Measurements, 
Vital Signs, Oxygen Saturation, 
and ECOG Performance Status
X
X
X
Weight, blood pressure, heart rate, body temperature, oxygen 
saturation by pulse oximetry, and ECOG Performance Status 
(Appendix 6).
Concomitant Medication Use
Continuously
Record at each visit.
Record continuously for a minimum of 
 (Part 1) or 
 (Parts 2 and 3), except if a participant has started a 
new anti-neoplastic therapy. However, any concomitant 
medication used to treat an AE suspected to be related to the 
study treatment by the investigator occurring after the start of a 
new treatment will be reported.
Subsequent Cancer Treatment
X
X
X
X
Monitor for AEs and SAEs
Continuously
Record at each visit.
Part 1: Collect continuously for a minimum of 
 
following discontinuation of study treatment, except in cases 
where a study participant has started a new anti-neoplastic 
therapy. However, any AE occurring after the start of a new 
treatment that is suspected to be related to study treatment by 
the Investigator will be reported. 
Beyond
 from the last dose of study therapy, 
participants will be followed for drug-related AEs/SAEs 
 
 
 
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DGKα/ζ Inhibitor
Table 2-4:
Follow-up Procedural Outline (CA099003) 
Procedure
Follow-up 
1
 days
(±7 Days)
Follow-up 
2a
60 days
(±7 Days)
Follow-up 
3a
100 days
(±7 Days)
Survival 
Follow-up
Notes
Part 1 has a safety follow-up period of
, with 1 
follow-up visit at 30 days after EOT.
Part 2 and Part 3 have a safety follow-up period of 
 
 with 3 follow-up visits at 
 
after EOT.
Follow-up visits should be conducted in person and occur 
relative to the last dose of study treatment or EOT visit, 
whichever is later.
Parts 2 and 3: Collect continuously for a minimum of 
 
 following discontinuation of study treatment, except in 
cases where a study participant has started a new anti-
neoplastic therapy. However, any AE occurring after the start 
of a new treatment that is suspected to be related to study 
treatment by the Investigator will be reported. 
Beyond 
 from the last dose of study therapy, 
participants will be followed for drug-related AEs/SAEs 
 
 
 
Laboratory Tests
Clinical Laboratory Assessments
X
X
X
See Section 9.4.4 for the list of laboratory tests.
Urinalysis
X
X
X
Pregnancy Test (WOCBP only) 
X
X
X
Serum or urine test. Pregnancy test: minimum sensitivity 
25 IU/L or equivalent units of hCG.
PK and Immunogenicity Assessments
PK and Immunogenicity 
Collections 
See Table 9.5-2 (Part 1, Groups A, B, B2, 
and C), Table 9.5-3 (Part 2, Groups D, F, 
and G and Part 3), Table 9.5-4 (Part 2, 
Group E), and Table 9.5-5 (Part 2, 
Group G, Cycle 0).
Refer. to PK/immunogenicity collection tables in Section 9.5
for timing of collections.
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DGKα/ζ Inhibitor
Table 2-4:
Follow-up Procedural Outline (CA099003) 
Procedure
Follow-up 
1
 days
(±7 Days)
Follow-up 
2
60 days
(±7 Days)
Follow-up 
3
100 days
(±7 Days)
Survival 
Follow-up
Notes
Part 1 has a safety follow-up period of 
, with 1 
follow-up visit at 
 after EOT.
Part 2 and Part 3 have a safety follow-up period of 
 
 with 3 follow-up visits at 
 days 
after EOT.
Follow-up visits should be conducted in person and occur 
relative to the last dose of study treatment or EOT visit, 
whichever is later.
Biomarker Assessments
Biomarker Sample Collections
See Table 9.8-1.
Refer to Section 9.8 for timing of collections, including a 
tumor biopsy.
Efficacy Assessments
Body Imaging
See notes.
Participants will have imaging assessments completed every 
12 weeks (± 7 days) from EOT until withdrawal of consent, 
death, study termination, or initiation of another anti-cancer 
treatment, whichever occurs first, for up to 
 after EOT. 
Contrast enhanced CT of the chest, abdomen, pelvis, and all 
other known and/or suspected sites of disease should be 
completed. CT/MRI of the neck is required for HNSCC 
participants. See Section 9.1.1.1 for further details. If 
pregnancy is the reason for study drug discontinuation, no 
imaging is performed.
Brain Imaging
See notes.
Participants with a history of brain metastasis or symptoms 
should have a surveillance MRI study per standard of care 
(approximately every 12 weeks ± 7 days), or sooner if 
clinically indicated, until discontinuation of body imaging. CT 
of the brain without and with contrast can be performed if MRI 
is contraindicated. See Section 9.1.1.1 for further details.
Assessment of Participant 
Survival Status
X
X
X
X
During Safety Follow-up (clinic visits) and every 
12 weeks ± 2 weeks (clinic visit or by telephone) during 
survival phase for up to 
 after EOT.
Include documentation of subsequent cancer treatments.
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BMS-986408
DGKα/ζ Inhibitor
Abbreviations: AE, adverse event; CT, computed tomography; ECOG, Eastern Cooperative Oncology Group; EOT, end of treatment; hCG, human chorionic 
gonadotrophin; HNSCC, squamous cell carcinoma of the head and neck; MRI, magnetic resonance imaging; PE, physical exam; PK, pharmacokinetics;
SAE, serious adverse event; SARS-CoV-2, severe acute respiratory syndrome-coronavirus 2; WOCBP, women of childbearing potential.
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DGKα/ζ Inhibitor
In the event that multiple procedures are required at a single time point after dosing BMS-986408 
during any visit, the procedures should occur with the following priority:
1) Post-dose electrocardiograms (ECGs) for PK-QT relationship analysis.
2) Post-dose pharmacokinetic (PK) sampling.
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DGKα/ζ Inhibitor
3
INTRODUCTION
CA099003 is a Phase 1/2 first-in-human (FIH) study of BMS-986408, an oral inhibitor of 
diacylglycerol kinase (DGK)α and DGKζ, in participants with advanced solid tumors. The main 
goals of the study are to characterize the safety profile of BMS-986408 as monotherapy and in 
combination with nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy and
to establish the maximum tolerated dose (MTD) and the recommended Phase 2 dose(s) (RP2D) 
that optimize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of BMS-986408. 
Additional goals are to evaluate preliminary PD and anti-tumor activity through analyses of several
biomarkers aimed at establishing proof-of-mechanism for DGKα/ζ inhibition in human tumors.
3.1
Study Rationale
The discovery of T cell checkpoint inhibitor therapy has revolutionized the treatment of a 
multitude of previously fatal cancers, resulting in improved quality of life and long-term survival 
benefit for a substantial number of patients. However, a significant fraction of patients continue to 
demonstrate resistance to existing therapies, underscoring the need for a next generation of
immune-modulating approaches that will expand the life-saving benefits of immune therapy.
DGKs are a family of lipid kinases that terminate diacylglycerol (DAG)-mediated signaling 
through the direct conversion of DAG into phosphatidic acid. In T cells, the diacylglycerol kinase 
(DGK)α and DGKζ isozymes serve as intra-cellular T cell receptor (TCR)-signaling, 
negative-regulatory checkpoints. DGKα and DGKζ are broadly expressed among human T cell 
populations, enabling the DGK checkpoint to regulate all phases of T cell activation including 
T cell priming, effector response, and memory recall responses. As such, DGKα and DGKζ 
impede T cell-mediated anti-tumor immunity and serve as a resistance mechanism to both
anti-programmed death protein-1 (PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 
(CTLA-4) therapy.
BMS-986408 is a novel small-molecule dual inhibitor of DGKα and DGKζ, 
 
 
 
 
 
 
3.2
Background
A detailed description of the chemistry, pharmacology, and preclinical toxicity of BMS-986408 is 
provided in the BMS-986408 Investigator’s Brochure (IB).1 Detailed information on nivolumab 
and ipilimumab is provided in their respective IB.2,3 A summary of the data is provided below.
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3.2.1
BMS-986408
3.2.1.1
BMS-986408 Mechanism of Action
BMS-986408 is a substrate-competitive inhibitor of both the DGKα and DGKζ lipid kinases. 
Inhibition of the DGK intracellular T cell checkpoint is differentiated from and complementary to 
both anti-PD-1 and anti-CTLA-4 blockade.
3.2.1.2
BMS-986408 Nonclinical Pharmacology
BMS-986408 exhibits superior potentiation of T cell activation in a human mixed lymphocyte 
reaction assay compared to either nivolumab (BMS-986558, anti-PD-1 monoclonal antibody 
[mAb]) or ipilimumab (BMS-734016, anti-CTLA-4) alone, and the combination of BMS-986408 
with either nivolumab or ipilimumab is additive compared to each of the single agents.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
.6
 
 
 
 
 
 
 
 
 
 
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3.2.1.4
BMS-986408 Nonclinical Toxicology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Collectively, the results of the nonclinical toxicology studies indicate an acceptable monitorable 
and manageable safety profile and supports the continued clinical development of BMS-986408.
3.2.1.5
BMS-986408 Clinical Activity
As of the data cut-off 19-Jun-2023, 
 participants have been treated across 5 dose levels of 
BMS-986408 monotherapy:
 
 and 
has been treated in combination 
with nivolumab (BMS-986408 
 plus nivolumab 480 mg intravenously [IV] once every 
4 weeks [Q4W]). 
 
 
 
 
 
 
 
To date, the preliminary clinical safety data are consistent with the nonclinical assessment of 
toxicity, and the data support the continued exploration of BMS-986408 alone and in combination.
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3.2.2
Nivolumab
3.2.2.1
Nivolumab Mechanism of Action
Nivolumab (also referred to as BMS-936558, MDX1106, or ONO-4538) is a human monoclonal 
antibody (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, programmed death ligands 1 (PD-L1) and 2 (PD-L2), results in the 
down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its 
ligands promotes immune responses and antigen-specific T cell responses to both foreign antigens 
as well as self-antigens. Nivolumab is expressed in Chinese hamster ovary 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 US (Dec-2014), the European Union (EU, Jun-2015), and Japan (Jul-2014).
3.2.2.2
Nivolumab Clinical Activity
Nivolumab has demonstrated durable responses exceeding 6 months as monotherapy in several 
tumor types, including non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma 
(RCC), classical Hodkin lymphoma, small cell lung cancer, gastric cancer, squamous cell 
carcinoma of the head and neck (HNSCC), urothelial cancer, hepatocellular carcinoma (HCC), 
and colorectal cancer. In confirmatory trials, nivolumab as monotherapy demonstrated a 
statistically significant improvement in overall survival (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 HNSCC. Details of the clinical activity in 
these various malignancies are provided in the United States Prescribing Information (USPI)10 and 
Summary of Product Characteristics (SmPC).11
3.2.3
Ipilimumab Mechanism of Action
Ipilimumab (BMS-734016, MDX010, MDX-CTLA4) is a fully human monoclonal 
immunoglobulin G1 kappa specific for human CTLA-4 (CD152), which is expressed on a subset 
of activated T cells. CTLA-4 is a negative regulator of T cell activity. Ipilimumab is a monoclonal 
antibody that binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, 
CD80/CD86. Blockade of CTLA-4 has been shown to augment T cell activation and proliferation, 
including the activation and proliferation of tumor-infiltrating T effector cells. Inhibition of 
CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general 
increase in T cell responsiveness, including the anti-tumor response.
3.2.4
Nivolumab Combined with Ipilimumab Clinical Activity
Multiple clinical studies have evaluated nivolumab combined with ipilimumab at different doses 
and schedules. Based on Phase 3 data showing improved survival over standard-of-care therapies, 
nivolumab combined with ipilimumab has been approved in multiple countries for the treatment 
of patients with cancer in various settings, including unresectable or metastatic melanoma, 
intermediate or poor risk previously untreated advanced RCC, first line metastatic NSCLC 
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expressing PD-L1 (≥ 1%) and 
 
 
 
in these various malignancies are provided in the USPI and 
SmPC.10,11
3.2.5
Nivolumab Combined with Ipilimumab Clinical Pharmacology
Nivolumab PK was assessed using a population PK approach for both single-agent nivolumab and 
nivolumab with ipilimumab.
Nivolumab as a single agent: The PK of single-agent nivolumab was studied in patients over a 
dose range of 0.1 to 20 mg/kg administered as a single dose or as multiple doses of nivolumab as 
a 60-minute intravenous (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 clearance is 24% lower in this patient population 
compared with patients with metastatic melanoma at steady state. The geometric mean Vss (CV%) 
is 6.8 L (27.3%), and geometric mean elimination half-life is 25 days (77.5%). Steady-state 
concentrations of nivolumab were reached by 12 weeks when administered at 3 mg/kg every 
2 weeks, and systemic accumulation was 3.7-fold. The exposure to nivolumab increases dose 
proportionally over the dose range of 0.1 to 10 mg/kg administered every 2 weeks. The predicted 
exposure (average concentration [Cavg] and Cmax) of nivolumab after a 30-minute infusion is 
comparable to that observed with a 60-minute infusion.
Nivolumab with ipilimumab: When nivolumab 1 mg/kg was administered in combination with 
ipilimumab 3 mg/kg, the CL of nivolumab was increased by 29%, and the CL of ipilimumab was 
unchanged compared to nivolumab administered alone. When nivolumab 3 mg/kg once every 
2 weeks (Q2W), was administered in combination with ipilimumab 1 mg/kg, the CL of nivolumab 
and ipilimumab were unchanged. When nivolumab was administered in combination with 
ipilimumab, the presence of anti-nivolumab antibodies increased the CL of nivolumab by 20% and 
the CL of ipilimumab was unchanged in presence of anti-ipilimumab antibodies.
Specific Populations: The population PK 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 
population PK analysis in patients with mild (estimated glomerular filtration rate [eGFR] 60 to 
89 mL/min/1.73 m2), moderate (eGFR 30 to 59 mL/min/1.73 m2), or severe (eGFR 15 to 
29 mL/min/1.73 m2) renal impairment. No clinically important differences in the CL of nivolumab 
were found between patients with renal impairment and patients with normal renal function.
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Hepatic Impairment: The effect of hepatic impairment on the CL of nivolumab was evaluated by 
population PK 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 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 clearance of nivolumab were found between patients 
with mild/moderate hepatic impairment.
Full details on the clinical pharmacology aspects of nivolumab can be found in the IB and product 
label.3,10
Nivolumab 480 mg Q4W dose levels are approved in the following indications: unresectable or 
metastatic melanoma; adjuvant treatment of melanoma; advanced RCC as monotherapy or in 
combination with cabozantinib; recurrent or metastatic HNSCC; urothelial cancer (adjuvant or 
treatment of locally advanced metastatic disease); microsatellite instability-high metastatic 
colorectal cancer; esophageal squamous cell carcinoma and adjuvant treatment of resected 
esophageal or gastroesophageal cancer, and it will be used in this study.
Nivolumab 360 mg (Q2W) / ipilimumab 1 mg/kg once every 6 weeks (Q6W) is approved in the 
following indications: malignant pleural mesothelioma and metastatic NSCLC (in combination 
with 2 cycles of PDCT), and it will be used in this study.
3.2.6
Nivolumab plus PDCT Clinical Activity
Clinical activity of nivolumab plus PDCT in chemotherapy-naïve NSCLC has been demonstrated 
in 2 clinical studies. In Study CA209012, a multi-arm Phase 1 safety study of nivolumab in 
chemotherapy naïve NSCLC, 56 participants received nivolumab in combination with 
cisplatin/gemcitabine, cisplatin/pemetrexed, or carboplatin/paclitaxel. The objective response rate 
(ORR) with the different combinations ranged from 33% to 47%.12 Nivolumab in combination 
with histology-based PDCT was also studied in Part 2 of the Phase 3 trial CA209227.15 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 demonstrated trends towards improved efficacy with nivolumab in combination with 
chemotherapy 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 participants 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 randomized population as well as in the non-squamous (48.1% vs 25.7%) and the squamous 
(59.8% vs 32.4%) participant sub-groups.
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3.3
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
anticipated adverse event (AEs) of BMS-986408 may be found in the IB.1
BMS-986408 is a novel small-molecule dual inhibitor of DGKα and DGKζ that has demonstrated 
robust preclinical efficacy as monotherapy and in combination with anti-PD-1, anti-PD-1 plus 
anti-CTLA4, and anti-PD-1 plus chemotherapy. It is hypothesized
 
 
 
 
It is unknown whether the study treatments increase the risk for contracting severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or increase the severity or duration 
of symptoms. This unknown risk must be considered when enrolling a participant. No additional 
safety monitoring or routine screening tests will be required due to SARS-CoV-2. 
The study has been designed with study visits that allow for close monitoring of participants’ safety 
throughout the clinical trial (Section 2), and participants are encouraged to contact the Investigator 
if an intercurrent illness develops between study visits. Testing for COVID-19 to inform decisions 
about clinical care during the study should follow local standard practice.
3.3.1
Risk Assessment
Participants who enroll on this proposed study will have an unmet medical need due to advanced 
cancer without curative treatment options. While this study may not provide clinical benefit to the 
enrolled participants, taking into account the measures taken to minimize risk to participants in 
this study, BMS-986408 is a novel immunotherapy that has the potential to significantly improve 
outcomes in a similar population of patients once an optimal human dose and schedule is identified, 
supporting its evaluation in clinical studies. 
 
 
 
 
 
 
 
 
 in Table 3.3.1-1.
Extensive details on the safety profile of nivolumab alone or in combination with ipilimumab, 
including results from other clinical studies, are available in the nivolumab and ipilimumab IBs.2,3
The combination of BMS-986408 and nivolumab may have overlapping toxicities, including 
immune-mediated adverse events (IMAEs). A pattern of IMAEs, 
 
has been defined for both nivolumab and 
the combination of nivolumab and ipilimumab. Most high-grade events were manageable with the 
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use of corticosteroids or hormone replacement therapy (endocrinopathies) as indicated in these 
algorithms.
BMS-986408 in combination with nivolumab plus PDCT may have overlapping toxicities. 
Nivolumab in combination with chemotherapy has been assessed in a variety of studies and has 
demonstrated an acceptable safety profile that was consistent with the established safety profile of 
each component of the regimen. 13 The combination of BMS-986408 and PDCT may have 
overlapping toxicities
 
 
. Dose modification criteria for study 
treatments,
 are provided.
Table 3.3.1-1:
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of 
Data/Rationale for 
Risk
Mitigation Strategy
Study Interventions(s)
 
BMS-986408 IB1
Carboplatin USPI
Cisplatin USPI
Paclitaxel USPI
Pemetrexed USPI
 
 
 

 
 
 
.

Dose modification criteria 
 
 
 
BMS-986408 IB1
Carboplatin USPI
Cisplatin USPI
Paclitaxel USPI
Pemetrexed USPI

Routine scheduled clinical laboratory 
monitoring throughout treatment of 
 
for early detection of abnormalities. 
BMS-986408 IB1

 
 
 
 
 
 
 
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Table 3.3.1-1:
Risk Assessment
Potential Risk of Clinical 
Significance
Summary of 
Data/Rationale for 
Risk
Mitigation Strategy

Inclusion of a comprehensive list of QTc 
modulators that should be avoided in the study 
BMS-986408 IB1
Carboplatin USPI
Cisplatin USPI
Paclitaxel USPI
Pemetrexed USPI

Routine scheduled clinical laboratory 
monitoring throughout treatment of 
hematologic, hepatic, and metabolic parameters 
for early detection of abnormalities. 

 
IMAEs (eg, pneumonitis, colitis, 
hepatitis, myocarditis, nephritis, 
endocrinopathy, neurologic and 
skin AEs)
Nivolumab IB3, 
ipilimumab IB2,
BMS-986408 IB1

Recommended IMAE 
 
or per institutional 
protocol/Investigator discretion.
Potential Developmental 
Toxicity
Nivolumab IB3, 
ipilimumab IB2, 
BMS-986408 IB1
Carboplatin USPI
Cisplatin USPI
Paclitaxel USPI
Pemetrexed USPI

Exclusion criteria (Section 6.2), pregnancy 
testing, contraception per protocol (Section 6.1).
Study Procedures
Tumor Biopsy (eg, pain, 
infection)
Not applicable

Per institutional protocol/Investigator discretion.
Phlebotomy (eg, pain, 
ecchymosis, bleeding, syncope)
Not applicable

Per institutional protocol/Investigator discretion.
Other (if applicable)
Allergy to Contrast Agent (eg, 
hives, anaphylaxis)
Not applicable

Prophylaxis and/or treatment per institutional 
protocol/Investigator discretion.
Abbreviations: AE, adverse event; 
 IB, Investigator’s Brochure; IMAE, immune-mediated adverse event; 
; QTc, 
corrected QT interval, USPI, United States Prescribing Information.
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3.3.2
Benefit Assessment
CA099003 is the first Phase 1 clinical trial evaluating the safety of BMS-986408 in human 
participants with advanced solid tumors. Although benefits might be hypothesized based on 
mechanism of action and/or preclinical observations, actual clinical benefits of BMS-986408 to 
patients with advanced cancer have not been established. Clinical activity of nivolumab plus PDCT 
in chemotherapy-naïve NSCLC has been demonstrated (see Section 3.2.6) with participants that 
express PDL1 having the greatest benefit.
3.3.3
Overall Benefit/Risk Conclusion
Taking into account the measures implemented to minimize risk to participants in this study, the 
potential risk identified and associated with BMS-986408 are justified by the anticipated benefits 
that may be afforded to participants with advanced cancers. In addition, first-line therapy of 
BMS-986408 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 risk/benefit 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-986408 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 unreasonable and significant risk of illness or injury.
If such evaluation suggests that the risk/benefit profile of the study has become unfavorable to 
participants, the Sponsor will pause enrollment and/or treatment until further evaluation of data, 
and interaction with the appropriate Health Authority(ies) can take place on 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

To characterize the safety and tolerability, and to 
establish the MTD, maximum administered dose, 
and/or RP2D(s), and optimal schedule of oral 
BMS-986408, administered as monotherapy and in 
combination with nivolumab ±
ipilimumab
or 
chemotherapy to participants with advanced cancer.
Primary

Incidence of DLTs, AEs, SAEs, AEs leading to 
discontinuation, and deaths.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Secondary

To characterize the PK profile of BMS-986408 
following oral administration as monotherapy and in 
combination with nivolumab ± ipilimumab
or 
chemotherapy to participants with advanced solid 
tumors. 
Secondary

Summary 
measures 
of 
BMS-986408 
PK 
parameters in plasma, such as, but not limited to, 
Cmax, 
Tmax, 
and 
AUC(0-T), 
from 
concentration-time data during BMS-986408 
monotherapy and in combination with nivolumab 
± ipilimumab or chemotherapy.

