Clinical trial NCT02737475
Conditions: Advanced Cancer
Sponsor: Bristol-Myers Squibb
Start date: 2016-06-17; Completion date: 2020-11-02
Enrollment: 166 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to determine the safety and tumor-shrinking ability of experimental medication BMS-986178, when given by itself or in combination with Nivolumab and/or Ipilimumab, in participants with solid cancers that are advanced or have spread.

Detailed description:

Arms: arm 1: * BMS-986178 at specified doses at specified intervals
* Enrollment is closed for this arm arm 2: * BMS-986178 in combination with Nivolumab at specified doses at specified intervals
* Enrollment is closed for this arm arm 3: * BMS-986178 in combination with Ipilimumab at specified doses at specified intervals
* Enrollment is closed for this arm arm 4: * BMS-986178/Nivolumab at specified doses at specified intervals
* Enrollment is closed for this arm arm 5: * BMS-986178/Ipilimumab at specified doses at specified intervals
* Enrollment is closed for this arm arm 6: * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
* Enrollment is closed for this arm arm 7: * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
* Enrollment is closed for this arm arm 8: * BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
* Enrollment is closed for this arm arm 9: * BMS-986178/Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 1) at specified doses at specified intervals OR Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 2) at specified doses at specified intervals
* Enrollment is open for this arm \[Tumor type triple negative breast cancer (TNBC)\]
Interventions: intervention 1: BMS-986178 intervention 2: Nivolumab intervention 3: Ipilimumab intervention 4: Tetanus vaccine intervention 5: DPV-001 vaccine intervention 6: Cyclophosphamide
Intervention descriptions: intervention 1: Specified dose on specified days intervention 2: Specified dose on specified days intervention 3: Specified dose on specified days intervention 4: Specified dose on specified days intervention 5: DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days intervention 6: Specified dose on specified days

Protocol documents:
Prot_000.pdf: 


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Revised Protocol No.: 06
Date: 08-Feb-2019
2
to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a copy 
of this revised protocol to all study personnel under your supervision, and archive the previous 
versions.
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Clinical Protocol
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BMS-986178
anti-OX40 mAb
Revised Protocol No.: 06
Date: 08-Feb-2019
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 06
08-Feb-2019
To remove retreatment and Survival/Response FU visits for subjects in 
Part 1-8.
To remove certain PK/PD samples
Revised 
Protocol 05
11-Dec-2017
Incorporates Administrative Letters 04, 05, 06, and 07 and the following:
•
Addition of Part 8
•
Update of Appendix 1
•
Update schedule of assessments
•
Update of address
•
Typographical errors were corrected, and edits were made for 
consistency and clarity
Administrative 
Letter 07
19-Oct-2017
Clarify that if subjects continue for additional cycles, past cycle 4, all 
study drugs will continue for all cycles in Parts 7A and 7B in Sections 
3.1.4.2 and 3.1.5.8 and acknowledge the ommission of the word 
‘Beyond’ in Table 5.1-6
Administrative 
Letter 06
11-Jul-2017
Correction of typographical errors in Sections 5.1 and 5.5.1
Administrative 
Letter 05
03-May-2017
Correction of typographical error in Section 3.1.6
Administrative 
Letter 04
02-May-2017
Correction of typographical error in Section 3.1.6
Revised 
Protocol 04
04-Apr-2017
Incorporates Amendment 04 and Administrative Letters 02 and 03
Amendment 04
04-Apr-2017
The amendment includes the following:
•
Addition of Parts 4, 5, 6, and 7
•
Update of study title
•
•
•
Update of study design and study visit schematic
•
Update of inclusion and exclusion criteria to include the new parts and 
clarify the maximum number of prior treatments allowed
•
Update of study drug dosing and method of assigning subjects
•
Update of dose delay language and addition of criteria for resuming 
treatment in subjects with an infusion reaction
•
Update/addition of tables for treatment procedures, pharmacokinetic 
and anti-drug antibody sampling schedule, and pharmacodynamic/
biomarker sampling schedule
•
Update of sample size information to include the new parts
•
Update of Appendix 1 to include statistical methods for the new parts
•
Typographical errors were corrected, and edits were made for 
consistency and clarity.
Administrative 
16-Dec-2016
Change in Study Director/Medical Monitor address
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Revised Protocol No.: 06
Date: 08-Feb-2019
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Document
Date of Issue
Summary of Change
Letter 03
Administrative 
Letter 02
12-Dec-2016
Correction of typographical error in Section 3.1.3.6, first paragraph, first 
sentence
Revised 
Protocol 03
23-Nov-2016
Incorporates Amendment 03 and Administrative Letter 01
Amendment 03
23-Nov-2016
The amendment includes the following:
•
Removal of Part 1B
•
Addition of Part 2D, 2E, 3C and Part 2A cohort dose -1
•
Change to have imaging as central read
•
Add text to allow for intermediate and lower doses in escalation
•
Included text to add potentially more than 1 dose at RP2D
•
Updated versions numbers for current IB’s.
•
Updating to the new PMD for WOCBP Section
•
Require fresh tumor biopsy from all subjects
•
Additional sample to be collected in combination cohorts for RO
•
Update to not require archived tumor biopsies
•
Updated Statistical Analysis section 
•
Typographical errors were corrected, and clarifications were made for 
consistency.
Administrative 
Letter 01
14-Jun-2016
Correction of typographical error in Section 3.3.1, inclusion criterion
10(g) and Table 5.1-1, Screening Procedure Outline, complete blood 
count (CBC) with differential
Revised 
Protocol 02
08-Jun-2016
Incorporates Amendment 02
Amendment 02
08-Jun-2016
The purpose of this amendment is to address comments received from 
Health Authorities.
The amendment includes the following:
•
Change the definition for “Related AE’s” and “Not Related AE’s”.
•
Update prior therapy inclusion criteria for dose escalation subjects.
•
Remove timeframe from hematologic DLT grade 3 febrile 
neutropenia.
•
Change to have CBC with differential processed through LLDS.
•
Add new model document language for Additional Research 
Collection and Imaging scans.
•
Typographical errors were corrected, and clarifications were made for 
consistency.
Revised 
Protocol 01
26-Apr-2016
Incorporates Amendment 01
Amendment 01
26-Apr-2016
The purpose of this amendment is to address comments received from 
Health Authorities. The amendment includes the following:
•
The timing of the initiation of combination therapy dose escalation 
cohorts was revised, a sentinel subject was added to all dose cohorts, 
Parts 1B and 2B were removed and the subsequent study parts were 
renamed (Part 1C to Part 1B, Part 2C to Part 2B, and Part 2D to Part 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Revised Protocol No.: 06
Date: 08-Feb-2019
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Document
Date of Issue
Summary of Change
2C), DLT period across the study (28 days) was made uniform, the 
post-infusion observation period was extended to 4 hours, 
contraceptive requirements were updated, lipase and amylase ≤ 
1.5×ULN were removed as criteria for adequate organ function, DLT 
criteria were revised, a timepoint was added for safety monitoring, the 
rationale for use of blood and tumor tissue in biomarker studies was 
clarified, prior therapy requirements for dose expansion cohorts were 
updated, and BLRM language was clarified. 
•
Typographical errors were corrected, and clarifications were made for 
consistency.
Original 
Protocol
18-Feb-2016
Not applicable
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 06
Section Number & 
Title
Description of Change
3.1.6, Study Schedule
Deleted references to Response 
Follow-up and Survival Follow-up 
periods.
Figure 3.1.6-1: Study Visit 
Schematic
Deleted references to Response 
Follow-up and Survival Follow-up 
periods as well as to retreatment 
options for all parts.
3.1.6.4, Survival Follow-up
Deleted entire section.
3.1.6.5, Response Follow-
up
Deleted entire section.
3.1.7, Treatment with 
Additional Cycles
Deleted reference to retreatment 
options.
3.1.9, Retreatment during 
Response Follow-Up
Deleted entire section.
3.4.1. Prohibited and/or 
Restricted Treatments
Deleted reference to the survival 
follow-up period.
3.5.1.2, Assessment 
Schedule for Subjects with 
Post-progression Treatment
Deleted reference to Retreatment 
Table 5.1-9.
3.6, Post-study Drug 
Follow-up
Deleted references to Response 
Follow-up and Survival Follow-up 
periods.
4.5.5.1, Criteria to resume 
treatment in subjects with a 
dose delay.
Clarified bullet regarding resumption 
of treatment after grade 1 
pneumonitis.
Revised Protocol No.: 06
Date: 08-Feb-2019
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CA012004
BMS-986178
anti-OX40 mAb
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 06
Section Number & 
Title
Description of Change
5.1, Flow Chart/Time and 
Events Schedule
Table 5.1-2, Table 5.1-3, 
Table 5.1-4, Table 5.1-5, 
Table 5.1-6, Table 5.1-7, 
Table 5.1-8, Table 5.1-9.
Deleted reference to retreatment, 
including references to retreatment 
PK and Biomarker tables (Table 
5.5.1-3, Table 5.5.1-5, Table 5.5.1-7, 
Table 5.5.1-9, and Table 5.6-6) in 
Table 5.1-2 through Table 5.1-8.
Deleted Retreatment Table 5.1-9.
5.3, Safety Assessments
Deleted reference to Retreatment 
Table 5.1-9.
5.3.2, Laboratory Test 
Assessments
Deleted reference to retreatment 
period.
5.4, Efficacy Assessments
Added part of sentence: “then every 
12 weeks during the Response 
Follow-up phases (for subjects who 
already have data collected)”, to keep 
consistency with Synopsis.
5.5, Pharmacokinetic 
Assessments
Deleted references to retreatment PK 
tables (Table 5.5.1-3, Table 5.5.1-5, 
Table 5.5.1-7, and Table 5.5.1-9).
5.5.1, Pharmacokinetics and 
Immunogenicity Collection 
and Processing
Deleted references to retreatment PK 
tables (Table 5.5.1-3, Table 5.5.1-5, 
Table 5.5.1-7, and Table 5.5.1-9).
Table 5.5.1-1, Table 5.5.1-2, 
Table 5.5.1-4, Table 5.5.1-6, 
Table 5.5.1-8, and Table 
5.5.1-10
Deleted all assessments beginning 
with Cycle 5 including follow-up 
assessment (retained EOT 
assessments).
Table 5.5.1-3, Table 5.5.1-5, 
Table 5.5.1-7, and Table 
5.5.1-9
Deleted entire retreatment tables.
5.6, Biomarker Assessments
Deleted reference to retreatment, 
Biomarker table (Table 5.6-6).
Table 5.6-1, Table 5.6-2, 
and Table 5.6-3
Deleted all assessments beginning 
with Cycle 5 (retained EOT 
assessments).
Table 5.6-6
Deleted entire retreatment table.
5.7.1.2, Whole Blood Gene 
Expression
Deleted reference to retreatment, 
Biomarker table (Table 5.6-6).
5.7.1.3, Whole Blood 
Immune Assay
Deleted reference to retreatment, 
Biomarker table (Table 5.6-6).
5.7.1.4, Serum and Plasma 
Factors
Deleted reference to retreatment, 
Biomarker table (Table 5.6-6).
Revised Protocol No.: 06
Date: 08-Feb-2019
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CA012004
BMS-986178
anti-OX40 mAb
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 06
Section Number & 
Title
Description of Change
5.7.2.1, Tissue Biopsies 
from All Subjects
Deleted reference to retreatment, 
Biomarker table (Table 5.6-6).
8.3.2.1, Efficacy
Added part of sentence: “then every 
12 weeks during the Response 
Follow-up phases (for subjects who 
already have data collected)”, to keep 
consistency with Synopsis.
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Date: 08-Feb-2019
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CA012004
BMS-986178
anti-OX40 mAb
Figure -1:
Study Design Schematic (Parts 1 to 8)
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Clinical Protocol
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BMS-986178
anti-OX40 mAb
Dose levels are specific for each part. Dose expansion will begin only after MTD/RP2D determination in the
corresponding dose escalation phases of the study.
Abbreviations: MTD = maximum tolerated dose; RP2D = recommended Phase 2 dose.
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Date: 08-Feb-2019
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BMS-986178
anti-OX40 mAb
Summary of Study Design: 
Dose Escalation (Parts 1A, 2A, and 3A):
The dose escalation part of the study will evaluate the safety and tolerability of BMS-986178 alone or in combination 
with nivolumab or ipilimumab in subjects with advanced solid tumors.
The initial dose level of BMS-986178 planned for this study is 20 mg. Dose escalation decisions for subsequent doses 
will be based on DLTs using a Bayesian Logistic Regression Method (BLRM; for BMS-986178 monotherapy) or a 
BLRM (-Copula) model (for BMS-986178 in combination with nivolumab and/or ipilimumab). The DLT period is 
28 days for both monotherapy and combination therapy dose escalation parts. The DLT rate will be determined based 
on the incidence, severity, and duration of AEs that occur within the DLT period and for which no alternative cause 
can be identified. Dose selection for the next monotherapy cohort/dose level will take into account the BLRM (-
Copula) recommendation in conjunction with the clinical recommendation and all available PK, PD, immunogenicity, 
and clinical and laboratory safety data from all treated subjects. Starting dose selection of BMS-986178 for Part 2A 
will be determined using data available from Part 1A, including clinical and laboratory safety assessments, PK/PD 
data, immunogenicity, and modeling recommendation within Bayesian modeling framework by incorporating 
single-agent toxicity profiles of both BMS-986178 (Part 1A) and nivolumab (CA209-003). Starting dose selection of
BMS-986178 for Part 3A will be determined using data available from Parts 1A and 2A, including clinical and 
laboratory safety assessments, PK/PD data, and modeling recommendation within Bayesian modeling framework by 
incorporating single-agent toxicity profiles of both BMS-986178 (Part 1A) and ipilimumab (CA184-022). The final 
dose escalation decision will be made after discussion and agreement between the investigators and the BMS Medical 
Monitor. Actual doses can be modified per the BLRM (-Copula) but will not exceed doubling of the previously tested 
doses. Escalation by more than 1 dose level (dose skipping) is not permitted.
During dose escalation for all dose cohorts, the initial subject (sentinel subject) will be observed for 5 days before 
additional subjects in that cohort are treated with study drug.
Approximately 30 subjects will be enrolled in each dose escalation part. The number of subjects in each dose escalation 
cohort may vary depending on the BLRM (-Copula) recommendations. Initially, approximately 3 subjects will be 
treated at the starting dose levels of BMS-986178 or BMS-986178 in combination with nivolumab or ipilimumab. 
Additional cohorts of approximately 3 evaluable subjects will be treated at recommended dose levels per
BLRM (-Copula) during the dose escalation phase. At least 6 DLT-evaluable subjects will be treated at the MTD.
Part 1A: Enrollment will begin in Part 1A, BMS-986178 monotherapy dose escalation. The initial dose of 
BMS-986178 for Part 1A will be 20 mg with expected subsequent doses of 40, 80, 160, and 320 mg. Actual doses can 
be modified per the BLRM but will not exceed doubling of the previously tested dose.
Parts 2A and 3A: Part 2A is the combination arm of BMS-986178 with nivolumab that will be initiated only after at 
least 3 dose levels in the monotherapy dose escalation have been found to be tolerated or an MTD/RP2D has been 
determined in the monotherapy dose escalation (Part 1A). The starting dose of BMS-986178 in Part 2A will be at least 
1 dose level below a dose that was demonstrated to be tolerated in Part 1A, and at no time will the dose for BMS-
986178 in Part 2A exceed the highest tolerated dose in Part 1A. To ensure further safety of the combination. Part 3A 
is the combination arm of BMS-986178 with ipilimumab that will be initiated only after at least 3 dose levels in the 
monotherapy dose escalation have been found to be tolerated or an MTD/RP2D has been determined in the 
monotherapy dose escalation (Part 1A) and at least 1 dose cohort has been found to be tolerated in the BMS-986178 
with nivolumab dose escalation part (Part 2A). The starting dose of BMS-986178 in Part 3A will be at least 1 dose 
level below a dose that was demonstrated to be tolerated in Part 1A, and at no time will the dose for BMS-986178 in 
Part 3A exceed the highest tolerated dose in Part 1A to further ensure safety of the combination doses in treated 
subjects. In Parts 2A and 3A, doses intermediate to previously tested doses or doses lower than the starting dose may 
be explored to further characterize the dose response for safety, PK, or PD as appropriate based on clinical data 
collected.
Schedule and Dose Exploration (Parts 4, 5, and 8):
Part 4: Part 4 is the combination arm of BMS-986178 with nivolumab (480 mg) to be administered every 4 weeks 
(q4w). The dose of BMS-986178 will be a dose previously evaluated in Part 2A that has been found to have a 
manageable safety profile and at no time will the dose for BMS-986178 exceed the highest tolerated dose in Part 2A, 
in which every 2 weeks (q2w) dosing is explored. Approximately 6 to 12 subjects will be treated in this cohort. 
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CA012004
BMS-986178
anti-OX40 mAb
Part 5: Part 5 is the combination arm of BMS-986178 with ipilimumab (3 mg/kg) to be administered every 3 weeks 
(q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). The dose of BMS-986178 
will be a dose previously evaluated in Part 3A that has been found to have a manageable safety profile and at no time 
will the dose for BMS-986178 exceed the highest tolerated dose in Part 3A. Approximately 6 to 12 subjects will be 
treated in this cohort.
Part 8: Part 8 is the dose regimen exploration arm of BMS-986178 with a less frequent dosing schedule at either 20 
mg, 40 mg, and 80 mg q12w in combination with nivolumab flat dose (480 mg; q4w) dose level (Cohort 1-3) or 
nivolumab 480 mg flat dose q4w monotherapy (Cohort 4) A tetanus vaccine (Tdap preferred, Td or equivalent after 
discussion with the medical monitor) will be administered to all subjects on Cycle 1 Day 1. Approximately 20 subjects 
will be treated in each cohort. Administration of a recall antigen such as tetanus toxoid may provide potent recall 
response with BMS-986178 in combination with nivolumab or nivolumab monotherapy.
Safety Cohorts (Parts 6A and 7A):
Part 6A: Part 6A is the safety cohort for combination of BMS-986178 with ipilimumab and nivolumab in subjects 
with renal cell carcinoma (RCC). BMS-986178 will be administered at a flat dose of 40 mg in combination with 
nivolumab (240 mg) and ipilimumab (1 mg/kg) q3w during Cycles 1 to 4 followed by maintenance therapy in which 
BMS-986178 (40 mg) and nivolumab (480 mg) will be administered q4w. 
Part 7A: Part 7A is the safety cohort for combination of BMS-986178 with ipilimumab and nivolumab in subjects 
with non-small cell lung cancer (NSCLC). BMS-986178 will be administered at a flat dose of 40 mg (q2w) in 
combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles.
Dose Expansion (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B, and 7B):
Treatment in the dose expansion cohorts will be initiated when the MTD/RP2D has been determined based on the 
evaluation of totality of available clinical safety (DLTs, AEs occurring after the DLT period), PK, PD, 
immunogenicity, and modeling data from the dose escalation parts (1A, 2A, and 3A) or schedule and dose exploration 
parts (4 and 5). Approximately 294 subjects will be treated in all dose expansion cohorts.
Parts 2B, 2C, 2D, and 2E (combination with nivolumab) are the dose expansion parts in subjects with colorectal 
cancer, bladder cancer, cervical cancer, and other tumors from dose escalation for signal finding, respectively, at the 
MTD/RP2D(s) determined in Parts 2A or 4.
Part 3B (combination with ipilimumab) is the dose expansion part in subjects with ovarian cancer at the MTD/RP2D(s)
determined in Parts 3A or 5. Part 3C (combination with ipilimumab) is the dose expansion part in subjects with other 
tumors from dose escalation for signal finding at the MTD/RP2D(s) determined in Part 3A or 5.
Part 6B (combination with nivolumab and ipilimumab) is the dose expansion part in subjects with RCC at a tolerable 
dose determined in Part 6A.
Part 7B (combination with nivolumab and ipilimumab) is the dose expansion part in subjects with NSCLC at a 
tolerable dose determined in Part 7A.
Summary of Study Periods: 
Subjects will complete: Screening (up to 28 days), Treatment (up to 24 weeks of dosing for Part 1-7, up to 24 months 
of dosing for Part 8, or until meeting protocol-specified discontinuation criteria) and Safety Follow-up of
approximately 100 days. As of Protocol Revision 06, no new subjects will enter the Response Follow-up or Survival 
Follow-up period. For Part 8 subjects and any subjects in Part 2, 4, 6, or 7 that have approval for additional cycles up 
to 2 years of treatment. The study visit schematic is presented in Figure -2.
Revised Protocol No.: 06
Date: 08-Feb-2019
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CA012004
BMS-986178
anti-OX40 mAb
Figure -2:
Study Visit Schematic
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anti-OX40 mAb
Screening Period:
The Screening period will last for up to 28 days. The screening period begins by establishing the subject’s initial 
eligibility and signing of the informed consent form. Subjects will be enrolled using an Interactive Response 
Technology (IRT). 
Treatment Period:
The Treatment period consists of up to 24 weeks of dosing for Part 1-7. Part 8 will have a treatment period for up to 
24 months of dosing. Following each treatment cycle, the decision to treat a subject with the next cycle of study 
therapy, up to 24 weeks of treatment or Part 8 up to 24 months, will be based on risk/benefit and tumor assessments. 
Tumor assessments will be performed every 8 weeks for Part 1-7 or every 12 weeks for Part 8 (± 1 week). Assessments 
of partial response (PR) and complete response (CR) must be confirmed at least 4 weeks following initial assessment. 
Tumor progression or response endpoints will be assessed using Response Evaluation Criteria In Solid Tumors 
(RECIST) v1.1.
Subjects with a response of stable disease (SD), PR, or CR at the end of a given cycle will continue to the next 
treatment cycle. Subjects will generally be allowed to continue study therapy until the first occurrence of one of the 
following: 1) completion of the maximum number of cycles; 2) progressive disease; 3) clinical deterioration 
suggesting that no further benefit from treatment is likely; 4) intolerability to therapy; or 5) meeting the criteria for 
discontinuation of study therapy as outlined in the protocol. 
Safety Follow-up:
Upon completion of study therapy, subjects will enter the Safety Follow-up period. After the end of treatment (EOT)
visit, subjects will be evaluated for any new adverse events (AEs) for approximately 100 days after the last dose of 
therapy. Follow-up visits should occur at Days 30, 60 and 100 after the last dose or the date of discontinuation. 
Subjects (except those who withdraw consent for study participation) are expected to complete the 3 clinical Safety 
Follow-up visits regardless of whether they start new anti-cancer therapy.
Duration of Study: The total duration of study time for any individual subject is expected to be approximately 2.5 
years (depending on Part subject is randomized to). The study will end when the last subject completes their last study 
visit, which is planned to be about 4 years after the start of the study.
Number of Subjects: Approximately 604 subjects will be enrolled, and approximately 515 subjects will be treated in 
the study.
Study Population: Subjects must be at least 18 years old and have histologic or cytologic confirmation of a 
malignancy that is advanced (metastatic, recurrent, refractory and/or unresectable) with measurable disease per 
RECIST v1.1.
Study Drug: Investigational products are as listed in Table -1.
Table -1:
Study Drugs for CA012004
Product 
Description 
Class and 
Dosage Form
Potency
IP/Non-
IP
Blinded 
or Open 
Label
Packaging/Appearance
Storage 
Conditions
(per label)
BMS-986178 
Injection
25 mg/mL
(80 mg/vial)
IP
Open
Colorless to pale yellow liquid. 
Clear to slightly opalescent. 
Light (few) particulates 
(consistent in appearance to 
proteinaceous particulates) may 
be present.
Store at 2°C to 
8°C; do not 
freeze; 
protected from 
light.
Nivolumab 
Injection
10 mg/mL
(100 mg/vial)
IP
Open
Clear to opalescent, colorless to 
pale yellow liquid. Light (few) 
particulates may be present.
Store at 2°C to 
8°C; store in 
original 
package; do not 
freeze; 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table -1:
Study Drugs for CA012004
Product 
Description 
Class and 
Dosage Form
Potency
IP/Non-
IP
Blinded 
or Open 
Label
Packaging/Appearance
Storage 
Conditions
(per label)
protected from 
light.
Ipilimumab 
Injection
5 mg/mL
(200 mg/vial)
IP
Open
Clear, colorless liquid. Light 
(few) particulates may be 
present.
Store at 2°C to 
8°C; do not 
freeze; 
protected from 
light.
Tetanus vaccine
Per locala
IP
Open
Various packaging configuration
Refer to the 
label on 
container and/or 
pharmacy 
manual
Abbreviation: IP = investigational product
a Tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor)will be obtained as 
local commercial product in countries if allowed by local regulations or through investigating sites standard 
prescribing procedures.
Study Assessments:
•
Physical examinations, vital sign measurements, 12-lead electrocardiograms (ECGs), and clinical laboratory 
evaluations will be performed at selected times throughout the dosing interval. Subjects will be closely monitored 
for AEs throughout the study.
•
Safety Assessments: AEs will be assessed during the study and for 100 days after the last treatment. AEs will be 
evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. AEs 
will be coded using the most current version of Medical Dictionary for Regulatory Activities and reviewed for 
potential significance and importance. Subjects will be followed until all treatment-related AEs have recovered 
to baseline or are deemed irreversible by the investigator.
•
Efficacy Assessments: Disease assessment with computed tomography and/or magnetic resonance imaging as 
appropriate will be performed at baseline and every 8 weeks (± 1 week) per RECIST v1.1 until discontinuation 
of treatment or withdrawal from study. Tumor assessments at other time points may be performed if the 
investigator is concerned about tumor progression. Assessment of tumor response will be reported by the 
investigator as defined by RECIST v1.1 for subjects with advanced solid tumors.
•
Pharmacokinetic and Immunogenicity Assessments: Samples for PK and immunogenicity assessments will be 
collected for subjects receiving BMS-986178 alone or in combination with nivolumab and/or ipilimumab. The 
PK of BMS-986178 will be characterized by non-compartmental analysis method. Immunogenicity samples will 
be analyzed for anti-BMS-986178 antibodies and/or anti-nivolumab antibodies and/or anti-ipilimumab antibodies 
by validated immunoassays.
 