To evaluate the preliminary anti-tumor activity of 
BMS-986408 as monotherapy and in combination 
with nivolumab ± ipilimumab or chemotherapy in 
participants with advanced cancer.

ORR and DOR per RECIST v1.1.
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Table 4-1:
Objectives and Endpoints
Objectives
Endpoints
Abbreviations: AE, adverse event; AUC(0-T), area under the concentration-time curve from time 0 to time of last 
quantifiable concentration; 
 Cmax, maximum concentration; 
 DLT, dose-limiting toxicity; DOR, duration of response; 
 
ORR, objective response rate; 
 PDCT, platinum-doublet chemotherapy; 
 PK, pharmacokinetics; 
 RECIST, Response 
Evaluation Criteria in Solid Tumors; RP2D, recommended Phase 2 dose; SAE, serious adverse event; 
 Tmax, time of maximum observed concentration.
5
STUDY DESIGN
5.1
Overall Design
CA099003 is a Phase 1/2, FIH, multi-center, open-label study of oral BMS-986408 administered 
as a single agent, and in combination with nivolumab, nivolumab and ipilimumab, or nivolumab 
and chemotherapy in participants with advanced solid tumors. The primary objectives of the 
proposed study are to characterize the safety and tolerability; to establish the maximum tolerated 
dose (MTD), if reached; to evaluate the maximum administered dose if the MTD is not reached;
and to establish the recommended Phase 2 dose/s (RP2D[s]), at the optimal dosing schedule. 
Secondary objectives of the study are to characterize the PK profile and evaluate preliminary 
anti-tumor activity of BMS-986408 as both monotherapy and in combination with nivolumab,
nivolumab and ipilimumab, or nivolumab and PDCT.
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The study is composed of 3 parts, with monotherapy dose escalation evaluated in Part 1 and 
combination therapy of escalating doses of BMS-986408 with nivolumab, nivolumab and
ipilimumab, or nivolumab and PDCT evaluated in Part 2. Part 3 will include expansion cohorts to 
evaluate the combination of BMS-986408 with nivolumab or nivolumab and PDCT. Part 3 
combination with nivolumab and ipilimumab may be added in a future amendment.
All participants will complete 3 study periods: Screening 
, Treatment
 and Follow-up 
 
 The duration of study participation for individual 
participants will be approximately 4 years.
5.1.1
Part 1 Monotherapy Cohorts
Part 1 will evaluate BMS-986408 monotherapy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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5.1.2
Part 2 Combination Therapy Cohorts
Part 2 will evaluate BMS-986408 in combination with nivolumab in Group D, nivolumab and 
ipilimumab in Group E, or nivolumab and PDCT in Group F. In Group G, single-dose 
BMS-986408 with and without a proton pump inhibitor (PPI) will be evaluated followed by 
continuous dosing of BMS-986408 and nivolumab. 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.1.2.1
BMS-986408 in Combination with Nivolumab with or without Ipilimumab
(Groups D and E)
The dual combination of BMS-986408 and nivolumab (480 mg once every 4 weeks [Q4W]) will 
be evaluated in participants with HNSCC, NSCLC, melanoma, and RCC, who have previously 
experienced disease progression during checkpoint inhibitor therapy. Triple combination therapy 
of BMS-986408 with nivolumab (480 mg Q4W) and ipilimumab (1 mg/kg once every 8 weeks 
[Q8W]) will be evaluated in participants with HNSCC, NSCLC, melanoma, and RCC who have 
previously experienced disease progression during checkpoint inhibitor therapy (prior PD-[L]1 
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treatment or CTLA-4 treatment as monotherapy or in any combination).
 
 
 
 
 
 
 
5.1.2.2
BMS-986408 in Combination with Nivolumab and PDCT (Group F)
The combination of BMS-986408 with nivolumab (360 mg Q3W) and PDCT will be evaluated in 
participants with advanced/metastatic NSCLC who have not had systemic therapy for 
advanced/metastatic disease. Participants with non-squamous NSCLC will be treated with 
carboplatin or cisplatin and pemetrexed, while participants with squamous histology will be treated 
with carboplatin and paclitaxel (see Section 7.1 for additional information on dosing). 
 
 
5.1.2.3
pH Effect PK Sub-study 
 (Group G)
Group G will be an open-label, single dose PK cohort to explore the potential pH effect on the 
single dose PK 
 of BMS-986408 followed by continuous 
dosing with BMS-986408 in combination with nivolumab. 
 
 
 
 
 Prolonged increases in gastric pH occur with 
administration of rabeprazole (model PPI), which irreversibly bind to and inactivate the proton 
pump (H+ -K+-ATPase), resulting in suppression of stimulated and basal acid secretion produced 
by acetylcholine and histamine release.14 In general, the PD effects of PPIs take up to 3 days with 
 dosing to reach steady state. 
 
 
 
 
 
 
 
 
 
 
 
 
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5.1.3
Part 3 Expansion Cohorts
Part 3 is an open-label, dose expansion part to assess the preliminary efficacy, safety, and 
tolerability of the optimal dose level(s) of BMS-986408 in combination with nivolumab 
(Group D2) or nivolumab and PDCT (Group F2).
 
 
 
 
 
 
 
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5.1.4
Screening
The screening period will be 
 and begins by establishing the participant’s initial 
eligibility after signing of the informed consent form. Participants will be enrolled using interactive 
response technology (IRT). The screening assessments are shown in Table 2-1.
For Part 1, Group C and Part 2, tumor tissue must be obtained and submitted to central laboratory 
prior to treatment assignment except if biopsy was attempted but was not completed due to safety 
concerns. See Section 6.1 (Inclusion Criteria) and Section 9.8 (Biomarkers) for specifications and 
the laboratory manual for additional details.
If a participant exceeds 
 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.
5.1.5
Treatment Period
The treatment period for monotherapy and combination treatment will last approximately
104 weeks from the first dose of study treatment. 
 
 
On-treatment monitoring will include planned clinic visits with standard safety monitoring and 
blood draws for laboratory testing, PK, and biomarkers as indicated in Table 2-2 (Part 1) and Table 
2-3 (Parts 2 and 3). Imaging for tumor assessment will occur every 8 weeks during the first 48 
weeks of treatment, followed by every 12 weeks until 104 weeks and the end of study treatment
phase (all groups). For cardiovascular monitoring, safety ECGs are planned for all groups and 
multiple additional ECGs are planned for the monotherapy portion of the study to evaluate for 
. Participants 
will be supplied with an 
 
 
 All participants will be supplied with a 
mechanism to capture daily pill intake of BMS-986408. 
5.1.6
Follow-up Period
The follow-up period includes a safety follow-up and a survival follow-up, which begin in parallel 
after the end of treatment (EOT) visit. EOT is defined as the visit where the decision is made to 
discontinue the participant from treatment. Evaluations will be performed prior to study discharge, 
or for participants who are prematurely discontinued. For participants who complete all scheduled 
cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment 
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visit (eg, C26D1) and the start of the safety follow-up period. For participants who do not complete 
all scheduled cycles of therapy, the EOT visit will be the most recent on treatment visit (with all 
available safety and response data); it does not need to be repeated and will be considered as the 
start of the safety follow-up period.
The safety follow-up period is 
for participants in Part 1, with a visit at 
 after 
the EOT visit. For Part 2 combinations, Groups D and E, the safety follow-up period will be 
days after the end-of-treatment visit, with visits to occur at 
 
 after the end of treatment visit. Survival follow-up for all parts will begin at the 
EOT visit and last for a period of
, or until death, lost to follow-up, withdrawal of consent, 
conclusion of the study, or study termination, whichever comes first.
5.1.7
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) and 
this will be employed in this study. Dose escalation decisions and decisions to continue enrollment 
according to the outlined study protocol will be made by the Sponsor in collaboration with 
Investigators, and take into consideration all available safety, PK, and PD data.
To support safety oversight, BMS has established ongoing processes for collection, review, 
analysis, and submission of individual AE 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.
BMS WWPS is an internal group that operates independently from the clinical team to monitor 
safety across all BMS protocols and analyze all data in an unblinded fashion. Within BMS, an 
SMT is established for investigational therapies under clinical development, and a member of 
WWPS chairs this team. In addition, signal detection is performed at least quarterly and ad hoc 
throughout the study by the SMT composed, at a minimum, of the WWPS medical safety 
assessment physician (Chair of the SMT), the Study Physician, Global Regulatory Lead, and 
Pharmacovigilance Scientist; all of whom, analyze the data in an unblinded fashion. Extended 
SMT members may include medical review safety physician(s), epidemiologist(s), clinical safety 
strategy and solutions, Global Risk Management, toxicologist, clinical pharmacologist, 
biostatistician, clinical scientist(s), labeling, Medical Affairs, legal representative, and project lead 
and/or project manager. 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).
5.2
Number of Participants
The approximate total number of participants treated will be 402 for Parts 1, 2, and 3:
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
Part 1 Monotherapy: The total sample size is approximately 
 participants: approximately
 participants for Group A dose escalation, 
 participants each for Groups B and B2 (if
evaluated), and 
participants for Group C.

Part 2 Combination Therapy: The total sample size is approximately 
 participants:
participants each for Groups D and E, 
 participants for Group F, and
 participants for
Group G.

Part 3 Combination Therapy Expansion cohorts: The total sample size is approximately
participants: 
 participants per indication for Groups D2 and F2.
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 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 shown 
in the Schedule of Activities.
5.4
Scientific Rationale for Study Design
BMS-986408 is a novel small-molecule dual inhibitor of DGKα and DGKζ, intracellular 
check-points broadly expressed in T cells.
 
. Due to the 
broad expression of DGKand DGKamong T cell lineages, 
 
 
 
. The FIH study is designed to thoroughly evaluate the safety, PK, and peripheral 
blood and tumor PD of BMS-986408 alone and in combination with other check-point inhibitors 
in a broad population of patients with solid tumors. 
In Part 1, the monotherapy evaluation of BMS-986408 will guide dosing and schedule selection 
for combination testing, with the objective of identifying a dose and schedule 
 
,6 while remaining safe and well tolerated.
 
 
 
 
 
 
 
 
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Parts 2 and 3 are focused on evaluating the safety and preliminary efficacy of BMS-986408 in 
combination with either nivolumab (Groups D and D2), nivolumab and ipilimumab (Group E), or 
nivolumab and PDCT (Groups F and F2). Given the growing knowledge around check-point 
inhibitor therapy and the landscape of single-agent versus combination efficacy, 15 , 16 , 17 , 18
evaluation of combination regimens in this FIH study will provide important safety and PD 
insights on targeted, rational combination approaches that can be employed within a variety of 
tumor indications. The study design includes the following:

Screening period

Treatment period of approximately

Safety follow-up period of 
 from EOT for participants receiving monotherapy and 
from EOT for participants receiving combination therapy

Survival follow-up period of up to 
 from EOT.
The rationales for individual elements of the study design are given below.
5.4.2
Rationale for 2-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 suggest that benefit can be maintained in the absence of continued treatment. A 
retrospective pooled analysis of 2 melanoma studies suggests the majority of patients who 
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discontinue nivolumab and/or ipilimumab for toxicity maintain disease control in the absence of 
further treatment.21 Furthermore, a limited duration of ipilimumab, including only 4 induction 
doses, resulted in long term survival in patients with metastatic melanoma, with a sustained plateau 
in survival starting around 2 years after the start of treatment.22
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 overall survival (OS) curve begins to plateau after 2 years, 
with an OS rate of 25% at 2 years and 18% at 3 years.23 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).24
Taken together, these data suggest that treatment beyond 2 years is unlikely to confer additional 
clinically meaningful benefit and that the risk of progression after discontinuing treatment at 
2 years is low.
In contrast, a shorter duration of nivolumab of only 1 year was associated with increased risk of 
progression in previously treated patients with NSCLC, suggesting that treatment beyond 1 year 
is likely needed. In CA209153, patients with previously treated advanced NSCLC who completed
1 year of nivolumab therapy were randomized to either continue or stop treatment, with the option 
of retreatment upon progression. Among 163 patients still on treatment at 1 year and without 
progression, those who were randomized to continue nivolumab had significant improvement in 
PFS compared to those who were randomized to stop treatment, with median PFS 
(post-randomization) not reached vs 10.3 months, respectively; hazard ratio (HR)=0.42 (95% CI, 
0.25 to 0.71). With a median follow-up of 14.9 months post-randomization, there also was a trend 
for patients on continued treatment to live longer (OS HR = 0.63 [95% confidence interval 
(CI): 0.33, 1.20]). Of note, the PFS curves in both groups plateau approximately 1 year after 
randomization (ie, 2 years after treatment initiation), suggesting that there may be minimal benefit 
in extending treatment beyond a total of 2 years.25
Collectively, these data suggest that there is minimal if any benefit derived from continuing 
immuno-oncology (IO)
treatment beyond 2
years in advanced tumors. Even though 
immunotherapy is well tolerated, patients will be at risk for additional toxicity with longer term 
treatment. Therefore, in this study, treatment will be given for a maximum of 2 years from the start 
of study treatment.
5.4.3
Rationale for BMS-986408 in Combination with Nivolumab and PDCT
The 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 
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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 chemotherapy. 
 
 
 The safety profile of nivolumab in combination with chemotherapy has 
been manageable. 
 
 
 
 
5.5
Justification for Dose
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5.5.2
Nivolumab
The nivolumab dose of 480 mg Q4W was selected for Part 2, Groups D, E, and G and Part 3,
Group D2 based on clinical data and modeling and simulation approaches using population PK 
(PPK) and exposure-response (E-R) analyses of data from studies in multiple tumor types 
(melanoma, NSCLC, and RCC) where body weight normalized dosing (mg/kg) was used. The 
nivolumab dose of 360 mg Q3W was selected for Part 2, Group F and Part 3, Group F2.
Nivolumab PK has been extensively studied in multiple tumor types, including melanoma, 
NSCLC, RCC, classical Hodgkin’s lymphoma, HNSCC, colorectal cancer, and urothelial 
carcinoma and has been safely administered at doses up to 10 mg/kg Q2W. Nivolumab 
monotherapy was originally approved as a body-weight based dose of 3 mg/kg Q2W, and was 
updated to 240 mg Q2W or 480 mg Q4W in multiple indications.10,11 Nivolumab 360 mg Q3W is 
also under evaluation in monotherapy and in combination therapy studies. When used in 
combination with ipilimumab and chemotherapy, nivolumab 360 mg Q3W is approved for the 
treatment of first line (1L) NSCLC. Less frequent 360 mg Q3W and 480 mg 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. 
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The benefit-risk profiles of nivolumab 240 mg Q2W, 360 mg Q3W, and 480 mg Q4W are 
predicted to be comparable to 3 mg/kg Q2W. This assessment is based on a comprehensive 
characterization of nivolumab PK, safety, efficacy, and E-R relationships across indications. 
Population PK (PPK) analyses have shown that the PK of nivolumab is linear with proportional 
exposures over a dose range of 0.1 to 10 mg/kg; no clinically meaningful differences in PK across 
ethnicities and tumor types were observed. Using the PPK model, the exposures following 
administration of several dosing regimens of nivolumab administered as a flat dose were 
simulated, including 240 mg Q2W, 360 mg Q3W, and 480 mg Q4W. The simulated average serum 
concentration at steady state [Cavgss] following administration of nivolumab 360 mg Q3W and 
480 mg Q4W are predicted to be similar to those following administration of nivolumab 240 mg 
Q2W and nivolumab 3 mg/kg Q2W administered to patients over a wide body weight range 
(34 to 180 kg) across tumor types. 
Extensive E-R analyses of multiple PK measures (maximum serum concentration at Day 1
[Cmax1], average serum concentration at Day 28 [Cavg28], and trough serum concentration at 
Day 28 [Cmin28]) and efficacy and safety endpoints indicated that the efficacy of the flat-dose 
480 mg IV regimen is similar to that of the 3 mg/kg Q2W IV regimen. In E-R efficacy analyses 
for OS and objective response rate (ORR) conducted in melanoma, RCC, and NSCLC using 
Cavg28 as the exposure measure, probabilities of achieving a response and survival probabilities 
at 1 year and 2 years for IV 480 mg Q4W were similar to that of IV 3 mg/kg Q2W. In E-R safety 
analyses, it was demonstrated that the exposure margins for safety are maintained following 
nivolumab 480 mg Q4W, and the predicted risks of discontinuations due to AEs or death, AE 
Grade 3+, and immune-mediated AEs (IMAEs) Grade 2+ are similar following nivolumab 480 mg 
Q4W relative to nivolumab 3 mg/kg Q2W across tumor types. In addition, nivolumab exposures 
with 240 mg Q2W, 360 mg Q3W, and 480 mg Q4W flat-dose IV regimens across tumor types are 
maintained well below the corresponding exposures observed with the well-tolerated 10 mg/kg IV 
nivolumab Q2W dose regimen.
5.5.3
Ipilimumab
Ipilimumab at a dose of 1 mg/kg Q8W infused over 30 minutes will be administered in 
combination with BMS-986408 and nivolumab 480 mg Q4W in Part E. 
Ipilimumab is approved as monotherapy for the treatment of advanced melanoma and adjuvant 
melanoma with 3 mg/kg Q3W for 4 doses and 10 mg/kg Q3W for 4 doses followed by maintenance 
dose, respectively. Ipilimumab is also approved in combination with nivolumab for the treatment 
of various cancers, including melanoma, RCC, colorectal cancer, and HCC with a dosing regimen 
of 1 mg/kg Q3W or 3 mg/kg Q3W for 4 doses, depending on tumor type. In addition, a less frequent 
but continuous ipilimumab regimen (1 mg/kg once every 6 weeks [Q6W]) was evaluated in 
combination with nivolumab or nivolumab plus chemotherapy in a number of pivotal studies, 
including 1L NSCLC studies (Studies CA209227 and CA2099LA), 1L HNSCC study (Study 
CA209651), and 1L mesothelioma study (Study CA209743). Ipilimumab 1 mg/kg Q6W is 
currently approved for the treatment of 1L NSCLC in combination with nivolumab or with 
nivolumab and 2 cycles of chemotherapy and is also approved for the treatment of 1L 
mesothelioma in combination with nivolumab.26
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In CA209012, ipilimumab 1 mg/kg using Q6W and once every 12 weeks (Q12W) schedules were 
assessed and were found to have acceptable safety in combination with nivolumab 3 mg/kg once 
every 2 weeks (Q2W). Both the Q6W and Q12W arms were associated with improved and 
manageable tolerability compared to the arms with more frequent ipilimumab dosing (once every 
3 weeks; [Q3W]). Both arms also had encouraging efficacy in all participants and enhanced benefit 
in participants with PD-L1 expression, with Q6W arm having numerically higher median
progression-free survival (PFS) compared to the Q12W arm. There were some imbalances 
observed between the Q6W and Q12W arms, as follows:

There were more never-smokers in Arm Q (Q6W schedule) than Arm P (Q12W schedule).
Current and former smokers have been shown to respond better to immunotherapy.

Participants in Arm Q progressed, died, or came off treatment more frequently in the first 
3 months; however, this did not appear to be related to the schedule.

Overall rates of treatment-related AEs leading to discontinuation were 11% and 13% in the
Q12W and Q6W arm, respectively. While there were more AEs leading to discontinuation
in the first 3 months in Arm Q (n=3) versus Arm P (n=1), 2 of the 
 who 
discontinued < 3 months on arm Q discontinued before receiving the second dose of 
ipilimumab; therefore, these discontinuations are unlikely to be due to the more frequent 
dosing on the Q6W arm.

There were early clinical progressors and (unrelated) deaths in the Q6W arm compared to
the Q12W arm (8% and 15%, respectively), more likely due to imbalances in baseline
characteristics, rather than differences in treatment schedule.
With both schedules showing a similar safety and efficacy profile and considering imbalances in
treatment arms favoring the Q12W arm, for this study a Q8W schedule was chosen for the 
ipilimumab administration, to align with nivolumab dosing and maintain expected safety and 
efficacy.
6
STUDY POPULATION
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 (see Appendix 13 for country- and region-specific requirements) must have 
signed and dated an Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
institutional guideline. This signature must be obtained before the performance of any 
protocol-related procedures that are not part of normal patient care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory testing, and other requirements of the study.
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2) Type of Participant and Target Disease Characteristics
a) Participants in Part 1, Groups A, B, and B2 must have a histologically or cytologically 
confirmed, advanced, unresectable/metastatic, solid malignancy of any histology 
measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and have 
received, be refractory to, ineligible for, or intolerant of existing therapy(ies) known to 
provide clinical benefit for the condition of the participant.
b) Participants in Part 1, Group C and Part 2, Groups D and E must have a histologically or 
cytologically confirmed, advanced, unresectable/metastatic malignancy measurable by 
RECIST v1.1, with the following histologies: HNSCC, NSCLC, melanoma, or RCC, and 
have received, be refractory to, ineligible for, or intolerant of existing therapy(ies) known 
to provide clinical benefit for the condition of the participant.
i)
 
 
 
 
 
 
v) Participants with melanoma should have documentation of mutation status for BRAF 
and NRAS, if known.
c) Not applicable per Protocol Amendment 04. 
d) Participants in Part 1, Group C and Part 2, Groups D, E, F, and G must have tumor lesions 
that can be biopsied at acceptable risk and must consent to undergo pre-treatment and on-
treatment biopsy collection. Only core, excisional, incisional, or surgical biopsies are 
acceptable. A formalin-fixed, paraffin-embedded (FFPE) tissue block of tumor tissue from 
a core biopsy, punch biopsy, excisional or incisional biopsy, or surgical specimen obtained 
during screening or within 3 months before start of screening period, with no intervening 
systemic anti-cancer treatment between time of acquisition and enrollment, must be sent to 
the central laboratory. Fine needle aspirates or other cytology samples are not acceptable.
e) Participants in Part 1, Group C and Part 2, Groups D and E must have received previous 
treatment with PD-1, PD-L1, and/or CTLA-4 checkpoint inhibitor (CPI) 
 
 
 
 
 
 
f)
Participants must have experienced radiographically documented progressive disease on 
or after the most recent therapy.
g) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 
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h) Participants in Part 2, Group G and Part 3, Group D2:
i)
Measurable disease by RECIST v1.1.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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i)
Part 2, Group F and Part 3, Group F2:
i)
Documented histologically or cytologically confirmed metastatic Stage IV A/B 
NSCLC of non-squamous or squamous histology (as defined by the 8th International 
Association for the Study of Lung Cancer Classification).
ii) Must be eligible to receive PDCT based on local guidelines.
iii)
 
iv)
 
 
v)
 
vi)
 
vii)
 
 
 
 
viii)
Part 3, Group F2 only: A formalin-fixed, paraffin-embedded (FFPE) tumor tissue 
block or unstained slides of tumor tissues obtained during screening or prior to 
enrollment (within 3 months of enrollment and with no intervening systemic anti-
cancer therapies between the time of acquisition and enrollment) must be sent for 
confirmation of PD-L1 status to the central laboratory prior to treatment assignment.
Results are not required prior to starting treatment. Samples may be from core biopsy, 
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punch biopsy, excisional biopsy, or surgical specimen. On-treatment biopsies are 
optional.
3) Age of Participant 
a) Participant must be age ≥18 years or local age of majority at the time of 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)
Female participants must have documented proof that they are not of childbearing 
potential.
ii) Women who are not of childbearing potential are exempt from contraceptive 
requirements.
iii) WOCBP must have a negative highly sensitive urine or serum pregnancy test 
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin 
[hCG]) within 24 hours prior to the start of study intervention. An extension up to 
72 hours prior to the start of study treatment is permissible in situations where results 
cannot be obtained within the standard 24-hour window.

Additional requirements for pregnancy testing during and after study intervention are located 
in Section 2, Schedule of 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.
iv) WOCBP must agree to follow instructions for method(s) of contraception defined in 
Appendix 4 and as described below and included in the informed consent form (ICF).

WOCBP are permitted to use hormonal contraception methods (as described in Appendix 4)
but WOCBP using hormonal contraceptives must also be utilizing a second contraception
method that is highly effective (with a failure rate of < 1% per year) as described in Appendix 
4, due to the potential for lack of efficacy of hormonal contraception methods from potential 
drug-drug interactions with BMS-986408. Oral contraceptives alone do not fulfill the 
contraception requirement for this study. WOCBP that are not utilizing hormonal 
contraceptives must be utilizing 1 highly effective contraceptive method, as described in 
Appendix 4.
v) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least 1 of the following conditions applies:
(1) Is not a WOCBP 
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OR
(2) Is a WOCBP and using a contraceptive method that is not a hormonal contraceptive
method and is highly effective (with a failure rate of < 1% per year) as described in 
Appendix 4. Duration of required contraception use is described in Appendix 4,
during the intervention period and for the following time periods and agrees not to 
donate eggs (ova, oocytes) for the purpose of reproduction for the same time 
periods:
(a)
 
 
(b) For the duration of chemotherapy plus 7 months after last dose of chemotherapy 
(applicable to paclitaxel, pemetrexed, and carboplatin) or a total of 14 months 
after the last dose of cisplatin and agrees not to donate eggs (ova, oocytes) for 
the purpose of reproduction for the same time period as contraception 
requirements listed above.
b) Male Participants:
i)
Male participants, including azoospermic males, will be required to always use a latex 
or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with 
WOCBP, even if the participants have undergone a successful vasectomy or if their 
partner is already pregnant or breastfeeding. Males should continue to use a condom 
during the intervention period,
and at least 
 after the last chemotherapy (applicable to paclitaxel, pemetrexed, 
and carboplatin) dose of study intervention (or a total of 11 months for male 
participants receiving cisplatin).
ii) Female partners of males participating in the study should be advised to use a highly 
effective method of contraception during the intervention period,
 
, and at least 
 after the last chemotherapy 
(applicable to paclitaxel, pemetrexed, and carboplatin) dose of study intervention (or a 
total of 11 months for male participants receiving cisplatin).
iii) Male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from sexual activity or use a male condom during any sexual activity 
(eg, vaginal, anal, oral), even if the participants have undergone a successful 
vasectomy, during the intervention period,
 
and for at least 
 after the last chemotherapy (applicable to 
paclitaxel, pemetrexed, and carboplatin) dose of study intervention (or a total of 11 
months for male participants receiving cisplatin).
iv) Male participants must refrain from donating sperm during the intervention period,
 
 
and for at least 
 after the last chemotherapy (applicable to 
paclitaxel, pemetrexed, and carboplatin) dose of study intervention (or a total of 11 
months for male participants receiving cisplatin).
v) 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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6.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1) Medical Conditions
a) Participants with an active, known or suspected autoimmune disease. Participants with 
type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin 
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or 
conditions not expected to recur in the absence of an external trigger are permitted to enroll.
b) Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily 
prednisone equivalent) within 14 days or other immunosuppressive medications within 
30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal 
replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the 
absence of active autoimmune disease.
c)
 
 
 
 
 
f)
Current or recent (within 3 months of study drug administration) gastrointestinal disease 
or gastrointestinal surgery (eg, intestinal/gastric/colon resection) that could impact the 
absorption of study drug.
g) 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.
h)
 
 
 
 
 
 
 
 
 
 
 
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k) Untreated central nervous system (CNS) metastases. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2) Reproductive Status
a) Women who are breastfeeding or are pregnant.
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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4) Physical and Laboratory Test Findings
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5) Allergies and Adverse Drug Reaction
a) History of allergy or hypersensitivity to study drug components.
b) History of life-threatening toxicity related to prior immune therapy (eg, anti-CTLA-4 or 
anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T cell 
co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur 
with standard countermeasures (eg, hypothyroidism).
c) Any contraindication to any of the study drugs. Investigators should refer to local package 
insert or summary of product characteristics (SmPC).
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) Inability to comply with restrictions as listed in Section 6.3, Lifestyle Restrictions.
c) Participation in another clinical trial concurrent with this study.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
6.3
Lifestyle Restrictions
 
 
 
 
 
 
.
6.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but who 
are not subsequently entered in the study/included in the analysis population. 
A minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, as applicable, and to respond to queries from regulatory authorities. 
Minimal information includes date of consent, demography, screen failure details, eligibility 
criteria, and any serious AEs.
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6.4.1
Retesting During Screening or 
 Period
Retesting of laboratory parameters and/or other assessments within any single Screening 
or
 period will be permitted (in addition to any parameters that require a confirmatory 
value).
The most current result prior to administration of study intervention is the value by which study 
inclusion will be assessed, because it represents the participant’s most current clinical state.
Laboratory parameters and/or assessments that are included in Table 2-1, Screening Procedural 
Outline, may be repeated in an effort to find all possible well-qualified participants. Consultation 
with the Medical Monitor may be needed to identify whether repeat testing of any particular 
parameter is clinically relevant.
Testing for asymptomatic SARS-CoV-2 infection by reverse transcription polymerase chain 
reaction (RT-PCR) or viral antigen is not required. However, 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.

At least 24 hours have passed since last fever without the use of fever-reducing medications.

Acute symptoms (eg, cough, shortness of breath) have resolved.

In the opinion of the Investigator, there are no COVID-19 sequelae that may place the 
participant at a higher risk of receiving investigational treatment.
In the instance of a SARS-CoV-2 infection during screening, the screening period may be extended 
beyond the protocol-specified timeframe with Medical Monitor approval. Any screening tests 
already performed which could potentially be affected by the SARS-CoV-2 infection or its 
complications on an individual basis and agreed upon with the Medical Monitor (eg safety 
laboratory assessments, oxygen saturation, chest computed tomography [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 Investigational [Medicinal] Product (IP/IMP) as indicated in Table 7-
1.
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 
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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/auxiliary medicinal products (AxMPs).
Table 7-1:
Study Intervention(s) for CA099003
Product 
Description/Class 
and Dosage Form
Potency
IMP/
Non-IMP
Blinded or 
Open Label
Packaging/ 
Appearance
Storage 
Conditions 
(per label)
BMS-986408
Formulation 1, 
Formulation 2, and 
Formulation 3 
Tablets
Formulation 1: 
0.75 mg and 5 mg
Formulation 2: 5 mg 
and 15 mg
Formulation 3: 5 mg
IMP
Open Label
Bottle
Refer to the label 
on container and/or 
pharmacy manual
Nivolumab
(BMS-936558-01)
Solution for 
Injection
100 mg/vial
(10 mg/mL)
IMP
Open Label
Vial
Refer to the label 
on container and/or 
pharmacy manual
Ipilimumab
Solution for 
Injection
(BMS-734016)
50 mg/vial 
(5 mg/mL)
IMP
Open Label
Vial
Refer to the label 
on container and/or 
pharmacy manual
Carboplatin
450 mg/vial
IMP
Open Label
Vial
Refer to the label 
on container and/or 
pharmacy manual
Paclitaxel
100 mg/vial
IMP
Open Label
Vial
Refer to the label 
on container and/or 
pharmacy manual
Pemetrexed
500 mg/vial
IMP
Open Label
Vial
Refer to the label 
on container and/or 
pharmacy manual
Cisplatin
100 mg/vial
IMP
Open Label
Vial
Refer to the label 
on container and/or 
pharmacy manual
Rabeprazole
20 mg
IMP
Open Label
Bottle
Refer to the label 
on container and/or 
pharmacy manual
Abbreviations: IMP, investigational medicinal product; Non-IMP, non- investigational medicinal product.
7.1
Study Interventions Administered
Dose and route of administration for study intervention in each arm are presented in Table 7.1-1. 
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Table 7.1-1:
Study Intervention(s) Administered
ARM Name
Part 1,
Groups A, B, 
B2, and C
Part 2,
Group D
Part 2,
Group G 
(Starting 
C1D1)
Part 3,
Group D2
Part 2,
Group E
Part 2, 
Group G
(Cycle 0)
Part 2, Group F
Part 3, Group F2
Intervention 
Name
BMS-986408 
monotherapy
BMS-986408 + 
nivolumab
BMS-986408 
+ nivolumab + 
ipilimumab
BMS-986408
Rabeprazole
BMS-986408 + 
nivolumab + PDCT
Type 
Drug
Drug + Biologic
Drug + 
Biologics
Drugs
Drugs + Biologics
Dose 
Formulation
BMS-986408 
Formulations
1 and 2: 
tablet
Nivolumab: 
Solution in a 
single-use vial
Part 2, 
Group D:
BMS-986408 
Formulations 1
and 2: tablet
Part 2, Group G 
and Part 3,
Group D2:
BMS-986408 
Formulations 1, 
2, and 3: tablet
Nivolumab 
and 
ipilimumab: 
Solutions in 
single-use 
vials
BMS-986408 
Formulations 1 
and 2: tablet
BMS-986408 
Formulation 1, 
2, and 3: tablet
Rabeprazole: 
tablet
Nivolumab and PDCT: 
solutions in single-use 
vials
Part 2, BMS-986408 
Formulation 1 and 2: 
tablet
Part 3, BMS-986408 
Formulation 1, 2, and 3: 
tablet
Unit Dose 
Strength(s)
BMS-986408: 
0.75 mg, 5 mg, 
and 15 mg 
Nivolumab: 
100 mg/vial
BMS-986408: 
Same as Part 1
Nivolumab: 
100 mg/vial
Ipilimumab: 
50 mg/vial
BMS-986408: 
Same as Part 1
BMS-986408:
5 mg
Rabeprazole:
20 mg
Nivolumab: 100 mg/vial
BMS-986408: same as 
Part 1
Carboplatin:
450 mg/45 mL vial
Pemetrexed 500 mg/vial
Cisplatin:
100 mg/100 mL vial
Paclitaxel:
100 mg/16.7 mL vial
Dosage 
Level(s)
BMS-986408 
QD* (mg): 
0.75, 1.5, 3, 
5, 10, 20, 30, 
45, and 60.
*Alternative 
BID schedule 
may be 
evaluated in 
Group B.
Nivolumab: 480 
mg Q4W
BMS-986408: 
Dose TBD
Nivolumab: 
480 mg Q4W
Ipilimumab: 
1 mg/kg Q8W
BMS-986408: 
Dose TBD
BMS-986408: 
5 mg once
Rabeprazole:
20 mg QD
Nivolumab: 
360 mg Q3W
BMS-986408: 
Dose TBD
Carboplatin AUC 6 + 
paclitaxel 200 mg/m2
Carboplatin AUC 5 or 6 
or cisplatin 75 mg/m2 + 
pemetrexed 500 mg/m2
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Table 7.1-1:
Study Intervention(s) Administered
ARM Name
Part 1,
Groups A, B, 
B2, and C
Part 2,
Group D
Part 2,
Group G 
(Starting 
C1D1)
Part 3,
Group D2
Part 2,
Group E
Part 2, 
Group G
(Cycle 0)
Part 2, Group F
Part 3, Group F2
Route of 
Adminis-
tration
Oral
BMS-986408: 
oral
Nivolumab: IV 
infusion
BMS-986408: 
oral
Nivolumab 
and 
ipilimumab: 
IV infusion
Oral
BMS-986408: oral
Nivolumab and PDCT: 
IV infusion
Use
Experimental
Experimental
Experimental
Experimental
Experimental
IMP and 
NIMP/
AxMP
IMP
IMP
IMP
IMP
IMP
Sourcing
Provided 
centrally by 
the Sponsor
Provided 
centrally by the 
Sponsor
Provided 
centrally by 
the Sponsor
BMS-986408: 
Provided
centrally by the 
Sponsor
Rabeprazole: 
Provided 
locally by the 
study sitea
BMS-986408, 
nivolumab: Provided 
centrally by the Sponsor
PDCT: Provided locally 
by the study sitea
Packaging 
and Labeling
BMS-986408 
will be 
provided in 
bottles. Each 
bottle will be 
labeled as 
required per 
country 
requirement.
Nivolumab will 
be provided in 
vials. 
BMS-986408 
will be provided 
in bottles. Each 
bottle and vial 
will be labeled 
as required per 
country 
requirement.
Ipilimumab 
and nivolumab 
will be 
provided in 
vials. 
BMS-986408 
will be 
provided in 
bottles. Each 
vial and bottle 
will be labeled 
as required per 
country 
requirement.
BMS-986408 
will be 
provided in 
bottles. Each 
bottle will be 
labeled as 
required per 
country 
requirement.
PDCT and nivolumab 
will be provided in 
vials. BMS-986408 will 
be provided in bottles. 
Each vial and bottle will 
be labeled as required 
per country requirement.
Current/
Former 
Name(s) or 
Alias(es)
DGK
inhibitor 
(BMS-98640
8)
DGK inhibitor 
(BMS-986408)
Anti-PD-1 
(nivolumab)
DGK inhibitor 
(BMS-986408)
Anti-PD-1 
(nivolumab)
Anti-CTLA-4 
(ipilimumab)
DGK inhibitor 
(BMS-986408)
DGK inhibitor 
(BMS-986408)
Anti-PD-1 (nivolumab)
Abbreviations: AxAMP, auxillary medicinal product; BID, twice daily; CTLA-4, cytotoxic T lymphocyte associated 
protein 
4; 
DGK, 
diacylglycerol 
kinase; 
IMP, 
investigational medicinal 
product; 
IV, 
intravenous; 
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NIMP, noninvestigational medicinal product; PD-1, programmed death protein-1; QD, once daily; QxW, once every 
x weeks; SOC, standard of care; TBD, to be determined.
a The Sponsor may provide in regions where it is not available through insurance or as part of SOC.
Restrictions related to food and fluid intake are described in Section 6.3. 
7.1.1
BMS-986408 Dosing
For Part 1, Groups A and B2 (if evaluated), participants will take oral BMS-986408 
 
 
 For scheduled clinic visit days, BMS-986408 will be administered to the participant 
in the clinical facility. 
 
 
 
 
 
For scheduled clinic visit days, the first 
 dose of BMS-986408 will be administered to the participant in the clinical facility. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. For all parts of the 
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study, under certain circumstances,
 
 
Dosing information for BMS-986408 should be recorded in the study diary and the case report 
form (CRF). If a dose of BMS-986408 is missed, the dose should be skipped, and dosing should 
resume at the next scheduled dose.
 
. Missed dosing information should be recorded in the study diary, the CRF, 
and medical record along with a description of the reason for the missed dose. The next dosing 
day should be kept on schedule. If the participant misses a dose, BMS must be notified.
Participants should bring all containers for BMS-986408 to each study visit for drug reconciliation. 
Empty drug containers should be collected at each visit (or reconciled at least once every cycle, 
whichever is prior). Table 7.1-1 indicates the dose and dosage form for treatments to be 
administered in this study. Refer to the current IB and/or pharmacy manual for further details 
regarding storage of BMS-986408.
 
 
 
 
 
7.1.2
BMS-986408 in Combination with Nivolumab or with Nivolumab and 
Ipilimumab
For the combination of BMS-986408 and nivolumab, participants will receive nivolumab at a dose 
of 480 mg over an approximately 30-minute infusion on Day 1 of each treatment cycle until 
progression, unacceptable toxicity, withdrawal of consent, completion of 104 weeks of treatment, 
or the study ends, whichever occurs first. The IV line must be flushed 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. 
. BMS-986408 will be 
administered as described in Section 7.1.1.
 
 
 Participants will receive nivolumab at a dose of 480 mg infusion every cycle Q4W 
(28 days) and ipilimumab at 1 mg/kg every 2 cycles Q8W (56 days) until progression, 
unacceptable toxicity, withdrawal of consent, completion of 26 cycles of treatment (104 weeks) 
from first treatment regardless of treatment delays, or the study ends, whichever occurs first. 
Nivolumab will be administered over an approximately 30 minutes infusion period and must be 
promptly followed by a flush of diluent to clear the line of nivolumab before starting the 
ipilimumab infusion. The second infusion will always be the ipilimumab study treatment and will 
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start after the infusion line has been flushed, filters changed, and participant has been observed to 
ensure no infusion reaction has occurred. There should be a 30-minute waiting period between the 
completion of the nivolumab infusion and the start of the ipilimumab infusion. The duration of the 
ipilimumab infusion should be approximately 30 minutes.
7.1.3
BMS-986408 in Combination with Nivolumab and PDCT
In Groups F (Part 2) and F2 (Part 3), 4 cycles of the histology-based PDCT option selected by the 
investigator will be administered on Day 1 Q3W. Participants with non-squamous (NSQ) histology 
may also receive optional maintenance therapy with 500 mg/m2 pemetrexed alone on Day 1 of 
each 3-week cycle until disease progression, unacceptable toxicity, or other reasons specified in 
the protocol.
Histology-based PDCT:

Squamous histology: Carboplatin AUC 6 plus paclitaxel 200 mg/m2

Non-squamous histology: Carboplatin AUC 5 or 6 or cisplatin 75 mg/m2 plus pemetrexed 
500 mg/m2 (optional maintenance therapy with 500 mg/m2 Q3W pemetrexed)
BMS-986408 and nivolumab will be administered as described in Sections 7.1.1 and 7.1.2. All 
chemotherapy agents’ preparation, premedication, administration, monitoring, and management 
of complications are to follow local prescription guidelines and regulations. The dose of 
chemotherapy may be capped per local standards.
Note: The investigator must decide prior to starting treatment whether or not a participant with 
NSQ histology will receive cisplatin, if eligible.
7.1.3.1
Paclitaxel and Carboplatin
Participants will receive paclitaxel 200 mg/m2 as a 180-minute IV infusion with carboplatin at a 
dose of AUC 6 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 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.
Carboplatin should be given following paclitaxel on Day 1 of each cycle. The carboplatin dose 
will be calculated using the Calvert formula as follows:
Carboplatin dose (mg) = target AUC × (CrCl [mL/min] + 25)
Creatinine clearance (CrCl) calculation is based on the Cockcroft-Gault formula and should 
include the most recent serum 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.
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DGKα/ζ Inhibitor
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 and 6 hours prior to paclitaxel administration (oral or IV).

IV diphenhydramine (or its equivalent) 50 mg and histamine H2-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.
7.1.3.2
Pemetrexed and Cisplatin
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 BID on the day prior to, the day of, and the day after the administration 
of pemetrexed.

Oral folic acid 350 to 1000 μg daily 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 daily throughout the treatment with pemetrexed and for 21 
days after the last dose of pemetrexed. Intramuscular (IM) 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 NSQ histology may begin folic acid 
and vitamin B12 prior to randomization 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 
premedications 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 
with cisplatin at a dose of 75 mg/m2 infusion per local standard practice on Day 1 of a 3-week 
treatment cycle for up to 4 cycles.
Dosing calculations should be based on the body surface area calculation and may be capped per 
local standards. The dose may remain the same if the participant’s weight is within 10% of the 
baseline weight or prior dose weight.
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Cisplatin will be administered to participants at least 30 minutes following the end of the 
pemetrexed infusion. Pretreatment hydration for cisplatin can follow local standard of care or use 
1 to 2 liters of fluid (per local standards) infused IV for 8 to 12 hours prior to cisplatin infusion 
(recommended). Adequate hydration and urinary output must be maintained for at least 24 hours 
following cisplatin administration. Administration and monitoring should be performed according 
to local standards. Use of mannitol following the cisplatin infusion should also follow local 
standards of care.
Doses of pemetrexed and/or cisplatin may be interrupted, delayed, reduced, or discontinued, 
depending on how well the participant tolerates the treatment.
All participants who will receive cisplatin should have audiometric testing performed prior to 
initiation of therapy and prior to subsequent doses of cisplatin or per local standards of care (SOC).
Participants who discontinue cisplatin alone may, at the investigator’s discretion, be switched to 
pemetrexed/carboplatin for the remainder of the PDCT (up to 4 cycles in total). Dosing for 
pemetrexed/carboplatin for such participants should follow the instructions in Section 7.1.3.3.
7.1.3.3
Pemetrexed and Carboplatin
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:

Oral or IV corticosteroid premedication for pemetrexed should be given according to local 
standards at a dose equivalent to dexamethasone 4 mg BID on the day prior to, the day of, and 
the day after the administration of pemetrexed.