 
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Statistical Considerations: 
Sample Size Determination:
Dose Escalation (Parts 1A, 2A, and 3A):
As a Phase 1 dose escalation trial, the sample size for each dose escalation cohort depends on observed toxicity and 
posterior inference. Approximately 30 subjects are expected to be treated during each dose escalation part 
(BMS-986178 monotherapy [Part 1A], BMS-986178 in combination with nivolumab [Part 2A], and BMS-986178 in 
combination with ipilimumab [Part 3A]) for a combined total of approximately 90 subjects in Parts 1A, 2A and 3A. 
Initially, approximately 3 subjects will be treated at the starting dose levels of BMS-986178 or BMS-986178 in 
combination with nivolumab or ipilimumab. Additional cohorts of approximately 3 evaluable subjects will be treated 
at recommended dose levels per BLRM (-Copula) recommendations during the dose escalation phase. At least 
6 DLT-evaluable subjects will be treated at the MTD.
Schedule and Dose Exploration (Parts 4, 5, and 8):
Approximately 6 to 12 subjects are expected to be treated during each schedule and dose exploration part 
(BMS-986178 in combination with nivolumab [Part 4] and BMS-986178 in combination with ipilimumab [Part 5] for 
a combined total of approximately 12 to 24 subjects in Parts 4 and 5).
Approximately 20 evaluable subjects per dose cohort will be treated in Part 8 of the study, BMS-986178 in 
combination with nivolumab (Cohort 1-3) and monotherapy nivolumab (Cohort 4). Total number of subjects in this 
Part 8 will be approximately 80.
Safety Cohorts (Parts 6A and 7A):
Approximately 6 to 12 subjects are expected to be treated during each safety cohort part (BMS-986178 in combination 
with nivolumab and ipilimumab q3w, followed by maintenance therapy with combination of BMS-986178 and
nivolumab q4w [Part 6A], and BMS-986178 in combination with nivolumab [q2w] and ipilimumab [q6w; Part 7A]),
for a combined total of approximately 12 to 24 subjects in Parts 6A and 7A.
Cohort Expansion (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B, and 7B):
In general terms, the expansion phase sizing is guided by Simon 2-stage design, which is based on target response 
rates (target overall response rate) and the ability to identify a signal for such clinical response that is above the 
standard of care (historical overall response rate). It is not the intent of this study to use Simon 2-stage design for 
formal hypothesis testing.
Disease-restricted population cohorts will be guided by the Simon 2-stage design. Approximately 35 subjects will be 
treated in the Part 2B dose expansion cohort. Approximately 27 subjects will be treated in the Part 2C dose expansion 
cohort. Approximately 37 subjects will be treated in the Part 2D dose expansion cohort. Approximately 35 subjects 
will be treated in the Part 3B dose expansion cohort. Approximately 40 subjects will be treated in each Parts 2E and 
3C of dose expansion portion will include other tumors from dose escalation for signal seeking. Due to the 
heterogeneity of response rates of the mixed tumors, Simon 2-stage design is not pursued for Parts 2E and 3C. 
Approximately 40 subjects each will be treated in dose expansion Parts 6B and 7B. Additional subjects may be treated 
in order to have sufficient response-evaluable subjects per expansion cohort. 
Endpoints:
Primary Endpoints:
The assessment of safety will be based on the incidence of AEs, serious AEs, AEs leading to discontinuation, and 
deaths. In addition, clinical laboratory test abnormalities will be examined.
Secondary Endpoints:
Efficacy: The anti-tumor activity of BMS-986178 alone or in combination with nivolumab and/or ipilimumab will be 
measured by ORR, duration of response, and progression free survival rate (PFSR) at 24 weeks based on RECIST 
v1.1. The above will be determined based on tumor measurements occurring at baseline, every 8 weeks (± 1 week) 
during the treatment period, and every 12 weeks during the Response Follow-up phases (for subjects who already 
have data collected). 
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In a 1-month intermittent repeat-dose exploratory study in cynomolgus monkeys (Section 1.4.2), 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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highest tolerated dose in the monotherapy dose escalation arm (Part 1A). The initial subject will 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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agents results in a safety profile with similar types of AEs to either agent alone, but in some cases, 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
ICH and in accordance with the ethical principles underlying European Union Directive 
2001/20/EC and the US Code of Federal Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a breach 
of the conditions and principles of GCP in connection with the study or the protocol, which is 
likely to affect, to a significant degree, the safety or physical or mental integrity of the subjects of 
the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
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2.2
Institutional Review Board/Independent Ethics Committee
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects. The investigator 
or BMS should also provide the IRB/IEC with a copy of the IB or product labeling information to 
be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other information 
(eg, expedited safety reports, amendments, and administrative letters) according to regulatory 
requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives (as
per country guidelines) are clearly and fully informed about the purpose, potential risks, and other 
critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form(s) which will include all elements required by ICH, GCP, and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
•
Provide a copy of the consent form(s) and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 
•
Allow time necessary for subject or subject’s legally acceptable representative to inquire about 
the details of the study.
•
Obtain an informed consent signed and personally dated by the subject or the subject’s legally 
acceptable representative and by the person who conducted the informed consent discussion. 
•
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects, prior to the beginning of the study, 
and after any revisions are completed for new information.
•
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject.
•
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject’s consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject’s legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject’s willingness to continue participation in the study. This communication should be 
documented.
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The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects’ signed ICF and, in 
the US, the subjects’ signed HIPAA Authorization.
The consent form(s) must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to refuse 
participation in, or to be withdrawn from, the clinical study at any time should be considered by 
the investigator. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a Phase 1/2a, open-label study of BMS-986178 in subjects with advanced solid tumors that 
integrates initial BMS-986178 monotherapy with subsequent nivolumab and/or ipilimumab 
combination therapy. Study sections (dose escalation and dose expansion) will proceed in a phased 
approach that is based upon study-emergent safety, PK, and PD data. The first section of the study 
will begin with BMS-986178 monotherapy dose escalation cohorts. The clinical data from the first 
3 monotherapy dose cohorts will serve as a foundation for initiating dose escalation of 
BMS-986178 in combination with nivolumab. The clinical data from the first 3 monotherapy dose 
cohorts in addition to the clinical data from the first cohort of BMS-986178 in combination with 
nivolumab will then serve as a foundation for initiating dose escalation of BMS-986178 in 
combination with ipilimumab. The clinical data for BMS-986178 in combination with nivolumab 
and BMS-986178 in combination with ipilimumab will serve as the foundation for initiating 
combination therapy of BMS-986178 with nivolumab and ipilimumab in Parts 6 and 7. After 
establishment of a tolerable and pharmacologically active MTD/RP2D of BMS-986178 in the dose 
escalation and schedule and dose exploration sections, dose expansion in specific tumor cohorts 
will be initiated. Recent preclinical and clinical data will serve as the foundation for focusing on 
further optimizing the dose of BMS-986178 in combination with nivolumab.
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Figure 3.1-1:
Study Design Schematic (Parts 1 to 8)
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Dose levels are specific for each part. Dose expansion will begin only after MTD/RP2D determination in the 
corresponding dose escalation phases of the study.
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3.1.1
Study Outline (All Parts)
3.1.2
Dose Escalation (Parts 1A, 2A, and 3A)
The dose escalation part of the study will evaluate the safety and tolerability of BMS-986178 alone 
or in combination with nivolumab or ipilimumab in subjects with advanced solid tumors (listed in 
Section 3.3.1 [Inclusion criteria 2]).
The initial dose level of BMS-986178 planned for this study is 20 mg. Dose escalation decisions 
for subsequent doses will be based on DLTs using a BLRM (for BMS-986178 monotherapy) or a 
BLRM (-Copula) model (for BMS-986178 in combination with nivolumab or ipilimumab). The 
DLT period is 28 days for both monotherapy and combination therapy dose escalation parts. The 
DLT rate will be determined based on the incidence, severity, and duration of AEs that occur 
within the DLT period and for which no alternative cause can be identified. Dose selection for the 
next monotherapy cohort/dose level will take into account the BLRM (-Copula) recommendation 
(Section 3.1.2.4) in conjunction with clinical recommendation and all available PK, PD, 
immunogenicity, and clinical and laboratory safety data from all treated subjects. Starting dose 
selection of BMS-986178 for Part 2A will be determined using data available from Part 1A, 
including clinical and laboratory safety assessments, PK/PD data, immunogenicity, and modeling 
recommendation within Bayesian modeling framework by incorporating single-agent toxicity 
profiles of both BMS-986178 (Part 1A) and nivolumab (CA209003). Starting dose selection of 
BMS-986178 for Part 3A will be determined using data available from Parts 1A and 2A, including 
clinical and laboratory safety assessments, PK/PD data, and modeling recommendation within 
Bayesian modeling framework by incorporating single-agent toxicity profiles of both 
BMS-986178 (Part 1A) and ipilimumab (CA184022). The final dose escalation decision will be 
made after discussion and agreement between the investigators and the BMS Medical Monitor. 
Actual doses can be modified per the BLRM (-Copula) but will not exceed doubling of the 
previously tested dose. In Parts 2A and 3A, doses intermediate to previously tested doses or doses 
lower than the starting dose may be explored to further characterize the dose response for safety, 
PK, or PD as appropriate based on clinical data collected.
During dose escalation for all dose cohorts, the initial subject (sentinel subject) will be observed 
for 5 days before additional subjects in that cohort are treated with study drug. 
All safety signals throughout the conduct of the study will be reviewed by the BMS-986178 
Medical Surveillance Team (MST). If unexpected safety findings are identified between scheduled 
MST meetings, an ad hoc meeting will be convened, as appropriate.
Approximately 30 subjects will be enrolled in each dose escalation part. The number of subjects 
in each dose escalation cohort may vary depending on the BLRM (-Copula) recommendations. 
Initially, approximately 3 subjects will be treated at the starting dose levels of BMS-986178 or 
BMS-986178 in combination with nivolumab or ipilimumab. Additional cohorts of approximately 
3 evaluable subjects will be treated at recommended dose levels per BLRM (-Copula) during the 
dose escalation phase. At least 6 DLT-evaluable subjects will be treated at the MTD.
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3.1.2.1
Part 1A: Monotherapy Dose Escalation
Part 1A is BMS-986178 monotherapy dose escalation. The initial dose of BMS-986178 for Part 1A 
will be 20 mg with expected subsequent doses of 40, 80, 160, and 320 mg. Dosing of BMS-986178 
will begin on Day 1 of each cycle and will be administered q2w for up to 12 cycles.
3.1.2.2
Part 2A: Combination with Nivolumab Dose Escalation
Part 2A is the combination arm of BMS-986178 with nivolumab that will be initiated only after at 
least 3 dose levels in the monotherapy dose escalation have been found to be tolerated or an 
MTD/RP2D has been determined in the monotherapy dose escalation (Part 1A). The starting dose 
of BMS-986178 in Part 2A will be at least 1 dose level below a dose that was demonstrated to be 
tolerated in Part 1A to ensure further safety of the combination. At no time will the dose for 
BMS-986178 in Part 2A exceed the highest tolerated dose in Part 1A. Nivolumab will be 
administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study 
drugs will be administered q2w starting on Day 1 of each cycle for up to 12 cycles.
3.1.2.3
Part 3A: Combination with Ipilimumab Dose Escalation
Part 3A is the combination arm of BMS-986178 with ipilimumab that will be initiated only after 
at least 3 dose levels in the monotherapy dose escalation have been found to be tolerated or an 
MTD/RP2D has been determined in the monotherapy dose escalation (Part 1A) and at least 1 dose 
cohort has been found to be tolerated in the BMS-986178 with nivolumab dose escalation part 
(Part 2A). The starting dose of BMS-986178 in Part 3A will be at least 1 dose level below a dose 
that was demonstrated to be tolerated in Part 1A. At no time will the dose for BMS-986178 in 
Part 3A exceed the highest tolerated dose in Part 1A to further ensure safety of the combination 
doses in treated subjects. Ipilimumab will be administered at a dose of 1 mg/kg. Each treatment 
cycle will be 3 weeks in length. BMS-986178 will be administered q3w starting on Cycle 1 Day 1, 
up to and including 8 cycles, and ipilimumab will be administered q3w starting on Day 1 for 
4 cycles. Only BMS-986178 will be administered in the last 4 cycles.
3.1.2.4
BLRM Dose Escalation and Stopping Rules
In Parts 1A, 2A, and 3A, the BLRM and BLRM (-Copula) models (Section 1.1.13) will be utilized 
for dose escalation recommendations after DLT information becomes available for each cohort of 
subjects. BMS-986178 dose selection for the next cohort/dose level will take into account the 
BLRM (-Copula) recommendation in conjunction with clinical recommendation and all available 
PK, PD, and clinical and laboratory safety data from all treated subjects. The final dose escalation 
decision will be made after discussion and agreement between investigators and the BMS Medical 
Monitor. 
BLRM Dose Escalation Rules (Parts 1A, 2A, and 3A)
Cohort tolerability assessment and subsequent dose recommendation will occur when 2 evaluable 
subjects within a dose cohort have completed the 28-day DLT period. If the potential DLT 
occurring in the third evaluable subject at a specific dose level does not influence the dose 
recommendation by BLRM (-Copula), the BLRM (-Copula)-recommended next dose level may 
proceed without waiting for the third subject to complete the corresponding DLT observation 
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period after discussion and agreement between the Sponsor and investigators. While waiting for 
the DLT information of those 2 or 3 subjects, if additional subjects are available, these subjects 
could be enrolled to the current dose level. Continuous re-assessment of dose recommendation by 
BLRM (-Copula) will be carried out at every dose level of each cohort of subjects, taking into 
consideration all available DLT information.
The BLRM (-Copula) model will first exclude doses that are intolerable (with overdosing 
probabilities > 25%). Among those qualified candidate doses that are considered “safe”, the model 
will select the dose that maximizes the probability of being within the target toxicity range (DLT 
rate of 16% to up to 33%). 
•
Dose levels for the next cohort will be based on evaluating 4 potential recommendations: 
escalate, de-escalate, stay at same dose level, or stop and select a new dose other than pre-
specified doses.
•
Escalation by more than 1 dose level (dose skipping) is not permitted. 
•
Based on model suggestions and a review of the available safety, PK, and PD data in 
combination with clinical recommendation, lower doses of BMS-986178 may be tested if none 
of the planned doses are found to be tolerated as monotherapy or in combination with 
nivolumab or ipilimumab. Such decisions will be made after discussion and agreement 
between the investigators and the BMS Medical Monitor.
•
No intra-subject dose escalation of BMS-986178 is allowed at any dose level.
•
Dose de-escalation can be recommended by the model, and the final decision will be made 
based on clinical recommendation.
BLRM Stopping Rules during Dose Escalation (Parts 1A, 2A, and 3A)
•
If all of the current pre-specified doses are considered intolerable according to the pre-specified 
cutoff, then the model will recommend stopping the current dose level and a new dose level 
lower than the current lowest dose level will need to be identified (EWOC stopping). 
•
The maximum number of subjects in a dose level will be 12. This limit is set to avoid instances 
in which the model could recommend adding subjects indefinitely to a specific dose level due 
to uncertainty in the tolerability profile. 
•
If, for a specific dose level, 6 subjects have been treated and the chance of determining that 
dose level to be the “target” dose is > 50%, then the model will suggest to stop the arm and 
declare the current dose level to be MTD.
Appendix 1 provides further detailed explanation along with an illustration of the BLRM dose 
escalation design.
3.1.2.5
Dose-Limiting Toxicity in Dose Escalation Parts
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, severity, 
and duration of AEs for which no clear alternative cause is identified. The DLT period will be 
28 days after initial dosing in monotherapy and combination parts of dose escalation. 
For the purpose of defining MTD/RP2D, the incidence of DLTs during the DLT period will be 
used. AEs occurring after the DLT period will be considered for the purposes of defining the RP2D 
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upon agreement between the Sponsor, Medical Monitor, and investigators, if they are determined 
to have no clear alternative cause and are not related to disease progression.
For the purpose of subject management, any AE that meets DLT criteria, regardless of the cycle 
in which it occurs, will lead to discontinuation of study drug. Subjects experiencing a DLT will 
not be retreated with study drug(s) and will enter the Safety Follow-up period of the study for up 
to 100 days from the last administration of the study drug(s). Subjects who withdraw from the 
study during the DLT evaluation interval for reasons other than a DLT may be replaced with a 
new subject at the same dose level.
Further details on DLTs are included in Section 4.5.1.
3.1.3
Schedule and Dose Exploration
3.1.3.1
Part 4: Combination with Nivolumab on a 4-week Schedule
Part 4 is the combination arm of BMS-986178 with nivolumab (480 mg) to be administered q4w. 
The dose of BMS-986178 will be a dose previously evaluated in Part 2A that has been found to 
have a manageable safety profile. If the starting dose of BMS-986178 is not tolerated or to further 
characterize the dose response for safety, PK, or PD as appropriate based on clinical data collected, 
a dose(s) lower or higher than the previously administered dose in this part may be explored. To 
further ensure safety of the combination, at no time will the dose for BMS-986178 in Part 4 exceed 
the highest tolerated dose in Part 2A, in which q2w dosing is explored. Approximately 6 to 
12 subjects will be treated in this schedule and dose exploration cohort.
3.1.3.2
Part 5: Combination with Ipilimumab at 3 mg/kg
Part 5 is the combination arm of BMS-986178 with ipilimumab 3 mg/kg q3w for 4 doses, followed 
by monotherapy with BMS-986178 (maintenance therapy). The dose of BMS-986178 will be a 
dose previously evaluated in Part 3A that has been found to have a manageable safety profile. If 
the starting dose of BMS-986178 is not tolerated or to further characterize the dose response for 
safety, PK, or PD as appropriate based on clinical data collected, a dose(s) lower or higher than 
the previously administered dose in this part may be explored. To further ensure safety of the 
combination, at no time will the dose for BMS-986178 in Part 5 exceed the highest tolerated dose 
in Part 3A. Approximately 6 to 12 subjects will be treated in this schedule and dose exploration 
cohort.
3.1.3.3
Part 8: Dose Regimen Exploration of Combination with Nivolumab in 
Bladder Cancer
Part 8 is a dose regimen exploration of BMS-986178 in combination with nivolumab or nivolumab 
monotherapy. Nivolumab will be administered at a flat dose of 480 mg to be administered every 4 
weeks.
Approximately 20 evaluable subjects per cohort will be treated in Part 8.
Part 8 Cohort 1-3: BMS-986178 will be administered as a flat dose of either 20 mg, 40 mg, or 
80 mg q12w in combination with nivolumab flat dose (480 mg; q4w). Each treatment cycle will 
be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 
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24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with 
the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of
nivolumab and BMS-986178.
Part 8 Cohort 4: Nivolumab monotherapy will be administered as a flat dose of 480 mg (q4w). 
Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months 
of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. A tetanus vaccine (Tdap 
preferred, Td or equivalent after discussion with the medical monitor) will be administered first 
on Cycle 1 Day 1 prior to administration of nivolumab monotherapy.
3.1.4
Safety Cohorts
3.1.4.1
Part 6A: Combination with Nivolumab and Ipilimumab in RCC
Part 6A is the safety cohort for the combination of BMS-986178 with ipilimumab and nivolumab 
in subjects with RCC. BMS-986178 will be administered at a flat dose of 40 mg in combination 
with nivolumab (240 mg) and ipilimumab (1 mg/kg) q3w during Cycles 1 to 4, followed by 
maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab 
(480 mg) will be administered q4w. Study drugs will be administered accordingly starting on 
Day 1 of each cycle. If the starting dose of BMS-986178 is not tolerated or to further characterize 
the dose response for safety, PK, or PD as appropriate based on clinical data collected, a dose(s) 
lower than the previously administered dose in this part may be explored. Approximately 6 to 12 
subjects will be treated in this safety cohort.
3.1.4.2
Part 7A: Combination with Nivolumab and Ipilimumab in NSCLC 
Part 7A is the safety cohort for the combination of BMS-986178 with ipilimumab and nivolumab 
in subjects with NSCLC. BMS-986178 will be administered at a flat dose of 40 mg (q2w) in 
combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week 
cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If the starting 
dose of BMS-986178 is not tolerated or to further characterize the dose response for safety, PK, 
or PD as appropriate based on clinical data collected, a dose(s) lower than the previously 
administered dose in this part may be explored. If subjects continue for additional cycles, past 
cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. 
Approximately 6 to 12 subjects will be treated in this safety cohort.
3.1.5
Dose Expansion Parts (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B, and 7B)
Treatment in the dose expansion cohorts will be initiated when the MTD/RP2D(s) has been 
determined based on the evaluation of totality of available clinical safety (DLTs, AEs occurring 
after the DLT period), PK, PD, immunogenicity, and modeling data from the dose escalation parts 
(1A, 2A, and 3A) or schedule and dose exploration parts (4 and 5). Mandatory pre- and on-
treatment biopsies of tumor will be obtained for all study subjects.
3.1.5.1
Part 2B: Combination with Nivolumab Dose Expansion in Colorectal 
Cancer
Part 2B is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with CRC at the MTD/RP2D(s) determined in Parts 2A or 4. Nivolumab will be administered at a 
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flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in 
length and study drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for 
up to 12 or 6 cycles, respectively. Approximately 35 subjects will be treated in this expansion 
cohort.
3.1.5.2
Part 2C: Combination with Nivolumab Dose Expansion in Bladder 
Cancer
Part 2C is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with BC at the MTD/RP2D(s) determined in Parts 2A or 4. Nivolumab will be administered at a 
flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in 
length and study drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for 
up to 12 or 6 cycles, respectively. Approximately 27 subjects will be treated in this expansion 
cohort.
3.1.5.3
Part 2D: Combination with Nivolumab Dose Expansion in Cancer of the 
Cervix 
Part 2D is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with cervical cancer at the MTD/RP2D(s) determined in Part 2A or 4. Nivolumab will be 
administered at a flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 
4 (480 mg) weeks in length and study drugs will be administered every 2 or 4 weeks starting on 
Day 1 of each cycle for up to 12 or 6 cycles, respectively. Approximately 37 subjects will be 
treated in this expansion cohort.
3.1.5.4
Part 2E: Combination with Nivolumab Dose Expansion in Other Tumors 
for Signal Finding
Part 2E is the combination therapy (BMS-986178 with nivolumab) dose expansion part at the 
MTD/RP2D(s) determined in Part 2A or 4. Nivolumab will be administered at a flat dose of 240 
or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in length and study 
drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for up to 12 or 6 
cycles, respectively. Approximately 40 subjects will be treated in this expansion cohort. 
Tumor types for this cohort will be selected by Sponsor from those permitted in dose escalation 
which do not have a dedicated expansion cohort or plans for evaluation in other studies and those 
tumors selected will be communicated to the investigators. This cohort will allow for further 
exploration of early signs of clinical activity observed in tumors during the dose escalation phase 
of the trial as well as potential signals arising from ongoing trials of other anti OX40 agonists in 
combination with anti-PD(L)-1. Subjects enrolled in this cohort must be refractory to or intolerant 
of established therapy known to provide clinical benefit for their condition, i.e., subjects must not 
be candidates for regimens known to provide clinical benefit.
3.1.5.5
Part 3B: Combination with Ipilimumab Dose Expansion in Ovarian 
Cancer
Part 3B is the combination therapy (BMS-986178 with ipilimumab) dose expansion part in 
subjects with OC at the MTD/RP2D(s) determined in Part 3A or 5. Each treatment cycle will be 
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3 weeks in length. Ipilimumab will be administered in the initial 4 cycles in combination with 
BMS-986178. Then the subject will continue on BMS-986178 monotherapy for up to an additional 
4 cycles for a total of up to 24 weeks (8 cycles) of treatment. Approximately 35 subjects with OC 
will be treated in this expansion cohort.
3.1.5.6
Part 3C: Combination with Ipilimumab Dose Expansion in Other Tumors 
for Signal Finding
Part 3C is the combination therapy (BMS-986178 with ipilimumab) dose expansion part in 
subjects with other tumors from dose escalation for signal finding at the MTD/RP2D(s) determined 
in Part 3A or 5. Each treatment cycle will be 3 weeks in length. Ipilimumab will be administered 
in the initial 4 cycles in combination with BMS-986178. Then the subject will continue on 
BMS-986178 monotherapy for up to an additional 4 cycles for a total of up to 24 weeks (8 cycles) 
of treatment. Approximately 40 subjects will be treated in this expansion cohort.
Tumor types for this cohort will be selected by Sponsor from those permitted in dose escalation 
which do not have a dedicated expansion cohort or plans for evaluation in other studies and those 
selected tumors will be communicated to the investigators. This cohort will allow for further 
exploration of early signs of clinical activity observed in tumors during the dose escalation phase 
of the trial as well as potential signals arising from ongoing trials of other anti OX40 agonists in 
combination with anti-CTLA-4. Subjects enrolled in this cohort must be refractory to or intolerant 
of established therapy known to provide clinical benefit for their condition, i.e., subjects must not 
be candidates for regimens known to provide clinical benefit.
3.1.5.7
Part 6B: Combination with Nivolumab and Ipilimumab in Renal Cell 
Carcinoma
Part 6B is the combination therapy (BMS-986178, nivolumab, and ipilimumab) dose expansion 
part in subjects with RCC at a dose determined to be tolerated in Part 6A. BMS-986178 will be 
administered at the RP2D(s) in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) 
q3w during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which 
BMS-986178 and nivolumab (480 mg) will be administered q4w. Study drugs will be administered 
accordingly starting on Day 1 of each cycle. Approximately 40 subjects will be treated in this 
expansion cohort.
3.1.5.8
Part 7B: Combination with Nivolumab and Ipilimumab in Non-small Cell 
Lung Cancer
Part 7B is the combination therapy (BMS-986178, nivolumab, and ipilimumab) dose expansion 
part in subjects with NSCLC at a dose determined to be tolerated in Part 7A. BMS-986178 will be 
administered at the RP2D(s) (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab 
(1 mg/kg; q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on 
Day 1 of each cycle. If subjects continue for additional cycles, past Cycle 4, all study drugs 
(BMS-986178/nivolumab/ipilimumab) will continue for all cycles. Approximately 40 subjects will 
be treated in this expansion cohort.
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3.1.5.9
Stopping Rules during Dose Expansion
•
Evaluation of toxicity will be performed throughout enrollment in the dose expansion cohorts. 
•
If the rate of DLTs exceeds 33% in any cohort, the findings will be discussed between the 
investigators and Sponsor, and further enrollment may be interrupted in that expansion cohort. 
•
If an expansion cohort is discontinued due to toxicity, a new cohort at a previously tested lower 
dose level may be considered based on the aggregate safety experience and in consultation and 
agreement between the investigators and Sponsor.
•
During dose expansion, a specific cohort may be stopped due to lack of efficacy per Simon 
2-stage design recommendation.154,155 Due to the heterogeneous nature of tumor responses 
seen with immunotherapy (eg, late responses), such a decision would not be strictly based on 
the number of responses but would include all available efficacy data.
•
The non-binding nature of stopping boundaries allows for flexibility of examination on the 
totality of data to determine the risk/benefit ratio.
3.1.6
Study Schedule
In all cohorts, subjects will complete: Screening (up to 28 days), Treatment (up to 24 weeks
[Part 1-7], until meeting protocol-specified discontinuation criteria), and Safety Follow-up 
(approximately 100 days), as described below. Screening and the Treatmentperiod are calculated 
relative to the first dose of study drug, while Safety Follow-up periods are calculated relative to 
the last dose. The study visit schematic is presented in Figure 3.1.6-1. The study will end when the 
last subject completes their last study visit, which is planned to be about 4 years after the start of 
the study. Part 8 subjects will receive treatment up to 24 months. Safety Follow-up period will be 
approximately 100 days from the end of treatment.
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Figure 3.1.6-1:
Study Visit Schematic
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3.1.6.1
Screening Period
The screening period will last for up to 28 days. The screening period begins by establishing the 
subject’s initial eligibility and signing of the ICF. Subjects will be enrolled using an Interactive 
Response Technology (IRT).
If a subject surpasses the 28-day window during the screening period due to a study-related 
procedure (eg, scheduling of a tumor biopsy or waiting time for a study-related laboratory value), 
the subject must be re-consented, but does not need to be assigned a new subject identification 
number. In this situation, the fewest number of procedures from the initial screening should be 
repeated to qualify the subject, while maintaining safety and eligibility under the discretion of the 
BMS Medical Monitor and investigator, to reduce any undue burden of procedures in this subject 
population.
3.1.6.2
Treatment Period
Eligible subjects will be assigned to the open parts/cohorts by IRT (see Section 4.4).
The treatment period consists of up to 24 weeks of dosing for Part 1-7. Part 8 will have a treatment 
period up to 24 months of dosing.
Following each treatment cycle, the decision to treat a subject with the next cycle of study therapy, 
up to 24 weeks of treatment or Part 8 up to 24 months, will be based on risk/benefit and tumor 
assessments. Tumor assessments will be performed every 8 weeks for Part 1-7 or every 12 weeks 
for Part 8 (± 1 week). Assessments of partial response (PR) and complete response (CR) must be 
confirmed at least 4 weeks following initial assessment. Tumor progression or response endpoints 
will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Appendix 3).
Subjects with a response of SD, PR, or CR at the end of a given cycle will continue to the next 
treatment cycle. Subjects will generally be allowed to continue study therapy until the first 
occurrence of one of the following: 1) completion of the maximum number of cycles; 2) PD; 
3) clinical deterioration suggesting that no further benefit from treatment is likely; 4) intolerability 
to therapy; or 5) the subject meets criteria for discontinuation of study therapy as outlined in 
Section 4.5.6. Individual subjects with confirmed CR will be given the option to discontinue study 
therapy on a case-by-case basis after specific consultation and agreement between the investigator 
and BMS Medical Monitor in settings where risk/benefit justify discontinuation of study therapy.
Approximately 604 subjects will be enrolled, and approximately 515 subjects will be treated in the 
study.
3.1.6.3
Safety Follow-up
Upon completion of study therapy, subjects will enter the Safety Follow-up period.
After the end of treatment (EOT) visit, subjects will be evaluated for any new AEs for at least 
100 days after the last dose of therapy. Follow-up visits should occur at Days 30, 60, and 100 after 
the last dose or the date of discontinuation. Subjects (except those who withdraw consent for study 
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participation) are expected to complete the 3 clinical Safety Follow-up visits regardless of whether 
they start new anti-cancer therapy.
For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the 
last scheduled and completed on-treatment visit, and the start of Week 1 Safety Follow-up visit. 
For subjects 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); the visit does not need to be 
repeated and will be considered the start of the Safety Follow-up period.
3.1.7
Treatment with Additional Cycles
Part 1-7 subjects will be treated for 24 weeks unless criteria for study drug discontinuation are met 
earlier (Section 4.5.6). Subjects in Parts 2, 4, 6, and 7 completing approximately 24 weeks of 
treatment with ongoing disease control (CR, PR, or SD) may be eligible for an additional 
18 months of study therapy beyond the initial 24 weeks, on a case-by-case basis, after discussion 
and agreement with the BMS Medical Monitor that the risk/benefit assessment favors continued 
administration of study therapy. Upon completion of the additional 18 months of study therapy,
subjects will enter Safety Follow-up period. Part 8 subjects will not be eligible for treatment with 
additional cycles. The maximum treatment allowed for any subject  is 2 years from the first dose 
of study treatment regardless of dose delays.
Parts 3 and 5 subjects completing approximately 24 weeks of treatment with ongoing disease 
control (CR, PR, or SD) may be eligible for an additional 24 weeks of study therapy beyond the 
initial 24 weeks, on a case-by-case basis, after discussion and agreement with the BMS Medical 
Monitor that the risk/benefit assessment favors continued administration of study therapy. Upon 
completion of the additional 24 weeks of study therapy, subjects will enter Safety Follow-up 
period. 
3.1.8
Treatment Beyond Progression
Treatment beyond progression may be allowed in select subjects with initial RECIST v1.1-defined 
progressive disease after discussion and agreement with the BMS Medical Monitor that the 
benefit/risk assessment favors continued administration of study therapy (eg, subjects are 
continuing to experience clinical benefit as assessed by the investigator, tolerating treatment, and 
meeting other criteria specified in (Section 3.5.1).
Subjects must be re-consented with an Informed Consent Form addendum to continue treatment 
beyond progression.
3.2
Post-study Access to Therapy
At the end of the study, BMS will not continue to provide BMS-supplied study drug to subjects 
and investigators unless BMS chooses to extend the study. The investigator should ensure that the 
subject receives appropriate SOC to treat the condition under study.
3.3
Study Population
For entry into the study, the following criteria MUST be met prior to dosing on Day 1. No 
exceptions will be granted.
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3.3.1
Inclusion Criteria
1) Signed Written Informed Consent
a) The subject must sign the ICF prior to the performance of any study-related procedures 
that are not considered part of SOC.
b) Consent for tumor biopsy samples (mandatory pre- and on-treatment biopsies) are required 
for all subjects enrolled.
2) Target Population
Subjects must be at least 18 years old and have histologic or cytologic confirmation of a 
malignancy that is advanced (metastatic, recurrent, refractory, and/or unresectable) with 
measurable disease per RECIST v1.1 (see Appendix 3).
1) Dose Escalation/Schedule and Dose Exploration/Safety Cohorts/Dose 
Expansion (Part 2E/3C) Subjects must be refractory to or intolerant of established 
therapy known to provide clinical benefit for their condition, i.e., subjects must not 
be candidates for regimens known to provide clinical benefit.
The following tumor histologies will be permitted except for subjects with primary central 
nervous system (CNS) tumors, or with CNS metastases as the only site of active disease.
Parts 1A, 2A, 2E, 3A, 3C, 4, and 5
(i)
Melanoma: BRAF mutation status must be documented if known
(ii)
NSCLC: EGFR, anaplastic lymphoma kinase (ALK), KRAS, and ROS1 
mutational status must be documented if known
(iii)
Head and neck cancer restricted to squamous cell carcinoma: HPV status 
must be documented if known
(iv)
Transitional cell carcinoma of the genitourinary tract
(v)
Renal cell carcinoma
(vi)
Pancreatic adenocarcinoma
(vii)
CRC: MSI, KRAS, and BRAF status must be documented if known
(viii)
Cervical cancer: HPV status must be documented if known
(ix)
Triple negative breast cancer HER2, ER, and PR status must be 
documented
(x)
Adenocarcinoma of the endometrium
(xi)
Ovarian cancer
(xii)
Prostate adenocarcinoma
(xiii)
Hepatocellular cancer-Child Pugh A only
(xiv)
Small cell lung cancer
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(xv)
Gastric and gastric esophageal junction cancer: HER2 status must be 
documented if known
(xvi)
Thyroid cancer
Part 6A (RCC)
(xvii)
Subjects with histological confirmation of RCC with a clear-cell 
component
(xviii) Subjects must have received at least 1, but no more than 2, prior systemic 
therapies in the advanced/metastatic setting.
Part 7A (NSCLC)
Subjects must have histologic or cytologic confirmation of NSCLC (per the seventh 
International Association for the Study of Lung Cancer [IASLC]156) with squamous or 
nonsquamous histology that is advanced (metastatic and/or unresectable).
(xix)
Subjects must have had at least 1, but no more than 2, prior systemic 
therapies 
for NSCLC. Maintenance, adjuvant, or neoadjuvant 
(chemotherapy or chemoradiation) therapy does not count as an additional 
line of treatment.
(xx)
Subjects should have been offered a platinum-based chemotherapy for 
NSCLC. The platinum-based chemotherapy may have been in the 
adjuvant, neoadjuvant, or recurrent setting. Prior adjuvant or neoadjuvant 
chemotherapy is permitted as long as the last administration of the prior 
regimen occurred at least 4 weeks prior to enrollment.
(xxi)
Prior definitive chemoradiation for locally advanced disease is also 
permitted as long as the last administration of chemotherapy or 
radiotherapy (whichever was given last) occurred at least 4 weeks prior to 
enrollment.
(xxii)
Subjects with known EGFR mutations or ALK rearrangements must have 
received EGFR or ALK inhibitors, respectively.
(xxiii) EGFR, ALK, KRAS, ROS1 mutational status must be documented if 
known.
2) Dose Expansion: Parts 2B, 2C, 2D, 3B, 6B, and 7B
The following tumor types will be permitted:
(a) Cervical Cancer - Part 2D
(i)
Histologically confirmed cervical cancer that is unresectable, metastatic, 
or recurrent with documented disease progression
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(ii)
Document tumor HPV status if known. If tumor HPV status is unknown, 
subjects must consent to allow their submitted archived tumor tissue 
sample (block or unstained slides) to be tested.
(iii)
Prior therapy requirement:
•
Subjects must have been offered and/or have received or refused at 
least 1 prior platinum-based therapy for metastatic and/or unresectable 
disease. Subjects must have not received more than 2 prior systemic 
therapies. Reason(s) for refusal should be documented. Concurrent 
chemotherapy administered with primary radiation and adjuvant 
chemotherapy given following completion of radiation therapy do not 
count as systemic therapies, though patients who progressed less than 
6 months from primary platinum-based therapy are eligible.
(b) Colorectal Cancer - Part 2B 
(i)
Histologically confirmed CRC that is metastatic or recurrent with 
documented disease progression
(ii)
Document MSI, MMR, KRAS, and BRAF status if known. If unknown, 
subjects must consent to allow their submitted archived tumor tissue 
sample (block or unstained slides) to be tested.
(iii)
Prior therapy requirement:
Subjects must have received at least 1, but no more than 3, prior 
systemic therapies for metastatic and/or unresectable disease (or have 
progressed within 6 months of adjuvant therapy).
(c) Bladder Cancer - Part 2C 
(i)
Histologically or cytologically confirmed urothelial carcinoma (including 
mixed histologies of urothelial carcinoma with elements of other 
subtypes) of the renal pelvis, ureter, bladder, or urethra with progression 
or refractory disease
(ii)
Prior therapy requirement:
Subjects must have been offered and/or have received or refused 1 prior 
platinum-based therapy for the treatment of metastatic or locally 
advanced unresectable disease. Subjects must have not received more 
than 2 prior systemic therapies. Reason(s) for refusal should be 
documented. 
(d) Ovarian - Part 3B
(i)
Histologically or cytologically confirmed ovarian carcinoma (including 
epithelial OC, primary peritoneal, or fallopian tube carcinoma) with 
documented disease progression
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(ii)
Documented germline BRCA mutation status, if known. If unknown, 
subjects must consent to allow their submitted archived tumor tissue 
sample (block or unstained slides) to be tested.
(iii)
Prior therapy requirement: 
Subjects must have received no more than 3 prior systemic therapies. 
One regimen must have been a prior platinum-based chemotherapy 
regimen for primary disease, possibly including intra-peritoneal therapy 
consolidation, biologic/targeted (non-cytotoxic) agents, or extended 
therapy (maintenance/consolidation) administered after surgical or 
non-surgical assessment. Patients must have progressed less than 
12 months after completion of their last platinum-based chemotherapy. 
The number of months (platinum-free interval) should be calculated 
from the date of the last administered dose of platinum therapy to the 
date of the documentation of progression.
(e) RCC (Part 6B)
(i)
Subjects with histologically confirmed RCC with a clear-cell component 
(ii)
Advanced (not amenable to curative surgery or radiation therapy) or 
metastatic (AJCC Stage IV) RCC
(iii)
No prior systemic therapy for RCC with the following exception:
One prior adjuvant or neoadjuvant therapy for completely resectable 
RCC if such therapy did not include an agent that targets VEGF or 
VEGF receptors and if recurrence occurred at least 6 months after the 
last dose of adjuvant or neoadjuvant therapy.
(iv)
Subjects with favorable-, intermediate-, and poor-risk categories will be 
eligible for the study. Subjects must be categorized according to 
favorable- versus intermediate-/poor-risk status at registration according 
to the International Metastatic RCC Database Consortium (IMDC) 
criteria (Appendix 5).
(f) NSCLC (Part 7B)
(i)
Subjects with histologically confirmed Stage IV or recurrent NSCLC (per 
the 7th IASLC) squamous or nonsquamous histology, with no prior 
systemic anticancer therapy (including EGFR and ALK inhibitors) given 
as primary therapy for advanced or metastatic disease. 
(ii)
Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the 
last administration of the prior regimen occurred at least 6 months prior 
to enrollment. 
(iii)
Prior definitive chemoradiation for locally advanced disease is also 
permitted as long as the last administration of chemotherapy or 
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radiotherapy (which ever was given last) occurred at least 6 months prior 
to enrollment.
(g) Bladder (Part 8)
(i)
Histologically or cytologically confirmed urothelial carcinoma (including 
mixed histologies of urothelial carcinoma with elements of other 
subtypes) of the renal pelvis, ureter, bladder, or urethra with progression 
or refractory disease.
(ii)
Subjects will need to have a pre-treatment and 2 on-treatment biopsies.
(iii)
Prior therapy requirement:
Subjects must have been offered and/or have received or refused 1 prior 
platinum-based therapy for the treatment of metastatic or locally 
advanced unresectable disease. Subjects must have not received more 
than 1 prior systemic therapy. Reason(s) for refusal should be 
documented.
Subjects must be immunotherapy treatment naïve (eg, no prior therapy 
with experimental anti-tumor vaccines; any T-cell co-stimulation or 
checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-
CD137, or anti-CTLA-4 antibody, including ipilimumab; or other 
medicines specifically targeting T-cells).
(iv)
Within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment 
with a platinum agent in the setting of cystectomy for localized muscle-
invasive urothelial cancer.
(v)
Sequential chemotherapy given as a planned sequence to optimize 
response will count as 1 regimen.
(vi)
Vaccines for infectious disease (e.g., influenza) allowed, provided they 
are administered ≥2 weeks prior to or ≥2 weeks after study
treatment/vaccine.
3) Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
4) Presence of at least 1 lesion with measurable disease as defined by RECIST v1.1 for response 
assessment. Subjects with lesions in a previously irradiated field as the sole site of measurable 
disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression 
and can be measured accurately. 
5) All subjects require a fresh tumor biopsy, these subjects must have at least one lesion accessible 
for pre- and on-treatment biopsy, in addition to the minimum one RECIST v1.1 measureable 
lesion required for response assessment. This lesion needs to be distinct from index lesion(s) 
being evaluated for radiological response.
6) Parts 1-7 subjects with prior exposure to therapy with any agent specifically targeting 
checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-LAG-3, and 
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anti-CTLA-4 antibody) are permitted after a washout period of any time greater than 4 weeks 
from the last treatment.
Note: (i) Subjects who experienced prior Grade 1 to 2 checkpoint therapy-related immune-
mediated AEs must have confirmed recovery from these events at the time of study entry, 
other than endocrinopathies treated with supplementation, as documented by resolution 
of all related clinical symptoms, abnormal findings on physical examination, and/or 
associated laboratory abnormalities. Where applicable, these subjects must also have
completed steroid tapers for treatment of these AEs by a minimum of 14 days prior to 
commencing treatment with study therapy.
(ii) Eligibility of subjects with prior ≥Grade 3 checkpoint therapy-related immune AEs, 
will be considered on a case-by-case basis after discussion and agreement between the 
investigators and the medical monitor (eg, asymptomatic isolated Grade 3 lipase 
elevations without clinical or radiological features of pancreatitis will be permitted to 
enroll).
7) Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose of 
study drug. Subjects with symptomatic tumor lesions at baseline that may require palliative 
radiotherapy within 4 weeks of first dose of study drug are strongly encouraged to receive 
palliative radiotherapy prior to enrollment.
8) All Subjects must consent to the acquisition of fresh pre- and on-treatment tumor biopsies for 
performance of correlative biomarker studies. Archival specimens may not be substituted for 
fresh baseline specimens but can be submitted to help understand the evolution of the tumor 
(ie, PD-L1 expression changes over time) for performance of correlative studies. Subjects who 
either do not consent to a pre-treatment tumor biopsy or do not have accessible lesions are not 
eligible. (However, subjects whose pre-treatment biopsy yields inadequate tissue quantity or 
quality will not be ineligible on this basis alone). 
9) All Subjects enrolled will be required to undergo mandatory pre- and on-treatment biopsies 
at acceptable clinical risk as judged by the investigator.
(a) The solid tumor tissue specimen must be a core needle, excisional, or incisional 
biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, or punch 
biopsies are not considered adequate for biomarker review. Biopsies of bone lesions 
that do not have a soft tissue component or decalcified bone tumor samples are also 
not acceptable. 
(b) Biopsied lesions should be distinct from index lesion(s) being evaluated for 
radiological response
10) Adequate organ function for subjects as defined by the following:
(a) Neutrophils ≥1500/μL
(b) Platelets ≥80 × 103/μL (transfusion to achieve this level is not permitted within 2 
weeks of first study drug administration)
(c) Hemoglobin ≥8 g/dL (transfusion to achieve this level is not permitted within 
2 weeks of first study drug administration)
(d) ALT and AST ≤3× upper limit of normal (ULN)
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(e) Total bilirubin ≤1.5 × ULN (except subjects with Gilbert’s Syndrome who must 
have normal direct bilirubin)
(f) Normal thyroid function or stable on hormone supplementation, per investigator 
assessment
(g) Albumin ≥2 g/dL
(h) Serum creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥40 mL/min (measured 
using the Cockcroft-Gault formula below):
Female CrCl = 
(140 - age in years) × weight in kg × 0.85
72 × serum creatinine in mg/dL
Male CrCl =
(140 - age in years) × weight in kg × 1.00 
72 × serum creatinine in mg/dL
11) Ability to comply with treatment, PK, and PD sample collection and required study follow-up
Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the 
study as a pre-treatment failure (eg, subject has not been treated). If re-enrolled, the subject must 
be re-consented.
3) Age and Reproductive Status
a) Men and women, ages ≥18 years at the time of informed consent
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic 
gonadotrophin [hCG]) within 24 hours prior to the start of study drug.
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration 
of treatment with study drug BMS-986178 plus 5 half-lives of study drug plus 30 days. 
This duration should be 12 weeks for Parts 1 and 3 subjects (50 days plus 30 days) or 
5 months for Part 2 subjects (130 days plus 30 days [duration of ovulatory cycle]), for a 
total of up to 160 days post-treatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug BMS-986178 plus 
5 half-lives of the study drug plus 90 days. The duration should be 20 weeks for Parts 1 
and 3 subjects (50 days plus 90 days) or 7 months for Part 2 subjects (130 days plus 90 days 
[duration of sperm turnover]), for a total of up to 220 days post-treatment completion. In 
addition, male subjects must be willing to refrain from sperm donation during this time.
f)
Azoospermic males are exempt from contraceptive requirements. WOCBP who are 
continuously not heterosexually active are also exempt from contraceptive requirements, 
but must still undergo pregnancy testing as described in this section.
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Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise on the use of highly effective methods of contraception, which have a 
failure rate of < 1% when used consistently and correctly.
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently and 
correctly. WOCBP and female partners of male subjects who are WOCBP are expected to use one 
of the highly effective methods of contraception (listed below). Local laws and regulations may 
require use of alternative and/or additional contraception methods. Male subjects must inform their 
female partners who are WOCBP of the contraceptive requirements of the protocol and are 
expected to adhere to using contraception with their partner. Male subjects are expected to use a 
condom, in addition to a highly effective method as noted in the list below:
1. Progestogen only hormonal contraception associated with inhibition of ovulation
2. Hormonal methods of contraception including oral contraceptive pills containing 
combined estrogen and progesterone, vaginal ring, injectables, implants, and intrauterine 
devices (IUDs) such as Mirena®
3. Nonhormonal IUDs, such as ParaGard®
4. Bilateral tubal occlusion
5. Vasectomized partner with documented azoospermia 90 days after procedure
♦Vasectomy is a highly effective birth control method provided that the partner is the 
sole sexual partner of the WOCBP trial participant and that the vasectomized partner 
has received medical assessment of the surgical success.
6. Intrauterine hormone-releasing system
7. Complete abstinence
♦Complete abstinence is defined as the complete avoidance of heterosexual intercourse 
(refer to Glossary of Terms)
♦Complete abstinence is an acceptable form of contraception for all study drugs and 
must be used throughout the duration of the study treatment (plus 5 half-lives of the 
study drug(s) plus 30 days).
♦It is not necessary to use any other method of contraception when complete abstinence 
is elected.
♦Subjects who choose complete abstinence must continue to have pregnancy tests, as 
specified in Section 5.1.
♦Acceptable alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
♦The reliability of sexual abstinence needs to be evaluated in relation to the duration of 
the clinical trial and the preferred and usual lifestyle of the subject.
8. Use a condom in male subjects with female partners.
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UNACCEPTABLE METHODS OF CONTRACEPTION
1) Periodic abstinence (calendar, symptothermal, and/or post-ovulation methods)
2) Withdrawal (coitus interruptus)
3) Spermicide only
4) Lactation amenorrhea method
5) Diaphragm with spermicide
6) Cervical cap with spermicide
7) Vaginal sponge with spermicide
8) Male or female condom with or without spermicide*
9) Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary 
mode of action.
* A male and a female condom must not be used together.
3.3.2
Exclusion Criteria
1) Target Disease Exceptions
a) Subjects with known or suspected CNS metastases or untreated CNS metastases, or with 
the CNS as the only site of disease, are excluded. However, subjects with controlled brain 
metastases will be allowed to enroll. Controlled brain metastases are defined as no 
radiographic progression for at least 4 weeks following radiation and/or surgical treatment 
(or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for 
at least 2 weeks, and no new or progressive neurological signs and symptoms.
b) Subjects with carcinomatous meningitis
c) For ovarian cancer (Part 3B):
i)
Ovarian cancer subjects with history of bowel obstruction in the prior 6 months or with 
intraperitoneal catheter (eg.Tenckhoff) will be excluded. 
ii)
Not applicable
d) For NSCLC (Part 7B)
i)
Subjects with known EGFR mutations, which are sensitive to available targeted 
inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 21 
[L858R] substitution mutations), are excluded. All subjects with non-squamous 
histology must have been tested for EGFR mutation status; use of an FDA-approved 
test is strongly encouraged. Subjects with non-squamous histology and unknown or 
indeterminate EGFR status are excluded.
ii) Subjects with known ALK translocations, which are sensitive to available targeted 
inhibitor therapy, are excluded. If tested, the use of an FDA-approved test is strongly 
encouraged. Subjects with unknown or indeterminate ALK status may be enrolled.
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e) For Bladder Cancer (Part 8)
i)
Prior therapy with experimental anti-tumor vaccines, any T-cell co-stimulation or 
checkpoint pathways, such as anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-
CTLA-4 antibody, including ipilimumab, or other medicines specifically targeting T-
cells is also prohibited in this part of the study.
ii) No prior adverse reaction to tetanus toxoid-containing vaccines.
iii) Subjects with known allergies to egg products, neomycin, or tetanus toxoid are also 
considered ineligible.
2) Medical History and Concurrent Diseases
a) Subjects with a prior malignancy, different from the one used for enrollment in this study, 
diagnosed within less than 2 years prior to study entry are excluded (except non-melanoma 
skin cancers and in situ cancers such as bladder, colon, cervical/dysplasia, melanoma, or 
breast). In addition, subjects with other second malignancies diagnosed more than 2 years 
ago who have received therapy with curative intent with no evidence of disease during the 
interval who are considered by the investigator to present a low risk for recurrence will be 
eligible.
b) Subjects with other active malignancy requiring concurrent intervention are excluded.
c) Prior organ allograft
d) Previous treatment:
i)
Prior anti-cancer treatments are permitted (ie, chemotherapy, radiotherapy, hormonal, 
or immunotherapy) except in Parts 6B (Inclusion criteria 1.a)(1)2)(e)) and 7B 
(Inclusion criteria 1.a)(1)2)(f)). 
ii) Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery must 
either have resolved, returned to baseline or Grade 1, or have been deemed irreversible.
iii) For cytotoxic agents, at least 4 weeks must have elapsed between the last dose of prior 
anti-cancer therapy and initiation of study therapy.
iv) For non-cytotoxic agents, at least 4 weeks or 5 half-lives (whichever is shorter) must 
have elapsed from last dose of prior anti-cancer therapy and the initiation of study 
therapy. If 5 half-lives is shorter than 4 weeks, agreement with Sponsor/medical 
monitor is mandatory. 
e) Subjects with prior therapy with any agent specifically targeting T-cell co-stimulation
pathways such as anti-OX40 antibody, anti-CD137, anti-GITR antibody, and anti-CD27 
are excluded.
f)
Subjects with active, known, or suspected autoimmune disease are excluded. Subjects with 
vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition 
only requiring hormone replacement, euthyroid subjects with a history of Grave’s disease 
(subjects with suspected autoimmune thyroid disorders must be negative for thyroglobulin 
and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first 
dose of study drug), psoriasis not requiring systemic treatment, or conditions not expected 
to recur in the absence of an external trigger are permitted to enroll. Subjects with well 
controlled asthma and/or mild allergic rhinitis (seasonal allergies) are eligible.
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g) Subjects with history of life-threatening toxicity related to prior immune therapy (eg, anti-
CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting 
T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to 
re-occur with standard countermeasures (eg, hormone replacement after adrenal crisis)
h) Subjects with interstitial lung disease that is symptomatic or that may interfere with the 
detection or management of suspected drug-related pulmonary toxicity
i)
Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg 
daily prednisone equivalents) or other immunosuppressive medications within 14 days of 
study drug administration except for adrenal replacement steroid doses > 10 mg daily 
prednisone equivalent in the absence of active autoimmune disease. Note: Treatment with 
a short course of steroids (< 5 days) up to 7 days prior to initiating study drug is permitted.
j)
Uncontrolled or significant cardiovascular disease, including but not limited to any of the 
following:
i)
Myocardial infarction or stroke/transient ischemic attack within the past 6 months
ii) Uncontrolled angina within the past 3 months
iii) Any history of clinically significant arrhythmias (such as ventricular tachycardia, 
ventricular fibrillation, or torsades de pointes)
iv) History of other clinically significant heart disease (eg, cardiomyopathy, myocarditis, 
congestive heart failure with New York Heart Association functional classification III-
IV, pericarditis, significant pericardial effusion)
v) Cardiovascular disease-related requirement for daily supplemental oxygen therapy
vi) QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation 
> 480 msec
k) History of any chronic hepatitis as evidenced by the following:
i)
Positive test for hepatitis B surface antigen
ii) Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR])
Note: Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by 
PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion 
criterion.
Additional testing or substitute testing per institutional guidelines to rule out infection is 
permitted.
l)
Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal 
therapy ≤7 days prior to initiation of study drug therapy (does not apply to viral infections 
that are presumed to be associated with the underlying tumor type required for study entry)
m) Known history of testing positive for HIV or known acquired immunodeficiency 
syndrome. Note: Testing for HIV must be performed at sites where mandated by local 
requirements.
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n) Any major surgery within 4 weeks of study drug administration. Subjects must have 
recovered from the effects of major surgery or significant traumatic injury at least 14 days 
before the first dose of study drug.
o) Use of non-oncology vaccines containing live virus for prevention of infectious diseases 
within 4 weeks prior to study drug. The use of inactivated seasonal influenza vaccines, eg, 
Fluzone®, will be permitted on study without restriction.
p) Use of packed red blood cell or platelet transfusion within 2 weeks prior to the first dose 
of study drug
q) A known or underlying medical or psychiatric condition and/or social reason that, in the 
opinion of the investigator or Sponsor, could make the administration of study drug 
hazardous to the subject or could adversely affect the ability of the subject to comply with 
or tolerate the study.
3) Allergies and Adverse Drug Reaction
a) History of allergy to nivolumab or ipilimumab (Parts 2 and 4 or 3 and 5, respectively) or 
history of allergy to the combination of nivolumab and ipilimumab (Parts 6 and 7)
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) to prior anti-
cancer immune modulating therapies (eg, checkpoint inhibitors, T-cell co-stimulatory 
antibodies)
4) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances, a person who has been imprisoned may be included or permitted to continue 
as a subject. Strict conditions apply, and BMS approval is required.)
b) Subjects who are compulsorily detained for the treatment of either psychiatric or physical 
(eg, infectious disease) illness
c) Inability to comply with restrictions and prohibited activities/treatments as listed in 
Section 3.4
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
WOCBP is defined as any female who has experienced menarche and who has not undergone 
surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. 
Menopause 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 documented serum follicle stimulating hormone (FSH) level > 40 mIU/mL to confirm 
menopause.
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 
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RECIST v1.1 (see Appendix 3)-defined progressive disease as long as they meet the following 
criteria:
•
Investigator-assessed clinical benefit and without rapid disease progression
•
Continue to meet all other study protocol eligibility criteria
•
Subject tolerates study drug
•
Subject has stable performance status
•
Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, CNS metastases).
•
Subject provides written informed consent prior to receiving any additional BMS-986178, 
nivolumab, and/or ipilimumab treatment using an ICF describing any reasonably foreseeable 
risks or discomforts or other alternative treatment options.
The assessment of clinical benefit should take into account whether the subject is clinically
deteriorating and unlikely to receive further benefit from continued treatment. All decisions to 
continue treatment beyond initial progression must be discussed with the BMS Medical Monitor, 
and an assessment of the risk/benefit of continuing with study therapy must be documented in the 
study records. Subjects will be re-consented to explain the rationale for this ongoing treatment. 
3.5.1.1
Discontinuation due to Further Progression 
Subjects should discontinue study therapy upon further evidence of further progression, defined 
as an additional 10% or greater increase in tumor burden volume from the time of initial 
progression (including all target lesions and new measurable lesions). 
The tumor burden volume from the time of initial progression should be used as the reference 
baseline for comparison with the postprogression assessment.
Any new lesion considered non-measurable at the time of initial progression may become 
measurable, and therefore, must be included in the tumor burden measurement as follows:
For solid tumors: New lesions are considered measurable at the time of initial progression if the 
longest diameter is at least 10 mm (except for pathological lymph nodes, which must have a short 
axis of at least 15 mm). 
For statistical analyses that include the investigator-assessed progression date, subjects who 
continue treatment beyond the initial investigator-assessed, RECIST v1.1-defined progression will 
be considered to have investigator-assessed progressive disease at the time of the initial 
progression event.
3.5.1.2
Assessment Schedule for Subjects with Post-progression Treatment
Subjects should continue to receive monitoring according to the on-treatment assessments in Table 
5.1-1, Table 5.1-2, Table 5.1-3, Table 5.1-4, Table 5.1-5, Table 5.1-6, Table 5.1-7, and Table 5.1-
8. Radiographic assessment by computed tomography (CT) (preferred) or MRI described in 
Section 5.1 and Appendix 3 is required when subjects continue post-progression treatment. For 
subjects that discontinue postprogression treatment with study therapy, no additional radiographic 
assessments will be required.
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3.6
Post-study Drug Follow-up
Post-study follow-up is of critical importance and is essential to preserving subject safety and the 
integrity of the study. Subjects who discontinue study drug must continue to be followed per the 
Safety Follow-up (approximately 100 days). 
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug 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 subject 
specifically withdraws consent for any further contact with him/her or persons previously 
authorized by the subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug 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 subject 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.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing status. 
This includes follow-up with persons authorized by the subject as noted above. Lost to follow-up 
is defined by the inability to reach the subject after a minimum of 3 documented phone calls, faxes, 
texts, or emails as well as lack of response by the subject to 1 registered mail letter. All attempts 
should be documented in the subject’s medical records. If it is determined that the subject has died, 
the site will use permissible local methods to obtain the 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 subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’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 subject remains lost to follow-up, then the last known alive date as determined by the 
investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
In this study, all drugs will be considered investigational products: BMS-986178, nivolumab,
ipilimumab, and tetanus vaccine (Table 4.-1).
Product description and storage information are described in Table 4.-1.
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Table 4.-1:
Study Drugs for CA012004
Product 
Description 
Class and 
Dosage Form
Potency
IP/Non-
IP
Blinded or 
Open 
Label
Packaging/Appearance
Storage 
Conditions
(per label)
BMS-986178 
Injection
25 mg/mL
(80 mg/vial)
IP
Open
Colorless to pale yellow 
liquid. Clear to slightly 
opalescent. Light (few) 
particulates (consistent in 
appearance to proteinaceous 
particulates) may be present.
Store at 2°C to 
8°C; do not 
freeze; protected 
from light.
Nivolumab 
Injection
10 mg/mL
(100 mg/vial)
IP
Open
Clear to opalescent, 
colorless to pale yellow 
liquid. Light (few) 
particulates may be present.
Store at 2°C to 
8°C; store in 
original 
package; do not 
freeze; protected 
from light.
Ipilimumab 
Injection
5 mg/mL
(200 mg/vial)
IP
Open
Clear, colorless liquid. Light 
(few) particulates may be 
present.
Store at 2°C to 
8°C; do not 
freeze; protected 
from light.
Tetanus vaccine
Per locala
IP
Open
Various packaging 
configuration
Refer to the 
label on 
container and/or 
pharmacy 
manual
Abbreviations: IP = investigational product
a  Tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be obtained as 
local commercial product in countries if allowed by local regulations or through investigating sites standard 
prescribing procedures.
4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined as a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that the investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, the investigational products are BMS-986178, nivolumab, ipilimumab, and 
tetanus vaccine.
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4.2
Non-Investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the SOC for a given diagnosis, may be considered as non-investigational 
products.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug 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 drug arise, the study drug should not be dispensed 
and contact BMS immediately.
Nivolumab and ipilimumab will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets). Please 
refer to Section 9.2.2 for guidance on IP records and documentation.
BMS-986178 Preparation
Calculated dosages for solutions for infusion may be mixed in a D5W bag or normal saline (0.9% 
NaCl) bag to a recommended concentration. Further details with regard to specific concentrations 
for drug dilution and administration will be provided in the pharmacy dosing manual for 
BMS-986178.
BMS-986178 Administration
The administration of the entire bag or syringe (if syringe pump is used) contents should be infused 
over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion 
line), through an IV infusion set (sterile, non-pyrogenic diethylhexyl phthalate [DEHP]-free and 
non-DEHP free components, low protein binding, polyethersulfone or nylon 0.2-μm in line filter, 
which will be supplied by the site). Care must be taken to ensure the sterility of the prepared 
solution, as the drug product does not contain antimicrobial preservatives or bacteriostatic agents. 
Equilibration to room temperature is recommended for the drug product, infusion fluid, and their 
combination prior to administration.
Diluted solutions of BMS-986178 for injection are stable for up to 24 hours, at either refrigerated 
conditions, 2° to 8°C (36° to 46°F), and light protected; 4 hours of which can be under ambient 
temperature 15 to 25°C (59° to 77°F), and ambient light conditions. The diluted bag should not be 
shaken. Infusion of BMS-986178 injection must be completed within 24 hours of dilution. The 
start of drug infusion equals zero (0) hour.
For treatment visits in which both BMS-986178 and nivolumab are administered, nivolumab will 
be administered first followed by BMS-986178 after a minimum of 30 minutes following 
completion of the nivolumab infusion and flush. Further details regarding preparation and 
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administration will be provided separately in site/pharmacy training materials and Investigator’s 
Brochure for BMS-986178.146
For treatment visits in which both BMS-986178 and ipilimumab are administered, ipilimumab will 
be administered first followed by BMS-986178 after a minimum of 30 minutes following 
completion of the ipilimumab infusion and flush. Further details regarding preparation and 
administration will be provided separately in site/pharmacy training materials and Investigator’s 
Brochure for BMS-986178.146
For treatment visits in which BMS-986178, nivolumab, and ipilimumab are administered, 
nivolumab will be administered first followed by ipilimumab then BMS-986178. After each 
30-minute infusion, there will be a 30-minute waiting period and a flush before starting the next 
study drug infusion. Further details regarding preparation and administration will be provided 
separately in site/pharmacy manual and Investigator’s Brochure for BMS-986178.146
4.4
Method of Assigning Subject Identification
This is an open-label study. All enrolled subjects, including those not dosed, will be assigned 
sequential subject numbers starting with 00001, (eg, 00001, 00002, 00003... 00010). Those 
enrolled subjects meeting the inclusion and exclusion criteria will be eligible to be dosed.
Once informed consent has been obtained, the investigator (or designee) will register the subject 
by an IRT.
The following information is required for registration:
•
Gender
•
Diagnosis (if applicable)
•
Statement that subject is eligible
•
Date of informed consent
•
Date of Birth
Based on the rate of subject enrollment, the Sponsor will implement an IRT to assign subject 
numbers, study part and dose level as well as manage drug supply. IRT instructions will be 
provided to the sites in a separate instruction manual.
Treatment group/dose level will be provided to the site study team through the IRT after the subject 
has been deemed eligible and is assigned for the study. Site personnel/investigator will receive a 
receipt confirming the treatment assignment. A copy of this documentation should remain in the 
subject’s chart. Because of the nature of the study design, limited early access to the assignment 
information will be granted to the study team.
Once it is determined that the subject meets the eligibility criteria, the investigative site will register 
the subject through IRT prior to the first study drug administration. 
Subjects will be assigned to a part or a cohort within a part by IRT. Details about how the subjects 
will be assigned to a specific part/cohort will be provided in IRT training documentation.
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In the dose escalation phases, if a subject discontinues treatment with either BMS-986178, 
nivolumab, or ipilimumab during the DLT period for reasons other than a DLT, the subject may 
be replaced with a new subject, if necessary, for safety assessments. Replacement subjects will 
receive the same treatment but will be assigned a new subject number.
Additional subjects may be added to expansion cohorts and Part 8 if adequate paired pre-treatment 
and on-treatment biopsy specimens are not obtained from previously assigned subjects. The 
additional subjects will receive the same treatment as the subjects being replaced, but new subject 
numbers will be assigned.
Subjects may be permitted to rescreen for the study following agreement between the investigator 
and the Sponsor/medical monitor.
4.5
Selection and Timing of Dose for Each Subject
Each subject will be assigned to a specific dose level as listed in Section 4.4 during dose escalation. 
Subjects in the dose expansion will be treated at the MTD, or at the RP2D, as agreed upon by the 
investigators and the Sponsor.
Nivolumab will be administered as flat doses. There will be no dose escalations or reductions of 
nivolumab allowed once assigned. There are no premedications recommended for nivolumab on 
the first cycle. If an acute infusion reaction is noted, the subjects should be managed according to 
Section 4.5.7.
Ipilimumab will be administered at 1 or 3 mg/kg. There will be no dose escalations or reductions 
of ipilimumab allowed once assigned. There are no premedications recommended for ipilimumab 
on the first cycle. If an acute infusion reaction is noted, the subjects should be managed according 
to Section 4.5.7.
There will be no dose escalations or reductions of BMS-986178 allowed once assigned.
4.5.1
Dose Limiting Toxicity
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, severity, 
and duration of AEs, for which no clear alternative cause is identified and that occur within 28 days
of initiation of study drug(s). AEs will be graded according to the NCI CTCAE v4.03.
For the purpose of subject management, potential DLTs that occur at any time, whether during 
dose escalation or dose expansion, will result in all study drug(s) being held pending evaluation of 
the event’s relatedness to study drug, severity, duration, and in accordance with Section 4.5.4. 
Subjects must meet criteria for treatment prior to re-initiation of study treatment (see 
Section 4.5.5).
For the purpose of subject management, an AE that meets the DLT criteria, regardless of the cycle 
in which it occurs, will lead to discontinuation of study drug(s) except for exceptions as outlined 
in Section 4.5.6. Such subjects will not be retreated with study drug(s) and will enter the Safety 
Follow-up period of the study.
Subjects who withdraw from the study during the DLT evaluation interval for reasons other than 
a DLT may be replaced with a new subject at the same dose level. The incidence of DLT(s) during 
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the DLT evaluation period will be used in dose escalation decisions and to define the MTD. All 
AEs for which no clear alternative cause is identified occurring after the 28-day DLT period may 
be considered to represent DLTs for the purposes of defining the RP2D upon agreement between 
the Sponsor, medical monitor, and investigators, if they are determined to have no clear alternative 
cause and not related to disease progression. DLT criteria will be utilized for the evaluation of a 
manageable and tolerable dose in the schedule and dose exploration parts (Parts 4, 5, and 8) and 
safety cohorts (Parts 6A and 7A).
Any one of the following events for which an alternative cause cannot be identified will be 
considered a DLT:
A. Hepatic DLT
•
Any ≥Grade 3 elevation of AST, ALT, or total bilirubin
•
Grade 2 AST or ALT with symptomatic liver inflammation (eg, right upper quadrant 
tenderness, jaundice, pruritus)
•
AST or ALT > 3 × ULN and concurrent total bilirubin > 2 × ULN without initial findings 
of cholestasis (elevated serum alkaline phosphatase (eg, findings consistent with Hy’s law 
or FDA definition of potential drug-induced liver injury [pDILI]) (Note that this special 
category of DLT uses ULN rather than CTC Grade for definition.)
B. Non-hepatic DLT
•
Grade 2 or greater uveitis, episcleritis, or iritis
•
Any other Grade 2 eye pain or blurred vision that does not respond to topical therapy and 
does not improve to Grade 1 severity within 2 weeks OR requires systemic treatment 
•
Grade 3 or greater pneumonitis, bronchospasm, neurologic toxicity, hypersensitivity 
reaction, or infusion reaction 
•
Any Grade 3 or greater non-dermatologic, non-hepatic toxicity will be considered a DLT 
with the following specific EXCEPTIONS:
♦Grade 3 or Grade 4 electrolyte abnormalities that are not complicated by associated 
clinical adverse experiences, last less than 72 hours, and either resolve spontaneously 
or respond to conventional medical intervention
♦Grade 3 nausea, vomiting, or diarrhea that lasts less than 72 hours, and either resolves 
spontaneously or responds to conventional medical intervention
♦Grade 3 or 4 elevation of amylase or lipase not associated with clinical or radiographic 
evidence of pancreatitis
♦Isolated 
Grade 
3 
fever 
not 
associated 
with 
hemodynamic 
compromise 
(eg, hypotension, clinical, or laboratory evidence of impaired end-organ perfusion)
♦Grade 3 endocrinopathy that is well controlled by hormone replacement
♦Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to sites of known 
or suspected tumor)
♦Grade 3 fatigue for ≤7 days
♦Grade 3 infusion reaction that returns to Grade 1 in less than 6 hours
C. Dermatologic DLT
•
Grade 4 rash
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•
Grade 3 rash if no improvement (ie, resolution to ≤Grade 1) after a 1- to 2-week infusion 
delay. Subjects who have not experienced a Grade 3 skin AE may resume treatment in the 
presence of Grade 2 skin toxicity.
D. Hematologic DLT
•
Grade 4 neutropenia ≥7 days in duration
•
Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant 
bleeding, or any requirement for platelet transfusion
•
Grade 4 anemia not explained by underlying disease
•
Grade ≥3 febrile neutropenia
•
≥Grade 3 hemolysis (ie, requiring transfusion or medical intervention such as steroids)
4.5.2
Management Algorithms for Immuno-Oncology Agents
IO agents are associated with AEs that can differ in severity and duration from AEs caused by 
other therapeutic classes. Nivolumab, ipilimumab, and BMS-986178 are considered IO agents in 
this protocol. Early recognition and management of AEs associated with IO agents may mitigate 
severe toxicity. Management algorithms have been developed from extensive experience with 
nivolumab and ipilimumab to assist investigators in assessing and managing the following groups 
of AEs:
•
Gastrointestinal
•
Renal
•
Pulmonary
•
Hepatic
•
Endocrinopathies
•
Skin
•
Neurological
•
The clinical nature of AEs noted with BMS-986178 will determine the role of the above 
algorithms for use in toxicities related to its use in this study. 
The algorithms recommended for utilization in this protocol are included in Appendix 2.
4.5.3
Guidelines for Dose Modification
Intra-subject dose escalation or reduction of BMS-986178, nivolumab, or ipilimumab is not 
permitted in this study in order to allow better evaluation of the extended safety and efficacy at 
individual dose levels and schedules.
4.5.4
Dose Delays due to Toxicity
Subjects who experience the following must have all study drug(s) held:
•
Potential DLTs, until DLT relatedness is defined.
•
Select AEs and laboratory abnormalities: 
−
≥Grade 1 pneumonitis
−
≥Grade 2 abnormality in AST, ALT, total bilirubin 
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−
≥Grade 2 creatinine
−
≥Grade 2 non-skin, drug related AE, with the exception of fatigue
−
≥Grade 2 diarrhea or colitis
−
≥Grade 2 neurological AE 
−
Grade 4 amylase and/or lipase abnormalities regardless of symptoms or clinical 
manifestation. (Grade 3 amylase or lipase increase that is not associated with symptoms or 
clinical manifestations of pancreatitis does not require dose delay)
•
AE, laboratory abnormality, or concurrent illness that, in the judgment of the Investigator, 
warrants delaying the dose of study drug.
If a dose delay is necessary for subjects who are receiving study treatment, all study drugs must 
be held. Dosing visits are to be delayed but not skipped to ensure that subjects will receive all
scheduled treatment cycles if toxicity allows. During treatment, dosing will be as follows:
•
Part 2 subjects will receive 12 doses (12 cycles) of q2w BMS-986178 and nivolumab 
combination therapy.
•
Parts 3 and 5 subjects will receive up to 4 doses of q3w BMS-986178 and ipilimumab 
combination therapy and 4 doses of q3w BMS-986178 monotherapy during maintenance.
•
Part 4 subjects will receive 6 doses (6 cycles) of q4w BMS-986178 and nivolumab 
combination therapy.
•
Part 6 subjects will receive 4 doses of q3w BMS-986178, nivolumab, and ipilimumab 
combination therapy and 3 doses of q4w BMS-986178 and nivolumab during maintenance.
•
Part 7 subjects will receive 4 cycles (1 cycle = 6 weeks) of q2w BMS-986178 and nivolumab 
and q6w ipilimumab combination therapy.
•
Part 8
−
Cohorts 1-3 subjects will receive 9 doses of BMS-986178 (q12w) and 27 doses of 
nivolumab (q4w) combination therapy.
−
Cohort 4 subjects will receive 27 doses of nivolumab (q4w) monotherapy.
Subjects receiving BMS-986178 in combination with nivolumab and/or ipilimumab who have 
study treatment-related toxicities that meet the criteria for a dose delay should have all study drugs 
held until the criteria to resume treatment are met (see Section 4.5.5). Subjects who require a dose 
delay should be re-evaluated weekly, or more frequently if clinically indicated, and resume 
treatment when criteria are met. Because nivolumab-, ipilimumab- and/or BMS-986178-related 
AEs require early recognition and prompt intervention, management algorithms have been 
developed for suspected pulmonary toxicity, gastrointestinal toxicity, hepatotoxicity, 
endocrinopathy, skin toxicity, neurological toxicity, and renal toxicity (algorithms are provided in 
Appendix 2).
For subjects who have dose delays, the total study treatment period should not exceed 36 weeks, 
unless approved by the BMS Medical Monitor (or designee). Extensions to the period of dose 
delays may be granted for individual subjects on a case by case basis after specific consultation 
and agreement between the investigator and BMS medical monitor in settings where risk/benefit
may justify continued study therapy (eg, subject deriving clinical benefit who requires prolonged 
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steroid taper for the management of non-DLT drug-related AEs, or experiences delays for the 
management of a non-drug-related AE).
The end of cycle tumor assessments (ie, CT/MRI, etc) will continue every 8 weeks Part 1-7 or 
every 12 weeks Part 8 (± 1 week) relative to the subject’s first dose of BMS-986178, regardless of 
any treatment delay incurred.
4.5.5
Criteria to Resume Treatment
4.5.5.1
Criteria to Resume Treatment in Subjects with a Dose Delay
If a dose delay is necessary for subjects who are receiving study treatment, all study drugs must 
be held.
Subsequent dosing with study therapy may resume once non-DLT AEs resolve to Grade 1 or 
baseline. 
Subjects experiencing AEs not meeting the criteria for permanent discontinuation as outlined in 
Section 4.5.6 may resume treatment with study medication under the following criteria:
•
Subjects may resume treatment with study drug when the AE(s) resolve to Grade ≤1 or 
baseline value with the following exceptions:
−
Subjects may resume treatment in the presence of Grade 2 fatigue.
−
Subjects who have not experienced a Grade 3 skin AE may resume treatment in the 
presence of Grade 2 skin toxicity.
−
Subjects with Grade 2 eye pain or blurred vision not meeting DLT criteria (Section 4.5.1) 
must resolve to baseline prior to resuming study therapy.
−
Any pulmonary toxicity, diarrhea, or colitis must have resolved to baseline before 
treatment is resumed. Subjects with persistent Grade 1 pneumonitis after completion of a 
steroid taper over at least 1 month may be eligible for resumption of treatment if discussed 
with and approved by BMS Medical Monitor (or designee).
−
Subjects with endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment after consultation with the BMS Medical Monitor (or 
designee). Adrenal insufficiency requires discontinuation regardless of control with 
hormone replacement.
−
For subjects with Grade 2 AST, ALT and/or total bilirubin abnormalities, dosing may 
resume when laboratory values return to baseline and management with corticosteroids, if 
needed, is complete.
−
Subjects with a Grade 4 amylase or lipase increase that is not associated with symptoms or 
clinical manifestations of pancreatitis can be restarted on therapy once the levels have 
decreased to Grade 3 or lesser - and after consultation with the BMS Medical Monitor.
•
If study treatment is delayed past the scheduled dosing visit per protocol, the scheduled study 
treatment administration will be delayed, but not skipped, until dosing resumes to ensure that 
subjects will receive all scheduled treatment cycles if toxicity allows.
•
The consideration to re-initiate study therapy under these exceptions will be made on a case 
by case basis after considering the overall risk/benefit profile and in consultation between the 
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investigator and the study Sponsor. Any AE with clinical risk will be assessed on a case by 
case basis with the investigator and the BMS Medical Monitor to determine the risks and 
benefits of continuing on therapy following resolution versus discontinuing therapy 
permanently.
•
If dosing is delayed ≥9 weeks, the subject must be permanently discontinued from study 
treatment, except as specified in Section 4.5.6. Extensions to the period of dose delays may be 
granted for individual subjects on a case by case basis after specific consultation and agreement 
between the investigator and BMS medical monitor in settings where risk/benefit may justify 
continued study therapy (eg, subject deriving clinical benefit who requires prolonged steroid 
taper for the management of non-DLT immune-related AEs, or experiences delays for 
management of a non-drug-related AE).
•
Dosing delays to allow prolonged steroid tapers to manage AEs are allowed. Additionally, 
dosing delays ≥9 weeks (as noted above) that occur for non-drug-related reasons may be 
allowed if approved by the BMS Medical Monitor.
•
If the toxicity resolves to ≤Grade 1 or baseline > 9 weeks after the last dose, the subject does 
not meet the criteria for permanent discontinuation (see Section 4.5.6), and the investigator 
believes that the subject is deriving clinical benefit, the subject may be eligible to resume study 
treatment(s) following approval from the BMS Medical Monitor (or designee).
•
Tumor assessments should continue as per protocol even if dosing is delayed.
4.5.5.2
Criteria for Resuming Treatment in Subjects with an Infusion Reaction
In subjects experiencing an infusion reaction with study drug administration, the following 
guidelines for dose delay and criteria to resume treatment are to be followed:
•
Parts 2, 4, 6, 7, and 8 on days with administration of BMS-986178 and nivolumab only: If a 
nivolumab-related infusion reaction prevents subsequent infusion of BMS-986178 on the same 
day, the dose of BMS-986178 should be replaced as soon as possible. In such instances, at 
least 12 days must elapse between the replacement dose of BMS-986178 and the 
administration of the next dose of nivolumab combined with BMS-986178.
•
Parts 3 and 5: If an ipilimumab-related infusion reaction prevents subsequent infusion of
BMS-986178 on the same day, the dose of BMS-986178 should be replaced as soon as 
possible. In such instances, at least 19 days must elapse between the replacement dose of 
BMS-986178 and the administration of the next dose of ipilimumab combined with 
BMS-986178 on a q3w schedule.
•
Parts 6 or 7: If a nivolumab-related infusion reaction prevents subsequent infusion of 
ipilimumab and/or BMS-986178 on the same day, the dose of ipilimumab and BMS-986178 
should be replaced as soon as possible. In such instances, at least 19 days must elapse between 
the replacement dose of ipilimumab and the administration of the next dose of BMS-986178 
and nivolumab combined with ipilimumab on a q3w schedule. However, if an ipilimumab-
related infusion reaction prevents subsequent infusion of BMS-986178 on the same day, the 
dose of BMS-986178 should be replaced as soon as possible. In such instances, at least 19 days 
must elapse between the replacement dose of BMS-986178 and the administration of the next 
dose of BMS-986178 and nivolumab combined with ipilimumab.
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Guidelines for management of an infusion reaction during study drug administration are included 
in Section 4.5.7.
4.5.6
Guidelines for Permanent Discontinuation
Subjects will be required to permanently discontinue all study drugs for the following AEs:
•
Progressive Disease (see also Section 3.5.1 for details regarding continuing treatment beyond 
disease progression)
•
Clinical deterioration, as assessed by the investigator
•
Grade 3 infusion reaction that does not return to Grade 1 in less than 6 hours
•
Grade 3 or greater pneumonitis, bronchospasm or, neurologic toxicity
•
Life-threatening skin toxicity (toxic epidermal necrolysis)
•
Grade 2 or greater episcleritis, or iritis. Any Grade 2 or greater drug-related uveitis, eye pain 
or blurred vision that does not respond to topical therapy and does not improve to Grade 1 
severity within the re-treatment period OR requires systemic treatment.
•
Any Grade 4 AE; however, an exception may be made for the following upon consultation 
between the investigator and BMS medical monitor:
−
Grade 4 electrolyte abnormalities ≤72 hours in duration
−
Grade 4 neutropenia ≤7 days in duration
−
Grade 4 lymphopenia or leukopenia.
−
Grade 4 increase in amylase or lipase that is not associated with clinical or radiographic 
evidence of pancreatitis
−
Grade 4 drug-related endocrinopathy adverse events, such as, hyper- or hypothyroidism, 
or glucose intolerance, which resolve or are adequately controlled with physiologic 
hormone replacement (corticosteroids, thyroid hormones) or glucose-controlling agents, 
respectively, may not require discontinuation after discussion with and approval from the 
BMS Medical Monitor.
•
Any toxicity that meets DLT criteria as defined in Section 4.5.1; however, an exception may 
be made on a case-by-case basis upon consultation between the investigator and BMS medical 
monitor:
−
Grade 3 diarrhea, nausea, vomiting, or abdominal pain that returns to Grade 1 or baseline 
within 3 days with medical intervention
−
AST or ALT > 5× and < 8× institutional ULN for < 2 weeks
−
Grade 3 pruritus or rash that returns to Grade 1 or baseline within 7 days with medical 
intervention
The consideration to re-initiate study therapy under these exceptions will be made on a 
case-by-case basis after considering the overall risk/benefit profile and in consultation 
between the investigator and the Sponsor.
•
Confirmed CR
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•
Completion of 24 weeks of treatment (Parts 1-7) or 24 months for Part 8. Subjects in Part 2, 4 
6, or 7 that continue for additional cycles up to 24 months of treatment.
All subjects who discontinue study drug(s) should comply with protocol-specified follow-up 
procedures as outlined in Section 5.1. The only exception to this requirement is when a subject 
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 a 
psychiatric or physical illness).
If study treatment is discontinued prior to the subject’s completion of treatment, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate CRF page.
4.5.7
Treatment of Drug-Related Infusion Reactions
Since BMS-986178, nivolumab, and ipilimumab contain only human immunoglobulin protein 
sequences, they are unlikely to be immunogenic and induce infusion reactions. However, if an 
infusion reaction or a hypersensitivity reaction were to occur, it might manifest with fever, chills, 
rigors, headache, rash, pruritus, arthralgias, hypo- or hypertension, bronchospasm, or other 
symptoms. All Grade 3 or 4 infusion reactions should be reported within 24 hours to the BMS 
Medical Monitor and reported as an SAE if criteria are met. Infusion reactions should be graded 
according to NCI CTCAE v4.03 guidelines and reported on the appropriate CRF.
Treatment recommendations are provided below and may be modified based on local treatment 
standards and guidelines as appropriate:
For Grade 1 symptoms: Mild reaction; infusion interruption not indicated; intervention not 
indicated.
Remain at bedside and monitor subject until recovery from symptoms. The following prophylactic 
premedications are recommended for future infusions: diphenhydramine 50 mg (or equivalent) 
and/or acetaminophen/paracetamol 325 to 1000 mg, to be given at least 30 minutes before 
additional study drug administrations.
For Grade 2 symptoms: Moderate reaction; requires therapy or infusion interruption but 
responds promptly to symptomatic treatment [eg, antihistamines, non-steroidal 
anti-inflammatory
drugs, 
narcotics, 
corticosteroids, 
bronchodilators, 
IV 
fluids]; 
prophylactic medications indicated for ≤24 hours.
•
Stop the drug being infused (either BMS-986178, nivolumab, or ipilimumab infusion), begin 
an IV infusion of normal saline, and treat the subject with diphenhydramine 50 mg IV (or 
equivalent) and/or paracetamol 325 to 1000 mg (acetaminophen); monitor subject until 
resolution of symptoms.
•
Bronchodilator or corticosteroid therapy may also be administered as appropriate.
•
The infusion may be restarted at 50% of the original infusion rate when symptoms resolve; if 
no further complications ensue after 30 minutes, the rate may be increased to 100% of the 
original infusion rate. Monitor subject closely.
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•
The amount of study drug infused must be recorded on the CRF.
•
If symptoms recur, then no further dosing with the relevant drug and/or subsequent drug, as 
the case may be, will be administered at that visit.
•
The following prophylactic premedications are recommended for future infusions: 
diphenhydramine 50 mg (or equivalent) and/or paracetamol 325 to 1000 mg (acetaminophen) 
should be administered at least 30 minutes before additional BMS-986178, nivolumab, or 
ipilimumab administrations (whichever caused the reaction). If necessary, corticosteroids (up 
to 25 mg of SoluCortef or equivalent) may be used.
Late-occurring Symptoms:
In the 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).
For Grade 3 or Grade 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 other clinical sequelae 
[eg, renal impairment, pulmonary infiltrates]. Grade 4: life-threatening; pressor or 
ventilatory support indicated. 
Immediately discontinue study drug infusion. Begin an IV infusion of normal saline and treat the 
subject as follows. Recommend bronchodilators, epinephrine 0.2 to 0.5 mg (1:1,000 solution) for 
subcutaneous administration or 0.1 to 0.25 mg (1:10,000 solution) injected slowly for IV 
administration, and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV (or 
equivalent), as needed. Subject should be monitored until the investigator is comfortable that the 
symptoms will not recur. Study drug(s) will be permanently discontinued. Investigators should 
follow their institutional guidelines for the treatment of anaphylaxis. Remain at bedside and 
monitor subject until recovery from symptoms. In the 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).
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Study drug will be administered in the clinical facility by trained medical personnel. The 
investigator and the study personnel will ensure that each subject receives the prescribed dose of 
study drug. Treatment compliance will be monitored by drug accountability as well as by recording 
BMS-986178, nivolumab, and/or ipilimumab administration in subjects’ medical records and 
CRFs.
Drug supplies will be inventoried and accounted for throughout the study. The Drug 
Accountability Log will be reviewed by the study monitor during site visits and at the completion 
of the study. Any discrepancy should be brought to the attention of the Sponsor.
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4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as partially 
used study drug containers, vials, and syringes may be destroyed on site.
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible BMS study monitor unless study drug containers must be immediately destroyed as 
required for safety or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:
•
On-site disposal practices must not expose humans to risks from the drug.
•
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
•
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s standard operating procedures (SOPs) and a copy provided to BMS upon 
request.
•
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, (ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor) must be documented.
•
Accountability and disposal records are complete, up-to-date, and available for the monitor to 
review throughout the clinical trial period.
If conditions for on-site destruction cannot be met, the responsible BMS study monitor will make 
arrangements for the return of study drug to the Sponsor.
It is the investigator’s responsibility to arrange for disposal of all empty containers, 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.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused and/or 
partially used study drug that was supplied by BMS must be returned to BMS. The return of study 
drug will be arranged by the responsible study monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, 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. 
4.10
Retained Samples for Bioavailability/Bioequivalence
Not Applicable.
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5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Study assessments and procedures are presented in Table 5.1-1, Table 5.1-2, Table 5.1-3, Table 
5.1-4, Table 5.1-5, Table 5.1-6, Table 5.1-7, and Table 5.1-8. In limited instances, scheduled events 
can occur outside of the indicated timeframes; BMS should be notified of these instances.
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Table 5.1-1:
Screening Procedural Outline (CA012004) - Parts 1 - 8
Procedure
Screening
Visit
(-28 day 
to -1 Visit)
D -14 to -1
Visit
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed consent is 
signed.
Inclusion/Exclusion Criteria
X
Medical History
X
Include any toxicities or allergy related to previous treatments.
Prior Cancer Therapies
X
ECOG Performance
X
See Appendix 4.
Archived Tumor Tissue Sample
X
An archival, FFPE tumor tissue block, or slide samples (a minimum of 15 unstained 
slides [25 preferred]), may be provided by all subjects. Samples should be shipped to 
the central laboratory. 
Fresh Pre-treatment Tumor Biopsy
X
All subjects require a mandatory pre- and on-treatment biopsy.
Archival specimens may not be substituted for fresh baseline specimens but can be 
submitted to help understand the evolution of the tumor (ie, PD-L1 expression 
changes over time).
Blood PD, Blood Genotype, and 
Blood TCR
X
Safety Assessments
Physical Examination (PE)
X
If the screening PE is performed within 24 hours prior to dosing on D1, then a single 
exam may count as both the screening and predose evaluations.
Physical Measurements
X
Includes height and weight.
Vital Signs
X
Includes body temperature, respiratory rate, seated blood pressure, and heart rate. 
Oxygen Saturation
X
Pulse oximetry collected at rest.
Electrocardiogram (ECGs)
X
ECGs should be recorded after the subject has been supine for at least 5 minutes.
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-1:
Screening Procedural Outline (CA012004) - Parts 1 - 8
Procedure
Screening
Visit
(-28 day 
to -1 Visit)
D -14 to -1
Visit
Notes
All ECG tests should be performed as a single measurement. 
Laboratory Tests
Laboratory tests listed below must be completed within 2 weeks of D1 unless otherwise noted.
Serology
X
Within 28 days of dosing, if required: Hep B surface antigen, and Hep C antibody (if 
Hep C antibody is positive reflex to Hep C RNA), or Hep C RNA.
Note: Testing for HIV-1 and HIV-2 must be performed at sites where mandated by 
local requirements.
Chemistry (Excluding LFTs)
X
See Section 5.3.2. Includes assessments for sodium, potassium, chloride, total serum 
calcium, magnesium, carbon dioxide, phosphorus, BUN, creatinine, creatinine 
clearance, fasting glucose, total protein, albumin, amylase, lipase, uric acid, ferritin, 
CRP, and LDH.
CBC with Differential and Platelets
X
LFT Assessment
X
See Section 5.3.2.
Urinalysis
X
See Section 5.3.2.
Thyroid Function Tests (TFTs)
X
TSH with free T3 and free T4.
Genetic Mutations
X
See Section 5.7. Collected as part of the medical history on appropriate CRF
Tumor Markers (Serum)
X
CA125, AFP, CEA, CA19-9, and PSA for all subjects
Pregnancy Test
X
For WOCBP only; serum will be collected at screening and within 24 hours prior to 
dosing. The serum pregnancy test may be completed on the first day of treatment, 
provided the results are available before the start of study therapy.
If performed within 24 hours of dosing on C1D1, then C1D1 pregnancy test is not 
required.
Follicle Stimulating Hormone (FSH)
X
If needed to document post-menopausal status as defined in Section 3.3.3.
.
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Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-1:
Screening Procedural Outline (CA012004) - Parts 1 - 8
Procedure
Screening
Visit
(-28 day 
to -1 Visit)
D -14 to -1
Visit
Notes
Adverse Event Reporting
Clinical Complaints
X
Collected during the 2 weeks prior to C1D1.
Monitor for Serious Adverse Events
X
All SAEs must be collected from the date of the subject’s written consent until 100 days
of discontinuation of dosing. SAEs should be approved in eCRF directly within 5 
business days of entry.
Efficacy Assessments
Tumor Assessments
X
CT with contrast is the preferred modality (MRI if CT is not feasible). Assessment 
should include the chest/abdomen/pelvis at a minimum and should include other 
anatomic regions as indicated by individual subject disease histories.
Brain Imaging
X
Brain imaging (CT/MRI) for subjects with history or symptoms of brain metastases and 
who have not had brain imaging within 30 days of anticipated first study drug 
administration.
Bone Scan
X
As clinically indicated (eg, subjects with history or symptoms of bone metastases), but 
bone scans will not be considered a modality for the assessment for measurable disease.
IRT Subject Assignment/ Treatment 
Assignment
X
X
After the subject consents, the sites will use the IRT to have the subject number 
assigned. After the subject has completed all screening procedures, IRT will be used for 
treatment assignment or discontinuing the subject. Subsequent visits will need to be 
registered into the IRT system for drug supply.
Abbreviations: AFP = alpha fetal protein; BUN = blood urea nitrogen; C = Cycle; CEA = carcinoembryonic antigen; CBC = complete blood count; CRC = 
colorectal cancer; CRF = case report form; CRP = C-reactive protein; CT = computed tomography; D = Day; ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group; FFPE = formalin-fixed, paraffin-embedded; HIV = human immunodeficiency virus; HPV = Human papillomavirus; IRT = 
Interactive Response Technology; LDH = lactic acid dehydrogenase; LFT =liver function test; MSI = microsatellite instability; MRI = magnetic resonance imaging; 
PD = pharmacodynamic; PSA = Prostate-Specific Antigen; RNA = ribonucleic acid; T3 =triiodothyronine; T4 = thyroxine; TCR = T-cell receptor; TSH = thyroid-
stimulating hormone; WOCBP = women of child bearing potential.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-2:
On Treatment Procedural Outline Parts 1 and 2 (CA012004 - q2w Dosing)
(C1-C12, 
Additional Cycles)
Cycle = 2 Weeks
C1
C2-C8 
C9 
C10 -
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D1
D1
D1
EOTa,b,c
Notesd
Safety Assessments
Physical 
Examination (PE)
X
X
Predose (C1 only); See note in screening.
Symptom-directed 
PE
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only
Vital Signs 
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion 
C1D1 and C2D1
12-Lead 
Electrocardiogram 
(ECG) 
X
X
All ECG tests should be performed as a 
single measurement.
ECGs will be done at both predose and 4 
hours when BMS-986178 PK sample is 
collected (ECGs should be done prior to the 
PK sample) at C1D1 and C9D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
Collect on C1D1, C1D2 and C1D8 and 
every cycle D1
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
LFT Assessment
X
X
X
X
X
X
X
AST, ALT, ALP, and T. Bilirubin. Direct 
Bilirubin (only if T. Bilirubin is elevated); 
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Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-2:
On Treatment Procedural Outline Parts 1 and 2 (CA012004 - q2w Dosing)
(C1-C12, 
Additional Cycles)
Cycle = 2 Weeks
C1
C2-C8 
C9 
C10 -
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D1
D1
D1
EOTa,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-1 for specific samples at each cycle during the study
Serial Serum PK 
Sampling for BMS-
986178 
See Table 5.5.1-1 for specific samples at each cycle during the study.
BMS-986178 ADA 
Sample
See Table 5.5.1-1 for specific samples at each cycle during the study
Serial Serum PK 
Sampling for 
Nivolumab (Part 2 
Only) 
See Table 5.5.1-1 for specific samples at each cycle during the study
Nivolumab ADA 
Sample (Part 2 Only)
See Table 5.5.1-1 for specific samples at each cycle during the study
Biomarker 
Assessments
See Table 5.6-1 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-1 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-1 for specific samples at each cycle during the study.
PBMC
See Table 5.6-1 for specific samples at each cycle during the study.
Blood 
Multiparameter Flow
See Table 5.6-1 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-1 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-1 for specific samples at each cycle during the study.
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Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-2:
On Treatment Procedural Outline Parts 1 and 2 (CA012004 - q2w Dosing)
(C1-C12, 
Additional Cycles)
Cycle = 2 Weeks
C1
C2-C8 
C9 
C10 -
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D1
D1
D1
EOTa,b,c
Notesd
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-1 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-1 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. Same modality 
should be used for all assessments. Assessed 
by RECIST v1.1; see Appendix 3.
Assessment to be performed prior to 
initiating next cycle of treatment.
An unconfirmed PR or unconfirmed CR 
must be confirmed at least 4 weeks after 
initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
Parts 1 and 2
BMS-986178
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Part 2 ONLY
Nivolumab (240 mg 
Flat Dose)
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
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Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
= Prostate-Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; 
T4 = thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C12D14) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For these treatment groups, 1 cycle = 2 weeks, up to 12 cycles of dosing. Subjects who 
have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). For nivolumab, vital signs will be obtained before 
the infusion and then every 30 minutes (± 10 minutes) until the start of BMS-986178 infusion or per institution guidelines for administration of nivolumab. The 
30-minute post nivolumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event BMS-986178 administration is delayed, nivolumab 
vital signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, 
the subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Safety Assessments
Physical 
Examination (PE)
X
X
Predose (C1 Only)
See note in screening
Symptom-directed 
PE
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only 
Vital Signs
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion 
C1D1 and C2D1 
12-Lead 
Electrocardiogram 
(ECGs)
X
X
All ECG tests should be performed as a 
single measurement. 
ECGs will be done at both predose and 4 
hours when BMS-986178 PK sample is 
collected (ECGs should be done prior to the 
PK sample) at C1D1 and C4D1. 
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
Collect on C1D1, C1D2, C1D8, and C1D15, 
and every cycle D1
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
LFT Assessment
X
X
X
X
X
X
X
X
AST, ALT, ALP, and T. Bilirubin. Direct 
Bilirubin (only if T. Bilirubin is elevated); 
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-3
Serial Serum PK 
Sampling 
BMS-986178 
Refer to Table 5.5.1-3.
BMS-986178 ADA 
Sampling
Refer to Table 5.5.1-3.
Serial Serum PK 
Sampling for 
Ipilimumab 
Refer to Table 5.5.1-3.
Ipilimumab ADA 
sampling 
Refer to Table 5.5.1-3.
Biomarker 
Assessments
See Table 5.6-2 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-2 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-2 for specific samples at each cycle during the study.
PBMC
See Table 5.6-2 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow
See Table 5.6-2 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-2 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-2 for specific samples at each cycle during the study.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-2 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-2 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor Assessments 
Every 8 weeks (± 1 week)
Note: If subject completes 24 weeks of dosing, C8D21 will be the last 
cycle visit (EOT), this will be at Week 25, and the 27-week scan should 
be done at this time.
X
By methods used at baseline. Same modality 
should be used for all assessments
Assessed by RECIST v1.1; see Appendix 3. 
Assessment to be performed prior to 
initiating next cycle of treatment.
An unconfirmed PR or unconfirmed CR 
must be confirmed at least 4 weeks after 
initial assessment. 
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
X
X
X
X
All subjects
Supplied by BMS
Use vials assigned per IRT
Part 3
Ipilimumab 
(1 mg/kg)
X
X
X
Supplied by BMS
Use vials assigned per IRT 
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Part 5
Ipilimumab 
(3 mg/kg)
X
X
X
Supplied by BMS
Use vials assigned per IRT 
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; BMS = Bristol-Myers Squibb; C=Cycle; CBC = complete blood count; CEA = 
carcinoembryonic antigen; CR = complete response; CRC = colorectal cancer; D = Day; ECG = electrocardiogram; EOT = end of treatment; LFT = liver function 
test; IRT = Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; 
PSA = Prostate-Specific Antigen; RNA = ribonucleic acid; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; VS 
= vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C8D21) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For these treatment groups 1 cycle = 3 weeks, up to 8 cycles of dosing. Subjects who 
have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
then every 30 minutes (± 10 minutes) until the start of BMS-986178 infusion or per institution guidelines for administration of ipilimumab. The 30-minute post 
ipilimumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event BMS-986178 administration is delayed, ipilimumab vital signs will 
be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the subject must 
be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-4:
On Treatment Procedural Outline Part 4 (CA012004 - q4w Dosing)
(C1-C6, Additional 
Cycles )
Cycle = 4 weeks
C1 
C2-C4
C5
C6-
beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D15
D1
D1
EOTa,b,c
Notesd
Safety Assessments
Physical 
Examination (PE)
X
X
Predose (C1 only). See note in screening.
Symptom-directed 
PE
X
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion C1D1 and 
C2D1 
12-Lead 
Electrocardiogram 
(ECGs)
X
X
All ECG tests should be performed as a single 
measurement.
ECGs will be done at both predose and 4 hours 
when BMS-986178 PK sample is collected (ECGs 
should be done prior to the PK sample) at C1D1 and 
C5D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
X
LFT Assessment
X
X
X
X
X
X
X
X
X
AST, ALT, ALP, and T. Bilirubin. Direct Bilirubin 
(only if T. Bilirubin is elevated); GGT (if ALP 
increase is clinically significant)
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-4:
On Treatment Procedural Outline Part 4 (CA012004 - q4w Dosing)
(C1-C6, Additional 
Cycles )
Cycle = 4 weeks
C1 
C2-C4
C5
C6-
beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D15
D1
D1
EOTa,b,c
Notesd
BMS-986178 ADA 
Sample
See Table 5.5.1-2 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab
See Table 5.5.1-2 for specific samples at each cycle during the study.
Nivolumab ADA 
Sampling
See Table 5.5.1-2 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-3 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-3 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-3 for specific samples at each cycle during the study.
PBMC
See Table 5.6-3 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow 
See Table 5.6-3 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-3 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-3 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-3 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-3 for specific samples at each cycle during the study.
Efficacy 
Assessments
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-4:
On Treatment Procedural Outline Part 4 (CA012004 - q4w Dosing)
(C1-C6, Additional 
Cycles )
Cycle = 4 weeks
C1 
C2-C4
C5
C6-
beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D15
D1
D1
EOTa,b,c
Notesd
Tumor Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. Same modality should 
be used for all assessments Assessed by RECIST 
v1.1; see Appendix 3.
Assessment to be performed prior to initiating next 
cycle of treatment.
An unconfirmed PR or unconfirmed CR must be 
confirmed at least 4 weeks after initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Nivolumab
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = 
carcinoembryonic antigen; CR = complete response; CRC = colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; IRT = Interactive 
Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA = Prostate-
Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = 
thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C6D28) 
and the start of the Week 1 Safety Follow-up visit.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For these treatment groups 1 cycle = 4 weeks, up to 6 cycles of dosing. Subjects who 
have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). For nivolumab, vital signs will be obtained before 
the infusion and then every 30 minutes (± 10 minutes) until the start of BMS-986178 infusion or per institution guidelines for administration of nivolumab. The 
30-minute post nivolumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event BMS-986178 administration is delayed, nivolumab 
vital signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, 
the subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Revised Protocol No.: 06
Date: 08-Feb-2019
140
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
Predose (C1 Only)
See note in screening
Symptom-directed 
PE
X
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only
Vital Signs
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion C1D1 and 
C2D1 
12-Lead 
Electrocardiogram 
(ECGs)
X
X
All ECG tests should be performed as a single 
measurement.
ECGs will be done at both predose and 4 hours 
when BMS-986178 PK sample is collected (ECGs 
should be done prior to the PK sample) on C1D1 
and C4D1. 
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
Revised Protocol No.: 06
Date: 08-Feb-2019
141
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8.0
v




Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Monitor for Non-
Serious Adverse 
Events
Non-serious AEs will be collected starting with the first dose of study medication 
and through 100 days after discontinuation of dosing.
Monitor for 
Serious Adverse 
Events
See note in screening procedures (Table 5.1-1)
Pharmacokinetic 
Assessments
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling 
BMS-986178 
See Table 5.5.1-6 for specific samples at each cycle during the study.
BMS-986178 
ADA Sampling 
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab
See Table 5.5.1-6 for specific samples at each cycle during the study.
Nivolumab ADA 
Sampling
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Ipilimumab 
See Table 5.5.1-6 for specific samples at each cycle during the study.
Revised Protocol No.: 06
Date: 08-Feb-2019
143
8.0
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8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Ipilimumab ADA 
sampling
See Table 5.5.1-6 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-2 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-2 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-2 for specific samples at each cycle during the study.
PBMC
See Table 5.6-2 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow 
See Table 5.6-2 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-2 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-2 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-2 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-2 for specific samples at each cycle during the study.
Revised Protocol No.: 06
Date: 08-Feb-2019
144
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Efficacy 
Assessments
Tumor 
Assessments
Every 8 weeks (± 1 week)
Note: If subject completes 24 weeks of dosing, C7D21 will be the last cycle visit 
(EOT), this will be at Week 24, and the 27 week scan should be done at this 
time.
By methods used at baseline. Same modality should 
be used for all assessments Assessed by RECIST 
v1.1; see Appendix 3.
Assessment to be performed prior to initiating next 
cycle of treatment.
An unconfirmed PR or unconfirmed CR must be 
confirmed at least 4 weeks after initial assessment. 
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
(C1-C4, q3w; C5
and beyond, q4w)
Dosing will be on C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, and 
C7D1, which corresponds to Weeks 1, 4, 7, 10, 13, 17, and 21
Supplied by BMS
Use vials assigned per IRT
Nivolumab 
(240 mg flat dose)
(C1-C4, q3w)
Dosing will be on C1D1, C2D1, C3D1, and C4D1, 
which corresponds to Weeks 1, 4, 7, and 10
Supplied by BMS
Use vials assigned per IRT
Revised Protocol No.: 06
Date: 08-Feb-2019
145
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Nivolumab 
(480 mg flat dose)
(C5 and beyond, 
q4w)
Dosing will be on C5D1, C6D1, and C7D1, 
which corresponds to Weeks 13, 17, and 21
Supplied by BMS
Use vials assigned per IRT
Ipilimumab 
(1 mg/kg)
(C1-C4, q3w)
Dosing will be on C1D1, C2D1, C3D1, and C4D1, 
which corresponds to Weeks 1, 4, 7, and 10
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = 
carcinoembryonic antigen; CR = complete response; CRC = colorectal cancer; D = Day; ECG = electrocardiogram; EOT = end of treatment; LFT = liver function 
test; IRT = Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; 
PSA = Prostate-Specific Antigen; RNA = ribonucleic acid; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; VS 
= vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C7D21) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For C1 to C4, 1 cycle = 3 weeks, and for C5 and beyond, 1 cycle = 4 weeks. Subjects 
who have additional cycles will follow this same time and events table.
Revised Protocol No.: 06
Date: 08-Feb-2019
146
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8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion, 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
then every 30 minutes (± 10 minutes) until the start of the next study drug infusion or per institution guidelines for administration of ipilimumab and/or 
nivolumab. The 30-minute post nivolumab infusion VS may correspond to the pre-infusion ipilimumab or BMS-986178 VS and the 30-minute post ipilimumab 
infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event the next study drug administration is delayed, nivolumab and/or ipilimumab vital 
signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the 
subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Revised Protocol No.: 06
Date: 08-Feb-2019
147
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
Predose (C1 only); See note in 
screening.
Symptom-directed 
PE
X
X
X
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements
X
X
X
X
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours 
post-infusion C1D1 and C2D1
12-Lead 
Electrocardiogram 
(ECG) 
X
X
All ECG tests should be performed 
as a single measurement.
ECGs will be done at both predose 
and 4 hours when BMS-986178 PK 
sample is collected (ECGs should be 
done prior to the PK sample) at 
C1D1 and C4D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
X
X
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
X
X
X
Revised Protocol No.: 06
Date: 08-Feb-2019
148
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930092029
8.0
v




Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Serial Serum PK 
Sampling for 
BMS-986178 
See Table 5.5.1-5 for specific samples at each cycle during the study.
BMS-986178 ADA 
Sample
See Table 5.5.1-5 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab 
See Table 5.5.1-5 for specific samples at each cycle during the study.
Nivolumab ADA 
Sample 
See Table 5.5.1-5 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Ipilimumab
See Table 5.5.1-5 for specific samples at each cycle during the study.
Ipilimumab ADA 
Sample
See Table 5.5.1-5 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-4 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-4 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-4 for specific samples at each cycle during the study.
PBMC
See Table 5.6-4 for specific samples at each cycle during the study.
Revised Protocol No.: 06
Date: 08-Feb-2019
150
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Blood 
Multiparameter 
Flow
See Table 5.6-4 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-4 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-4 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-4 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-4 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor 
Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. Same 
modality/ should be used for all 
assessments. Assessed by 
RECIST v1.1; see Appendix 3.
Assessment to be performed prior to 
initiating next cycle of treatment.
An unconfirmed PR or unconfirmed 
CR must be confirmed at least 4 
weeks after initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Revised Protocol No.: 06
Date: 08-Feb-2019
151
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Clinical Drug 
Supplies
BMS-986178
(q2w)
Dosing will be on C1D1, C1D15, C1D29, C2D1, C2D15, 
C2D29, C3D1, C3D15, C3D29, C4D1, C4D15, and C4D29, 
which corresponds to Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 
21, and 23
X
X
X
Supplied by BMS
Use vials assigned per IRT
Nivolumab 
(240 mg q2w Flat 
Dose)
Dosing will be on C1D1, C1D15, C1D29, C2D1, C2D15, 
C2D29, C3D1, C3D15, C3D29, C4D1, C4D15, and C4D29, 
which corresponds to Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 
21, and 23
X
X
X
Supplied by BMS
Use vials assigned per IRT
Ipilimumab 
(1 mg/kg q6w) 
Dosing will be on Day 1 of each cycle, 
X
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
= Prostate-Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; 
T4 = thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C4D35) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
Revised Protocol No.: 06
Date: 08-Feb-2019
152
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
d Subjects will have procedures listed in this table completed at all cycles. One cycle = 6 weeks. Subjects who have additional cycles will follow this same time 
and events table. BMS-986178, nivolumab, and ipilimumab will continue for all additional cycles.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion, 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
then every 30 minutes (± 10 minutes) until the start of the next study drug infusion or per institution guidelines for administration of ipilimumab and nivolumab. 
The 30-minute post nivolumab infusion VS may correspond to the pre-infusion ipilimumab VS and the 30-minute post ipilimumab infusion VS may correspond 
to the pre-infusion BMS-986178 VS. In the event the next study drug administration is delayed, nivolumab and/or ipilimumab vital signs will be obtained until 
60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the subject must be observed 
further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Revised Protocol No.: 06
Date: 08-Feb-2019
153
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
X
Predose (C1 only); See note in 
screening.
Symptom-directed 
PE
X
X
X
X
X
X
X
To include signs and symptoms; 
Physical 
Measurements
X
X
X
X
X
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours 
post-infusion C1D1 and C2D1
12-Lead 
Electrocardiogram 
(ECG) 
X
All ECG tests should be performed 
as a single measurement.
ECGs will be done at both predose 
and 4 hours when BMS-986178 PK 
sample is collected (ECGs should 
be done prior to the PK sample) at 
C1D1 and C2D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on all dosing days
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
X
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
X
X
Revised Protocol No.: 06
Date: 08-Feb-2019
154
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Approved
930092029
8.0
v




Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
BMS-986178 
(cohort 1-3 only)
See Table 5.5.1-6 for specific samples at each cycle during the study.
BMS-986178 
ADA Sample
(cohort 1-3 only)
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab 
See Table 5.5.1-6 for specific samples at each cycle during the study.
Nivolumab ADA 
Sample 
See Table 5.5.1-6 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-5 for specific samples at each cycle during the study.
Blood RNA, 
Blood RO
See Table 5.6-5 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-5 for specific samples at each cycle during the study.
PBMC
See Table 5.6-5 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow
See Table 5.6-5 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-5 for specific samples at each cycle during the study.
Revised Protocol No.: 06
Date: 08-Feb-2019
156
8.0
Approved
930092029
8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
PD Plasma
See Table 5.6-5 for specific samples at each cycle during the study.
ctDNA
See Table 5.6-5 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-5 for specific samples at each cycle during the study.
On treatment C1D15 and C1D78
Blood TCR
See Table 5.6-5 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor 
Assessments 
Every 12 weeks (± 1 week)
X
By methods used at baseline. Same 
modality/ should be used for all 
assessments. Assessed by 
RECIST v1.1; see Appendix 3.
Assessment to be performed prior 
to initiating next cycle of treatment.
An unconfirmed PR or 
unconfirmed CR must be 
confirmed at least 6 weeks after 
initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
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Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
Clinical Drug 
Supplies
BMS-986178 
(q12w) Cohort 1-
3 Only
Dosing on Day 1 of each cycle 
Supplied by BMS
Use vials assigned per IRT
Nivolumab 
(480 mg Flat 
Dose q4w)
Dosing on Day 1, 29, and 57 of each cycle 
Supplied by BMS
Use vials assigned per IRT
Tetanus Vaccine
C1D1 Only
Locally Sourced
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
= Prostate-Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; 
T4 = thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C9D78) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. One cycle = 12 weeks. 
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion, 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
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then every 30 minutes (± 10 minutes) until the start of the next study drug infusion or per institution guidelines for administration of nivolumab. The 30-minute 
post nivolumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event the next study drug administration is delayed, nivolumab vital 
signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the 
subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
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Table 5.1-8:
Follow-up Procedural Outline Parts 1 - 8 (CA012004)
Procedure
Safety Follow-up
FU 1
30 Daysa
(± 7 days) 
FU 2
60 Days 
(± 7 days)
FU 3
100 Days 
(± 10 days)
Notes
Safety Assessments
Physical Examination (PE)
X
X
X
Vital Signs
X
X
X
Includes body temperature, seated 
blood pressure, and heart rate. 
Laboratory Tests
Chemistry (excluding LFTs)
X
X
X
See Section 5.3.2.
CBC with Differential and 
Platelets
X
X
X
LFT Assessment
X
X
X
LFTs will be monitored following 
the last dose of BMS-986178. 
Includes AST, ALT, total 
bilirubin, direct bilirubin (only if 
total bilirubin is elevated) alkaline 
phosphatase, and GGT (if ALP 
increase is clinically significant).
Urinalysis
As clinically indicated. See Section 5.3.2.
Pregnancy Test
X
X
X
For WOCBP; serum or urine 
pregnancy test may be performed 
(clinic urine pregnancy test: 
minimum sensitivity 25 IU/L or 
equivalent units of hCG).
If positive, perform confirmatory 
testing. If pregnancy is confirmed, 
immediately notify the BMS 
Medical Monitor/designee per 
Section 6.4.
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Table 5.1-8:
Follow-up Procedural Outline Parts 1 - 8 (CA012004)
Procedure
Safety Follow-up
FU 1
30 Daysa
(± 7 days) 
FU 2
60 Days 
(± 7 days)
FU 3
100 Days 
(± 10 days)
Notes
Efficacy Assessments
Tumor / Response 
Assessments
X
Diagnostic imaging by method 
used at baseline; an unconfirmed 
PR or unconfirmed CR must be 
confirmed at least 4 weeks after 
initial assessment.
Assessed by RECIST v1.1; see 
Appendix 3.
Subjects who discontinue study 
drug must continue to be followed 
per the Safety Follow-up 
(approximately 100 days).
Subsequent Treatments 
(Anti-cancer)
X
X
X
Abbreviations: ADA = anti-drug antibody; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; BMS = Bristol-Myers 
Squibb; CBC = complete blood count; CR = complete response; EOT = end of treatment; FU = Follow-Up; LFT = liver function test; GGT = gamma-glutamyl 
transferase; hCG = human chorionic gonadotropin; LFT = liver function test; PD = pharmacodynamic; PR = partial response; RO = receptor occupancy; SAE = 
serious adverse event; SD =stable disease; SOC = standard of care; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = 
thyroxine; WOCBP = women of child bearing potential.
a Follow-up visits at Days 30, 60 (±7 days), and 100 (±10 days) should occur after the last dose or coinciding with the date of discontinuation ±7 days if the date 
of discontinuation is greater than 30 days after the last dose to monitor for adverse events.
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In the event that multiple procedures are required at a single time point, the following is a list of 
procedures from highest to lowest priority:
1) PK Sampling
2) Safety (ECG)
3) Safety (clinical laboratories)
5.1.1
Retesting During Screening 
Retesting of laboratory parameters and/or other assessments within any single screening will be 
permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (ie, the most current result prior to Randomization) 
and is the value by which study inclusion will be assessed, as it represents the subject’s most 
current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1 may be repeated in an 
effort to find all possible well-qualified subjects. Consultation with the Medical Monitor (or 
designee) may be needed to identify whether repeat testing of any particular parameter is clinically 
relevant.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (ie, relevant clinical 
laboratory tests and urine drug screens). The site will have a well-calibrated scale available for
recording body weight, a 12-lead ECG machine, and a calibrated sphygmomanometer, a syringe 
pump, 0.2-μm filter infusion sets, and a thermometer for vital signs assessments. A current and 
fully stocked advanced cardiac life support cart will be immediately available on the premises. The 
site will have a refrigerated centrifuge, a monitored and alarmed refrigerator, and freezer (-70°C 
preferred, -20°C acceptable), as well as containers and dry ice for shipment and storage of blood 
samples. The site will provide all materials required for accurate source documentation of study 
activities and for housing the subjects during the study. The site will source marketed product from 
a single commercial lot.
BMS will provide a Sponsor-approved protocol and any amendments or administrative letters (if 
required) and an IB. CRFs (electronic or hard copy) will be provided by BMS. BMS/central 
laboratory will provide labels and tubes for the collection of blood samples for PK/PD and for 
genotyping analysis.
5.3
Safety Assessments
AEs will be assessed during the study and for 100 days after the last treatment. AEs will be 
evaluated according to NCI CTCAE v4.03 and should be followed per requirements in Section 6.1
and Section 6.2. AEs will be coded using the most current version of Medical Dictionary for 
Regulatory Activities and reviewed for potential significance and importance. Subjects should be 
followed until all treatment-related AEs have recovered to baseline or are deemed irreversible by 
the investigator.
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Protocol-specified assessments are described in Table 5.1-1 (Screening), Table 5.1-2 (On 
Treatment - Parts 1 and 2), Table 5.1-3 (On Treatment - Parts 3 and 5), Table 5.1-4 (On Treatment 
- Part 4), Table 5.1-5 (On Treatment - Part 6), Table 5.1-6 (On Treatment - Part 7), Table 5.1-7
(On Treatment - Part 8), and Table 5.1-8 (Follow-up - Parts 1 - 8).
5.3.1
Imaging Assessment for the Study
1) CT/MRI
a) Contrast-enhanced CT scans acquired on dedicated CT equipment is preferred for this 
study. CT with contrast of the chest, abdomen, and pelvis are to be performed for tumor 
assessments. CT scans should be acquired with 5-mm slices and no intervening gap 
(contiguous).
(1).Should a subject have a contraindication for CT IV contrast, a non-contrast CT of 
the chest and a contrast-enhanced MRI of the abdomen and pelvis may be obtained. 
MRIs should be acquired with slice thickness of < 5 mm with no gap (contiguous). 
(2).Every attempt should be made to image each subject using an identical acquisition 
protocol on the same scanner for all imaging time points.
(3).Note on the use of the CT component of a positron emission tomography (PET)/CT 
scanner:
Combined modality scanning such as with fluorodeoxyglucose (FDG)-PET/CT is 
increasingly used in clinical care and is a modality/technology that is in rapid evolution; 
therefore, the recommendations outlined here may change rather quickly with time. At 
present, low-dose or attenuation-correction CT portions of a combined FDG-PET/CT 
are of limited use in anatomically based efficacy assessments; it is therefore suggested 
that they should not be substituted for dedicated diagnostic contrast-enhanced CT scans 
for anatomically based RECIST measurements. However, if a site can document that 
the CT performed as part of a FDG-PET/CT is of identical diagnostic quality to a 
diagnostic CT (with IV and oral contrast), then the CT portion of the FDG-PET/CT can 
be used for RECIST 1.1 measurements. Note, however, that the FDG-PET portion of 
the CT introduces additional data that may bias an investigator if it is not routinely or 
serially performed.
2) Brain MRI
a) MRI of the brain is required at screening if subject is symptomatic or has a history of brain 
metastasis. Subjects with a history of brain metastasis should have surveillance MRI 
approximately every 12 weeks or sooner, if clinically indicated.
b) MRI brain scans during on-study treatment and follow-up periods are required only if there 
is a prior history of lesions present at Screening, or as clinically indicated for new signs 
and symptoms that suggest central nervous system (CNS) involvement.
3) Bone Scan
a) Bone scans can be used to evaluate metastatic disease.
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Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the Study Investigator as per 
standard medical/clinical judgment.
5.3.2
Laboratory Test Assessments
Each site’s local laboratory will perform the analyses and will provide reference ranges for these 
tests.
Results of clinical laboratory tests performed on Day 1 must be available prior to dosing.
The following clinical laboratory tests will be performed:
Hematology
Hemoglobin
Hematocrit
Platelet count
Total leukocyte count, including differential
CBC and differential results will be monitored on an ongoing basis and should be sent to the 
local laboratory data service upon receipt of the results. Others will be sent to the local 
laboratory data service.
Serum Chemistry
AST
ALT
Amylase
Total bilirubin
Direct bilirubin (only as reflex when T 
bilirubin elevated)
ALP
Lactate dehydrogenase
Lipase
Creatinine 
Blood urea nitrogen
Uric acid (at screening only)
Glucose (fasting at screening)
Gamma-glutamyl transferase (only as reflex 
when ALP increase is clinically significant)
Total protein
Albumin
Sodium
Potassium
Chloride
Calcium
C-reactive protein
Ferritin
Carbon dioxide
Phosphorus
Magnesium
CrCL(screening only)
Thyroid Laboratories
Thyroid-stimulating hormone (TSH)
Free T3 and free T4 (at screening and reflex when TSH abnormal)
Urinalysis
Protein
Glucose
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Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein, or leukocytes esterase are positive 
Serology
Hepatitis B surface antigen
Serum for hepatitis C antibody(if Hep C Ab is positive reflex to Hep C RNA) or Hep C RNA, 
HIV-1 and -2 antibody (testing for HIV-1 and HIV-2 must be performed at sites where 
mandated by local requirements).
Other Analyses
Pregnancy test (WOCBP only: serum testing at screening and within 24 hours prior to dosing; 
urine or serum at all other time points).
FSH (screening only for women only) 
Tumor Specific Serum Markers
CA125 testing for all subjects with OC
Alpha fetal protein (AFP) testing for all subjects with hepatocellular carcinoma
Carcinoembryonic antigen (CEA) testing for all subjects with CRC
CA19-9 testing for all subjects with pancreatic cancer
Prostate-Specific Antigen test for all subjects with prostate cancer
Results of all laboratory tests required by this protocol must be provided to BMS, either recorded 
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 (see Section 6.3).
5.4
Efficacy Assessments
Disease assessment with CT and/or MRI as appropriate will be performed at baseline and every 
8 weeks Parts 1-7 or every 12 weeks for Part 8 (± 1 week) per RECIST v1.1 (see Appendix 3) until 
discontinuation of treatment or withdrawal from study. Tumor assessments at other time points 
may be performed if the investigator is concerned about tumor progression. Assessment of tumor 
response will be reported by the investigator for appropriate populations of subjects as defined by 
RECIST v1.1157 (see Appendix 3) for subjects with advanced solid tumors. The same modality 
should be used and the same scanner is preferred for all assessments.
Investigators will also report the number and size of new lesions that appear while on study. The 
time point of tumor assessments will be reported on the CRF based on the investigators’ 
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assessment using RECIST criteria. Please refer to Appendix 3 for specifics of RECIST v1.1 
criteria to be utilized in this study.
5.4.1
Primary Efficacy Assessment
Not applicable.
5.4.2
Secondary Efficacy Assessments
The efficacy assessments will include ORR (eg, PR and CR), duration of response, and 
progression-free survival rate (PFSR) at time points (eg, 24 weeks) based on assessment of tumor 
response using RECIST v1.1.
5.5
Pharmacokinetic Assessments
Samples for PK and immunogenicity assessments will be collected for subjects receiving 
BMS-986178 alone or in combination with nivolumab and/or ipilimumab, as described in Table 
5.5.1-1 (Parts 1 and 2), Table 5.5.1-2 (Part 4), Table 5.5.1-3 (Parts 3 and 5), Table 5.5.1-6 (Part 6),
Table 5.5.1-5 (Part 7), , and Table 5.5.1-6. The PK of BMS-986178 will be characterized by NCA 
method. Immunogenicity samples will be analyzed for anti-BMS-986178 antibodies and/or 
anti-nivolumab antibodies and/or anti-ipilimumab antibodies by validated immunoassays.
If data permit, the PK parameters might be assessed following Cycle 1 Day 1 and Cycle 9 Day 1 
for the q2w dosing regimen in monotherapy or in combination therapy, Cycle 4 Day 1 for the q3w 
or q6w dosing regimen in combination therapy with ipilimumab and/or nivolumab combination 
therapy, Cycle 5 Day 1 for q4w dosing regimen in combination therapy with nivolumab include 
the following:
Cmax
Maximum observed serum concentration
Tmax
Time of maximum observed concentration
AUC(0-t)
Area under the plasma concentration-time curve from time zero to time of
last quantifiable concentration
AUC(TAU)
Area under the concentration-time curve in 1 dosing interval
In addition, the PK parameters listed below may be assessed following dose administration in 
Cycle 9 Day 1 for the q2w or Cycle 5 Day 1 for q4w dosing regimen in monotherapy or in 
combination therapy and Cycle 4 Day 1 for the q3w and q6w dosing regimen in combination 
therapy with ipilimumab and/or nivolumab.
Ctau
The observed concentration at the end of a dosing interval 
CLT
Total body clearance 
Css-avg
Average concentration over a dosing interval (AUC(TAU)/tau) 
AI
Ratio of an exposure measure at steady state (eg, following Cycle 9 Day 1 
dose) to that after the first dose (exposure measure includes AUC(TAU), 
Cmax and Ctau).
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T-HALFeff
Effective elimination half-life that explains the degree of accumulation 
observed for a specific exposure measure (exposure measure includes 
AUC(TAU), Cmax and Ctau)
The following PK parameter will be reported as a separate listing, summary, and plot:
Ctrough
Trough observed plasma concentrations (this includes predose 
concentrations (C0) and Ctau)
5.5.1
Pharmacokinetics and Immunogenicity Collection and Processing
Detailed sampling schedules to be followed for the assessment of PK and immunogenicity for 
BMS-986178 monotherapy or in combination therapy are provided in Table 5.5.1-1 (Parts 1 and 
2), Table 5.5.1-2 (Part 4), Table 5.5.1-3 (Parts 3 and 5), Table 5.5.1-6 (Part 6), Table 5.5.1-5 (Part 
7), and Table 5.5.1-6 (Part 8). However, if there is a safety concern (e.g. Grade 3 or 4 AE, SAE, 
etc.), ad hoc PK and ADA sample collection would be permissible (using an Unscheduled Visit).
All predose samples should be taken within 30 minutes before the start of any dose infusion. All 
postdose PK sampling time points are relative to the start of BMS-986178 administration. 
End-of-infusion samples should be taken just prior to the end of infusion (EOI; preferably within 
2 minutes). Further details of sample collection, processing, and shipment will be provided in the 
laboratory procedure manual. On-treatment PK samples are intended to be drawn relative to actual 
dosing days; if a dose occurs on a different day within the cycle due to delays or minor schedule 
adjustments, PK samples should be adjusted accordingly.
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Table 5.5.1-1:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 Monotherapy or in Combination Therapy - Parts 1 
and 2 (CA012004 - q2w Dosing)
Study Day of 
Sample Collection 
(1 Cycle = 2 Weeks)
Event
Time 
(Relative to
start of 
BMS-
986178 
Infusion)
Hour: Min
BMS-
986178
PK Sample 
(All 
Subjects)
Nivolumab 
PK Sample 
(Part 2)
BMS-
986178 
ADA 
Sample (All 
Subjects)
Nivolumab 
ADA 
Sample 
(Part 2)
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
C3D1
Predosea
00:00a
X
X
X
X
C4D1
Predosea
00:00a
X
X
End of Treatment 
Unschedulede
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both nivolumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle.
e Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
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Table 5.5.1-2:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination Therapy - Part 4 (CA012004 - q4w 
Dosing)
Study Day of 
Sample Collection 
(1 Cycle = 
4 Weeks)
Event
Time 
(Relative to 
start of BMS-
986178 
Infusion)
Hour: Min
BMS-986178 
PK Sample
Nivolumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA 
Sample
C1D1s
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15e
336:00
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
C3D1
Predosea
00:00a
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
End of Treatment 
Unscheduledf
X
X
X
X
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
b EOI samples for both nivolumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle.
e D15 sample may be taken during D12 to D18 of a cycle.
f Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
Note: The time recorded is relative to BMS-986178 infusion.
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Table 5.5.1-3:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination with Ipilimumab - Parts 3 and 5 
(CA012004 - q3w Dosing)
Study Day of 
Sample Collection
(1 Cycle = 
3 Weeks)
Event
Time 
(Relative to 
start of 
BMS-986178 
Infusion)
Hour: Min
BMS-986178
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15d
336:00
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
C3D1
Predosea
00:00a
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C4D2
24:00
X
C4D4c
72:00
X
C4D8d
168:00
X
C4D15d
336:00
X
End of Treatment 
Unschedulede
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion; FU = Follow-Up.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both ipilimumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
the end of infusion). If the end of infusion is delayed to beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle; Day 15 sample may be taken during D13 to D17 of a cycle.
e Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
Revised Protocol No.: 06
Date: 08-Feb-2019
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8.0
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-4:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with RCC)
Study Day of 
Sample Collection 
(Cycle = 3 Weeks 
for C1 - C4
Cycle = 4 Weeks 
for C5 and 
Beyond)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15e
336:00
X
C2D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
C3D1
Predosea
00:00a
X
X
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C4D2
24:00
X
C4D4c
72:00
X
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-4:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with RCC)
Study Day of 
Sample Collection 
(Cycle = 3 Weeks 
for C1 - C4
Cycle = 4 Weeks 
for C5 and 
Beyond)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C4D8d
168:00
X
C4D15e
336:00
X
End of Treatment 
Unscheduledf
X
X
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for ipilimumab, nivolumab, and BMS-986178 should be collected at the end of the BMS-986178 infusion. The EOI sample should be taken 
immediately prior to stopping the infusion (preferably within 2 minutes prior to the end of infusion). If the end of infusion is delayed to beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle.
e D15 sample may be taken during D13 to D17 of a cycle.
f Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection would be permissible (using an Unscheduled 
Visit).
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-5:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with NSCLC)
Study Day of 
Sample Collection 
(1 Cycle = 
6 Weeks)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15e
Predosea
00:00a
X
X
C1D29f
Predosea
00:00a
X
X
C2D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
C3D1
Predosea
00:00a
X
X
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C4D2
24:00
X
C4D4c
72:00
X
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-5:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with NSCLC)
Study Day of 
Sample Collection 
(1 Cycle = 
6 Weeks)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C4D8d
168:00
X
C4D15e
Predosea
00:00a
X
X
C4D29f
Predosea
00:00a
X
X
End of Treatment 
Unscheduledg
X
X
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for ipilimumab, nivolumab, and BMS-986178 should be collected at the end of the BMS-986178 infusion. The EOI sample should be taken 
immediately prior to stopping the infusion (preferably within 2 minutes prior to the end of infusion). If the end of infusion is delayed to beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle. 
e D15 sample may be taken during D13 to D17 of a cycle.
f D29 sample may be taken during D26 to D30 of a cycle.
g Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection would be permissible (using an Unscheduled 
Visit).
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-6:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination - Part 8 (CA012004 - q12w Dosing)
Study Day of 
Sample 
Collection 
(1 Cycle = 
12 Weeks)
Event
Time 
(Relative to 
start of BMS-
986178 
Infusion)
Hour: Min
BMS-
986178 PK 
Sample
(Cohort 1-
3)
Nivolumab 
PK Sample
BMS-986178 
ADA 
Sample
(Cohort 1-3)
Nivolumab 
ADA 
Sample
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D8c
168:00
X
X
C1D15d
336:00
X
X
C1D29e
696:00
X
X
X
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C2D8c
168:00
X
X
C2D15d
336:00
X
C2D29e
696:00
X
X
C3D1
Predosea
00:00a
X
X
X
X
End of Treatment
Unscheduledf
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both nivolumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D8 sample may be taken during D7 to D9 of a cycle.
d D15 sample may be taken during D12 to D18 of a cycle.
e D29 sample may be taken prior nivolumab infusion.
f Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
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Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
5.5.2
Pharmacokinetic and Immunogenicity Sample Analyses
The serum samples will be analyzed for drug (BMS-986178 and/or nivolumab and/or ipilimumab) 
and ADA (anti-BMS-986178 antibodies and/or anti-nivolumab antibodies and/or anti-ipilimumab 
antibodies) by validated immunoassays. In addition, selected serum samples may be analyzed by 
an exploratory method that measures BMS-986178, nivolumab, and ipilimumab; or detect ADAs
for technology exploration purposes; exploratory results will not be reported. Serum samples 
designated for PK or biomarker assessments may also be used for immunogenicity analysis if 
required (eg, insufficient volume for complete immunogenicity assessment or to follow up on 
suspected immunogenicity-related AE).
5.5.3
Labeling and Shipping of Biological Samples
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the laboratory procedure manual.
5.6
Biomarker Assessments
To assess the PD effects of BMS-986178 as well as receptor occupancy (RO) in relation to dose 
and PK, whole blood samples (blood PD and blood RO) will be collected at the times indicated in 
Table 5.6-1 (Parts 1 and 2), Table 5.6-2 (Parts 3, 5, and 6), Table 5.6-3 (Part 4), Table 5.6-4
(Part 7), and Table 5.6-5 (Part 8). The sample testing plans associated with each are described in 
Section 5.7. Complete instructions on the collection, processing, handling, and shipment of all 
samples described herein will be provided in a separate laboratory procedure manual.
Blood samples for PD assessment will be analyzed by cytometry to determine baseline and serial 
on-treatment alterations in composition and/or activation status of lymphocyte subsets. 
Lymphocyte subsets to be assayed may include, but are not limited to, CD8+ and CD4+ T-cell 
subsets (activated; effector/memory; regulatory) and populations of those cells as defined by the 
expression of proliferation, activation, exhaustion, or signaling markers such as KI67, HLA-DR, 
PD-1, etc. Treatment-induced alterations in blood lymphocyte populations will be analyzed in 
relation to both dose and blood concentrations of BMS-986178.
Receptor occupancy of OX40 by BMS-986178 (RO) on peripheral blood mononuclear cells 
(PBMCs) may also be determined by flow cytometry. RO will be analyzed in relation to PK and 
PD effects. Samples will be collected to determine RO from subjects in Part 1A and 1B in this 
study. For combination cohorts, a blood tube will also be collected for exploratory purposes to 
measure pharmacodynamic endpoints including, but not limited to RO.
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Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-1:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Monotherapy and 
Combination Therapy - Parts 1 and 2 (CA012004 - q2w Dosing)
Study Day of 
Sample Collection 
(1 Cycle = 2 Weeks)
Event
Time 
(Relative to start of 
BMS-986178 
Infusion)
Hour: Min
Blood RNA, 
Blood ROa
Blood PD 
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc
Section 5.6
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C2D1
Predosef
00:00
X
X
X
Xh
C3D1
Predosef
00:00
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T cell receptor.
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments. Blood RNA samples will be collected from all subjects. Detailed instructions for 
the collection, processing, and shipping of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h C2D1 fresh tumor biopsy may be taken during C1D12-C2D4.
Revised Protocol No.: 06
Date: 08-Feb-2019
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8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-2:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Parts 3, 5, and 6 (CA012004)
Study Day of Sample 
Collection (Cycle = 3 Weeks 
for C1 - C8 for Parts 3 and 5)
(Cycle = 3 Weeks for C1 - C4
Cycle = 4 Weeks for C5 and 
Beyond for Part 6)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
Blood RO, 
Blood RNAa
Blood 
PD
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C1D15h
336:00
X
X
X
X
C2D1
Predosef
00:00
X
X
X
X
C2D8
C3D1
Predosef
00:00
X
X
X
C4D1
Predosef
00:00
X
X
X
X
EOT/Unscheduled/ Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RO=Receptor Occupancy RNA = ribonucleic acid; TCR = T cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments from all subjects. Detailed instructions for the collection, processing, and shipping 
of samples will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D13 to D17 of a cycle.
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-3:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 4 (CA012004 - q4w Dosing)
Study Day of Sample 
Collection (1 Cycle = 
4 Weeks
Event
Time 
(Relative to start of 
BMS-986178 Infusion)
Hour: Min
Blood RNA, 
Blood ROa
Blood PD
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C1D15h
336:00
X
X
X
X
C2D1
Predosef
00:00
X
X
X
X
C3D1
Predosef
00:00
X
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments from all subjects. Detailed instructions for the collection, processing, and shipping 
of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point.. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory manual
Revised Protocol No.: 06
Date: 08-Feb-2019
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D12 to D18 of a cycle.
Revised Protocol No.: 06
Date: 08-Feb-2019
184
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-4:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with NSCLC)
Study Day of 
Sample Collection 
(1 Cycle = 6 Weeks)
Event
Time 
(Relative to start of 
BMS-986178 Infusion)
Hour: Min
Blood RNA, 
Blood ROa
Blood PD 
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc
Section 5.6
Blood 
Genotype,d
Blood TCR
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C1D15h
Predosef
00:00
X
X
X
X
C1D29i
Predosef
00:00
X
X
X
C2D1
Predosef
00:00
X
X
X
X
C3D1
Predosef
00:00
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; PD = 
pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments. Blood RNA samples will be collected from all subjects. Detailed instructions for 
the collection, processing, and shipping of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
Revised Protocol No.: 06
Date: 08-Feb-2019
185
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8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D13 to D17 of a cycle.
i
D29 sample may be taken during D26 to D30 of a cycle.
Revised Protocol No.: 06
Date: 08-Feb-2019
186
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8.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-5
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 8 (CA012004 - q12w Dosing)
Study Day of 
Sample Collection 
(1 Cycle = 
12 Weeks)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
Blood RNA, 
Blood ROa
Blood 
PD 
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, 
Plasmab
Plasma for 
ctDNAj
Tumor 
Biopsyc, 
Section 5.6
Blood 
Genotype, 
Blood 
TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
X
C1D8g
168:00
X
X
X
C1D15h
336:00
X
X
X
X
X
C1D29i
672:00
X
X
X
X
C1D78
1848:00k
X
X
X
X
C2D1
Predosef
00:00
X
X
X
X
X
C2D8g
168:00
X
X
X
C2D15h
336:00
X
X
X
X
C2D29 i
672:00
X
X
X
X
C3D1
Predosef
00:00
X
X
X
X
X
C3D8g
168:00
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor.
Note: The time recorded is relative to BMS-986178 infusion.
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a Separate samples will be collected for blood RNA and blood RO assessments. Blood RNA samples will be collected from all subjects. Detailed instructions for 
the collection, processing, and shipping of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor 
at the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional 
biopsies may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D13 to D17 of a cycle. 
i
D29 sample may be taken during D26 to D30 of a cycle.
j
Blood samples to be collected in 2x 9ml Streck tubes.
k C1D78 sample may be taken during D71 to D85.
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5.8
Outcomes Research Assessments
Not applicable.
 