Oral folic acid 350 to 1000 μg daily 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 daily throughout the treatment with pemetrexed and for 
21 days after the last dose of pemetrexed. IM 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 NSQ histology may begin folic acid and 
vitamin B12 prior to randomization in anticipation of pemetrexed).
Participants will receive pemetrexed at a dose of 500 mg/m2 as a 10-minute IV infusion on Day 1, 
followed by carboplatin at a dose of AUC 5 or 6 as a 30-minute IV infusion on Day 1 of a 3-week 
treatment cycle for up to 4 cycles.
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% weight used to calculate the previous 
dose.
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DGKα/ζ Inhibitor
The carboplatin dose will be calculated using the Calvert formula as follows:
Carboplatin dose (mg) = Target AUC × (CrCl [mL/min] + 25)
CrCl calculation is based on the Cockcroft-Gault formula (see inclusion criterion in Section 6.1) 
and should include the most recent serum 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.
Doses of pemetrexed and/or carboplatin may be interrupted, delayed, reduced, or discontinued, 
depending on how well the participant tolerates the treatment. All chemotherapy agents’ 
preparation, premedication, administration, monitoring, and management of complications are to 
follow local prescription guidelines and regulations. The dose of chemotherapy may be capped per 
local standards.
7.1.3.4
Optional Continuation Maintenance
After Cycle 4 of chemotherapy, participants with NSQ histology who have stable disease or 
response are permitted to receive pemetrexed 500 mg/m2 Q3W alone as maintenance therapy until 
disease progression, unacceptable toxicity, or the maximum duration of treatment (2 years) has 
been reached.
7.2
Method of Study Intervention Assignment
All participants will be centrally assigned to treatment using IRT. Before the study is initiated, 
each user will receive log-in information and directions on how to access the IRT.
Study intervention will be dispensed at the study visits as listed in Schedule of Activities 
(Section 2). 
Enrolled participants, including those not dosed, will be assigned sequential participant numbers 
starting with 
 Those enrolled participants meeting 
inclusion and exclusion criteria will be eligible to be dosed. Sequential numbering may restart at 
 for each participating site as the distinct patient identification number (PID) will ultimately 
be comprised of the site number and participant number 
Once it is determined that the participant meets the eligibility criteria following the screening visit, 
the investigative site will utilize the IRT to centrally assign the participant into the open dose level 
within 3 days of starting the treatment. If multiple cohorts are simultaneously enrolling in Part 2,
Group G or Part 3, Groups D2 and F2, participants may be randomized to treatment assignment. 
7.3
Blinding
This is a non-randomized open-label study. It has been determined that blinding is not required to 
meet study objectives. Blinding procedures are not applicable and access to treatment assignment 
information is unrestricted. The specific treatment to be taken by a participant will be assigned 
using IRT. The site will contact the IRT prior to the start of study intervention administration for 
each participant. The site will record the treatment assignment on the applicable CRF, if required.
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DGKα/ζ Inhibitor
7.4
Dosage Modification
Participants will be monitored for AEs during 3 phases of the study: screening, treatment, and 
safety follow-up. Participants experiencing Grade ≥ 3 treatment-related AEs that do not qualify as 
DLT events will hold study treatment until symptoms resolve or return to baseline. Intraparticipant 
dose escalation of BMS-986408 is permitted per Section 5.1.1. Intraparticipant schedule 
modifications of BMS-986408 are not permitted at any time. Intraparticipant dose reductions of 
BMS-986408 are allowed after specific DLT criteria are met. No dose reductions or escalations of 
nivolumab or ipilimumab will be allowed throughout the study treatment period. Dose reductions 
of PDCT are permitted per Section 7.4.3.
The assessment for dose delays and modifications should be made separately for each study 
intervention administered. Dose modifications are required only for the study treatment considered 
to be related to the AE. Thus, in case of an AE relationship assignment to PDCT alone, dose
modifications for PDCT alone are allowed. Similarly, in case of assignment of AE relationship to 
BMS-986408 and nivolumab, dose reduction for PDCT is not mandated. If criteria for 
discontinuation of BMS-986408 and nivolumab are met, PDCT may continue until 4 cycles have 
been completed. If criteria for discontinuation of PDCT are met, BMS-986408 and nivolumab may 
continue until progression or unacceptable toxicity, whichever occurs first. In case of doubt, all
study treatments should be modified.
For participants who require delay of study treatment, 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.
 
 
See Section 7.4.4 for criteria to resume treatment.
Criteria for participants who are required to permanently discontinue study drugs are listed in 
Section 8.1. Participants not meeting guidelines for permanent discontinuation will be permitted 
to resume therapy as soon as criteria for resuming therapy specified in Section 7.4.4 are fulfilled.
7.4.1
Dose Delay and Discontinuation Criteria for BMS-986408, Nivolumab 
and Ipilimumab
Dose delay criteria apply for all drug-related AEs. Delay administration of all treatment if any of 
the delay criteria 
are met. Delay all treatment dosing for any AE, laboratory 
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BMS-986408
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abnormality, or intercurrent illness which, in the judgment of the Investigator, warrants delaying 
the dose of study medication.
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DGKα/ζ Inhibitor
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BMS-986408
DGKα/ζ Inhibitor
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7.4.2
Dose Delays for Chemotherapy
Chemotherapy drugs should be delayed for any of the events listed below. The delay should occur 
on treatment Day 1.

Absolute neutrophil count < 1500/μL (SI units: < 1.5× 109/L)

Platelets < 100,000/μL (SI units: < 100× 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 AST, 
ALT, or total bilirubin:

If a participant has a baseline AST, ALT, or total bilirubin that is within normal limits, 
delay dosing for drug-related Grade ≥ 2 toxicity.

If a participant has baseline AST, ALT, or total bilirubin 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.
Dose modifications listed are specific to US Prescribing Information (USPI). Variations may apply 
per local label. Participants receiving cisplatin with pemetrexed must discontinue cisplatin if the 
calculated CrCl decreases to < 50 mL/min (based on the Cockcroft-Gault formula). The other drug 
(pemetrexed) may be continued, and the platinum agent may, at the investigator’s discretion, be 
switched to carboplatin for the rest of the cycles when the participant meets retreatment criteria. 
Note that pemetrexed can only be administered if CrCl is ≥ 45 mL/min (calculated per Cockcroft-
Gault formula).
If a participant receiving carboplatin with paclitaxel must discontinue carboplatin, paclitaxel may 
be continued at the investigator’s discretion.
If any non-hematologic AE meeting the dose delay criteria above is felt to be related to only 
1 particular agent in the PDCT regimen, then that agent alone may be omitted for that cycle while 
the other agent is given. To maintain synchronized dosing of the regimen, the omitted agent should 
be resumed with the next scheduled cycle once the AE has improved and retreatment criteria are 
met. Please refer to Section 7.4.3 to determine if dose reduction of the resumed agent is required.
If both drugs in the PDCT regimen are delayed, then the participant should be re-evaluated weekly 
or more frequently if clinically indicated until re-treatment criteria are met (see Section 7.4.4).
7.4.3
Dose Reduction for Chemotherapy
Dose reductions for chemotherapy may be required and will be performed as described below or 
per institutional guidelines. Chemotherapy dose reductions are permanent: once the dose of any 
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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 in Table 7.4.3.1-1.
Table 7.4.3-1:
Dose Reduction for Chemotherapya
Dose Level
Carboplatin
Pemetrexed
Paclitaxel
Cisplatin
Starting Dose
AUC 6 or AUC 5
500 mg/m2
200 mg/m2
75 mg/m2b
First Dose 
Reduction
AUC 5 (if starting 
dose is AUC 6) or 
AUC 4 (if starting 
dose is AUC 5)
375 mg/m2
150 mg/m2
56 mg/m2
Second Dose 
Reduction
AUC 4 (if starting 
dose is AUC 6) or 
AUC 3 (if starting 
dose is AUC 5)
250 mg/m2
100 mg/m2
38 mg/m2
Third Dose 
Reduction
Discontinue
Discontinue
Discontinue
Discontinue
Abbreviations: AUC, area under the curve; CrCl, creatinine clearance.
a Starting dose and dose reductions per table or institutional guidelines.
b If CrCl ≥60 mL/min, then starting dose is cisplatin 75 mg/m2. If CrCl is 50-59 mL/min, then decrease by 75% or 
per local guidelines.
Dose modifications listed are specific to USPI. Variations may apply per local label.  
Any participant with 2 prior dose reductions for 1 agent who experiences a toxicity that would
cause a third dose reduction must be discontinued from that agent.
7.4.3.1
Chemotherapy: Dose Reductions for Hematologic Toxicity
Dose modifications for hematologic toxicities (according to Common Terminology Criteria for 
Adverse Events [CTCAE] v5) are summarized in Table 7.4.3.1-1. Dose adjustments are based on 
nadir blood counts (assessed 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. After the first cycle, growth factors may be used to assist hematologic recovery. For 
incidences of chemotherapy-induced anemia or cancer-associated anemia, red blood cell 
transfusions are highly recommended. In participants who refuse RBC
transfusions, 
erythropoiesis-stimulating agents may be administered per local standards.
Use local standards of care for other previously described supportive measures. Additionally, 
prophylactic antibiotics may be used according to local standards of care. Investigators are strongly 
recommended to have a high index of suspicion for infection and consider starting broad spectrum 
antibiotics early for any fever or signs of infection in participants with neutropenia. Please report 
any antibiotic or growth factor use on the electronic case report form (eCRF).
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Dose modifications listed are specific to USPI. Variations may apply per local label.
Table 7.4.3.1-1:
Dose Modification for Hematologic Toxicity (Based on Nadir 
Counts)
Toxicity
Carboplatin
Paclitaxel
Pemetrexed
Cisplatin
Neutrophil Count Decreased
Grade 4
(< 500/mm3 or < 0.5× 109/L)
Reduce 1 dose 
level
Reduce 1 dose 
level
Reduce 1 dose 
level
Reduce 1 dose 
level
Platelet Count Decreased
Grade 3
(< 50,000-25,000/mm3; 
< 50.0-25.0× 109/L)
Reduce 1 dose 
level
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
Reduce 1 dose 
level
7.4.3.2
Chemotherapy: Dose Reductions for Non-hematologic Toxicities
Dose adjustments for chemotherapy for non-hematologic toxicities during treatment are described 
in Table 7.4.3.2-1. All dose reductions should be made based on the worst-grade toxicity. 
Participants experiencing any of the toxicities during the previous cycle should have 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 7.4.3-1.
Table 7.4.3.2-1:
Dose Modification for Non-Hematologic Toxicity 
Toxicity
Carboplatin
Paclitaxel
Pemetrexed
Cisplatin
Febrile Neutropenia 
Grade ≥ 3
Reduce 1 dose level
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
No change
Allergic Reaction 
Grade ≥ 3
Discontinue
Discontinue
Discontinue
Discontinue
Neuropathy 
Grade 2
Reduce 1 dose level
Reduce 1 dose level
No change
Reduce 1 dose level
Neuropathy 
Grades 3 or 4
Discontinue
Discontinue
Discontinue
Discontinue
CrCl < 50 mL/min
No change
Discontinue if CrCl 
< 20 mL/min
No change
Discontinue
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Table 7.4.3.2-1:
Dose Modification for Non-Hematologic Toxicity 
Toxicity
Carboplatin
Paclitaxel
Pemetrexed
Cisplatin
Other Grade ≥ 3 
toxicity
(except for fatigue 
and transient 
arthralgia and 
myalgia)
Adjust as medically
indicated
Adjust as medically
indicated
Adjust as medically
indicated
Adjust as medically
indicated
Abbreviation: CrCl, creatinine clearance.
7.4.4
Criteria to Resume Treatment
7.4.4.1
Criteria to Resume Treatment with BMS-986408, Nivolumab, or 
Ipilimumab
Participants in all groups must not meet any relevant criteria for discontinuation described in 
Section 8.1 to be considered for resumption of study treatment. Medical Monitor should be 
consulted for any delay of study treatment > 4 weeks for non-drug-related AEs before resuming 
study treatment.
Participants
may resume study treatment
if they have completed AE management 
(ie, corticosteroid taper) or are on ≤ 10 mg prednisone or equivalent and meet the requirements 
.
Prior to re-initiating treatment in a participant with a dosing delay lasting > 10 weeks for Part 2 or 
Part 3, the Medical Monitor (or designee) must be consulted. Continue tumor assessments per 
protocol even if dosing is delayed. Continue periodic study visits to assess safety and laboratory 
studies per protocol or more frequently if clinically indicated during such dosing delays.
For Part 2, Group E, when doses of both nivolumab and ipilimumab have been delayed and criteria 
to resume treatment are subsequently met, resume both nivolumab and ipilimumab on the same 
day unless the Investigator determines that one of the agents must be discontinued due to toxicity 
attributed to that agent alone. Decisions to eliminate any component of the assigned study regimen 
must be discussed with and approved by the medical monitor.
7.4.4.2
Criteria to Resume Treatment with Chemotherapy
Participants may resume treatment with chemotherapy when the absolute neutrophil count returns 
to ≥ 1500/μL (≥ 1.5× 109/L), the platelet count returns to ≥ 100,000/μL (≥ 100× 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.
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When resuming chemotherapy treatment, follow the dose-reduction recommendations in 
Section 7.4.3.
7.4.5
Immuno-oncology (IO) agents are associated with AEs that can differ in severity and duration 
from AEs caused by other therapeutic classes. Nivolumab, ipilimumab, and BMS-986408 are 
considered IO agents and the 
 provide guidance on 
assessing and managing the following groups of AEs:

Gastrointestinal

Renal

Pulmonary 

Hepatic

Endocrinopathy

Skin

Neurological

Myocarditis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
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7.4.7
Treatment of Immunotherapy Infusion-related Reactions
Since nivolumab and ipilimumab contain only human immunoglobulin protein sequences, they are 
unlikely to be immunogenic and induce infusion or hypersensitivity reactions. However, if such a 
reaction were to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, 
arthralgias, hypotension, hypertension, bronchospasm, or other allergic-like reactions. Report all 
Grade 3 or 4 infusion reactions within 24 hours as a serious adverse event (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):
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
 
 
 
.
For Grade 2 symptoms: (Therapy or infusion interruption indicated but responds promptly to 
symptomatic treatment (eg, antihistamines, NSAIDS, narcotics, IV fluids); prophylactic 
medications indicated for ≤24 hours):

 
 
 
 
 
 
 
 
 
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):

 
 
 
 
 
 
 
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).
7.5
Preparation/Handling/Storage/Accountability
The IP/AxMP must be stored in a secure area according to local regulations. It is the responsibility 
of the Investigator, or designee where permitted, to ensure that IP/AxMP is only dispensed to study 
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participants. The IP/AxMP must be dispensed only from official study sites by authorized 
personnel according to local regulations.
The product storage manager should ensure that the study intervention is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study intervention arise, the study intervention
should not be dispensed, and BMS should be contacted immediately.
Study intervention not supplied by BMS will be stored in accordance with the package insert.
IP/AxMP documentation (whether supplied by BMS or not) must be maintained that includes all 
processes required to ensure the drug is accurately administered. This includes documentation of 
drug storage, administration and, as applicable, storage temperatures, reconstitution, and use of 
required processes (eg, required diluents, administration sets).

The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention.

The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records).

Further guidance and information for the final disposition of unused study interventions are 
provided in Appendix 2.
7.6
Treatment Compliance
Study intervention compliance will be periodically monitored by drug accountability (including
review of dosing diary). Drug accountability should be reviewed by the site study staff at each visit 
to confirm treatment compliance. Sites should discuss discrepancies with the participant at each 
on-treatment study visit and document these discussions and discrepancies within medical records. 

When participants are dosed at the site, they will receive study intervention directly from the 
Investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the CRF. 
The dose of study intervention and study participant identification will be confirmed at the 
time of dosing by a member of the study site staff other than the person administering the study 
intervention. Study site staff will examine each participant’s mouth to ensure that the study 
intervention was ingested.

When participants self-administer BMS-986408 at home, compliance with study intervention 
will be assessed at each visit. Compliance will be assessed by direct questioning, counting 
returned tablets/capsules, and review of Participant Diary (supplied by BMS) during the site 
visits and documented in the source documents and relevant form. Deviation(s) from the 
prescribed dosage regimen should be recorded in the CRF.

A record of the quantity of BMS-986408 dispensed to and administered by each participant 
must be maintained and reconciled with study intervention and compliance records. 
Intervention start and stop dates, including dates for intervention delays and/or dose reductions, 
will also be recorded in the CRF.
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During Study Visit days, all study treatment(s) will be administered in the clinical facility.
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):
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
 
 

The investigator must also adhere to the contraindications, precautions, and drug interactions 
found in the USPI or local label for each chemotherapy agent.
7.7.2
Other Restrictions and Precautions
Participants are prohibited from joining another clinical trial while they are participating in this 
study.

 
 
 
 
7.7.2.1
Imaging Restriction and Precautions
It is the local imaging facility’s responsibility to determine, based on participant attributes 
(eg, allergy history, diabetic history, and renal status), the appropriate imaging modality and 
contrast regimen 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.
7.7.2.2
Palliative Local Therapy
Palliative local therapy to non-target lesions, 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 the study intervention for participants who do not have 
evidence of overall clinical or radiographic progression per RECIST v1.1. The case must be 
discussed with 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 
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participants must either discontinue the study intervention or 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 the study interventions is not known. 
As concurrent radiotherapy and the regimens evaluated in this study have not been formally 
evaluated, whenever palliative radiotherapy is required for a tumor lesion, then treatment should 
be withheld for at least 1 week before, during, and 1 week after radiation if medically feasible. 
Participants should be closely monitored for any potential toxicity during and after receiving 
radiotherapy and AEs should resolve to Grade ≤ 1 prior to resuming treatment.
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 treatment 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.
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:

 
 
 
 
 
 
 
 
 
 
 
 
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
Study treatment must be permanently discontinued per criteria in 
 Section 7.4. 
Discontinue nivolumab and/or ipilimumab for any AE, laboratory abnormality, or intercurrent 
illness which, in the judgment of the Investigator, presents a substantial clinical risk to the 
participant with continued nivolumab dosing and/or ipilimumab.
Part 1 (BMS-986408 Monotherapy):
 
 
 
 
Parts 2 and 3:
 
 
 
 
 
All Study Parts:
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.
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8.1.1
Treatment Beyond Disease Progression
Accumulating evidence indicates a minority of participants treated with immunotherapy may 
derive clinical benefit despite initial evidence of progressive disease.28
Participants treated with study treatment will be permitted to continue all components of study 
treatment beyond initial RECIST v1.1 defined progressive disease, assessed by the Investigator up 
to a maximum of 24 months from date of first dose as long as they meet the following criteria:

Investigator-assessed clinical benefit.

Tolerance of study treatment.

Stable performance status.

Participant provides written informed consent prior to receiving additional 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).
Continue radiographic assessment/scan(s) in accordance with the Section 2 Schedule of Activities 
for the duration of the treatment beyond progression and submit to the central imaging vendor. 
Balance the assessment of clinical benefit with clinical judgment as to whether the participant is 
clinically deteriorating and unlikely to receive any benefit from continued treatment with the study 
intervention.
For the participants who continue the 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 progressive disease. This includes an increase in the sum of diameters of all 
target lesions and/or the diameters of new measurable lesions compared to the time of initial 
progressive disease. Upon documentation of further progression, permanently discontinue 
treatment unless the clinical judgement of the Investigator is that continuing the treatment is in the 
participant’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 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.
The assessment of clinical benefit should take into account whether the participant is clinically
deteriorating and unlikely to receive further benefit from continued treatment. If the Investigator
believes that the participant continues to achieve clinical benefit by continuing treatment with the 
study treatments, then the participant should remain on the trial and continue to receive monitoring 
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according to the Schedule of Activities (see Section 2). All decisions to continue treatment beyond 
initial progression must be discussed with and agreed upon by the BMS Medical Monitor 
(or designee) prior to treatment beyond progression, and an assessment of the benefit-risk of 
continuing with study therapy must be documented in the study records (see Appendix 2).
8.1.2
Post-study Intervention Study Follow-up
In this study, safety and efficacy are key endpoints of the study. Post-study follow-up is of critical 
importance and is essential to preserving participant safety and the integrity of the study. 
Participants who discontinue study 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.
8.2
Discontinuation From the Study
Participants who request to discontinue study intervention will remain in the study and must 
continue to be followed for protocol-specified follow-up procedures. The only exception to this is 
when a participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information. 

Participants should notify the Investigator of the decision to withdraw consent from future 
follow-up.

The withdrawal of consent should be explained in detail in the medical records by the 
Investigator, as to whether the withdrawal is from further treatment with study intervention
only or also from study procedures and/or post-treatment study follow-up, and entered on the 
appropriate CRF page.

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 (Section 2)
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.
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8.3
Lost to Follow-up
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:

All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of 
three (3) documented phone calls, faxes, or emails, as well as lack of response by participant
to one (1) registered mail letter. All attempts should be documented in the participant’s medical 
records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If the Investigator’s use of third-party representative to assist in the follow-up portion of the 
study has been included in the participant’s informed consent, then the Investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining the participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study. 

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.

If, after all attempts, the participant remains lost to follow-up, then the last known alive date 
as determined by the Investigator should be reported and documented in the participant’s 
medical records.
8.4
Study Stopping Criteria
Systematic review of SAEs experienced through the duration of therapy will serve as a key basis 
for pausing or prematurely stopping the study. Review of these SAEs, and any decision to stop 
enrollment or terminate the study, will be determined by the Sponsor in collaboration with the 
investigators regarding possible study continuation, adjustment of the dose/schedule, health 
authority consultation, and study termination.
During Parts 1 and 2, stopping rules based on 
 will be used to continuously monitor 
for excess toxicity, defined as the occurrence of AEs during any cycle that would fulfill the DLT 
criteria or AEs leading to dose reduction or treatment discontinuation.
The Sponsor and investigators will convene regularly to review all the available safety, PK, PD 
and efficacy data and the results of 
 and in the event of any of 
the following occurrences:

.

Unanticipated SAEs that are related to study treatment are reported.

Death attributable to study treatment is reported.
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
The Sponsor or IRB/IEC decides that subject safety may be compromised by continuing the 
study.
Decisions to stop the enrollment or terminate the study will be communicated promptly to 
investigators, to the IRBs/IECs, Institutional Biosafety Committees, if applicable, and to the 
appropriate regulatory authorities.
9
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and timing are summarized in the Schedule of Activities. 

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 study treatment assignment. 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.

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 electronic 
case report form (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.

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 
laboratory assessments until all study drug-related toxicities resolve, return to baseline, or are 
deemed irreversible.
9.1
Efficacy Assessments
Screening images should be acquired as outlined in Table 2-1. On-study images must be acquired 
as outlined in Table 2-2 and Table 2-3 from the date of first dose until the participant is off-study 
as defined in Section 8.1. For participants continuing past that period, imaging will continue as 
defined in Table 2-4. Any additional imaging that may demonstrate tumor response or progression 
(including scans performed at unscheduled time points and/or at an outside institution) should be 
collected for tumor assessment and be submitted to the central imaging vendor as defined in 
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Section 9.1.1. Imaging should continue until disease progression or discontinuation of all study 
treatment, whichever occurs later.
Efficacy assessments for the anti-tumor activity of BMS-986408, alone and in combination with 
nivolumab or with nivolumab and ipilimumab, will be based on tumor measurements using 
RECIST v1.1 with CT and/or MRI, as appropriate, at baseline, and during the treatment period. 
For all study parts, tumor assessments will occur every 8 weeks (Q8W; ± 7 days) for the first 
48 weeks of study treatment, then every 12 weeks (± 7 days) until disease progression or 
discontinuation of all study treatment, whichever occurs later. 
During Follow-up for all groups, participants will continue to have imaging assessments completed 
every 12 weeks (± 7 days) until withdrawal of consent, death, or initiation of another anti-cancer 
treatment, whichever occurs first, for up to 2 years from the date of EOT.
Only data for the procedures and assessments specified in this protocol should be submitted to the 
Sponsor or designee on a CRF. Additional procedures and assessments may be performed as part 
of standard of care. However, data for these assessments should remain in the participant’s medical
record and should not be provided to the Sponsor or designee, unless specifically requested from 
BMS or designee.
9.1.1
Efficacy Assessment for the Study
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 HNSCC, a 
contrast-enhanced CT or MRI of the neck is 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. Change in tumor measurements and tumor response to guide 
ongoing study treatment decisions will be assessed by the Investigator using the RECIST v1.1 
criteria (see 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 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 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 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 
positron emission tomography (PET)-CT, is increasingly used in clinical care and is a 
modality/technology that is in rapid evolution; therefore, the recommendations outlined here may 
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change rather quickly with time. At present, low-dose or attenuation correction CT portions of a 
combined PET-CT are of limited use in anatomically based efficacy assessments and it is therefore 
suggested that they should not be substituted for dedicated diagnostic contrast-enhanced CT scans 
for anatomically based RECIST v1.1 measurements. However, if a site can document that the CT 
performed as part of a PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and 
oral contrast),then the CT portion of the PET-CT can be used for RECIST v1.1 measurements. 
Note, however, that the PET portion of the CT introduces additional data which may bias an 
investigator if it is not routinely or serially performed.
Bone scan or PET scan are not adequate for assessment of RECIST v1.1 response in target lesions. 
In selected circumstances where such modalities are the sole modality used to assess certain non-
target organs, those non-target organs may be evaluated less frequently. For example, bone scans 
may need to be repeated only when complete response 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.
9.1.1.1
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 using RECIST v1.1 criteria. Investigators will report the 
number and size of new lesions that appear while on study. The time point of tumor assessments 
will be reported on the electronic case report form (eCRF) based on the Investigator’s assessment 
using RECIST v1.1 criteria (see Appendix 5 for specifics of RECIST v1.1 criteria to be used in 
this study). Assessments of partial response and complete response must be confirmed at least 
4 weeks (28 days) after initial response. 
See Appendix 5, Section 5.3.3 for determination of best 
overall response.
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. 
Use CTCAE v5 definitions and grading for safety reporting of all AEs and SAEs on the CRF.
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. 
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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.
Refer to Appendix 3 for SAE reporting. Refer to the eCRF instructions for additional 
guidance regarding the capture of an AE or SAE within the database. 
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
All SAEs and AEs, including those associated with SARS-CoV-2 infection, must be collected 
from the time of signing the consent, including those thought to be associated with protocol-
specified procedures, and within 
 following discontinuation for Part 1 monotherapy or 
within 
 following discontinuation of dosing for Parts 2 and 3 combinations.
The Investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study intervention or protocol-specified procedure (eg, a tumor 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 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 assigned to treatment and never treated with study drug, collect SAEs for 
 
from the date of treatment assignment. 
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. Collect all non-serious AEs (not only those 
deemed to be treatment-related) continuously during the treatment period and for a minimum of 
 (Part 1) or 
 (Parts 2 and 3) following discontinuation of study treatment.
9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. Care should be taken not to introduce bias when collecting AEs and/or 
SAEs. Inquiry about specific AEs should be guided by clinical judgement in the context of known 
AEs, when appropriate for the program or protocol.
Every AE must be assessed by the Investigator with regard to whether it is considered immune-
mediated. For events which are potentially immune-mediated, additional information will be 
collected on the participant’s CRF.
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9.2.3
Follow-up of AEs and SAEs

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.
All SAEs will be 
 
(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, 
 
, the Investigator must immediately notify the BMS Medical 
Monitor/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.
Not applicable for women not of childbearing potential - Protocol-required procedures for study 
discontinuation and follow-up must be performed on the participant.
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Any pregnancy that occurs in a female partner of a male study participant should be reported to 
the Sponsor or designee. In order for the Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
If any sexual activity involving penile intercourse (eg, vaginal, anal, oral) has occurred between a 
male participant and a pregnant partner(s) without the use of a condom 
 
 
 the information should be reported to the Sponsor or designee, even if the male 
participant has undergone a successful vasectomy.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE eCRF, as appropriate. Paper forms are only intended as a back-up option when the 
electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the participant to have study intervention
discontinued or interrupted

Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
It is expected that, wherever possible, the clinical rather than laboratory term would be used by the 
reporting Investigator (eg, anemia vs low hemoglobin value).
9.2.7
Potential Drug-induced Liver Injury
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential drug-induced liver injury (p-DILI) event. All occurrences 
of p-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× upper limit of normal (ULN)
AND

Total bilirubin > 2× ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase [ALP])
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.
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The key responsibilities for Investigators during p-DILI assessment include: (i) early detection, 
medical evaluation (including the exclusion of other potential causes), and rapid laboratory 
confirmation of liver-related abnormalities; and (ii) BMS notification of p-DILI cases via SAE 
forms. Following the gathering and assessment of relevant clinical information, BMS is 
responsible for: (i) timely evaluation and triaging of p-DILI cases; (ii) expedited reporting of 
p-DILI cases; and (iii) expanded review of p-DILI cases including a detailed assessment of all 
available clinical information, investigations, and biochemical data.
Investigators are expected to monitor ongoing routine and ad hoc hepatic laboratory test results to 
rapidly determine whether a participant meets p-DILI criteria. They are expected to promptly 
notify BMS of all p-DILI cases. p-DILI cases may be identified by abnormal liver biochemistry 
values, whether or not they are accompanied by liver-related signs and/or symptoms. In both cases, 
expedited confirmation with repeat laboratory testing should occur within 3 business days using a 
hepatic laboratory panel (ALT, AST, T. bili, ALP). Any participant with an abnormal hepatic 
laboratory panel that meets p-DILI criteria is a candidate for study treatment discontinuation. Any 
confirmed p-DILI events must be reported (along with a description of the clinical findings) to 
BMS as an SAE within 24 hours of confirmation.
An extensive clinical history, examination, and appropriate investigations should be obtained to 
exclude cholestatic and other apparent causes that may explain the observed abnormalities in liver 
function and/or hepatic signs and symptoms. Other apparent causes include, non-exhaustively and
by way of example only, the following: infectious diseases (such as active hepatitis A, B, and C), 
congenital diseases (such as Gilbert’s syndrome), neoplastic diseases, autoimmune diseases 
(such as primary biliary cirrhosis), and the use of concomitant hepatotoxic medications 
(such as antibiotics, the oral contraceptive pill, and herbal medicines). All investigations to 
exclude potential causes of liver function abnormalities or hepatic signs and/or symptoms should 
be guided by relevant factors such as the participant’s age, gender, clinical history, and signs and 
symptoms.
9.2.8
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 nonserious AE or SAE, as appropriate, and reported accordingly.
9.3
Overdose
For this study, any dose of study treatments greater than the assigned dose within a 24-hour time 
period will be considered an overdose. Overdoses that meet the regulatory definition of SAE will 
be reported as an SAE (see Appendix 3).
In the event of an overdose, the Investigator should:

Contact the Medical Monitor immediately

Closely monitor the participant for AEs/SAEs and laboratory abnormalities 

Document the quantity of the excess dose as well as the duration of the overdosing in the CRF
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Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.
9.4
Safety
Safety assessments will be based on reported AEs and the measurement results of vital signs, 
ECGs, physical examinations, and clinical laboratory tests. AEs will be coded using the most 
current version of Medical Dictionary for Regulatory Activities (MedDRA) and the incidence of 
observed AEs will be tabulated and reviewed for potential significance and clinical importance. 
AEs will be tabulated by system organ class, preferred term, and treatment and reviewed for 
potential significance and clinical importance. Clinical laboratory results will also be listed and 
tabulated.
AEs will be assessed continuously during the study and for a minimum of 
 after the last 
dose of BMS-986408 in the case of monotherapy. For Parts 2 and 3, AEs will be assessed 
continuously during the study and for a minimum of 
 after the last dose of nivolumab,
ipilimumab, or PDCT or 
 after the last dose of BMS-986408 (whichever is later). Local 
laboratory will perform the clinical laboratory tests and will provide reference ranges for these 
tests. Both AEs and laboratory tests will be graded using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
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 ECG assessments for safety in Table 2-1
(Screening), Table 2-2 (Part 1), and Table 2-3 (Parts 2 and 3). The Investigators will review the 
12-lead ECGs throughout the study. The corrected QTc will be applied to each ECG reading.
Refer to the schedule of specific ECG collections to analyze the effect of BMS-986408 on the QTc 
interval in Table 2-2 and Table 9.5-2 for all groups in Part 1. In Part 1 only, specifically on 
Days 1 and 15 of Cycle 1, all ECG tests will be performed in triplicate (ie, 1 ECG test equals 
3 consecutive individual 12-lead ECGs performed approximately 5 minutes apart) utilizing the 
ECG machine supplied by the Sponsor. For Part 1, all other visits including ECGs will require a 
single safety ECG, which should be performed using site ECG machines.
A separate manual will include additional details and instructions.
9.4.4
Clinical Safety Laboratory Assessments

Investigators must document their review of each laboratory safety report.

A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests performed on Day -1 must be available prior to dosing.
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
The laboratory tests that will be performed for study participants are shown in Table 9.4.4-1.

Results of all laboratory tests required by this protocol must be provided to the Sponsor, 
recorded either on the laboratory pages of the CRF or by another mechanism as agreed upon 
between the Investigator and BMS (eg, provided electronically). If the units of a test result 
differ from those printed on the CRF, the recorded laboratory values must specify the correct 
units.

Any abnormal laboratory test result considered clinically significant by the Investigator must 
be recorded on the appropriate AE page of the CRF.
Table 9.4.4-1:
Clinical Laboratory Assessments
Hematology - CBC
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Activated partial thromboplastin time
International normalized ratio and/or prothrombin time (at screening only)
Chemistry
AST
ALT
Total bilirubin
Direct Bilirubin (reflex if total bilirubin is abnormal)
ALP
LDH
Creatinine
BUN or serum urea
Glucose (fasting glucose at screening only)
Lipase
Amylase
Total protein
Troponin
Gamma-glutamyl transferase (reflex if liver function is 
abnormal)
Albumin - screening only
Sodium
Magnesium
Potassium
Chloride
Calcium
Phosphorus
TSH, free T3 and free T4 - screening 
TSH, with reflexive free T3 and free T4 if TSH is 
abnormal - Day 1 of each Cycle on treatment and EOT
NOTE: Total T3 may be allowed if collection of free T3 
is not feasible
Serology
Hepatitis B/C, (HBsAG, HCV antibody or HCV RNA)-screening only
HIV-1 and HIV-2 antibody - at screening and as mandated by local requirement
Other Analyses
Pregnancy test (WOCBP only: minimum sensitivity 25 IU/L or equivalent units of hCG). Serum or urine 
pregnancy test acceptable for eligibility and all other visits.
FSH screening - only required to confirm menopause in women < age 55 
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Table 9.4.4-1:
Clinical Laboratory Assessments
Urinalysis per Section 2
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein, or leukocytes esterase are positive on the dipstick
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; 
BUN, blood urea nitrogen; CBC, complete blood count;
; EOT, end of treatment; FSH, follicle 
stimulating hormone; HBsAG, hepatitis B surface antigen; hCG, human chorionic gonadotropin; HCV, hepatitis C 
virus; HIV, human immunodeficiency virus; LDH, lactate dehydrogenase; 
; RNA, 
ribonucleic acid; 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 per standard 
medical/clinical judgment.
9.5
Pharmacokinetics
Pharmacokinetics of BMS-986408 
 will be derived from plasma 
concentration versus time and urinary excretion data as shown in Table 9.5-1.
Plasma samples for PK assessments will be collected for all participants receiving BMS-986408, 
as described in Table 9.5-2 (Part 1, Groups A, B, B2, and C), Table 9.5-3 (Part 2, Groups D, F,
and G, after 
 pH effect study period; and Part 3, Groups D2 and F2), Table 9.5-4 (Part 2, 
Group E), and Table 9.5-5 (Part 2, Group G, pH effect study). All on-treatment PK time points are 
intended to align with days on which study treatment is administered. If it is known that a dose is 
going to be delayed, then collect the pre-dose sample just prior to the delayed dose. However, if a 
pre-dose sample is collected but the dose is subsequently delayed, do not collect an additional pre-
dose sample.
Blood samples should be drawn from a site other than the infusion site (ie, contralateral arm) on 
days of infusion for all pre-dose and end of infusion (EOI)-PK samples. Please ensure accurate 
documentation of the time and date of sample collection. If the infusion was interrupted, the 
interruption details will also be documented on the CRF. Further details of sample collection, 
processing, and shipment will be provided in the laboratory/procedure manual.
Urine will be collected on Cycle 1 Day 1 and Cycle 1 Day 15 in Part 1 monotherapy. The 
concentration of BMS-986408 
 in urine will be explored. On Day 1, urine 
will be collected and pooled as a single block over the intervals of 0 to 6 and 6 to 24 hours post
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dose. The 
 collected from the participant during each time interval should be 
recorded 
. For the interval of 6 to 24 hours, participants will be asked to take the 
 container with them and collect all urine voided during this interval at home. They 
will be asked to bring the collected urine back to the site on Day 2.
 and ipilimumab 
(in Part 2, Group E participants) serum samples will be collected and may be used in an integrated 
PPK or E-R analysis along with data from other nivolumab and/or ipilimumab studies, which 
would be the subject of a separate report. Separate samples will be collected for PK and anti-drug 
antibody (ADA) assessments using validated methods. 
Plasma concentrations of BMS-986408 will be measured using a validated liquid chromatography-
tandem mass spectrometry (LC-MS/MS) method. Urine concentrations of BMS-986408 will be 
measured using a qualified LC-MS/MS method. In addition, after the scheduled analysis of PK 
samples are complete, 
. PK 
samples will be analyzed for nivolumab and ipilimumab by validated ligand-binding assays. 
Immunogenicity samples for nivolumab and ipilimumab will be analyzed by validated methods. 
BMS-986408 PK parameters will be derived from plasma concentration-time data during 
BMS-986408 monotherapy, during combination treatment with nivolumab, during combination 
with nivolumab and chemotherapy, and during combination with nivolumab and ipilimumab. If
data permit, individual participant PK parameter values as described in Table 9.5-1 will be derived 
by non-compartmental methods by a validated PK analysis program. Actual times will be used for 
the analyses. 
The PK parameters of BMS-986408 to be assessed following the first dose and at steady state
administration, if data permit, include but are not limited to:
Table 9.5-1:
Pharmacokinetic Parameters
Parameters to be Reported for Monotherapy Dose Escalation Cohort (Part 1, Groups A, B, and C)a
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(0-T)
Area under the plasma concentration-time curve from time 0 to time of last quantifiable 
concentration
AUC(TAU)
Area under the concentration-time curve in 1 dosing interval
T-Halfeff
Effective terminal half life
CLT/F 
Apparent total body clearance
CLR/F
Apparent renal clearance
AI
Accumulation index
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Table 9.5-1:
Pharmacokinetic Parameters
UR
Total amount recovered in urine
%UR
Total percent of administered dose recovered in urine over a dosing interval at steady 
state.
Parameters to be Reported as a Separate Listing Summary and Plot for Group D and E
Cmax
Maximum observed plasma concentration (BMS-986408) 
Nivolumab and Ipilimumab Parameters to be Reported as a Separate Listing Summary and Plot for 
Group D and E
Ceoi
Observed nivolumab and ipilimumab serum concentrations at the end of infusion
a PK parameters will be reported as data permit.
Data may be pooled with other future studies for population PK analysis of BMS-986408, the 
results of which will be reported in a separate pharmacometric report. 
Treatment assignments will be released to the bioanalytical laboratory in order to minimize 
unnecessary analysis and/or reanalysis of PK/ADA samples.
Concentration analyses for BMS-986408 in the plasma, nivolumab, and ipilimumab will be 
performed by validated bioanalytical method(s).
Bioanalytical samples designated for assessments (eg, immunogenicity, PK, or biomarker) from 
the same collection time point may be used interchangeably for analyses, if required (including, 
but not limited to, insufficient volume for complement assessment, to follow-up on suspected 
immunogenicity related AE, etc).
Table 9.5-2:
Pharmacokinetic Sampling Schedule for Part 1, Groups A, B, B2, 
and C
Study Day of 
Sample Collection
(1 Cycle = 28 days)
Event
Time Relative to 
BMS-986408 Dose 
(hr:min)
BMS-986408 
PK Plasma 
Sample
BMS-986408 
Urine 
Samplea
12-Lead 
Triplicate 
ECGb
Cycle 1 Day 1
Predose
0:00
X
X (0-6 h)
X
1:00
X
X
2:00
X
X
4:00
X
X
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Table 9.5-2:
Pharmacokinetic Sampling Schedule for Part 1, Groups A, B, B2, 
and C
Study Day of 
Sample Collection
(1 Cycle = 28 days)
Event
Time Relative to 
BMS-986408 Dose 
(hr:min)
BMS-986408 
PK Plasma 
Sample
BMS-986408 
Urine 
Samplea
12-Lead 
Triplicate 
ECGb
6:00
X
X
Cycle 1 Day 2
Predosec
0:00
X
X (6-24 h)
4:00
X
Cycle 1 Day 8
Predosec
0:00
X
4:00
X
Cycle 1 Day 15
Predosec
0:00
X
X (0-6 h)
X
1:00
X
X
2:00
X
X
4:00
X
X
6:00
X
X
Cycle 1 Day 16
Predosec
0:00
X
X (6-24 h)
Cycle 1 Day 22
Predosec
0:00
X
4:00
X
Cycle 2 Day 1
Predosec
0:00
X
Cycle 2 Day 15d
Predosec
0:00
X
Cycle 3 Day 1
Predosec
0:00
X
Cycle 3 Day 15
Predosec
0:00
X
Every alternate cycle 
starting at Cycle 4 
Day 1 up to and 
including EOT
Predosec
0:00
X
Follow-up Periode
Follow-up 30 Day
X
Abbreviations: ECG, electrocardiogram; EOT, end of treatment; hr, hour; IV, intravenous; PK, pharmacokinetics; 
min, minute.
a Urine sample is a pooled sample for the indicated time intervals.
b All ECGs should be recorded after the participant has been supine for at least 5 minutes and prior to blood 
collections. 12-lead ECGs to be performed in triplicate (using the ECG machine supplied by the Sponsor).
c All pre-dose samples for BMS-986408 should be taken prior to dosing (preferably within 30 minutes). If it is known 
that a dose is going to be delayed, then collect the pre-dose sample just prior to delayed dose. However, if a pre-
dose sample is collected but the dose is subsequently delayed, do not collect additional pre-dose sample.
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d For participants in Group C only, C2D15 sample to be taken on the same day of on-treatment biopsy. If the on-
treatment biopsy sample is delayed, then collect the C2D15 sample on the delayed biopsy sampling day.
e If participant discontinues study drug treatment during the sampling period, they will move to sampling at the 
follow-up visits.
Table 9.5-3:
Pharmacokinetic and Immunogenicity Sampling Schedule for 
Part 2, Groups D (Combination Cohort with Nivolumab), F 
(Combination Cohort with Nivolumab and Chemotherapy), and G 
(Starting C1D1), and Part 3 Combination Expansion
Study Day of Sample 
Collection
(1 Cycle = 28 days)
Event
Time Relative 
to BMS-986408
Dose (hr:min)
BMS-986408 
PK plasma 
Sample
Nivolumab 
Serum PK 
Sample
Nivolumab 
Serum ADA 
Sample
Cycle 1 Day 1
Predosea
0:00
X
X
X
EOIb,c
1:00
X
X
2:00
X
4:00
X
6:00
X
Cycle 1 Day 2
Predosea
0:00
X
Cycle 1 Day 8 
Predosea
0:00
X
Cycle 1 Day 15
Predosea
0:00
X
Cycle 1 Day 22d
Predosea
0:00
X
Cycle 2 Day 1
Predosea
0:00
X
X
X
Cycle 2 Day 15e
Predosea
0:00
X
Every 4th cycle starting 
at Cycle 3 Day 1 up to 
and including EOT 
Predosea
0:00
X
X
X
Follow-up Periodf
Follow-up 30 Day
X
X
X
Abbreviations: ADA, anti-drug antibody; C, cycle; D, day; EOI, end of infusion; EOT, end of treatment; hr, hour;
IV, intravenous; min, minute; PK, pharmacokinetics.
a All pre-dose samples for BMS-986408 and nivolumab should be taken prior to BMS-986408 dosing (preferably 
within 30 minutes). If it is known that a dose is going to be delayed, then collect the pre-dose sample just prior to 
delayed dose. However, if a pre-dose sample is collected but the dose is subsequently delayed, do not collect an 
additional pre-dose sample.
b The EOI occurs when the entire nivolumab dose in the infusion bag is administered to the patient (after the flush is 
administered to clear the IV lines of the drug and to ensure delivery of the entire drug dose). Draw the EOI-PK 
sample within approximately 5 minutes after end of the flush. If the EOI is delayed to beyond the nominal infusion 
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duration (30 minutes), the collection of this sample should also be delayed accordingly. EOI samples may not be 
collected from the same IV access as the drug was administered.
c The Event label “EOI” only refers to nivolumab serum PK sample that is infused intravenously. For BMS-986408, 
no event label required for the 1:00 hour timepoint.
d Not applicable for Group F.
e C2D15 sample to be taken on the same day of on-treatment biopsy. If the on-treatment biopsy sample is delayed, 
then collect the C2D15 sample on the delayed biopsy sampling day.
f If participant discontinues study drug treatment during the sampling period, they will move to sampling at the 
follow-up visits.
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Table 9.5-4:
Pharmacokinetic and Immunogenicity Sampling Schedule for Part 2, Group E (Combination Cohort 
with Nivolumab and Ipilimumab) 
Study Day of 
Sample Collection
(1 Cycle = 28 days)
Event
Time Relative 
to BMS-986408
Dose (hr:min)
BMS-986408 
PK plasma 
Sample
Nivolumab 
Serum PK 
Sample
Nivolumab 
Serum ADA 
Sample
Ipilimumab 
Serum PK 
Sample
Ipilimumab 
Serum ADA 
Sample
Cycle 1 Day 1
Predosea
0:00
X
X
X
X
X
1:00
X
EOIb,c
2:00
X
X
X
4:00
X
6:00
X
Cycle 1 Day 2
Predosea
0:00
X
Cycle 1 Day 8
Predosea
0:00
X
Cycle 1 Day 15
Predosea
0:00
X
Cycle 1 Day 22
Predosea
0:00
X
X
X
Cycle 2 Day 1
Predosea
0:00
X
X
X
EOIb
2:00
X
Cycle 2 Day 15d
Predosea
0:00
X
Cycle 3 Day 1
Predosea
0:00
X
X
X
X
X
EOIb
2:00
X
X
Every 4th cycle 
starting at Cycle 5 
Day 1 up to and 
including EOT
Predosea
0:00
X
X
X
X
X
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Table 9.5-4:
Pharmacokinetic and Immunogenicity Sampling Schedule for Part 2, Group E (Combination Cohort 
with Nivolumab and Ipilimumab) 
Study Day of 
Sample Collection
(1 Cycle = 28 days)
Event
Time Relative 
to BMS-986408
Dose (hr:min)
BMS-986408 
PK plasma 
Sample
Nivolumab 
Serum PK 
Sample
Nivolumab 
Serum ADA 
Sample
Ipilimumab 
Serum PK 
Sample
Ipilimumab 
Serum ADA 
Sample
Follow-up Periode
Follow-up 30 Day
X
X
X
X
X
Abbreviations: ADA, anti-drug antibody; EOI, end of infusion; EOT, end of treatment; hr, hour; IV, intravenous; min, minutes; PK, pharmacokinetics.
a All pre-dose samples for BMS-986408 and nivolumab should be taken prior to BMS-986408 dosing (preferably within 30 minutes). If it is known that a dose is 
going to be delayed, then collect the pre-dose sample just prior to delayed dose. However, if a pre-dose sample is collected but the dose is subsequently delayed,
do not collect additional pre-dose sample.
b The EOI of nivolumab and ipilimumab occurs when the entire dose of the ipilimumab in the infusion bag is administered to the participant (after the flush is 
administered to clear the IV lines of the drug and to ensure delivery of the entire drug dose). Draw the EOI-PK sample within approximately 5 minutes after end 
of the flush. If the EOI is delayed to beyond the nominal infusion duration (30 minutes), the collection of this sample should also be delayed accordingly. EOI 
samples may not be collected from the same IV access as the drug was administered.
c The Event label “EOI” only refers to nivolumab and ipilimumab that are infused intravenously. For BMS-986408, no event label required for 2:00 hour time
point.
d C2D15 sample to be taken on the same day of on-treatment biopsy. If the on-treatment biopsy sample is delayed, then collect the C2D15 sample on the delayed 
biopsy sampling day.
e If participant discontinues study drug treatment during the sampling period, they will move to sampling at the follow-up visits.
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Table 9.5-5:
Pharmacokinetic Sampling Schedule for Part 2, Group G (Cycle 0 pH Effect)
Study Day of Sample 
Collection
Event
Time Relative to 
BMS-986408 Dose (hr:min)
BMS-986408 PK Plasma 
Sample
12-lead Triplicate ECGa
Cycle 0 Day 1
Predoseb
0:00
X
X
1:00
X
X
2:00
X
X
4:00
X
X
6:00
X
X
8:00
X
24:00
X
X
Cycle 0 Day 2
48:00
X
Cycle 0 Day 3
72:00
X
Cycle 0 Day 4
96:00
X
Cycle 0 Day 5
120:00
X
Cycle 1 Day 1
(Cycle 0 Day 8)
Predoseb
168:00
See Table 9.5-3.
X
End of 
 Period of BMS-986408
Additional PK sampling for cohort starting C1D1 per Table 9.5-3.
Abbreviations: ECG, electrocardiogram; hr, hour; min, minute; PK, pharmacokinetics.
a All ECGs should be recorded after the participant has been supine for at least 5 minutes and prior to blood draws. 12-lead ECGs to be performed in triplicate 
(using the ECG machine supplied by the Sponsor).
b All pre-dose samples for BMS-986408 should be taken prior to dosing (preferably within 30 minutes). If it is known that a dose is going to be delayed, then 
collect the pre-dose sample just prior to delayed dose. However, if a pre-dose sample is collected but the dose is subsequently delayed, do not collect additional 
pre-dose sample.
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9.6
Immunogenicity Assessments 
Antibodies to nivolumab and ipilimumab will be evaluated in serum samples collected from all 
participants in Parts 2 and 3 (Table 9.5-3 and Table 9.5-4). 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 nivolumab or ipilimumab, and the titer 
of confirmed positive samples will be reported. Other analyses may be performed to further 
characterize the immunogenicity of nivolumab or ipilimumab.
The detection and characterization of antibodies to nivolumab or ipilimumab will be performed 
using validated method(s) by or under the supervision of the Sponsor. All samples collected for 
detection of antibodies to nivolumab or ipilimumab will also be evaluated for nivolumab or 
ipilimumab serum concentration to enable interpretation of the antibody data. 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 nivolumab or ipilimumab.
9.7
Genetics
Details on genetic assessments are presented in Section 9.8.
9.8
Biomarkers
Peripheral blood and tumor tissue samples will be collected in certain groups during this study at 
baseline and several on-treatment time points to identify pharmacodynamic markers associated 
with response. Additional biomarkers related to mechanism of action of BMS-986408 will be 
explored. The pharmacodynamic changes between baseline and on-treatment measures will also 
be monitored and evaluated for associations with PK data and select AEs. Samples will be 
collected at the times indicated in Table 9.8-1 for biomarker assessments. If biomarker samples 
are collected but study treatment(s) is not administered, samples will be retained. Further details 
of blood and tumor tissue collection and processing will be provided to the site in the laboratory 
manual.
Other samples may be used for research to develop methods, assays, prognostics, and/or 
companion diagnostics related to BMS-986408 treatment.
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Table 9.8-1:
Biomarker Sampling Schedule for all Participants
Study Day of 
Sample Collection 
(Cycle = 4 weeks)
Event
Time Relative to 
BMS-986408 
Dose (hr:min)
Whole Blood: 
Immuno-
phenotyping
Whole Blood: 
RNASeq
Whole Blood: 
TCRSeq
Tumor Biopsy: 
IHC, 
TMB/RNASeq/
TCRSeq/WES
Plasma 
(Soluble 
Analytes)
Screening
Xa
Cycle 1 Day 1
Predoseb
0:00
X
X
X
X
Cycle 1 Day 8
Predoseb
0:00
X
X
Cycle 1 Day 15
Predoseb
0:00
X
X
Cycle 2 Day 15
Predoseb
0:00
X
Xa
Cycle 3 Day 1
Predoseb
0:00
X
Upon Progression
EOT
Xc
Complete Response
X
Follow-up Period
Follow-up Day 30
Abbreviations: C, cycle; D, day; EOT, end of treatment; hr, hour; IHC, immunohistochemistry; min, minutes; 
 PD-L1,
programmed death ligand 1; RNASeq, ribonucleic acid sequencing; TCRSeq, T cell receptor sequencing; TMB, tumor mutational burden; WES, whole exome 
sequencing.
a Tumor biopsy is optional for participants in Part 1, Groups A, B, and B2 and Part 3, Groups D2 and F2. During screening, tissue for PD-L1 IHC confirmation 
is mandatory for Part 3, Group F2, and must be submitted to central laboratory prior to treatment assignment.
b All pre-dose samples should be taken prior to BMS-986408 dosing (preferably within 30 minutes). If it is known that a dose is going to be delayed, then collect 
the pre-dose sample just prior to the delayed dose. However, if a pre-dose sample is collected but the dose is subsequently delayed, do not collect the additional 
pre-dose sample.
c EOT biopsy is optional for all participants.
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9.8.1
Peripheral Biomarkers
Blood samples will be collected prior to and during treatment with BMS-986408 as monotherapy 
and in combination with nivolumab, nivolumab and ipilimumab, or nivolumab and chemotherapy. 
These blood samples may be assessed for, but not limited to, 
, changes in 
quantity, phenotype and/or functionality of immune cell subsets, changes in gene expression, 
presence or absence of soluble analytes, and TCR repertoire profiling.
9.8.1.1
Immunophenotyping
Pre-treatment and on-treatment whole blood samples will be analyzed to study the effects of 
BMS-986408 as monotherapy and in combination with nivolumab, nivolumab and ipilimumab, or 
nivolumab and chemotherapy on various immune cell subsets. Whole blood and/or 
 