 
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5.10
Additional Research Collection
Additional research collections and retention are mandatory for all subjects, except where 
prohibited by local laws or regulations.
This protocol will include residual samples for additional research (AR).
This collection for additional research is intended to expand the translational 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. It may also be used to support health authority 
requests for analysis, and the advancement of pharmacodiagnostic development to better target 
drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring 
disease pathways, progression and response to treatment etc. 
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study sponsor’s senior leaders in Research and Development (or designee) to 
ensure the research supports appropriate and well-defined scientific research activities.
•
Additionally, residual blood (or blood derivatives such as serum, plasma, PBMCs and 
extracted RNA/DNA) or tumor tissue (archival or fresh biopsy and extracted RNA/DNA) (see 
Table 5.10-1) will also be retained for additional research purposes.
•
Samples will be securely stored by the BMS Biorepository in New Jersey or at a BMS approved 
third party storage management facility. 
•
Samples will be stored in a coded fashion; and no researcher will have access to the key, which 
is securely held at the clinical site, so that there is no direct ability for a researcher to connect 
a sample to a specific individual.
•
Additional research samples will be retained for 15 years or the maximum allowed by 
applicable law. No additional sampling is required for residual collections. 
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
Table 5.10-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time Points for which residual samples will be retained
PK
All
Archived Tumor Block or Slides
Pre-treatment
Fresh Tumor Biopsy
Pre-treatment, on-treatment and/or unscheduled/EOT
PBMC’s
All
Serum
All
Plasma
All
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Table 5.10-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time Points for which residual samples will be retained
Blood RNA
All
Blood Genotype/Blood TCR
All
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess all 
adverse events (AE). The causal relationship can be one of the following:
Related: There is no clear alternative cause for the AE that can be identified other than study 
treatment (e.g. disease progression, environmental causes, unrelated trauma).
Not related: There is a clear alternative cause identified for the AE other than study 
treatment.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.)
Sponsor or designee will be reporting adverse events to regulatory authorities and ethics 
committees according to local applicable laws including European Directive 2001/20/EC and FDA 
Code of Federal Regulations 21 CFR Parts 312 and 320.
6.1
Serious Adverse Events
An SAE is any untoward medical occurrence that at any dose: 
•
results in death
•
is life-threatening (defined as an event in which the subject 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)
•
results in persistent or significant disability/incapacity
•
is a congenital anomaly/birth defect 
•
is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
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of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (e.g., pathogenic or nonpathogenic) via the study 
drug is an SAE. 
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (See Section 6.1.1
for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy (e.g., death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as SAE (See Section 6.1.1 for reporting details).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
•
a visit to the emergency room or other hospital department < 24 hours, that does not result in 
admission (unless considered an important medical or life-threatening event)
•
elective surgery, planned prior to signing consent
•
admissions as per protocol for a planned medical/surgical procedure
•
routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)
•
medical/surgical admission other than to remedy ill health and planned prior to entry into the 
study. Appropriate documentation is required in these cases
•
admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (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)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the IB represent the Reference Safety Information to determine 
expectedness of SAEs for expedited reporting. Following the subject’s written consent to 
participate in the study, all SAEs, whether related or not related to study drug, must be collected, 
including those thought to be associated with protocol-specified procedures. All SAEs must be 
collected that occur during the screening period and within 100 days of discontinuation of dosing. 
If applicable, SAEs must be collected that relate to any later protocol-specified procedure (eg, a 
follow-up skin biopsy). 
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure.
An SAE report must be completed for any event where doubt exists regarding its seriousness. 
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If the investigator believes that an SAE is not related to study drug, but is potentially related to the 
conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study drug, and pregnancies must be reported to BMS or 
designee within 24 hours of awareness of the event. SAEs must be recorded on the SAE Report 
Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). The preferred 
method for SAE data reporting collection is through the electronic case report form (eCRF). The 
paper SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF 
system is not functioning. In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. In the event the electronic system is unavailable for transmission, 
paper forms must be used and submitted immediately. When paper forms are used, the original 
paper forms are to remain on site
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS (or 
designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious AE is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug until 100 days 
after discontinuation of dosing. Nonserious AE information should also be collected from the start 
of a placebo lead-in period or other observational period intended to establish a baseline status for 
the subjects. 
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment as 
appropriate. All identified nonserious AEs must be recorded and described on the nonserious AE 
page of the CRF (paper or electronic). 
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Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities that 
are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (electronic) as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.
•
Any laboratory test result that is clinically significant or meets the definition of an SAE 
•
Any laboratory test result abnormality that required the subject to have study drug discontinued 
or interrupted
•
Any laboratory test result abnormality that required the subject 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 versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the investigational product, it is subsequently discovered that a study 
subject is pregnant or may have been pregnant at the time of study exposure, including during at 
least 5 half-lives after product administration, 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 Section 6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner (eg, dose 
tapering if necessary for subject safety). Please call the BMS Medical Monitor within 24 hours of 
awareness of the pregnancy.
The investigator must immediately notify the BMS Medical Monitor or designee of this event and 
complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours of 
awareness of the event and in accordance with SAE reporting procedures described in 
Section 6.1.1. 
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.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 6.1.1 for reporting details.).
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6.6
Potential Drug-Induced Liver Injury
Specific criteria for identifying pDILI have not been identified for this protocol. Standard medical 
practice in identifying and monitoring hepatic issues should be followed.
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a pDILI event. All occurrences of pDILIs, meeting the defined 
criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
pDILI is defined as: 
1) Aminotransaminases (AT) (ALT or AST) elevation > 3 times ULN
AND 
2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum ALP),
AND 
3) No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic. 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a pDILI event. All occurrences of pDILIs meeting the defined 
criteria must be reported as SAEs (see Section 6.1.1 for reporting details).
6.7
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, x-ray 
filming, or any other potential safety assessment required or not required by protocol should also 
be recorded as a nonserious or serious AE, as appropriate, and reported accordingly. 
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
8.1.1
Dose Escalation
As a Phase 1 dose escalation trial, the sample size for each dose escalation cohort depends on 
observed toxicity and posterior inference. Approximately 30 subjects are expected to be treated 
during each dose escalation part (BMS-986178 monotherapy [Part 1A], BMS-986178 in 
combination with nivolumab [Part 2A], and BMS-986178 in combination with ipilimumab 
[Part 3A]) for a combined total of approximately 90 subjects in Parts 1A, 2A and 3A. Initially, 
approximately 3 subjects will be treated at the starting dose levels of BMS-986178 or 
BMS-986178 in combination with nivolumab or ipilimumab. Additional cohorts of approximately 
3 evaluable subjects will be treated at recommended dose levels per BLRM (-Copula) 
recommendations during the dose escalation phase. At least 6 DLT-evaluable subjects will be 
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treated at the MTD. At most, 12 DLT-evaluable subjects will be treated at each dose level. This 
limit is set to avoid instances in which the model could recommend adding subjects indefinitely to 
a specific dose level due to uncertainty in the tolerability profile. Escalation by more than 1 dose 
level (dose skipping) is not permitted.
As in any dose escalation study, the exact number of subjects in the dose escalation cannot be 
predicted. However, different estimates with the pre-specified parameters of the dose escalation 
design under various scenarios are provided (see Appendix 1). A maximum of 30 subjects is 
pre-specified as one of the simulation parameters (assuming approximately 6 subjects per dose 
level). The simulation provided in Appendix 1 uses combination therapy as an illustration 
(containing 5 dose levels for BMS-986178 and a fixed dose level for nivolumab [240 mg]). The 
simulation estimated a total of 15 to 21 subjects on average under different scenarios. Note the 
following difference between simulation setting and the conduct of the actual trial: 1) dose 
skipping is allowed in the simulation setting whereas in the actual clinical trial, dose skipping is 
not permitted, 2) the clinical team can override BLRM (-Copula) dose recommendation based on 
the totality of data (clinical safety data along with available PK and PD data). Based on these 
factors, there may be more subjects in the dose escalation phase than the number estimated in the 
simulation. For planning purposes, it is assumed that approximately 30 subjects may be treated in 
each dose escalation part.
8.1.2
Cohort Expansion
The purpose of cohort expansion is to gather additional safety, tolerability, preliminary efficacy, 
PK, and PD information regarding BMS-986178 alone or in combination with nivolumab and/or 
ipilimumab. 
In general, the estimated sample size for Parts 2B, 2C, 2D, 3B, 6B, and 7B in expansion phase is 
guided by Simon 2-stage design, which is based on target response rates (target ORR) and the 
ability to identify a signal for such clinical response that is above the SOC (historical ORR). 
Enrollment of subjects at the end of Stage 1 will continue while the initial efficacy evaluation is 
ongoing. Decisions regarding continuing or not continuing enrollment of a specific arm will be 
based on a combination of model guidance, clinical judgment on the totality of data (clinical safety, 
PK, PD, and efficacy), and communication between the Sponsor and investigators. Parts 2E and 
3C include tumors from dose escalation for signal seeking. Due to the heterogeneity of response 
rates of the mixed tumors, approximately 40 subjects is assigned for each part (Part 2E and 
Part 3C). It is not the intent of the study to use Simon 2-stage design for formal hypothesis testing 
for the following reasons:
•
At an early stage, the Sponsor would like to explore primary anti-tumor activity as a proof of 
confidence. According to the exploratory nature of an early phase design, the sample size is 
not large enough to clearly define the patient population. Meanwhile, there are no control arms 
planned as a comparison.
•
In immuno-oncology, it is known that response rate alone does not reflect all potential clinical 
benefits. Factors such as duration of response, the depth of response, and delayed response 
could become evident as potential benefits according to the nature of immunotherapy.
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•
Safety is still the primary objective of the study, and if there is evidence of accumulated toxicity 
for a dose cohort, the cohort may be discontinued.
The Simon 2-stage design will be used as a guide for the disease-restricted expansion cohorts in 
Parts 2B, 2C, 2D, 3B, 6B, and 7B.153,155 The total sample size for each expansion cohort will be 
calculated to provide a reasonable false-positive rate (FPR) and false-negative rate (FNR) based 
on assumptions of true (target) and historic ORR for each indication. The sample size and operating 
characteristics of the Simon 2-stage design are provided in Table 8.1.2-1, although this is not used 
for hypothesis testing. Approximately 12 subjects for CRC and OCs, 10 subjects for BC, 17 
subjects for cervical cancer, and 28 subjects for RCC and NSCLC will be treated in Stage 1 for an 
initial evaluation of efficacy. This will inform potential early decisions and guide 
planning/operations or early termination after taking into consideration additional data, 
(eg, duration of response and/or SD and safety). If the true response rate is 10% for CRC and OC, 
the study has a 66% probability of early termination of the cohort. If the true response rate is 25% 
for BC, the study has a 53% probability of early termination of the cohort. If the true response rate 
is 20% for cervical cancer, the study has a 55% probability of early termination of the cohort. If 
the true response rate is 40% for RCC and NSCLC, the study has a 55% probability of early 
termination of the cohorts.
For an expansion cohort of 35 subjects in CRC and OC and the assumed true response rate of 30%, 
there is a 94% chance of observing at least 7 responses (in other words, the FNR is 6%). If the true 
response rate is only 10% rather than 30%, then there is a 6% chance that there will be at least 
7 responses in 35 subjects (in other words, FPR is 6%). Also, if 7 responses are observed (eg, 20% 
observed response rate), the lower bound of the 80% CI for the ORR is 11% (higher than historical 
ORR of 10%). The CI is calculated using Clopper-Pearson method.
For an expansion cohort of 27 subjects with BC and the assumed true response rate of 50%, there 
is an 88% chance of observing at least 11 responses (in other words, the FNR is 12%). If the true 
response rate is only 25% rather than 50%, then there is a 5% chance that there will be at least 
11 responses in 27 subjects (in other words, FPR is 5%). If 11 responses are observed (eg, 41% 
observed response rate), the lower limit of the 80% CI for the ORR is 28% (higher than historical 
ORR of 25%). The CI is calculated using Clopper-Pearson method.
For an expansion cohort of 37 subjects with cervical cancer and the assumed true response rate of 
40%, there is an 87% chance of observing at least 12 responses (in other words, the FNR is 13%). 
If the true response rate is only 20% rather than 40%, then there is a 5% chance that there will be 
at least 12 responses in 37 subjects (in other words, FPR is 5%). If 12 responses are observed 
(eg, 32% observed response rate), the lower limit of the 80% CI for the ORR is 22% (higher than 
historical ORR of 20%). The CI is calculated using Clopper-Pearson method.
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Table 8.1.2-1:
Dose Expansion - Characteristics of the Simon 2-Stage Design158
Expansion Cohort
Historic 
ORR
(%)
Target 
ORR
(%)
Stage 1/ 
Total N
Stage 1 
Responses 
Futility 
Boundary
FPR/1-FNR
(%)
Probability 
of Early 
Stopping
(%)
CRC, Ovarian Cancer
10
30
12/35
1
10/90
66
Bladder Cancer
25
50
10/27
2
10/90
53
Cervical Cancer
20
40
17/37
3
10/90
55
NSCLC, RCC
40
60
28/41
11
10/90
55
Abbreviations: CRC = colorectal cancer; FNR = false-negative rate; FPR = false-positive rate.
The number of subjects receiving treatment for efficacy evaluation is approximate, and additional 
subjects may be treated in order to have sufficient response-evaluable subjects per expansion 
cohort.
8.1.3
Schedule and Dose Exploration and Safety Exploration
The purpose of Parts 4, 5, 6A, 7A, and 8 is to assess safety, tolerability, preliminary efficacy, PK, 
and PD information of BMS-986178 in combination with nivolumab administered with a less 
frequent dosing schedule (q4w Part 4 and q12w Part 8 for BMS-986178) or BMS-986178 in 
combination with higher dose of ipilimumab (Part 5) or BMS-986178 in combination with 
nivolumab and ipilimumab (Parts 6A and 7A). A minimum of 6 subjects will be treated at the 
MTD/RP2D chosen from Part 2A or Part 3A. Up to 12 subjects may be treated for further 
evaluation of safety, PK, or PD parameters. Administration of BMS-986178 in combination with 
nivolumab and/or ipilimumab in 6 to 12 subjects per dose and schedule level provides 90% 
probability of observing at least 1 occurrence of a specific AE that would occur with a 32% or 
17% incidence in the population, respectively. Furthermore, 6 to 12 subjects provide some 
precision of PD biomarker effect estimation. To assess the PD effects, pre-treatment and on-
treatment whole blood and serum samples and tumor biopsies will be required. It is of interest to 
ensure the precision of the estimate of the ratio of on-treatment biomarker assessments to pre-
treatment (baseline) levels. Assuming that a biomarker is measured as a continuous variable, a 
given number of subjects will provide the confidence that the estimate of the ratio of on-treatment 
to baseline values will be within 20% of the true value, as shown in Table 8.1.3-1.
Table 8.1.3-1:
Probability that Estimated Ratio of On-treatment to Pre-treatment 
(Baseline) Value is Within 20% of True Value
Intra-subject 
Standard Deviation 
(Log-scale)
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Probability
N = 6
92%
76%
62%
52%
44%
38%
34%
N = 12
99%
90%
78%
68%
59%
52%
46%
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For example, for a biomarker (eg, activated and memory CD4 and CD8 T-cells) with an 
intra-subject standard deviation of 0.5, if the true ratio of post-baseline to baseline geometric 
means is 1.2 (increase from baseline is 20%), there is 68% probability that the estimated ratio 
would be within 0.96 and 1.44 (or a percent change between -4% and 44%) with 12 subjects per 
treatment arm. If the true increase from baseline is 60%, for a biomarker with the same variability, 
then there is 68% probability that the estimated percent change would be between 28% and 92% 
with 12 subjects per treatment arm.
Up to approximately 20 evaluable subjects per dose cohort will be treated in Part 8. This sample 
size provides a 90% CI for the true proportion of subjects showing a change in receptor occupancy 
with width of 37% and 26% respectively when the observed proportion of subjects showing a 
change in receptor occupancy is 70% and 90%, as shown in Table 8.1.3-2. The maximum width 
of all 90% CIs is 40% and the maximum margin of error is 21% with a sample size of 20 per 
cohort.
Table 8.1.3-2:
90% Confidence Interval for the True Proportion 
of Subjects Showing a Biomarker Change
n
# subjects showing the trend
90% CI
20
14
(49%, 86%)
18
(72%, 98%)
8.2
Populations for Analyses
•
All Enrolled Subjects: All subjects who signed an ICF and are registered into the IRT.
•
All Treated Subjects: All subjects who received at least 1 dose of study medication.
•
The PK data set includes all available concentration-time data from subjects who received any 
BMS-986178, nivolumab, or ipilimumab.
•
The immunogenicity data set consists of all available immunogenicity data from subjects who 
received BMS-986178, nivolumab, or ipilimumab.
•
The biomarker data set includes all available biomarker data from subjects who received any 
study drug(s). 
•
Response-evaluable subjects: All treated subjects with measurable disease and any of the 
following: 1) at least 1 post-baseline tumor measurement , 2) clinical progression, or 3) death.
Analyses of safety, extent of exposure, biomarkers, PK, preliminary efficacy, immunogenicity, 
and PD will be based on all treated subjects.
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8.3
Endpoints
8.3.1
Primary Endpoint(s)
The assessment of safety will be based on the incidence of AEs, SAEs, AEs leading to 
discontinuation, and deaths. In addition, clinical laboratory test abnormalities will be examined.
AEs and laboratory values will be graded according to NCI CTCAE v4.03.
8.3.2
Secondary Endpoint(s)
8.3.2.1
Efficacy
The anti-tumor activity of BMS-986178 alone or in combination with nivolumab and/or 
ipilimumab will be measured by ORR, duration of response, and PFSR at 24 weeks based on 
RECIST v1.1. The above will be determined based on tumor measurements occurring at baseline, 
every 8 weeks (± 1 week) during the treatment period. and every 12 weeks during the Survival 
Follow-up Period.
•
Best overall response (BOR) is assessed by investigator and/or BICR per RECIST 1.1 criteria.
•
ORR is defined as the proportion of all treated subjects whose BOR is either CR or PR.
•
Duration of response, computed for all treated subjects with a BOR of CR or PR, is defined as 
the time between the date of first response and the date of disease progression or death, 
whichever occurs first.
•
PFSR at 24 weeks is defined as the proportion of treated subjects remaining progression free 
and surviving at 24 weeks. The proportion will be calculated by the Kaplan-Meier estimate, 
which takes into account censored data
8.3.2.2
Pharmacokinetics
Selected BMS-986178 parameters, such as Cmax, Tmax, AUC(0-t), and AUC(TAU), will be 
assessed in 2 cycles depending on the schedule for monotherapy or in combination with nivolumab 
and/or ipilimumab. Parameters such as Ctau, CLT, Css-avg, accumulation index (AI), and 
effective elimination half-life (T-HALFeff) will be assessed in the second cycle when intensive 
PK are collected. A separate listing, summary, and plot will be generated for Ctrough. 
8.3.2.3
Immunogenicity
The secondary objective of immunogenicity will be assessed by the frequency of positive ADA to 
BMS-986178 or nivolumab or ipilimumab.
8.3.2.4
Pharmacodynamics
The secondary objective of pharmacodynamics will be assessed by the proportion of subjects 
showing a change in pharmacodynamic biomarkers such as soluble OX40 and peripheral OX40 
receptor occupancy along with tumor pharmacodynamic of BMS-986178 in combination with 
nivolumab or nivolumab monotherapy (Part 8).
 