analyses will include, but not be limited to, monitoring the levels 
of regulatory T cells and detecting any change in number, phenotype, or functional status of 
circulating T cells and NK cells.
9.8.1.2
Peripheral Blood Gene Expression Profiling and TCR Sequencing
Total RNA and deoxyribonucleic acid (DNA) will be extracted from whole blood
 obtained 
at time points indicated in Table 9.8-1. RNA expression may be used to identify pharmacodynamic 
changes caused by treatment with BMS-986408 in monotherapy or in combination with 
nivolumab, nivolumab and ipilimumab, or nivolumab and chemotherapy. Pharmacodynamic 
changes and baseline levels of genes and TCR repertoire may be explored for association with 
clinical outcome.
9.8.1.3
Measurement of Soluble Analytes
Plasma will be separated from whole blood at time points indicated in Table 9.8-1. Soluble analytes
will be measured to assess pharmacodynamic changes and correlation with clinical outcomes 
following treatment with BMS-986408 alone or in combination with nivolumab, nivolumab and 
ipilimumab, or nivolumab and chemotherapy.
9.8.2
Tumor-based Biomarkers
Biopsy samples will be collected at screening and on-treatment from a lesion/site capable of 
providing sufficient tissue to characterize immune cell populations and expression of selected 
tumor markers during:

Part 1, Group C and 

Part 2, Groups D, E, F, and G. 
Biopsies are optional at the discretion of the investigator and/or participant in:

Part 1, Groups A, B, and B2 and 

Part 3, Groups D2 and F2. 
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Tumor biopsy samples should be either core needle biopsy, surgical, excisional, or incisional; fine 
needle aspirates and other cytology specimens are insufficient for downstream biomarker analyses. 
Bone lesion biopsies are unacceptable for submission since the decalcification process is not 
compatible with several of the planned biomarker analyses. Pathologic confirmation by touch prep 
is strongly encouraged at the time of tumor biopsy to confirm adequate tissue collection and biopsy 
quality. Both the screening and on-treatment tumor biopsies should be preferentially collected 
from the same site, if feasible. On-treatment biopsies are mandated at acceptable clinical risk (as 
determined by the Investigator). For participants in Part 1, Group C and Part 2, a repeat biopsy at 
screening or on-treatment from the same or an alternative site will be required if clinically feasible 
(at the discretion of the Investigator), and the initial attempt was unsuccessful in obtaining 
adequate tissue for biomarker analysis. Only 1 repeat attempt may be performed at each time point, 
if clinically feasible. An unsuccessful fresh tumor biopsy at screening or on-treatment will not 
exclude participants from receiving or continuing study treatment. Please notify the BMS Medical 
Monitor if on-treatment biopsy may pose unacceptable clinical risk or if tumor at the time of on-
treatment biopsy is not accessible for sampling. Institutional guidelines for the safe performance 
of biopsies should be followed. The screening and on-treatment biopsies will follow the same 
guidance methodology for sample collections, processing, and submission provided in the 
laboratory manual.
During screening, tissue or slides for PD-L1 IHC confirmation must be submitted to the central 
laboratory prior to treatment assignment for Part 3, Group F2.
9.8.2.1
Tumor Mutational Burden Assessment 
DNA will be extracted from the baseline FFPE tumor tissue. Tumor mutational burden will be 
assessed by next generation sequencing.
9.8.2.2
Characterization of Tumor Immune Microenvironment
The number, frequency, and composition of immune infiltrates in the tumor may be assessed 
before and after exposure to BMS-986408 as monotherapy and in combination with nivolumab or 
nivolumab and ipilimumab and combination with nivolumab and chemotherapy. Formalin-fixed 
paraffin-embedded tissue will be assessed by methodologies including but not limited to IHC, 
and/or multiplex immunofluorescence.
9.8.2.3
Tumor Gene Expression Profiling and TCR Sequencing
FFPE tumor tissue may be evaluated for gene expression and TCR repertoire. Alterations in the 
pattern of global gene expression in tumor samples will be assessed with particular emphasis on 
pathways of immune function. Baseline and on-treatment TCR repertoires will be profiled and 
correlated to response. All samples collected will be stored and may be used for subsequent 
research relevant to tumor immune response.
9.9
Additional Research
This protocol will include residual sample storage for additional research.
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For All sites:
Additional research is required for all study participants, except where prohibited by IRBs/ethics
committees, prohibited by local laws or regulations, or academic/institutional requirements.
Where one or more of these exceptions occurs, participation in the additional research should be 
encouraged but will not be a condition of overall study participation.

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.
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) may 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 15 years after 
the end of the study or the maximum allowed by applicable law.
Transfers of samples by research sponsor to third parties will be subject to the recipient’s 
agreement to establish similar storage procedures.
Samples will be stored in a coded fashion, and no researcher will have access to the key. The key 
is securely held by the Investigator at the clinical site, so there is no direct ability for a researcher 
to connect a sample to a specific individual.
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
Table 9.9-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time points for which residual samples may be retained
PK
All
ADA
All
Peripheral blood
All
Tumor Biopsy
All
Abbreviations: ADA, anti-drug antibodies; PK, pharmacokinetics.
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9.10
Other Assessments
Whole blood, serum, and plasma samples will be collected at the times indicated in Table 9.8-1
for the measurement of DNA, RNA, and protein biomarkers. 
 will be completed 
within 2 minutes (+ 3-minute window) after dosing and at 20 minutes (+ 5-minute window) after 
dosing per Table 2-2 and Table 2-3.
9.11
Health Economics OR Medical Resource Utilization and Health 
Economics
Health economics/medical resource utilization and health economics parameters will not be 
evaluated in this study.
10
STATISTICAL CONSIDERATIONS
10.1
Statistical Hypotheses
There is no formal primary research hypothesis for this study to be statistically tested.
10.2
Sample Size Determination 
The maximum number of participants treated will be approximately 
. The total sample size in 
Part 1 is approximately 
 participants, including approximately 
participants for Group A dose 
escalation, 
 participants each for Groups B and B2 (if evaluated), and 
participants for Group 
C PD cohorts. The total sample size in Part 2 is approximately 
participants, with sample sizes 
of approximately 
participants each for Groups D and E, 
 participants in Group F, and 
 
participants in Group G. The total sample size in Part 3 is approximately 
 participants with
approximately 
 participants for each dose level (up to 
 per indication (up to 
. In Part 3, an 
additional 
 participants may be enrolled in a cohort pending the totality of the data available 
including safety and efficacy. The sample sizes for the study are determined based on the number 
of anticipated dose levels and the number of participants per dose level. Specifically, it is assumed 
that Group A has dose levels of titration with participant per dose level and dose levels with 
per dose level. Additionally, it is assumed that Group B and B2 have 
dose levels with 
participants per dose level. Finally, it is assumed that Group C, D, E, and F have dose levels with 
participants per dose level.
10.3
Analysis Sets
For the purposes of analysis, the following populations are defined:
Population
Description
Enrolled 
All participants who sign informed consent (and are registered into the IRT)
Treated
All participants who received at least 1 dose of study intervention
Response-Evaluable
All participants who receive at least one dose of study intervention, have a 
baseline tumor assessment with measurable disease, and 1 of the following: 
1) at least 1 evaluable on-treatment tumor assessment, 2) clinical progression, 
or 3) death prior to the first on-treatment tumor evaluation
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Population
Description
Pharmacokinetic
All treated participants who have any available concentration-time data 
Evaluable Pharmacokinetic
All participants who have adequate PK profiles or have at least 1 evaluable PK 
parameter
Immunogenicity
All participants who receive nivolumab or ipilimumab who have baseline and 
at least 1 post baseline measurement
Biomarker
All participants who take at least one dose of study treatment and have at least 
one non-missing biomarker assessment, excluding the disqualified 
assessments.
Abbreviations: IRT, interactive response technology; PK, pharmacokinetic.
Unless otherwise specified, the safety analyses will include all treated participants.
10.4
Statistical Analyses
10.4.1
General Considerations
The dose escalation decisions in Part 1 and Part 2 will be guided by 
method. The 
study will start with an accelerated titration approach to limit the number of participants treated 
with sub-therapeutic doses in Part 1, Group A. Compared with standard designs, accelerated 
titration design can greatly reduce the number of undertreated participants without sacrificing 
safety. Once accelerated titration stops, at least  participants will be enrolled per dose level and 
dose escalation decisions will be guided by the 
design to identify the MTD. The 
 
design takes a very simple form, rendering it easy to implement in practice. The dose escalation 
and de-escalation in the 
 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. As an extension to the standard 
further allows 
real-time dose assignment decisions while some participants’ toxicity data are still pending, thus 
provides a practical design to accelerate early phase drug development. When there is no pending 
data, the 
will seamlessly reduce to the 
 design. A 
 dose-escalation 
decision table with a selected target DLT rate of 
, an escalation boundary of 
, and de-
escalation boundary of 
 is presented in 
 
Dose escalation may be stopped prior to reaching an MTD based on review of available safety, 
PK, and pharmacodynamic data and discussions between Sponsor and Investigators. While the 
 will use DLT and safety information only, clinical assessment will take into 
consideration of the totality of available data including PK/pharmacodynamics from all treated 
participants, in assigning the next dose level. The final recommended MTD/maximum 
administered dose/recommended Phase 2 dose will be based on the recommendation from the 
and overall clinical assessment of all available safety, PK, PD, and efficacy data.
10.4.2
Primary Endpoint(s)
Primary endpoints are described in Table 10.4.2-1.
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Table 10.4.2-1:
Primary Endpoints
Primary Endpoint
Description
Timeframe
Incidence of DLTs, AEs, 
SAEs, AEs leading to 
discontinuation, and 
death.
DLT rate by dose level, frequency distribution of treated 
participants with AE using the worst CTC grade. Participants 
will only be counted (1) once at the preferred term level, (2) 
once at the system organ class level, and (3) once in the 
‘total participant’ row at their worst CTC grade, regardless 
of system organ class or PT.
Select safety summaries will be presented separately for the 
monotherapy treatment combination treatment.
For DLTs, until end 
of DLT assessment 
period; Others, until 
end of safety follow-
up period.
Abbreviations: AE, adverse event; CTC, Common Terminology Criteria; DLT, dose limiting toxicity; PT, preferred 
term; SAE, serious adverse event.
10.4.3
Secondary Endpoint(s)
Secondary endpoints are described in Table 10.4.3-1.
Table 10.4.3-1:
Secondary Endpoints
Secondary Endpoint
Description
Timeframe
Summary measures of BMS-986408 PK 
parameters in plasma, such as but not 
limited to, Cmax, Tmax, AUC(0-T) from 
concentration-time data during 
BMS-986408 monotherapy and 
combination treatment with nivolumab or 
nivolumab and ipilimumab.
Summary statistics tabulations by dose: 
geometric means and coefficients of 
variation (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.
Up to the last PK 
sampling timepoint.
ORR and DOR per RECIST v1.1
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.
Up to last tumor 
assessments until 
disease progression 
or death.
Abbreviations: AUC(0-T), area under the concentration-time curve from time 0 to the time of the last quantifiable 
concentration; CI, confidence interval; Cmax, maximum concentration; DOR, duration of response; 
KM, Kaplan-Meier; ORR, objective response rate; PK, pharmacokinetic; RECIST, Response Evaluation Criteria in 
Solid Tumors; Tmax, time of maximum observed concentration.
10.4.4
Exploratory Endpoint(s)
Exploratory PK, biomarker, and efficacy analyses will be described in the statistical analysis plan 
finalized before final database lock. 
Unless specified otherwise, all safety analyses will be performed on all treated participants.
10.4.5
Other Analyses 
The PK analysis and PD analyses, if performed, will be presented separately from the main clinical 
study report. Frequency and percentage of participants reporting each 
 will 
be summarized by timepoint. 
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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
BMS-986408: Investigator’s Brochure Version 2.0. Bristol-Myers Squibb Company; 2023. 
Document Control No. 930168016.
2
BMS-734016: Ipilimumab Investigator’s Brochure Version 26. Bristol-Myers Squibb 
Company; 2023. Document Control No. 930017531.
3
BMS-936558: Nivolumab Investigator’s Brochure Version 22. Bristol-Myers Squibb Co. 
2023. Document Control No. 930038243.
6
BMS-986408: In Vitro Pharmacology (IO00341). Bristol-Myers Squibb Company; 2021. 
Document Control No. 930168970.
10 OPDIVO (nivolumab) US Prescribing Information. Bristol-Myers Squibb Company; 2021.
11 OPDIVO Annex I Summary of Product Characteristics. Bristol-Myers Squibb Company; 
2021.
12 Rizvi NA, Hellmann MD, Brahmer JR, et al. Nivolumab in Combination With Platinum-Based 
Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. 
J Clin Oncol. 2016;34:2969-79.
13 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.
14 Aciphex (rabeprazole sodium). US Prescribing Information. Eisai Inc; 2013.
15 Wei SC, Anang N-A AS, Sharma R, et al. Combination anti-CTLA-4 plus anti-PD-1 
checkpoint blockade utilizes cellular mechanisms partially distinct rom monotherapies. Proc 
Natl Acad Sci USA 2019;116:22699-709.
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16 Hellman MD, Paz-Ares, L, Caro, RB, et al. Nivolumab plus ipilimumab in advanced non-
small-cell lung cancer. N Engl J Med 2019;381:2020-381.
17 Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab versis sunitinib in first-
line treatmnt for advanced renal cell carcinoma: extended follow-up of efficacy and safety 
results from a randomised, controlled, phase 3 trial. Lancet Oncol 2019;20:1370-85.
18 Ferris RL, Licitra L, Fayette F, et al. Nivolumab in patients with recurrent or metastatic 
squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by prior 
cetuximab use. Clin Cancer Res 2019;25:5221-30.
19 Yuan Y, Lin R, Li D, et al. Time-to-event Bayesian Optimal Interval design to accelerate 
Phase 1 clinical trials. Cancer Res 2018;24: 4921-30.
20 Zhou, Y, Lin, R, Kuo, Y, et al. BOIN suite: a software platform to design and implement novel
early phase clinical trials. JCO Clin Cancer Inform 2021;5:91-101.
21 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.
22 Schadendorf D, Hodi SF, Robert C, et al. Pooled analysis of long-term survival data from 
Phase II and Phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin 
Oncol 2015;33:1889-94.
23 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: clinical characteristics
of long-term survivors. Proceedings of the American Association for Cancer Research 
(AACR); 2017 Apr 1-5; Washington, DC, USA.
24 Felip Font E, 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 lung 
cancer (NSCLC). Proceedings of the European Society of Medical Oncology; 2017 Sep 8-12; 
Madrid, Spain. Poster 1301PD.
25 Spigel DR, McLeod M, Hussein MA, et al. Randomized results of continuous vs 1-year fixed
duration in patients with advanced non-small cell lung cancer. Proceedings of the European 
Society of Medical Oncology; 2017 Sep 8-12; Madrid, Spain.
26 YERVOY (ipilimumab) US Prescribing Information. Bristol-Myers Squibb Company; 2021.
27 Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent 
advances in pathophysiology, diagnosis and treatment. Rheumatology 2019;58(1):5-17.
28 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.
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
1L
first-line
ADA
anti-drug antibody
AE
adverse event
AIDS
acquired immune deficiency syndrome
ALP
alkaline phosphatase
ALT
alanine aminotransferase
anti-mCTLA-4 mAb
mouse anti- cytotoxic T-lymphocyte-associated protein 4 monoclonal 
antibody
anti-mPD-1 mAb
mouse anti-programmed cell death-1 monoclonal antibody
AST
aspartate aminotransferase
AUC
area under the concentration-time curve 
AUC(0-T)
area under the concentration-time curve from time 0 to time of last 
quantifiable concentration
AUC(TAU)
area under the concentration-time curve in 1 dosing interval
AxMP
auxiliary medicinal product
BID
twice daily
BMS
Bristol-Myers Squibb
BRAF
B-type Raf proto-oncogene
BSEP
bile salt export pump
C
cycle
Cavg
average serum/plasma concentration
Cavg28
average serum/plasma concentration at Day 28
Cavgss
average serum/plasma concentration at steady-state
CD
cluster of differentiation
Ceoi
observed concentration at the end of infusion
CI
confidence interval
CL
clearance
CLss
steady-state clearance
Cmax
maximum concentration
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Term
Definition
Cmin28
trough concentration at Day 28
CNS
central nervous system
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
coronavirus disease 2019
CPI
checkpoint inhibitor
CR
complete response
CRF
case report form
CT 
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTLA-4
cytotoxic T-lymphocyte-associated protein 4
CV%
% coefficient of variation
D
day
DAG
diacylglycerol
DGK
diacylglycerol kinase
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
ECOG
Eastern Cooperative Oncology Group
eGFR
estimated glomerular filtration rate
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Term
Definition
EOI
end of infusion
EOT
end of treatment
E-R
exposure-response
EU
European Union
FDA
Food and Drug Administration
FFPE
formalin-fixed, paraffin-embedded
FIH
first-in-human
FSH
follicle-stimulating hormone
fT3
free triiodothyronine
fT4
free thyroxine
GLP
Good Laboratory Practice
HBsAg
hepatitis B surface antigen 
HBV
hepatitis B virus 
HCC
hepatocellular carcinoma
hCG
human chorionic gonadotropin
HCV
hepatitis C virus 
HED
human equivalent dose
HIV
human immunodeficiency virus 
HNSCC
squamous cell carcinoma of the head and neck
HR
hazard ratio
IB
Investigator’s Brochure
IC
inclusion criteria
ICF
informed consent form
IEC
Independent Ethics Committee
IF
interferon
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Term
Definition
IgG
immunoglobulin G
IgG4
immunoglobulin G4
IHC
immunohistochemistry
IL
interleukin
IM
intramuscular
IMAE
immune-mediated adverse event
IMP 
investigational medicinal product
IO
immuno-oncology
IP
investigational product
IRB
Institutional Review Board
IRT
interactive response technology
IV
intravenous
IVIG
Intravenous immune globulin
K-M
Kaplan-Meier
LDH
lactate dehydrogenase 
MAP
mean arterial blood pressure
MATE
multidrug and toxin extrusion protein
MRI
magnetic resonance imaging 
mRNA
messenger ribonucleic acid
MRP
multidrug resistance-associated protein
MSS
microsatellite stable
MTD
maximum tolerated dose 
 
NCI
National Cancer Institute
NIMP
non-investigational medicinal product
nivo
nivolumab
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Term
Definition
NOEL
no-observed-effect level
NRAS
neuroblastoma ras viral oncogene homolog
NSCLC
non-small cell lung cancer 
NSQ
non-squamous 
NTCP
sodium taurocholate cotransporting polypeptide
OAT
organic anion transporter
OATP
organic anion transporting polypeptide
OCT
organic cation transporter
ORR
objective response rate
OS
overall survival
 
PCR
polymerase chain reaction
PD
pharmacodynamic
PD-1
programmed death protein-1
PDCT
platinum-doublet chemotherapy
p-DILI
potential drug-induced liver injury 
PD-L1
programmed death ligand 1
PD-L2
programmed death ligand 2
PE
physical examination
PET
positron emission tomography
PFS
progression-free survival
PK
pharmacokinetic(s)
PPI
proton pump inhibitor
PPK
population PK
Q3D
every 3 days
QD
once daily
QTc
corrected QT interval
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Term
Definition
QxW
once every x weeks
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
RP2D
recommended Phase 2 dose(s)
RT-PCR
reverse transcription polymerase chain reaction,
SAE
serious adverse event
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SD
stable disease
SJS
Stevens-Johnson syndrome  
SmPC
Summary of Product Characteristics
SMT
Safety Management Team
SOC
standard of care
STD10
severely toxic dose in 10%
SUSAR
suspected, unexpected serious adverse reaction
T. bili
total bilirubin
T3
triiodothyronine
T4
thyroxine
TCR
T cell receptor
TEN
toxic epidermal necrolysis
T-Halfeff
effective terminal half life
Tmax
time of maximum observed concentration 
TSH
thyroid-stimulating hormone
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Term
Definition
ULN
upper limit of normal
US
United States
USPI
United States Prescribing Information
Vss
steady-state volume of distribution 
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 Regulation 536/2014 for clinical studies

European Medical Device Regulation 2017/745 for clinical device research

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 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 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.

Allow time necessary for participant to inquire about the details of the study.

Obtain an ICF signed and personally dated by participant and by the person who conducted 
the informed consent discussion. 

Include a statement in 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.
The rights, safety, and well-being of the study participants are the most important considerations 
and should prevail over interests of science and society.
BMS COMMITMENT TO DIVERSITY IN CLINICAL TRIALS
The mission of BMS is to transform patients’ lives through science by discovering, developing, 
and delivering innovative medicines that help them prevail over serious diseases. 
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BMS is committed to doing its part to ensure that patients have a fair and just opportunity to 
achieve optimal health outcomes.
BMS is working to improve the recruitment of a diverse participant population with the goal that 
the clinical trial becomes more reflective of the real-world population and the people impacted by 
the diseases studied.
DATA PROTECTION, DATA PRIVACY, AND DATA SECURITY
BMS collects and processes personal data of study participants, patients, health care providers, 
and researchers for biopharmaceutical research and development to advance innovative, high-
quality medicines that address the medical needs of patients. BMS ensures the privacy, protection, 
and confidentiality of such personal data to comply with applicable laws. To achieve these goals, 
BMS has internal policies that indicate measures and controls for processing personal data. BMS 
adheres to these standards to ensure that collection and processing of personal data are limited and 
proportionate to the purpose for which BMS collects such personal data. This purpose is clearly 
and unambiguously notified to the individual at the time of collection of personal data. In the true 
spirit of science, BMS is dedicated to sharing clinical trial information and data with participants, 
medical/research communities, the media, policy makers, and the general public. This is done in a 
manner that safeguards participant privacy and informed consent while respecting the integrity of 
national regulatory systems. Clinical trial data, health-related research, and pharmacovigilance 
activities on key-coded health data transferred by BMS across national borders is done in 
compliance with the relevant data protection laws in the country and GCP requirements.
BMS protects Personal Information with adequate and appropriate security controls as indicated 
under the data protection laws. To align with the recommended security standards, BMS has 
adopted internal security standards and policies to protect personal data at every stage of 
its processing.
To supplement these standards, BMS enters into Clinical Trial Agreements (CTAgs) with 
confidentiality obligations to ensure proper handling and protection of personal data by third 
parties accessing and handling personal data.
BMS takes unauthorized access and disclosure of Personal Information very seriously. BMS has 
adopted the security standards that include National Institute of Standards and Technology 
Cybersecurity Framework for studies in the US. BMS aligns with these standards to continuously 
assess and improve its ability to protect, detect, and respond to cyber attacks and other 
unauthorized attempts to access personal data. These standards also aid in mitigating possible 
adverse effects. Furthermore, BMS Information Technology has defined 6 principles to protect our 
digital resources and information: 

Responsibilities of IT Personnel

Securing the BMS Digital Infrastructure

Identity and Access Management

External Partner Connections

Cyber Threat Detection and Response
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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. 
1) The investigator may need to request previous medical records or transfer records depending 
on the study. Also, current medical records must be available.
2) 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 BMS-986408, nivolumab, and ipilimumab (whether supplied by 
BMS, its vendors, or the site) must substantiate study intervention integrity and traceability from 
receipt, preparation, administration, and through destruction or return. Records must be made 
available for review at the request of BMS/designee or a Health Authority.
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If
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number

amount dispensed to and returned by each 
participant, including unique participant
identifiers

amount transferred to another area/site for 
dispensing or storage

nonstudy disposition (eg, lost, wasted) 

amount destroyed at study site, if applicable

amount returned to BMS

retain samples for 
bioavailability/bioequivalence/biocomparability, 
if applicable 

dates and initials of person responsible for 
Investigational Product 
dispensing/accountability, as per the Delegation 
of Authority Form
Sourced by site and not supplied by BMS 
or 
its 
vendors 
(examples 
include 
Investigational Product sourced from the 
sites stock or commercial supply or a 
specialty pharmacy)
The investigator or designee accepts responsibility 
for documenting traceability and study treatment
integrity in accordance with requirements applicable 
under 
law 
and 
the 
standard 
operating 
procedures/standards of the sourcing pharmacy
BMS or its designee will provide forms to facilitate inventory control if the investigational site 
does not have an established system that meets these requirements.
CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents, or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory test result 
abnormalities that are reported or identified during the study.
For sites using the Sponsor or designee electronic data capture (EDC) tool, eCRFs will be prepared 
for all data collection fields except for fields specific to serious adverse events (SAEs) and 
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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 treatments (those supplied by BMS or a vendor or sourced by the 
investigator), such as partially used study treatment containers, vials, and syringes, may be 
destroyed on site.
If
Then
Study 
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 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)
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).
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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.
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.
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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.) 
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
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study using National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0
(NCI-CTCAE v 5.0)
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An event is defined as “serious” when it meets at least 1 of the predefined outcomes as described 
in the definition of an SAE, NOT when it is rated as severe.
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.
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 to this 
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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:
2
Measurable
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of:

10 mm by CT/MRI scan (scan slice thickness no greater than 5 mm), or ≥2x slice thickness if 
greater than 5mm.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node 
must be 15 mm in short axis when assessed by CT/MRI scan (scan slice thickness recommended 
to be no greater than 5 mm).
Lymph nodes merit special mention since they are normal anatomical structures which may be 
visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
15 mm by CT/MRI scan. Only the short axis of these nodes will contribute to the baseline sum. 
The short axis of the node is the diameter normally used by radiologists to judge if a node is 
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in which 
the image is obtained (for CT scan this is almost always the axial plane; for MRI the plane of 
acquisition may be axial, sagittal or coronal). The smaller of these measures is the short axis. For 
example, an abdominal node which is reported as being 20 mm x 30 mm has a short axis of 20 mm 
and qualifies as a malignant, measurable node. In this example, 20 mm should be recorded as the 
node measurement. All other pathological nodes (those with short axis 10 mm but < 15 mm) 
should be considered non-target lesions. Nodes that have a short axis < 10 mm are considered 
non-pathological and should not be recorded or followed.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
3
Non-Measurable
All other lesions are considered non-measurable, including small lesions (longest diameter 
< 10mm or pathological lymph nodes with 10 to < 15 mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: leptomeningeal 
disease, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques.
Note: Lesions on X-Ray are not to be selected as Target or Non-Target Lesions.
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3.1
Special considerations regarding lesion measurability
3.1.1
Bone lesions

Bone scan, PET scan and plain films are not considered adequate imaging techniques to 
measure bone lesions. However, these techniques can be used to confirm the presence or 
disappearance of bone lesions. 

Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that 
can be evaluated by cross sectional imaging techniques such as CT or MRI can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.

Blastic bone lesions are non-measurable.
4
Baseline Documentation Of ‘Target’ And ‘Non-Target’ Lesions
When more than one measurable lesion is present at baseline all lesions up to a maximum of five 
lesions total (and a maximum of two lesions per organ) representative of all involved organs should 
be identified as target lesions and will be recorded and measured at baseline (this means in 
instances where patients have only one or two organ sites involved a maximum of two and four 
lesions respectively will be recorded).
Note: A maximum of two lesions can be selected per organ system. For example, a maximum of 
two lung lesions can be selected (selected from one lung or one lesion from each). A maximum of 
two lymph nodes can be selected at baseline, as the lymphatic system is considered one organ.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), be 
representative of all involved organs, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion which 
can be measured reproducibly should be selected.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal progression’ 
(more details to follow). In addition, it is possible to record multiple non-target lesions involving 
the same organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’).
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5
RESPONSE CRITERIA
5.1
Evaluation of Target Lesions

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression).

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.

Not Evaluable (NE): If one or more target lesions cannot be measured or adequately assessed 
as either fully resolved or too small to measure (due to missing or poor quality images), and 
the sum of diameters of the remaining measured target lesions (if any) has not increased 
sufficiently to meet Progressive Disease as defined above. 
5.1.1
Special Notes on the Assessment of Target Lesions
5.1.1.1
Lymph nodes
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target lesions, 
the ‘sum’ of lesions may not be zero even if complete response criteria are met, since a normal 
lymph node is defined as having a short axis of < 10 mm. Case report forms or other data collection 
methods may therefore be designed to have target nodal lesions recorded in a separate section 
where, in order to qualify for CR, each node must achieve a short axis < 10 mm. For PR, SD and 
PD, the actual short axis measurement of the nodes is to be included in the sum of target lesions.
5.1.1.2
Target lesions that become ‘too small to measure’
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual 
measurements recorded at each subsequent evaluation, even when very small (eg, 2 mm). 
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline 
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact 
measure and may report them as being ‘too small to measure’. When this occurs it is important 
that a value be recorded on the case report form. If it is the opinion of the radiologist that the lesion 
has likely disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to 
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned
as the reference diameter. (Note: It is less likely that this rule will be used for lymph nodes since 
they usually have a definable size when normal and are frequently surrounded by fat such as in the 
retroperitoneum; however, if a lymph node is believed to be present and is faintly seen but too 
small to measure, a default value of 5 mm should be assigned in this circumstance as well). This 
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default value is derived from the 5 mm CT slice thickness (but should not be changed with varying 
CT slice thickness). The measurement of these lesions is potentially non-reproducible, therefore 
providing this default value will prevent false responses or progressions based upon measurement 
error. To reiterate, however, if the radiologist is able to provide an actual measure, that should be 
recorded, even if it is below 5 mm.
5.1.1.3
Lesions that split or coalesce on treatment
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should be 
added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane between 
them may be maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer separable, the 
vector of the longest diameter in this instance should be the maximal longest diameter for the 
‘coalesced lesion’.
5.2
Evaluation of Non-Target Lesions
This section provides the definitions of the criteria used to determine the tumor response for the 
group of non-target lesions. While some non-target lesions may actually be measurable, they need
not be measured and instead should be assessed only qualitatively at the time points specified in 
the protocol.

Complete Response (CR): Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10mm short axis). 

Non-CR/Non-PD: Persistence of one or more non-target lesion(s)

Progressive Disease (PD): Unequivocal progression of existing non-target lesions.
5.2.1
Special Notes on Assessment of Progression of Non-Target Disease
The concept of progression of non-target disease requires additional explanation as follows:
5.2.1.1
When the patient also has measurable disease
In this setting, to achieve ‘unequivocal progression’ on the basis of the non-target disease, there 
must be an overall level of substantial worsening in non-target disease such that, even in presence 
of SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy A modest ‘increase’ in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression status. Pleural effusions, pericardial 
effusions and ascites will not be followed as target or non-target lesions and will not contribute to 
response or progression. The designation of overall progression solely on the basis of change in 
non-target disease in the face of SD or PR of target disease will therefore be extremely rare.
5.2.1.2
When the patient has only non-measurable disease
This circumstance arises in some trials when it is not a criterion of study entry to have measurable 
disease. The same general concepts apply here as noted above, however, in this instance there is 
no measurable disease assessment to factor into the interpretation of an increase in non-measurable 
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 
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unequivocal progression is to consider if the increase in overall disease burden based on the change 
in non-measurable disease is comparable in magnitude to the increase that would be required to 
declare PD for measurable disease: ie, an increase in tumor burden representing an additional 73% 
increase in ‘volume’ (which is equivalent to a 20% increase diameter in a measurable lesion). 
Examples include, an increase in lymphangitic disease from localized to widespread, or may be 
described as ‘sufficient to require a change in therapy’. If ‘unequivocal progression’ is seen, the 
patient should be considered to have had overall PD at that point. While it would be ideal to have 
objective criteria to apply to non-measurable disease, the very nature of that disease makes it 
impossible to do so; therefore the increase must be substantial.
5.2.2
New Lesions
The appearance of new malignant lesions denotes disease progression; therefore, some comments 
on detection of new lesions are important. There are no specific criteria for the identification of 
new radiographic lesions; however, the finding of a new lesion should be unequivocal: ie, not 
attributable to differences in scanning technique, change in imaging modality or findings thought 
to represent something other than tumor (for example, some ‘new’ bone lesions may be simply 
healing or flare of pre-existing lesions). This is particularly important when the patient’s baseline 
lesions show partial or complete response. For example, necrosis of a liver lesion may be reported 
on a CT scan report as a ‘new’ cystic lesion, which it is not.
NOTE: Fluid collections (pleural effusions, pericardial effusions, and ascites) will not be 
considered new lesions and will not contribute to response or progression. In the event a new fluid 
collection is seen on a post-baseline imaging exam, a comment may be made, but the appearance 
of a new fluid collection alone should not result in an assessment of Progressive Disease (PD). A 
lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the patient 
who has visceral disease at baseline and while on study has a CT or MRI brain ordered which 
reveals metastases. The patient’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline. A lesion identified on Chest X-Ray that was not 
present in prior CT can be considered a new lesion and will result in Progressive Disease (PD).
If a new lesion is equivocal, for example because of its small size, continued follow-up evaluation 
will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. While FDG-PET 
response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly 
possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according 
to the following algorithm:
1) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion.
2) No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at 
follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive 
FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up 
CT scans are needed to determine if there is truly progression occurring at that site (if so, the 
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date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET 
at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the 
basis of the anatomic images, this is not PD.
5.3
Response Assessment
5.3.1
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until 
disease progression or the last response recorded, taking into account any requirement for 
confirmation and censoring rules regarding subsequent therapy. The patient’s best overall response 
assignment will depend on the findings of both target and non-target disease and will also take into 
consideration the appearance of new lesions. Furthermore, depending on the nature of the study 
and the protocol requirements, it may also require confirmatory measurement.
5.3.2
Time Point Response
At each protocol specified time point, a response assessment occurs. Table 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 is to be used. 
Table 1:
Time Point Response: Patients With Target (± Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all 
evaluated
No
PR
SD
Non-PD or not all 
evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes
PD
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease and NE = inevaluable
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Table 2:
Time Point Response: Patients with Non-target Disease Only
Non-Target Lesions
New Lesions
Overall Response
CR
No
CR
Non-CR/non-PD
No
Non-CR/non-PDa
Not all evaluated
No
NE
Unequivocal PD
Yes or No
PD
Any
Yes
PD
CR = complete response, PD = progressive disease and NE = inevaluable
a Non-CR/non-PD is preferred over SD for non-target disease since SD is increasingly used as endpoint for 
assessment of efficacy in some trials so to assign this category when no lesions can be measured is not advised.
5.3.3
Best Overall Response 
Best response determination of complete or partial response requires confirmation: Complete or 
partial responses may be claimed only if the criteria for each are met at a subsequent time point of 
4 weeks (28 days) later. In this circumstance, the best overall response can be interpreted as in 
Table 3. 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 3:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
CR
CR
CR
PR
SD, PD OR PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
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Table 3:
Best Overall Response (Confirmation of CR and PR Required)
Overall Response 
First Time Point
Overall Response 
Subsequent Time Point
Best Overall Response
CR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
PR
NE
SD provided minimum criteria for SD duration met, otherwise, 
NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and 
NE = inevaluable
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best 
response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed 
when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the 
first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR.
5.3.4
Confirmation Scans
Verification of Response: To be assigned a status of CR or PR, changes in tumor measurements 
must be confirmed by consecutive or subsequent repeat assessments that should be performed no 
less than 28 days after the criteria for response are first met. Subsequent documentation of a CR 
may provide confirmation of a previously identified CR even with an intervening NE or PR (eg, 
CR NE CR or CR PR CR). Subsequent documentation of a PR may provide confirmation of a
previously identified PR even with an intervening NE or SD (eg, PR NE PR or PR SD PR). 
However, only one (1) intervening time point will be allowed between PR/CRs for confirmation.
Verification of Progression: Progression of disease should be verified in cases where progression 
is equivocal. If repeat scans confirm PD, then progression should be declared using the date of the 
initial scan. If repeat scans do not confirm PD, then the subject is considered to not have 
progressive disease.
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
EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMACE 
STATUS
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APPENDIX 7
MANAGEMENT ALGORITHMS FOR STUDIES UNDER CTCAE 
VERSION 5.0
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APPENDIX 13
COUNTRY- AND REGION-SPECIFIC REQUIRMENTS
Country/Region
Requirement
All countries within the European 
Union or European Economic Area 
Persons under legal protection who require a legally 
authorized representative are prohibited (See Section 
6.1)
France
Only persons affiliated to social security can be 
included (see Section 6.1)
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APPENDIX 14
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for Protocol Amendment 03, 21-Apr-2023
The main purpose of this amendment is to add clarification around 
 exclusionary 
criteria, update 
 exclusionary criteria, add guidance regarding 
management, and to update the duration of contraception for 
males and females.
Revisions apply to future participants enrolled in the study and, where applicable, to all 
participants currently enrolled.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & 
Title
Description of Change
Brief Rationale
Table 2-2 On Treatment 
Procedural Outline (Part 
1, Groups A, B, and C)