 
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8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
Frequency distributions of gender and race will be tabulated. Summary statistics for age, body 
weight, and height will be tabulated.
8.4.2
Efficacy Analyses
The primary efficacy analyses will be performed on all treated subjects. Efficacy analyses based 
on response-evaluable subjects may be performed for interim analyses when the minimum 
follow-up period is less than sufficient to warrant adequate interpretation of results. Listing of 
tumor measurements will be provided by subject and study day in each arm and dose level. 
Individual subject’s BOR will be listed based on RECIST 1.1.
To describe the anti-tumor activity of BMS-986178 alone or in combination with nivolumab and/or 
ipilimumab, ORR will be calculated. ORR and corresponding two-sided exact 95% CI by the 
Clopper-Pearson method will be provided by treatment and/or dose level and tumor type. Median 
duration of response and corresponding two-sided 95% CI will be reported by treatment and/or 
dose level and tumor type. Duration of response will be analyzed using the Kaplan-Meier method.
In addition, PFSR, the probability of a subject remaining progression free or surviving to 24 weeks, 
will be estimated by the Kaplan-Meier methodology by treatment, tumor type, and dose level. The 
corresponding 95% CI will be derived based on Greenwood formula.
 
8.4.3
Safety Analyses
All recorded AEs will be listed and tabulated by system organ class, preferred term, and treatment. 
Vital signs and clinical laboratory test results will be listed and summarized by treatment. Any 
significant physical examination findings and clinical laboratory results will be listed. ECG 
readings will be evaluated by the investigator, and abnormalities, if present, will be listed
8.4.4
Pharmacokinetic Analyses
All individual PK parameters will be listed for each analyte, including any exclusions and reasons
for exclusion from summaries. Summary statistics will be tabulated for each PK parameter by 
treatment. Geometric means and coefficients of variation will be presented for Cmax, AUC(0-t), 
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AUC(TAU), Ctau, CLT, Css-avg, and AI. Medians and ranges will be presented for Tmax. 
Medians and ranges will be presented for Tmax. Means and standard deviations will be presented 
for all other PK parameters (eg, T-HALFeff). 
BMS-986178 dose dependency will be assessed in dose escalation monotherapy. To describe the 
dependency on dose of BMS-986178, scatter plots of Cmax, AUC(0-t), and AUC(TAU) versus 
dose may be provided at the cycles when these PK parameters are assessed, as specified in 
Section 5.5. Exploratory assessments of dose proportionality based on a power model with CI 
around the power coefficient may be performed. Nivolumab and ipilimumab EOI and trough 
(Ctrough) concentrations and BMS-986178 trough concentration will be tabulated by treatment 
and study day using summary statistics. These data may also be pooled with other datasets for 
population PK analysis, which will be presented in a separate report.
8.4.5
Biomarker Analyses
In Part 8, summary statistics for the proportion of subjects showing a change in pharmacodynamics 
biomarkers will be tabulated by treatment cohort.
 
 
 
 
 
8.4.7
Outcomes Research Analyses
Not applicable.
8.4.8
Other Analyses 
A listing of all available immunogenicity data will be provided by treatment, dose, and 
immunogenicity status. The frequency of subjects with positive ADA assessment of BMS-986178, 
nivolumab, and ipilimumab will be summarized.
8.5
Interim Analyses
Administrative interim analysis for internal decision making or external publication purpose may 
be performed. No formal inferences requiring any adjustment to statistical significance level will 
be performed. 
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
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opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change will be 
submitted to:
•
IRB/IEC for review and approval/favorable opinion
•
BMS
•
Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the subject: 
(1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a schedule 
of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable.
In addition, the study may be evaluated by BMS 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 BMS. 
9.1.2.1
Source Documentation
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records, AE
tracking/reporting, protocol required assessments, and/or drug accountability records).
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When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
BMS will provide quality investigational staff training prior to study initiation. Training topics 
will include but are not limited to: GCP, AE reporting, study details and procedure, electronic 
CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator 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, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study and BMS will notify the investigator 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, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include investigational product. 
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 subject, including unique subject 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
•
Retained samples for bioavailability/bioequivalence, if applicable 
•
Dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form.
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
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9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents, or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS EDC tool, electronic CRFs will be prepared for all data collection fields 
except for fields specific to SAEs and pregnancy, which will be reported on the or electronic SAE 
form and Pregnancy Surveillance form, respectively. If an electronic SAE form is not available, a 
paper SAE form can be used. Spaces may be left blank only in those circumstances permitted by 
study-specific CRF completion guidelines provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. For electronic CRFs, review and approval/signature is completed 
electronically through the BMS EDC tool. The investigator must retain a copy of the CRFs 
including records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements and 
must only access the BMS EDC tool using the unique user account provided by BMS. User 
accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report.
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria:
•
Subject recruitment (eg, among the top quartile of enrollers)
•
Involvement in trial design
•
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications or 
abstracts arising from this study require approval by BMS prior to publication or presentation and 
must adhere to BMS’s publication requirements as set forth in the approved clinical trial agreement 
(CTA). All draft publications, including abstracts or detailed summaries of any proposed 
presentations, must be submitted to BMS at the earliest practicable time for review, but at any 
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event not less than 30 days before submission or presentation unless otherwise set forth in the 
CTA. BMS shall have the right to delete any confidential or proprietary information contained in 
any proposed presentation or abstract and may delay publication for up to 60 days for purposes of 
filing a patent application.
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GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
Complete Abstinence is defined as complete avoidance of 
heterosexual intercourse and is an acceptable form of 
contraception for all study drugs. This also means that 
abstinence is the preferred and usual lifestyle of the patient. 
This does not mean periodic abstinence (e.g., calendar, 
ovulation, symptothermal, profession of abstinence for entry 
into a clinical trial, post-ovulation methods) and withdrawal, 
which are not acceptable methods of contraception. Women
must continue to have pregnancy tests. Acceptable alternate 
methods of highly or less effective contraception’s must be 
discussed in the event that the subject chooses to forego 
complete abstinence.
Additional Research
Those scientific activities which cannot be reasonably 
anticipated at the time of trial design, for which we would 
like to collect and/or retain samples from study subjects. 
Examples of additional research include, but are not limited 
to, new assay development and validation, companion 
diagnostic development, new hypotheses in the interaction of 
drug and the human body, and exploration of emerging 
science in the understanding of disease.
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LIST OF ABBREVIATIONS
Term
Definition
5-FU
5-fluorouracil
ADA
anti-drug antibody
ADCC
antibody-dependent cellular cytotoxicity
ADCP
antibody-dependent cellular phagocytosis
AE
adverse event
AFP
alpha fetal protein
AI
accumulation index
ALK
anaplastic lymphoma kinase 
ALP
alkaline phosphatase
ALT
alanine aminotransferase
APC
antigen-presenting cell
AST
aspartate aminotransferase
AT
Aminotransaminases
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-t)
Area under the plasma concentration-time curve from time zero to time 
of last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in 1 dosing interval
BC
bladder cancer 
BCR
B-cell receptor
BICR
Blinded Independent Central Review
BLA
Biologics License Application
BLRM
Bayesian Logistic Regression Method
BMS
Bristol-Myers Squibb
BOR
best overall response
BSC
best supportive care
BUN
blood urea nitrogen
C
Cycle
C12
concentration at 12 hours
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Term
Definition
CEA
carcinoembryonic antigen
Cavgss
steady-state time-averaged concentration
CBC
complete blood count
CFR
Code of Federal Regulations 
CI
confidence interval
CrCL
creatinine clearance
CLT
total body clearance
Cmax
maximum observed concentration
Cmaxss
steady-state peak concentration
CMI
cell-mediated immunity
Cminss
steady-state trough concentration
CNS
central nervous system
CR
complete response
CRC
colorectal cancer
CRF
case report form, paper or electronic
CRP
C-reactive protein
Css-avg
average concentration over a dosing interval (AUC[TAU]/tau)
CT
computed tomography
CTA
clinical trial agreement
Ctau
the observed concentration at the end of a dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
CTLA-4
cytotoxic T-lymphocyte associated antigen-4
Ctrough
Trough observed plasma concentration
D
Day
CV
coefficient of variation
DEHP
diethylhexyl phthalate 
DLT
dose-limiting toxicity
EC50
half maximal effective concentration
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
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Term
Definition
eCRF
electronic case report form
EDC
electronic data capture
EGFR
epidermal growth factor receptor
EOI
end of infusion
EOT
end of treatment
EWOC
escalation with overdose control
Fc
fragment crystallizable
FDA
Food and Drug Administration
FDG
Fluorodeoxyglucose
FFPE
formalin-fixed, paraffin-embedded
FIH
first-in-human
FNR
false-negative rate
FPR
false-positive rate
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
Geo Mean
geometric mean
GGT
gamma-glutamyl transferase
gMDSC
granulocytic myeloid-derived suppressor cell
GITR
glucocorticoid-induced TNFR-related gene
hCG
human chorionic gonadotrophin
hERG
human Ether-à-go-go-Related Gene (hERG)
HIV
human immunodeficiency virus
HPV
human papillomavirus
HRT
hormone replacement therapy
IASLC
International Association for the Study of Lung Cancer 
IB
Investigator Brochure
ICD
International Classification of Diseases
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
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Term
Definition
IFN-γ
interferon-γ
IgG1
immunoglobulin G1
IgG2
immunoglobulin G2
IHC
Immunohistochemistry
IMDC
International Metastatic RCC Database Consortium 
IMP
investigational medicinal products
IL
Interleukin
IO
immuno-oncology
IP
Intraperitoneal
IRB
Institutional Review Board
IRR
infusion-related reaction
IUD
intrauterine device
IV
Intravenous
IRT
Interactive Response Technology
KPS
Karnofsky Performance Scale
LDH
lactic acid dehydrogenase
LFT
liver function test
mAb
monoclonal antibody
MABEL
minimal anticipated biologic effect level
mCRC
metastatic colorectal cancer
MC38
murine colon carcinoma cell line 38
MDSC
myeloid-derived suppressor cell
mOS
median overall survival
mPFS
median progression free survival
mRCC
metastatic renal cell carcinoma 
MRI
magnetic resonance imaging
MSI
microsatellite instability
MSI-H
microsatellite instability-high
MSKCC
Memorial Sloan-Kettering Cancer Center
MST
Medical Surveillance Team
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Term
Definition
MTD
maximum tolerated dose
N
number of subjects or observations
NCA
non-compartmental analysis
NCI
National Cancer Institute
NK
natural killer
NKT
natural killer T
NSCLC
non-small cell lung cancer
OC
ovarian cancer
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PBT
platinum-based therapy
PCR
polymerase chain reaction
PD
Pharmacodynamics
PD-1
programmed cell death-1
pDILI
potential drug-induced liver injury
PET
positron emission tomography
PFS
progression free survival
PFSR
progression free survival rate
PK
Pharmacokinetics
PR
partial response
PSA
prostate-specific antigen
q2w
every 2 weeks
q3w
every 3 weeks
q4w
every 4 weeks
q6w
every 6 weeks
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria In Solid Tumors
RNA
ribonucleic acid
RO
receptor occupancy
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Term
Definition
RP2D
recommended Phase 2 dose (s)
RT-qPCR
real-time quantitative PCR
SAE
serious adverse event
SD
stable disease
SNP
single-nucleotide polymorphism
SOC
standard of care
T
Time
T3
triiodothyronine 
T4
Thyroxine
TCGA
The Cancer Genome Atlas
TCR
T-cell receptor
TF
tumor free
TGI
tumor growth inhibition
TIL
tumor-infiltrating lymphocyte
T-HALF
half life
T-HALFeff
effective elimination half-life that explains the degree of accumulation 
observed for a specific exposure measure (exposure measure includes 
AUC[TAU], Cmax and Ctau)
Tmax
time of maximum observed concentration
TNF-α
tumor necrosis factor-α
TNFRsf
tumor necrosis factor receptor super family
Treg
regulatory T-cell
TSH
thyroid-stimulating hormone
ULN
upper limit of normal
US
United States
Vc
volume of central
VEGF
vascular endothelial growth factor
VS
vital signs
Vss
volume of distribution at steady state
Vz
volume of distribution of terminal phase (if IV and if multi-exponential 
decline)
WOCBP
women of childbearing potential
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APPENDIX 3
RECIST 1.1
1
ASSESSMENT OF OVERALL TUMOR BURDEN AND MEASURABLE 
DISEASE
To assess objective response or future progression, it is necessary to estimate the overall tumor
burden at baseline and use this as a comparator for subsequent measurements. Measurable 
disease is defined by the presence of at least 1 measurable tumor lesion. When computed 
tomographic (CT) scans have slice thickness greater than 5 mm, the minimum size for a 
measurable lesion should be twice the slice thickness.
Central assessments may be planned for this study. Copies of all scans should be kept at the site 
as part of the subject study file.  At the Sponsor’s discretion, scans may be collected centrally for 
further analysis. 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows:
1.1
Measurable Lesions
Measurable lesions must be accurately measured in at least 1 dimension (longest diameter in the 
plane of the measurement to be recorded) with a minimum size of:
•
10 mm by CT/magnetic resonance imaging (MRI) scan (CT/MRI scan slice thickness no 
greater than 5 mm)
•
10-mm caliper measurement by clinical examination (lesions that cannot be accurately 
measured with calipers should be recorded as non-measurable)
•
20 mm by chest X-ray
•
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a 
lymph node must be ≥15 mm in the short axis when assessed by CT scan (CT scan slice 
thickness is recommended to be no greater than 5 mm). At baseline and in follow-up, only 
the short axis will be measured and followed.
1.2
Non-Measurable Lesions
•
All other lesions, including small lesions (longest diameter < 10 mm or pathological lymph 
nodes with ≥10 to < 15 mm short axis), as well as truly non-measurable lesions
•
Lesions considered truly non-measurable include the following: leptomeningeal disease, 
ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic 
involvement of the skin or lung, and abdominal masses/abdominal organomegaly identified 
by physical examination that are not measurable by reproducible imaging techniques
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1.3
Special Considerations Regarding Lesion Measurability
1.3.1
Bone Lesions
•
Bone scan, positron emission tomography (PET) scan or plain films are not considered 
adequate imaging techniques to measure bone lesions. However, these techniques can be 
used to confirm the presence or disappearance of bone lesions. 
•
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components
that can be evaluated by cross sectional imaging techniques such as CT or MRI, can be 
considered as measurable lesions if the soft tissue component meets the definition of 
measurability described above.
•
Blastic bone lesions are non-measurable.
1.3.2
Cystic Lesions
•
Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts.
•
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions if they meet the definition of measurability described above. However, if non-cystic 
lesions are present in the same subject, these are preferred for selection as target lesions.
1.3.3
Lesions with Prior Local Treatment
Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been demonstrated 
progression in the lesion.
1.4
Specifications by Methods of Measurements
1.4.1
Measurement of Lesions
All measurements should be recorded in metric notation (mm). All baseline evaluations should 
be performed as close as possible to the treatment start and never more than 30 days before the 
beginning of the treatment.
1.4.2
Method of Assessment
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation should 
always be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical examination.
1.4.2.1
CT/MRI Scan
CT/MRI is the best currently available and reproducible method to measure lesions selected for 
response assessment. Measurability of lesions on CT/MRI scan is based on the assumption that 
CT/MRI slice thickness is 5 mm or less. When CT scans have slice thickness greater than 5 mm, 
the minimum size for a measurable lesion should be twice the slice thickness.
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1.4.2.2
Chest X-ray
Chest CT is preferred over chest X-ray, particularly when progression is an important endpoint, 
since CT is more sensitive than X-ray, particularly in identifying new lesions. However, lesions 
on chest X-ray may be considered measurable if they are clearly defined and surrounded by 
aerated lung.
1.4.2.3
Clinical Lesions
Clinical lesions will only be considered measurable when they are superficial and ≥10 mm 
diameter as assessed using calipers. For the case of skin lesions, documentation by color 
photography including a ruler to estimate the size of the lesion is suggested. As previously noted, 
when lesions can be evaluated by both clinical examination and imaging, imaging evaluation 
should be undertaken since it is more objective and may also be reviewed at the end of the study.
1.4.2.4
Ultrasound
Ultrasound is not useful in assessment of lesion size and should not be used as a method of 
measurement. If new lesions are identified by ultrasound in the course of the study, confirmation 
by CT or MRI is advised. 
1.4.2.5
Endoscopy, Laparoscopy
The utilization of these techniques for objective tumor evaluation is not advised.
2
BASELINE DOCUMENTATION OF ‘TARGET’ AND ‘NON-TARGET’ 
LESIONS
2.1
Target Lesions
When more than 1 measurable lesion is present at baseline all lesions up to a maximum of 
5 lesions total (and a maximum of 2 lesions per organ) representative of all involved organs 
should be identified as target lesions and will be recorded and measured at baseline.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), 
should be representative of all involved organs, and should lend themselves to reproducible
repeated measurements.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted below, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
2.1.1
Lymph Nodes
Lymph nodes merit special mention since they are normal anatomical structures that may be 
visible by imaging even if not involved by tumor. Pathological nodes that are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
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≥15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. 
Nodes that have a short axis < 10 mm are considered non-pathological and should not be 
recorded or followed.
2.2
Non-Target Lesions
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal 
progression’. In addition, it is possible to record multiple non-target lesions involving the same 
organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ or 
‘multiple liver metastases’).
3
TUMOR RESPONSE EVALUATION
3.1
Evaluation of Target Lesions
Complete Response (CR):  Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.
Partial Response (PR):  At least a 30% decrease in the sum of diameters of target lesions,
taking as reference the baseline sum diameters.
Progressive Disease (PD):  At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. (Note: The appearance of 1 or more new lesions is also 
considered progression.)
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
3.1.1
Special Notes on the Assessment of Target Lesions
3.1.1.1
Lymph Nodes
Lymph nodes merit special mention since they are normal anatomical structures that may be 
visible by imaging even if not involved by tumor. Pathological nodes that are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. 
Nodes that have a short axis < 10 mm are considered non-pathological and should not be 
recorded or followed.
3.1.1.2
Target Lesions That Become ‘Too Small to Measure’
All lesions (nodal and non-nodal) recorded at baseline should have their actual measurements 
recorded at each subsequent evaluation, even when very small (eg, 2 mm). If the radiologist is 
able to provide an actual measurement, that should be recorded, even if it is below 5 mm.
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However, when such a lesion becomes difficult to assign an exact measure to then:
•
If it is the opinion of the radiologist that the lesion has likely disappeared, the measurement 
should be recorded as 0 mm.
•
If the lesion is believed to be present and is faintly seen but too small to measure, a default 
value of 5 mm should be assigned (note: in case of a lymph node believed to be present and 
faintly seen but too small to measure, a default value of 5 mm should be assigned in this 
circumstance as well). This default value is derived from the 5-mm CT slice thickness 
(but should not be changed with varying CT slice thickness).
3.1.1.3
Target Lesions That Split or Coalesce on Treatment
•
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions 
should be added together to calculate the target lesion sum.
•
As lesions coalesce, a plane between them may be maintained that would aid in obtaining 
maximal diameter measurements of each individual lesion. If the lesions have truly 
coalesced such that they are no longer separable, the vector of the longest diameter in this 
instance should be the maximal longest diameter for the ‘coalesced lesion’.
3.2
Evaluation of Non-Target Lesions
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the timepoints specified in the protocol. 
Complete Response (CR):  Disappearance of all non-target lesions. All lymph nodes must be 
non-pathological in size (< 10 mm short axis).
Non-CR/Non-PD:  Persistence of 1 or more non-target lesion(s) above the normal limits.
Progressive Disease (PD):  Unequivocal progression of existing non-target lesions. (Note: The 
appearance of 1 or more new lesions is also considered progression.)
3.2.1
Special Notes on Assessment of Non-Target Lesions
The concept of progression of non-target disease requires additional explanation as follows:
3.2.1.1
When the Subject Also Has Measurable Disease
•
To achieve ‘unequivocal progression’ on the basis of the non-target disease, there must be 
an overall level of substantial worsening in non-target disease such that, even in the 
presence of SD or PR in target disease, the overall tumor burden has increased sufficiently 
to merit discontinuation of therapy. 
•
A modest ‘increase’ in the size of 1 or more non-target lesions is usually not sufficient to 
quality for unequivocal progression status. 
3.2.1.2
When the Subject Has Only Non-Measurable Disease
•
To achieve ‘unequivocal progression’ on the basis of the non-target disease, there must be 
an overall level of substantial worsening such that the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy. 
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•
A modest ‘increase’ in the size of 1 or more non-target lesions is usually not sufficient to 
qualify for unequivocal progression status. 
•
Because worsening in non-target disease cannot be easily quantified (by definition: if all 
lesions are non-measurable), a useful test that can be applied when assessing subjects for 
unequivocal progression is to consider if the increase in overall disease burden based on the 
change in non-measurable disease is comparable in magnitude to the increase that would be 
required to declare PD for measurable disease: that is, an increase in tumor burden 
representing an additional 73% increase in ‘volume’ (which is equivalent to a 20% increase 
diameter in a measurable lesion). Examples include an increase in a pleural effusion from 
‘trace’ to ‘large’ or an increase in lymphangitic disease from localized to widespread or 
may be described in protocols as ‘sufficient to require a change in therapy’. 
•
If ‘unequivocal progression’ is seen, the subject should be considered to have had overall 
PD at that point.
3.2.1.3
Tumor Markers
Tumor markers alone cannot be used to assess objective tumor responses. If markers are initially 
above the upper normal limit, however, they must normalize in order for a subject to be 
considered as having attained a complete response.
3.3
New Lesions
The appearance of new malignant lesions denotes disease progression. The finding of a new 
lesion should be unequivocal: that is, not attributable to differences in scanning technique, 
change in imaging modality or findings thought to represent something other than tumor 
(eg, some ‘new’ bone lesions may be simply healing or flare of preexisting lesions). This is 
particularly important when the subject’s baseline lesions show partial or complete response. 
For example, necrosis of a liver lesion may be reported on a CT scan report as a ‘new’ cystic 
lesion, which it is not.
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. An example of this is 
the subject who has visceral disease at baseline and while on study has a CT or MRI brain scan 
ordered that reveals metastases. The subject’s brain metastases are considered to be evidence of 
PD even if he/she did not have brain imaging at baseline.
If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm there 
is definitely a new lesion, then progression should be declared using the date of the initial scan.
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3.3.1
FDG-PET Evaluation
While [18F] fluorodeoxyglucose (FDG)-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of the qualitative assessment of FDG-PET scanning 
to complement CT scanning in assessment of progression (particularly possible ‘new’ disease). 
New lesions on the basis of FDG-PET imaging can be identified according to the following 
algorithm: 
•
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion. 
•
No FDG-PET at baseline and a positive FDG-PET at follow-up: 
−
If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by 
CT, this is PD. 
−
If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial positive 
FDG-PET scan).
−
If the positive FDG-PET at follow-up corresponds to a preexisting site of disease on CT 
that is not progressing on the basis of the anatomic images, this is not PD.
4
RESPONSE CRITERIA
4.1
Timepoint Response
A response assessment should occur at each timepoint specified in the protocol. 
For subjects who have measurable disease at baseline Table 4.1-1 provides a summary of the 
overall response status calculation at each timepoint.
Table 4.1-1:
Timepoint Response: Subjects with Target (+/– Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
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Table 4.1-1:
Timepoint Response: Subjects with Target (+/– Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
Any 
PD
Yes or No
PD
Any
Any 
Yes
PD
Abbreviations: CR = complete response; NE =not evaluable; PD = progressive disease; PR = partial response; 
SD = stable disease.
Missing Assessments and Not Evaluable Designation
When no imaging/measurement is done at all at a particular timepoint, the subject is not 
evaluable (NE) at that timepoint. If only a subset of lesion measurements are made at an 
assessment, the case is also considered NE at that timepoint, unless a convincing argument can 
be made that the contribution of the individual missing lesion(s) would not have changed the 
assigned timepoint response.
4.1.1
Confirmation Scans
•
Verification of Response: Confirmation of PR and CR is required after at least 4 weeks
following initial assessment to ensure responses identified are not the result of 
measurement error.
4.2
Best Overall Response: All Timepoints
The best overall response is determined once all the data for the subject are known. It is the best 
response recorded from the start of the study treatment until the date of objectively documented 
progression based on RECIST v1.1, taking into account any requirement for confirmation, or the 
date of subsequent anti-cancer therapy, whichever occurs first in the study. The subject’s best 
overall response assignment will depend on the findings of both target and non-target disease and 
will also take into consideration the appearance of new lesions. 
Best response is defined as the best response across all timepoints with subsequent confirmation. 
Complete or partial responses may be claimed only if the criteria for each are met at a 
subsequent timepoint as specified in the protocol (generally 4 weeks later).
In this circumstance, the best overall response can be interpreted as specified in Table 4.2-1.
When SD is believed to be best response, it must meet the protocol specified minimum time 
from baseline. Measurements must have met the SD criteria at least once after study entry at a 
minimum interval (in general, not less than 6 to 8 weeks) that is defined in the study protocol.
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Table 4.2-1:
Best Overall Response When Confirmation of CR and PR Is 
Required
Overall Response
Overall Response
Best Overall Response
First Timepoint
Subsequent Timepoint
CR
CR
CR
CR
PR
SD, PD, or PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, PD
CR
PD
SD provided minimum criteria for SD duration met, otherwise, PD
CR
NE
SD provided minimum criteria for SD duration met, otherwise NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for SD duration met, otherwise, PD
PR
NE
SD provided minimum criteria for SD duration met, otherwise NE
NE
NE
NE
Abbreviations: CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response;
SD = stable disease.
a If a CR is truly met at first timepoint, then any disease seen at a subsequent timepoint, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since the disease must have reappeared after CR). 
The best response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may 
be claimed when subsequent scans suggest small lesions were likely still present and in fact the subject had PR, 
not CR at the first timepoint. Under these circumstances, the original CR should be changed to PR and the best 
response is PR.
4.3
Duration of Response
4.3.1
Duration of Overall Response
The duration of overall response is measured from the time measurement criteria are first met for 
CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded on study).
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The duration of overall complete response is measured from the time measurement criteria are 
first met for CR until the first date that recurrent disease is objectively documented.
4.3.2
Duration of Stable Disease
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum on 
study (if the baseline sum is the smallest, this is the reference for calculation of PD).
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APPENDIX 4
ECOG PERFORMANCE STATUS
ECOG Performance Statusa
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light housework, office work
2
Ambulatory and capable of all self-care but unable to carry out any work activities
Up and about more than 50% of waking hours
3
Capable of only limited self-care
Confined to bed or chair more than 50% of waking hours
4
Completely disabled
Cannot carry on any self-care
Totally confined to bed or chair
5
Dead
 