Specified that electrocardiograms (ECGs) 
should be predose and prior to blood 
draws.
Updated monitoring, exclusion 
criteria and dose modification 
based on potential 
 
 prolongation. 
Table 2-3:
On Treatment Procedural 
Outline (Part 2, Groups D 
and E)

For Part 2, added ECG timepoint on Cycle 
1 Day 1 at 6 hours after dosing 
BMS-986408.
Section 6.2:
Exclusion Criteria
Section 6.1:
Inclusion Criteria
Added cross-reference to new Appendix 13, for 
country- and region-specific requirements 
(#1a).
Clarification added that persons
under legal protection in EU are 
prohibited.
Appendix 13:
Country- and 
Region-specific 
Requirements
Added requirement for countries within the 
European Union or European Economic Area 
to prohibit inclusion of persons requiring a 
legally authorized representative and added 
requirement for France that only persons 
affiliated with social security can be included.
France-specific inclusion criteria 
regarding social security was 
added per 
request.
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 03
Section Number & 
Title
Description of Change
Brief Rationale
Section 6.1:
Inclusion Criteria
Section 9.2.5 Pregnancy

For female participants receiving 
BMS-986408, extended length of time 
during which donation of eggs is not 
allowed (#4a).

For male participants receiving 
BMS-986408, extended length of time for: 
use of condoms, refraining from sperm 
donation, abstaining or using a condom 
with pregnant/breastfeeding partners, and 
use of effective contraception by their 
female partners (#4b).

In Pregnancy section, extended the length 
of time for notifying BMS of pregnancy at 
the time of study exposure or of penile 
intercourse without a condom.
The current non-GLP 
genotoxicity package indicates 
that BMS-986408 is not 
genotoxic; however, given the 
potential for genotoxicity without 
a GLP genotoxicity package, the 
duration of contraception was 
aligned for potential genotoxicity.
Section 6.2:
Exclusion Criteria

Added details for uncontrolled 
hypertension (#1j[x] deleted and marked as 
Not Applicable; new #1j[xii] added).

Added laboratory test findings for 
electrolyte imbalances (#4[l]).
Clarifications.
Section 6.2:
Exclusion Criteria

Added exclusions for history of 
 
 (#1s) and for chronic active 
Given potential for 
 with 
immunotherapy, updated the 
exclusion criteria and added 
management guidelines.
Section 7.4.3:

Added management of effective treatment 
of 
.
Section 7.4.4:
For Grade 3 non-hematological toxicity, 
clarified “radiographic” manifestations of 
pancreatitis.
Clarification of dose-limiting 
toxicity criteria regarding 
increases in amylase or lipase.
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Overall Rationale for Protocol Amendment 02, 02-Dec-2022
The purpose of this amendment is to remove severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) serology requirements, add language to indicate the use of 2 BMS-986408 
 
add an exploratory biomarker collection to be 
correlated with clinical outcomes, add a 
 for BMS-986408 when 
administered 
. Several other changes, as noted below, were made to improve clarity 
and readability.
Revisions apply to future participants enrolled in the study and, where applicable, to all 
participants currently enrolled.
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Title Page

Updated the name and contact 
information for the clinical 
scientist.

Added EU CTR study number.

Updated 
due 
to 
administrative changes.
Protocol Summary

Updated the protocol summary 
to match the relevant protocol 
revisions.

Updated to reflect changes 
in the protocol body as 
summarized below.
Table 2-1: Screening Procedural 
Outline (CA099003)
Table 2-2: On Treatment Procedural 
Outline (Part 1, Groups A, B, and C)
Table 2-3: On Treatment Procedural
Outline (Part 2, Groups D and E) 
(Renamed)
Table 2-4: Follow-up Procedural 
Outline (CA099003) (Renumbered)
Section 3.3: Benefit/Risk Assessment
Table 4-1: Objectives and Endpoints
Table 9.4.4-1: Clinical Laboratory 
Assessments
Table 9.8-1: Biomarker Sampling 
Schedule for Part 1, Groups A and B 
(Monotherapy Cohorts)
Table 9.8-2: Biomarker Sampling 
Schedule for Part 1, Group C 
(Monotherapy Cohort) and Part 2, 
Groups D (Combination Cohort with 
Nivolumab) and E (Combination 
Cohort with Nivolumab and 
Ipilimumab) (Renamed)
Section 9.10: Other Assessments

Removed 
severe 
acute 
respiratory 
syndrome 
coronavirus 2 (SARS-CoV-2) 
serology language.

Based on the significant 
advancements 
in 
understanding 
SARS-CoV-2, 
available 
treatment 
options, 
including 
monoclonal 
antibodies, and effective 
vaccination, the collection 
of SARS-CoV-2 serologies 
are no longer warranted.
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Table 2-1: Screening Procedural 
Outline (CA099003)

Added 
 to screening 
visit procedures.


Combined all adverse events to 
one cell within table.

Updated to align with the 
rest of the document.


Combined for improved 
clarity.
Table 2-2: On Treatment Procedural 
Outline (Part 1, Groups A, B, and C)

Combined all adverse events to 
one cell within table.

Added collection window for 
clinical laboratory assessments.

Added “includes plasma and 
urine samples” to PK collection 
notes in schedule of activities 
for Part 1, Groups A, B, and C.

Added 
BMS-986408 
 
 
and Cycle 3 Day 1, under new 
table 
subsection 
Other 
Assessments.

Combined for improved
clarity.

Collection window added 
for 
clinical 
laboratory 
assessments to allow for 
flexibility 
given 
lab 
turnaround time.

Added language to clarify 
that Part 1 monotherapy PK 
collections 
will 
include 
both plasma and urine 
samples.

The 
palatability 
of 
BMS-986408 administered 
 will be 
assessed. Results will be 
summarized by timepoint.
Table 2-2: On Treatment Procedural 
Outline (Part 1, Groups A, B, and C)
Table 2-3: On Treatment Procedural 
Outline (Part 2, Groups D and E) 
(Renamed)
Section 5.1: Overall Design
Table 7.1-1: Study Intervention(s) 
Administered (Renamed)

Added 
language 
regarding 
BMS-986408 Formulation 1 
and Formulation 2.

Clarification that this study 
will include 2 BMS-986408 
tablet 
formulations 
(Formulation 
1 
and 
Formulation 2) to be used 
throughout study conduct.
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Table 2-3: On Treatment Procedural 
Outline (Part 2, Groups D and E)
(Renamed)

Table 
2-3: 
On 
Treatment 
Procedural Outline (Part 2, 
Group D) was modified to 
incorporate the schedule for 
Part 2 Group E from Table 2-4: 
On 
Treatment 
Procedural 
Outline (Part 2, Group E).

Added Cycle 1 Day 2 visit for 
Part 2, Groups D and E.

Combined all adverse events to 
one cell within table.

Indicated that EOT biopsy is 
optional at the discretion of the 
Investigator and/or participant. 

Added collection window for
clinical laboratory assessments.

Added 
BMS-986408 
 
for Cycle 1 Day 1, 
and Cycle 3 Day 1, under new 
table 
subsection 
Other 
Assessments.

Tables were combined for 
conciseness and to increase 
readability.

Cycle 1 Day 2 visit was 
inadvertently excluded.

Updated 
for 
improved 
clarity.


Collection window added 
for 
clinical 
laboratory 
assessments to allow for 
flexibility 
given 
lab 
turnaround time.

The 
palatability 
of 
BMS-986408 administered 
 will be 
assessed. Results will be 
summarized by timepoint.
Table 4-1: Objectives and Endpoints
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Table 4-1: Objectives and Endpoints
Table 9.8-2: Biomarker Sampling 
Schedule for Part 1, Group C 
(Monotherapy Cohort) and Part 2, 
Groups D (Combination Cohort with 
Nivolumab) and E (Combination 
Cohort with Nivolumab and 
Ipilimumab (Renamed)
Section 9.8.1: Peripheral Biomarkers

Added exploratory biomarker, 
collection of soluble analytes, 
for Part 1, Group C, and Part 2, 
Groups D and E at the following 
timepoints: 
C1D1 
predose, 
C3D1, C5D1, and on complete 
response.

Soluble analytes will be 
measured 
in 
Part 
1, 
Group C, 
and 
Part 
2, 
Groups D and E; changes in 
soluble analytes will be 
correlated 
with 
clinical 
outcomes 
and 
used to 
investigate 
pharmacodynamic effects.
Section 5.1: Overall Design
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SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 5.1.2: Treatment Period

Study treatment start language 
was moved from Section 7.1.2 
to Section 5.1.2.

Modified language for elements 
captured in the participant diary 
via the removal of ‘symptoms, 
concomitant medications taken 
for the symptoms as well as 
daily’.

Language 
was 
inadvertently 
placed 
in 
Section 7.1.2.

Updated to align with 
elements 
captured 
on 
participant 
diary 
intake 
form.
Section 6.1: Inclusion Criteria

Removed language referring to 
legally 
acceptable 
representative 
in 
Inclusion 
Criterion (IC) 1) a).

Added “CPI therapy does not 
have to be the most recent prior 
line therapy” to IC 2) e).

Added a new IC: Eastern 
Cooperative Oncology Group 
(ECOG) performance status 0 or 
1, IC 2) g).

Legally 
acceptable 
representatives will not be 
utilized in this study; this 
language was inadvertently 
included.

Added for clarification.

To 
ensure 
participants’ 
ECOG status is acceptable 
for enrollment into the trial. 
Section 6.2: Exclusion Criteria

Exclusion Criterion 1) j) ix) for 
hypertension was revised to be 
“not applicable per Protocol 
Amendment 02” and a new 
criterion 
for 
uncontrolled 
hypertension was added as 
exclusion criteria 1) j) x) 

Revised to align with target 
patient 
population 
for 
enrollment purposes. 
Section 7.1.1: BMS-986408 Dosing

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 
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Date: 11-Dec-2023
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5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Table 7.1: Study Intervention(s) for 
CA099003 (Renamed)
Table 7.1-1: Study Intervention(s) 
Administered (Renamed)
Appendix 2: Return of Study 
Intervention (Renamed)
Appendix 2: Study and Site Closure 
(Renamed)

Renamed table titles.

Renamed section titles.

Renamed to be consistent 
with section name and 
protocol model document.
Section 7.7.2.2: Palliative Local 
Therapy (New Section)

Added language/guidance for 
palliative local therapy as a new 
section.

Added to provide guidance 
for concomitant palliative 
local therapy.
Section 8.1.1: Treatment Beyond 
Disease Progression 

Updated section to refer to all 
study interventions. 

Language 
inadvertently 
referred to nivolumab only.
Section 9.2.3: Follow-up of AEs and 
SAEs

Updated statement for following 
SAEs until resolution.

Updated to align with rest 
of protocol language. 
Table 9.4.4-1: Clinical Laboratory 
Assessments

Removed hepatitis B virus 
"HBV" 
from 
serology 
assessments.

Updated 
thyroid-stimulating 
hormone (TSH) language to 
include “Day 1 of each cycle on 
treatment and EOT”.

Updated Urinalysis language to 
include “ per Section 2”

Hepatitis B surface antigen 
(HBsAG) is a marker of 
HBV; HBV language was 
inadvertently included.

Updated 
for 
improved 
clarity. 

Updated 
for 
improved 
clarity.
Section 9.5: Pharmacokinetics

Indicated 
details 
for 
 
 to be assessed on
specific day and time periods. 
Assessment 
will 
include 
concentration of BMS-986408 
 within the 
collected 
 samples.

Language added to align 
with rest of protocol. 
Table 9.5-4: Pharmacokinetic and 
Immunogenicity Sampling Schedule 
for Part 2, Group E (Combination 
Cohort with Nivolumab and 
Ipilimumab)

Removed ipilimumab Cycle 2 
Day 1 (C2D1) end of infusion 
(EOI) timepoint.

Ipilimumab should not have 
an EOI time point on C2D1 
as dosing schedule is once 
every 8 weeks (Q8W).
Section 9.8: Biomarkers

Removed “peripheral blood and 
tumor” specific language from 
collection statement.

Removed, 
since 
tumor 
samples are not collected 
for Groups A and B.
Protocol Amendment No.: 04
Date: 11-Dec-2023
225
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Table 9.8-1: Biomarker Sampling 
Schedule for Part 1, Groups A and B 
(Monotherapy Cohorts)

Added archival tumor tissue 
collection at screening within 
the 
table, 
and 
details 
of 
providing archival tumor tissue 
as optional, was denoted in 
footnote a.

Added 
to 
align 
with 
language in 
Section 
2 
schedule of activities. 
Section 9.8.1: Peripheral Biomarkers

Indicated that blood samples 
may be assessed for presence or 
absence of soluble analytes.  

Updated to align with 
addition 
of 
exploratory 
biomarker. 
Section 9.8.1.4: 
 

Updated technique used for 
preserving 
 
 
 
from “cryopreserved” to ”flash 
frozen”. 

Updated to align with 
laboratory manual.
Section 9.8.1.5: Measurement of 
Soluble Analytes (New Section)

Added 
new 
section 
for 
measurement 
of 
soluble 
analytes in plasma.

Soluble analytes will be 
measured 
in 
Part 
1, 
Group C, 
and 
Part 
2, 
Groups D and E; changes in 
soluble analytes will be 
correlated 
with 
clinical 
outcomes 
and 
used to 
investigate 
pharmacodynamic effects.
Section 9.8.2: Tumor-based 
Biomarkers

Fresh biopsy collection is now 
optional for Part 1, Groups A 
and B.

Language added to allow 
for 
flexibility 
regarding 
biopsy collection.
Table 9.8-2: Biomarker Sampling 
Schedule for Part 1, Group C 
(Monotherapy Cohort) and Part 2, 
Groups D (Combination Cohort with 
Nivolumab) and E (Combination 
Cohort with Nivolumab and 
Ipilimumab) (Renamed)

Table 
9.8.2: 
Biomarker 
Sampling Schedule for Part 1, 
Group C (Monotherapy cohort) 
and 
Part 
2, 
Group 
D 
(Combination 
Cohort 
with 
Nivolumab) was modified to 
incorporate the schedule for 
Part 2 Group E from Table 
9.8.3:
Biomarker 
Sampling 
Schedule for Part 2, Group E 
(Combination 
Cohort 
with 
Nivolumab and Ipilimumab).

Renamed Table to include the 
Group E Combination Cohort 
with 
Nivolumab 
and 
Ipilimumab).

Tables were combined for 
conciseness and to increase 
readability.
Protocol Amendment No.: 04
Date: 11-Dec-2023
226
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF CHANGES FOR PROTOCOL AMENDMENT 02
Section Number & Title
Description of Change
Brief Rationale
Section 9.10: Other Assessments

Updated language to mention 
tissue collections in Part 1, 
Group C, and Part 2, Groups D 
and E.

Included 
details 
for 
 
 to be completed 
within 2 minutes and 20 minutes 
upon dosing on Cycle1 Day 1 
and Cycle 3 Day 1
with 
 
BMS-986408 
.

Updated for clarification. 

The 
palatability 
of 
BMS-986408 administered 
 will be 
assessed. Results will be 
summarized by timepoint.
Section 10.4.1: General Considerations

Updated 
details 
for 
dose 
escalation decisions in Part 1 
and Part 2 of the study.

Sentence 
revised 
for 
improved clarity.
Section 10.4.5: Other Analyses

Added assessment technique 
details for participant’s 
 
 reporting.

The 
palatability 
of 
BMS-986408 administered 
 will be 
assessed. Results will be 
summarized by timepoint.
All

Minor 
formatting 
and 
typographical corrections.

Minor; therefore, they have 
not been summarized.
Protocol Amendment No.: 04
Date: 11-Dec-2023
227
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
Overall Rationale for Protocol Amendment 01: 25-Mar-2022
The purpose of this amendment is, 
 
to modify dose-limiting toxicity criteria, to align the discontinuation criteria for subjects with 
elevations in liver function laboratory values with current FDA guidance,
. In 
addition, minor edits were made to the Schedule of Activities and pharmacokinetics (PK) section 
to more accurately reflect the planned analysis.
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Title Page
Updated name and contact 
information for clinical trial 
physician.
Administrative
Section 2: 
Schedule of 
Activities
Removed pharmacodynamic blood, 
serum, and plasma sampling from 
Table 2-1 (Screening) 
To align with sampling schedules in 
Section 9.8 Biomarkers
Added optional biopsy collection at 
end of treatment in Table 2-2 (Part 
C), Table 2-3 (Part D), and Table 2-
4 (Part E)
To align with Table 9.8-2 9 (Parts C 
and D) and Table 9.8-3 (Part E)
Reversed the order in which PK 
sampling and ECGs should occur if 
multiple procedures are required at 
the same time point.
For operational efficiency.
Section 6.1: 
Inclusion 
Criteria
Modified IC 4 a) v) (2) first sub-
bullet as follows:
Original:
At least 14 days (or 5 half lives, 
once established, whichever is 
shorter)
Revised:
At least 14 days (or 5 half lives, 
once established)
For consistency with language in the 
rest of the document.
Protocol Amendment No.: 04
Date: 11-Dec-2023
228
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 6.1: 
Inclusion 
Criteria
Removed 4 b) i)
Modified 4 b) ii) [renumbered 4 b 
i)] as follows:
Original:
Male participants will be 
required...
Revised:
Male participants, including 
azoospermic males, will be 
required...
To remove redundancy.
Protocol Amendment No.: 04
Date: 11-Dec-2023
229
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
To align with FDA guidance on 
evaluation 
 
Section 7.4.2: 
Criteria to 
Resume 
Treatment
Added instruction for Part 2 Group 
E that decisions to eliminate any 
component of the assigned study 
regiment must be discussed with 
and approved by the medical 
monitor.
To ensure appropriate discontinuation 
of combination study therapy.
Protocol Amendment No.: 04
Date: 11-Dec-2023
230
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v

Clinical Protocol
CA099003
BMS-986408
DGKα/ζ Inhibitor
SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 01
Section 
Number & 
Title
Description of Change
Brief Rationale
Section 9.5: 
Pharmaco-
kinetics
Made the following changes to 
Table 9.5-1:

Removed AUC (INF)

Replaced T-Half with T-Halfeff

Removed Vss/F

Modified definition of %UR

Added Total UR

Added footnote
Sample collection at 24 h post dose 
does not permit calculation of AUC 
(INF), T-Half, or Vss/F.
Modified definition of UR and added 
footnote for clarity.
Added Total UR for completeness of 
analysis.
Section 9.8: 
Biomarkers
Created separate columns in Table 
9.8-2 and Table 9.8-3 for collection 
of whole blood for RNASeq and 
whole blood for TCRSeq
For clarity, as 2 separate samples are 
required.
Section 10.3: 
Analysis Sets
Added Evaluable PK population
For completeness of analysis.
Appendix 2: 
Study 
Governance 
Considerations
Added new sections on BMS 
Commitment to Diversity in 
Clinical Trials and Data Protection, 
Data Privacy, and Data Security
To align with BMS commitment to 
diversity in clinical trials and to 
comply with EU-CTR requirements 
on data protection.
All
Minor typographical or editorial 
corrections
Minor and therefore have not been 
summarized.
Protocol Amendment No.: 04
Date: 11-Dec-2023
231
5.0
Approved
930176449
5.0
v
Approved
1.0
v
Approved
1.0
v