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Protocol Amendment No.: 04 Site Specific
Date: 12-May-2021
Document
Date of Issue
Summary of Change
Changed to:
“1 mg/mL 0.7 mL/vial and as indicated in the Ubivac IB52”
Administrative 
Letter 08 
Specific
27-Jan-2020
•
Due to delay in Part 9, revprot05a was never implemented or 
distributed. Revprot05b is the updated version that has been 
distributed for HA/IRB review, and will be executed only at US sites 
0002, 0007, 0017, 0019 and 0024.
Revised 
Protocol 05b
Site-specific
26-Nov-2019
•
Included all changes from Revised Protocol 05a
•
Updated introduction, study and dosing rationales, objectives, and 
schedule and dose exploration and safety exploration to reflect the 
addition of Part 9
•
Clarified that Parts 1-8 have been completed
•
Updated subject treated numbers for BMS986178 and nivolumab 
based on most current IBs.
•
Added references to myocarditis based on most current nivolumab 
IB.
•
Removed Retreatment and Survival/Response FU visits for subjects 
in Part 1-9.
•
Defined maximum treatment duration.
•
Removed select PK/PD samples
•
Updated inclusion criteria for ER and PR for TNBC (Part 9) 
consistent with ASCO/CAP guidelines.
•
Updated criteria for complete abstinence.
•
Typographical errors were corrected, and edits were made for 
consistency and clarity
Revised 
Protocol 05a
Site-specific
22-Jun-2018
•
Incorporates DRibble vaccine (DPV-001) as a new combination with 
BMS 986178 in Part 9
•
Update Schedule of assessments to incorporate Part 9
•
Typographical errors were corrected, and edits were made for 
consistency and clarity
Revised 
Protocol 05
11-Dec-2017
Incorporates Administrative Letters 04, 05, 06, and 07 and the following:
•
Addition of Part 8
•
Update of Appendix 1
•
Update schedule of assessments
•
Update of address
Typographical errors were corrected, and edits were made for 
consistency and clarity
Administrative 
Letter 07
19-Oct-2017
Clarify that if subjects continue for additional cycles, past cycle 4, all 
study drugs will continue for all cycles in Parts 7A and 7B in Sections 
3.1.4.2 and 3.1.5.8 and acknowledge the ommission of the word 
‘Beyond’ in Table 5.1-6
Administrative 
Letter 06
11-Jul-2017
Correction of typographical errors in Sections 5.1 and 5.5.1
Administrative 
Letter 05
03-May-2017
Correction of typographical error in Section 3.1.6
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Protocol Amendment No.: 04 Site Specific
Date: 12-May-2021
Document
Date of Issue
Summary of Change
Administrative 
Letter 04
02-May-2017
Correction of typographical error in Section 3.1.6
Revised 
Protocol 04
04-Apr-2017
Incorporates Amendment 04 and Administrative Letters 02 and 03
Amendment 04
04-Apr-2017
The amendment includes the following:
•
Addition of Parts 4, 5, 6, and 7
•
Update of study title
•
•
•
Update of study design and study visit schematic
•
Update of inclusion and exclusion criteria to include the new parts and 
clarify the maximum number of prior treatments allowed
•
Update of study drug dosing and method of assigning subjects
•
Update of dose delay language and addition of criteria for resuming 
treatment in subjects with an infusion reaction
•
Update/addition of tables for treatment procedures, pharmacokinetic 
and anti-drug antibody sampling schedule, and pharmacodynamic/ 
biomarker sampling schedule
•
Update of sample size information to include the new parts
•
Update of Appendix 1 to include statistical methods for the new parts
•
Typographical errors were corrected, and edits were made for 
consistency and clarity.
Administrative 
Letter 03
16-Dec-2016
Change in Study Director/Medical Monitor address
Administrative 
Letter 02
12-Dec-2016
Correction of typographical error in Section 3.1.3.6, first paragraph, first 
sentence
Revised 
Protocol 03
23-Nov-2016
Incorporates Amendment 03 and Administrative Letter 01
Amendment 03
23-Nov-2016
The amendment includes the following:
•
Removal of Part 1B
•
Addition of Part 2D, 2E, 3C and Part 2A cohort dose -1
•
Change to have imaging as central read
•
Add text to allow for intermediate and lower doses in escalation
•
Included text to add potentially more than 1 dose at RP2D
•
Updated versions numbers for current IB’s.
•
Updating to the new PMD for WOCBP Section
•
Require fresh tumor biopsy from all subjects
•
Additional sample to be collected in combination cohorts for RO
•
Update to not require archived tumor biopsies
•
Updated Statistical Analysis section 
•
Typographical errors were corrected, and clarifications were made for 
consistency.
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Protocol Amendment No.: 04 Site Specific
Date: 12-May-2021
Document
Date of Issue
Summary of Change
Administrative 
Letter 01
14-Jun-2016
Correction of typographical error in Section 3.3.1, inclusion criterion 
10(g) and Table 5.1-1, Screening Procedure Outline, complete blood 
count (CBC) with differential
Revised 
Protocol 02
08-Jun-2016
Incorporates Amendment 02
Amendment 02
08-Jun-2016
The purpose of this amendment is to address comments received from 
Health Authorities.
The amendment includes the following:
•
Change the definition for “Related AE’s” and “Not Related AE’s”.
•
Update prior therapy inclusion criteria for dose escalation subjects.
•
Remove timeframe from hematologic DLT grade 3 febrile 
neutropenia.
•
Change to have CBC with differential processed through LLDS.
•
Add new model document language for Additional Research 
Collection and Imaging scans.
•
Typographical errors were corrected, and clarifications were made for 
consistency.
Revised 
Protocol 01
26-Apr-2016
Incorporates Amendment 01
Amendment 01
26-Apr-2016
The purpose of this amendment is to address comments received from 
Health Authorities. The amendment includes the following:
•
The timing of the initiation of combination therapy dose escalation 
cohorts was revised, a sentinel subject was added to all dose cohorts, 
Parts 1B and 2B were removed and the subsequent study parts were 
renamed (Part 1C to Part 1B, Part 2C to Part 2B, and Part 2D to Part 
2C), DLT period across the study (28 days) was made uniform, the 
post-infusion observation period was extended to 4 hours, 
contraceptive requirements were updated, lipase and amylase ≤ 
1.5×ULN were removed as criteria for adequate organ function, DLT 
criteria were revised, a timepoint was added for safety monitoring, the 
rationale for use of blood and tumor tissue in biomarker studies was 
clarified, prior therapy requirements for dose expansion cohorts were 
updated, and BLRM language was clarified. 
•
Typographical errors were corrected, and clarifications were made for 
consistency.
Original 
Protocol
18-Feb-2016
Not applicable
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 SITE 
SPECIFIC
Section Number & 
Title
Description of Change
Section 3.3.2, Exclusion 
Criteria
Added target disease exceptions for Part 9 
regarding controlled CNS metastases to 
include radiographic stability of CNS 
lesions within 28 days. 
Updated timeframe for major surgery.
Added pregnant and breast-feeding 
subjects to exclusion criteria.
 
Added language to exclude active or 
uncontrolled infection, SARS-CoV-2 
infection, and SARS-CoV-2 vaccination 
prior to initiation of study treatment with 
specified timeframe. 
 
Section 3.3.2, Exclusion 
Criteria; Section 3.4.1, 
Prohibited and/or Restricted 
Treatments
Updated washout period of cytotoxic 
agents, including investigational cytotoxic 
drugs.
Section 3.4.1, Prohibited 
and/or Restricted Treatments
Added language to prohibit investigational 
SARS-CoV-2 vaccine and/or 
live/attenuated vaccines.
Sections 3.4.3, Permitted 
Therapy
Updated to allow the treatment of active 
SARS-CoV-2 infections with 
investigational therapies.
Updated vaccine administration from ≥14 
days prior or after study treatment to ≥10 
days prior or after study treatment. 
Section 4.5.4, Dose Delays 
due to Toxicity;
Section 4.5.5.1 Criteria to 
Resume Treatment in 
Subjects with a Dose Delay
Added dose delays due to SARS-CoV-2 
infection.
Added language to continue tumor 
assessments and periodic study visit safety 
and laboratory assessments regardless of 
dose delays.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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SUMMARY OF KEY CHANGES FOR PROTOCOL AMENDMENT 04 SITE 
SPECIFIC
Section Number & 
Title
Description of Change
Table 5.1-1, Screening 
Procedural Outline Parts 1-9
Table 5.1-8, On Treatment 
Procedural Outline Part 9
Table 5.1-9, Follow-up 
Procedural Outline Parts 1-9
Added to table notes when assessment(s) 
must be done for informed consent and 
inclusion/exclusion criteria. 
Added SARS-CoV-2 to Adverse Event 
Reporting requirements. 
Added doses for UbiLT3 and UbiLT6
Added to table notes the timing from 
treatment/cohort assignment to receiving 
first dose of study medication.
Section 5.7.2.1, Tissue 
Biopsies from All Subjects
Added on-treatment biopsy timing for Part 
9.
 
Section 6, Adverse Events; 
Section 6.1.1, Serious 
Adverse Event Collection 
and Reporting
Updated to collect and follow all immune 
mediated AEs and AEs associated with 
SARS-CoV-2 infection to detect safety 
signal in study population or study 
treatment.
Section 6.4, Pregnancy
Changed time of study exposure if 
pregnant from 5 half-lives to 1 year.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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SYNOPSIS
Clinical Protocol CA012004
Protocol Title: A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination with Nivolumab and/or 
Ipilimumab in Subjects with Advanced Solid Tumors
Investigational Product(s), Dose and Mode of Administration, and Duration of Treatment with Investigational 
Product(s):
BMS-986178, an anti-OX40 agonist monoclonal antibody (mAb) supplied as a sterile 25-mg/mL formulation, is to be 
administered as an intravenous (IV) infusion alone or in combination with nivolumab and/or ipilimumab or DPV-001 
per the cohort assignment and the duration of treatment, as indicated in the protocol. Nivolumab, an anti-programmed 
cell death-1 (PD-1) mAb, is available as a sterile 10-mg/mL formulation to be administered as an IV infusion. 
Ipilimumab, an anti-cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) mAb, is available as a sterile 5-mg/mL 
formulation to be administered as an IV infusion. DPV-001 is composed of two cell-free microvesicle vaccines, 
UbiLT3 and UbiLT6, developed from two cancer cell lines (UbiLT3 and UbiLT6 cell lines respectively). UbiLT3 was 
derived from a cancer of mixed histology (Squamous and adenocarcinoma) and UbiLT6 was developed from an  
adenocarcinoma. It is available as a sterile 1 mg/mL formulation to be administered as an intranodal (IN)/intradermal 
(ID) injection.
Study Phase: 1/2a
Research Hypothesis: It is anticipated that anti-OX40 agonist antibody (BMS-986178), administered as a single 
agent or in combination with anti-PD-1 mAb (nivolumab) or anti-CTLA-4 mAb (ipilimumab) or DPV-001, will 
demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile, to support further clinical 
testing. No prospective hypotheses are being formally evaluated.
Objectives: 
Primary Objective:
The primary objective is to determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated 
dose (MTD)/recommended Phase 2 dose (RP2D) of BMS-986178 administered alone or in combination with 
nivolumab and/or ipilimumab or DPV-001 in subjects with advanced solid tumors.
Secondary Objectives:
Secondary Objectives for Parts 1-8
•
To investigate the preliminary anti-tumor activity of BMS-986178 administered alone or in combination with 
nivolumab and/or ipilimumab in subjects with advanced solid tumors
•
To characterize the pharmacokinetics (PK) of BMS-986178 administered alone or in combination with nivolumab 
and/or ipilimumab
•
To characterize the immunogenicity of BMS-986178 administered alone or in combination with nivolumab and/or 
ipilimumab and the immunogenicity of nivolumab or ipilimumab administered with BMS-986178
•
To assess the proportion of subjects showing a change in peripheral pharmacodynamic biomarkers such as soluble 
OX40 and peripheral OX40 receptor occupancy along with tumor pharmacodynamic of BMS-986178 in 
combination with nivolumab or nivolumab monotherapy (Part 8)
Secondary Objectives for Part 9
•
To investigate the preliminary anti-tumor activity of BMS 986178 in combination with nivolumab and DPV-001 
and nivolumab in combination with DPV-001 in subjects with triple negative breast cancer and estrogen receptor 
(ER)-low positive breast cancer
•
To characterize the pharmacokinetics (PK) of BMS 986178 in combination with nivolumab and DPV-001 
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CA012004
BMS-986178
anti-OX40 mAb
specific tumor cohorts will be initiated. Recent preclinical and clinical data will serve as the foundation for focusing 
on further optimizing the dose of BMS-986178 in combination with nivolumab. As of Revised Protocol 5b, Parts 1-8 
have been completed and Part 9 will be initiated.
Figure 1:
Study Design Schematic (Parts 1 to 9)
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Dose levels are specific for each part. Dose expansion will begin only after MTD/RP2D determination in the
corresponding dose escalation phases of the study.
Abbreviations: MTD = maximum tolerated dose; RP2D = recommended Phase 2 dose.
Part 8:
Cohort 1:
20 mg q12w/Nivo. 480 mg q4w
Combination Therapy: BMS-986178 + Nivolumab
Dose Regimen Exploration
Dose Exploration
Cohort 4:
Nivo. Mono. 480 mg q4w
Cohort 2:
40 mg q12w/Nivo. 480 mg q4w
Cohort 3:
80 mg q12w/Nivo. 480 mg q4w
Part 9:
Cohort 1:
BMS-986178 40 mg/Nivo 480 mg q4w/DPV-001 1 mg
Combination Therapy: DPV-001 + BMS-986178 + Nivolumab or DPV-
001 + Nivolumab Monotherapy Dose Regimen Exploration
Cohort 2:
Nivo 480 mg q4w/DPV-001 1 mg
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Summary of Study Design: 
Dose Escalation (Parts 1A, 2A, and 3A):
The dose escalation part of the study will evaluate the safety and tolerability of BMS-986178 alone or in combination 
with nivolumab or ipilimumab in subjects with advanced solid tumors.
The initial dose level of BMS-986178 planned for this study is 20 mg. Dose escalation decisions for subsequent doses 
will be based on DLTs using a Bayesian Logistic Regression Method (BLRM; for BMS-986178 monotherapy) or a 
BLRM (-Copula) model (for BMS-986178 in combination with nivolumab and/or ipilimumab). The DLT period is 
28 days for both monotherapy and combination therapy dose escalation parts. The DLT rate will be determined based 
on the incidence, severity, and duration of AEs that occur within the DLT period and for which no alternative cause 
can be identified. Dose selection for the next monotherapy cohort/dose level will take into account the BLRM
(-Copula) recommendation in conjunction with the clinical recommendation and all available PK, PD, 
immunogenicity, and clinical and laboratory safety data from all treated subjects. Starting dose selection of 
BMS-986178 for Part 2A will be determined using data available from Part 1A, including clinical and laboratory 
safety assessments, PK/PD data, immunogenicity, and modeling recommendation within Bayesian modeling 
framework by incorporating single-agent toxicity profiles of both BMS-986178 (Part 1A) and nivolumab (CA209003). 
Starting dose selection of BMS-986178 for Part 3A will be determined using data available from Parts 1A and 2A, 
including clinical and laboratory safety assessments, PK/PD data, and modeling recommendation within Bayesian 
modeling framework by incorporating single-agent toxicity profiles of both BMS-986178 (Part 1A) and ipilimumab 
(CA184022). The final dose escalation decision will be made after discussion and agreement between the investigators 
and the BMS Medical Monitor. Actual doses can be modified per the BLRM (-Copula) but will not exceed doubling 
of the previously tested doses. Escalation by more than 1 dose level (dose skipping) is not permitted.
During dose escalation for all dose cohorts, the initial subject (sentinel subject) will be observed for 5 days before 
additional subjects in that cohort are treated with study drug.
Approximately 30 subjects will be enrolled in each dose escalation part. The number of subjects in each dose escalation 
cohort may vary depending on the BLRM (-Copula) recommendations. Initially, approximately 3 subjects will be 
treated at the starting dose levels of BMS-986178 or BMS-986178 in combination with nivolumab or ipilimumab. 
Additional cohorts of approximately 3 evaluable subjects will be treated at recommended dose levels per
BLRM (-Copula) during the dose escalation phase. At least 6 DLT-evaluable subjects will be treated at the MTD.
Part 1A: Enrollment will begin in Part 1A, BMS-986178 monotherapy dose escalation. The initial dose of 
BMS-986178 for Part 1A will be 20 mg with expected subsequent doses of 40, 80, 160, and 320 mg. Actual doses can 
be modified per the BLRM but will not exceed doubling of the previously tested dose.
Parts 2A and 3A: Part 2A is the combination arm of BMS-986178 with nivolumab that will be initiated only after at 
least 3 dose levels in the monotherapy dose escalation have been found to be tolerated or an MTD/RP2D has been 
determined in the monotherapy dose escalation (Part 1A). The starting dose of BMS-986178 in Part 2A will be at least 
1 dose level below a dose that was demonstrated to be tolerated in Part 1A, and at no time will the dose for BMS-
986178 in Part 2A exceed the highest tolerated dose in Part 1A. To ensure further safety of the combination. Part 3A 
is the combination arm of BMS-986178 with ipilimumab that will be initiated only after at least 3 dose levels in the 
monotherapy dose escalation have been found to be tolerated or an MTD/RP2D has been determined in the 
monotherapy dose escalation (Part 1A) and at least 1 dose cohort has been found to be tolerated in the BMS-986178 
with nivolumab dose escalation part (Part 2A). The starting dose of BMS-986178 in Part 3A will be at least 1 dose 
level below a dose that was demonstrated to be tolerated in Part 1A, and at no time will the dose for BMS-986178 in 
Part 3A exceed the highest tolerated dose in Part 1A to further ensure safety of the combination doses in treated 
subjects. In Parts 2A and 3A, doses intermediate to previously tested doses or doses lower than the starting dose may 
be explored to further characterize the dose response for safety, PK, or PD as appropriate based on clinical data 
collected.
Schedule and Dose Exploration (Parts 4, 5, 8, and 9):
Part 4: Part 4 is the combination arm of BMS-986178 with nivolumab (480 mg) to be administered every 4 weeks 
(q4w). The dose of BMS-986178 will be a dose previously evaluated in Part 2A that has been found to have a 
manageable safety profile and at no time will the dose for BMS-986178 exceed the highest tolerated dose in Part 2A, 
in which every 2 weeks (q2w) dosing is explored. Approximately 6 to 12 subjects will be treated in this cohort. 
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CA012004
BMS-986178
anti-OX40 mAb
Part 5: Part 5 is the combination arm of BMS-986178 with ipilimumab (3 mg/kg) to be administered every 3 weeks 
(q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy). The dose of BMS-986178 
will be a dose previously evaluated in Part 3A that has been found to have a manageable safety profile and at no time 
will the dose for BMS-986178 exceed the highest tolerated dose in Part 3A. Approximately 6 to 12 subjects will be 
treated in this cohort.
Part 8: Part 8 is the dose regimen exploration arm of BMS-986178 with a less frequent dosing schedule at either
20 mg, 40 mg, and 80 mg q12w in combination with nivolumab flat dose (480 mg; q4w) dose level (Cohort 1-3) or 
nivolumab 480 mg flat dose q4w monotherapy (Cohort 4) A tetanus vaccine (Tdap preferred, Td or equivalent after 
discussion with the medical monitor) will be administered to all subjects on Cycle 1 Day 1. Approximately 20 subjects 
will be treated in each cohort. Administration of a recall antigen such as tetanus toxoid may provide potent recall 
response with BMS-986178 in combination with nivolumab or nivolumab monotherapy.
Part 9: Subjects will be randomized to cohort 1 or cohort 2 in Part 9. 
Part 9: Cohort 1
Is a combination of BMS-986178, nivolumab, DPV-001 vaccine, and single dose cyclophosphamide. 
3 days prior to C1D1, a single-dose cyclophosphamide 300 mg/m2 is to be administered IV over a 30 to 60 minute 
infusion. 
On C1D1 the subjects will receive DPV-001 followed by BMS-986178. DPV-001 on C1D1 will consist of both 
UbiLT3 0.5 mg IN and UbiLT6 0.5 mg IN by ultrasound guidance (total of 1.0 mL suspension, 0.5 mL suspension 
UbiLT3 into 1 lymph node and 0.5 mL of UbiLT6 into another lymph node). After the DPV-001, the subject will be 
administered BMS-986178, as a flat dose of 40 mg over a 30 minute infusion.
On C1D8, the subject will receive only DPV-001. DPV-001 will consist of both UbiLT3 and UbiLT6, at the same 
dose listed on C1D1, but it will be administered ID. 
On C1D15, the subject will receive DPV-001 followed by nivolumab. DPV-001 will consist of only UbiLT3 1 mg 
ID. After the administration of UbiLT3, the subject will be administered nivolumab at 240 mg infusion over 30 
minutes. 
Starting at cycle 2, nivolumab will be given on day 1 of each cycle as a 480 mg flat dose (q4w) infusion over 30 
minutes. BMS-986178 40 mg infusion will only be given on day 1 of cycles 1-6, 9, and 12. DPV-001 1 mg ID will 
alternate between either UbiLT3 or UbiLT6. UbiLT6 will be given on C2D1, C3D1, C5D1, and C9D1. UbiLT3 1 mg 
ID will be given on C2D15, C4D1, C6D1, and C12D1. 
Part 9: Cohort 2 
Is a combination of nivolumab, DPV-001 vaccine, and single dose cyclophosphamide. 
3 days prior to C1D1, a single-dose cyclophosphamide 300 mg/m2 is to be administered IV over a 30 to 60 minute
infusion.
On C1D1, the subjects will receive DPV-001. DPV-001 on C1D1 will consist of both UbiLT3 0.5 mg IN and
UbiLT6 0.5 mg IN by ultrasound guidance (total of 1.0 mL suspension, 0.5 mL suspension UbiLT3 into 1 lymph
node and 0.5 mL of UbiLT6 into another lymph node).
On C1D8, the subjects will receive only DPV-001. DPV-001 will consist of both UbiLT3 and UbiLT6 at the same dose
listed on C1D1, but it will be administered ID. 
On C1D15, the subjects will receive DPV-001 followed by nivolumab. DPV-001 will consist of only UbiLT3 1 mg ID.
After the administration of UbiLT3, the subject will be administered nivolumab at 240 mg infusion over 30 minutes.
Starting at cycle 2, nivolumab will be given on day1 of each cycle as a 480 mg flat dose (q4w) infusion over 30 
minutes. DPV-001 1 mg ID will alternate between either UbiLT3 or UbiLT6. UbiLT6 will be given on C2D1, C3D1, 
C5D1, and C9D1. UbiLT3 1 mg ID will be given on C2D15, C4D1, C6D1, and C12D1.
Safety Cohorts (Parts 6A ,7A):
Part 6A: Part 6A is the safety cohort for combination of BMS-986178 with ipilimumab and nivolumab in subjects 
with renal cell carcinoma (RCC). BMS-986178 will be administered at a flat dose of 40 mg in combination with 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
nivolumab (240 mg) and ipilimumab (1 mg/kg) q3w during Cycles 1 to 4 followed by maintenance therapy in which 
BMS-986178 (40 mg) and nivolumab (480 mg) will be administered q4w. 
Part 7A: Part 7A is the safety cohort for combination of BMS-986178 with ipilimumab and nivolumab in subjects 
with non-small cell lung cancer (NSCLC). BMS-986178 will be administered at a flat dose of 40 mg (q2w) in 
combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles.
Dose Expansion (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B, and 7B):
Treatment in the dose expansion cohorts will be initiated when the MTD/RP2D has been determined based on the 
evaluation of totality of available clinical safety (DLTs, AEs occurring after the DLT period), PK, PD, 
immunogenicity, and modeling data from the dose escalation parts (1A, 2A, and 3A) or schedule and dose exploration 
parts (4 and 5). Approximately 294 subjects will be treated in all dose expansion cohorts.
Parts 2B, 2C, 2D, and 2E (combination with nivolumab) are the dose expansion parts in subjects with colorectal 
cancer, bladder cancer, cervical cancer, and other tumors from dose escalation for signal finding, respectively, at the 
MTD/RP2D(s) determined in Parts 2A or 4.
Part 3B (combination with ipilimumab) is the dose expansion part in subjects with ovarian cancer at the MTD/RP2D(s)
determined in Parts 3A or 5. Part 3C (combination with ipilimumab) is the dose expansion part in subjects with other 
tumors from dose escalation for signal finding at the MTD/RP2D(s) determined in Part 3A or 5.
Part 6B (combination with nivolumab and ipilimumab) is the dose expansion part in subjects with RCC at a tolerable 
dose determined in Part 6A.
Part 7B (combination with nivolumab and ipilimumab) is the dose expansion part in subjects with NSCLC at a 
tolerable dose determined in Part 7A.
Summary of Study Periods: 
Subjects will complete: Screening (up to 28 days), Treatment (up to 24 weeks of dosing for Part 1-7, up to 24 months 
of dosing for Parts 8 and 9, or until meeting protocol-specified discontinuation criteria) and Safety Follow-up of 
approximately 100 days. As of Protocol Revision 05b, no new subjects will enter the Response Follow-up or Survival 
Follow-up. Any subjects in Part 2, 4, 6, or 7 may be eligible for an additional 18 months of study therapy beyond the 
initial 24 weeks. Part 8 and Part 9 subjects will not be eligible for treatment with additional cycles. The maximum 
treatment allowed for any subject is 2 years from the first dose of study treatment regardless of dose delays. The study 
visit schematic is presented in Figure 2.
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Figure 2:
Study Visit Schematic
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Subjects (except those who withdraw consent for study participation) are expected to complete the 3 clinical Safety 
Follow-up visits regardless of whether they start new anti-cancer therapy.
Duration of Study: The total duration of study time for any individual subject is expected to be approximately 2.5 
years (depending on Part subject is randomized to). The study will end when the last subject completes their last study 
visit, which is planned to be about 4 years after the start of the study.
Number of Subjects: Approximately 632 subjects will be enrolled, and approximately 539 subjects will be treated in 
the study.
Study Population: Subjects must be at least 18 years old and have histologic or cytologic confirmation of a 
malignancy that is advanced (metastatic, recurrent, refractory and/or unresectable) with measurable disease per 
RECIST v1.1.
Study Drug: Investigational products are as listed in Table -1.
Table -1:
Study Drugs for CA012004
Product 
Description 
Class and 
Dosage Form
Potency
IP/Non-IP
Blinded or 
Open Label
Packaging/
Product 
Description 
Class and 
Dosage Form
BMS-986178 
Injection
25 mg/mL
(80 mg/vial)
IP
Open Label
Vial
Store at 2°C to 
8°C; do not 
freeze; protected 
from light.
Nivolumab 
Injection
10 mg/mL
(100 mg/vial)
IP
Open Label
Vial
Store at 2°C to 
8°C; store in 
original 
package; do not 
freeze; protected 
from light.
Ipilimumab 
Injection
5 mg/mL
(200 mg/vial)
IP
Open Label
Vial
Store at 2°C to 
8°C; do not 
freeze; protected 
from light.
Tetanus vaccine
Per locala
IP
Open Label
Various 
packaging 
configurations
Refer to the 
label on 
container and/or 
package insert
UbiLT3 and 
UbiLT6 
vaccineb
1 mg/mL and as 
per Pharmacy 
Manual
IP
Open Label
Vial and various 
packaging 
configurations
Refer to label on 
container and/or 
package insert 
or pharmacy 
manual
Abbreviation: IB = Investigator Brochure; IP = investigational product
a Tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor)will be obtained as 
local commercial product in countries if allowed by local regulations or through investigating sites standard 
prescribing procedures.
b DPV-001(UbiLT3 and UbiLT6) will be provided by Ubivac
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CA012004
BMS-986178
anti-OX40 mAb
Study Assessments:
•
Physical examinations, vital sign measurements, 12-lead electrocardiograms (ECGs), and clinical laboratory 
evaluations will be performed at selected times throughout the dosing interval. Subjects will be closely monitored 
for AEs throughout the study.
•
Safety Assessments: AEs will be assessed during the study and for 100 days after the last treatment. AEs will be 
evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. AEs 
will be coded using the most current version of Medical Dictionary for Regulatory Activities and reviewed for 
potential significance and importance. Subjects will be followed until all treatment-related AEs have recovered 
to baseline or are deemed irreversible by the investigator.
•
Efficacy Assessments: Disease assessment with computed tomography and/or magnetic resonance imaging as 
appropriate will be performed at baseline and every 8 weeks (± 1 week) per RECIST v1.1 until discontinuation 
of treatment or withdrawal from study. Tumor assessments at other time points may be performed if the 
investigator is concerned about tumor progression. Assessment of tumor response will be reported by the 
investigator as defined by RECIST v1.1 for subjects with advanced solid tumors.
•
Pharmacokinetic and Immunogenicity Assessments: Samples for PK and immunogenicity assessments will be 
collected for subjects receiving BMS-986178 alone, in combination with nivolumab and/or ipilimumab, or in 
combination with nivolumanb and DPV-001. The PK of BMS-986178 will be characterized by 
non-compartmental analysis method. Immunogenicity samples will be analyzed for anti-BMS-986178 antibodies 
and/or anti-nivolumab antibodies and/or anti-ipilimumab antibodies by validated immunoassays.
 
 
Statistical Considerations: 
Sample Size Determination:
Dose Escalation (Parts 1A, 2A, and 3A):
As a Phase 1 dose escalation trial, the sample size for each dose escalation cohort depends on observed toxicity and 
posterior inference. Approximately 30 subjects are expected to be treated during each dose escalation part 
(BMS-986178 monotherapy [Part 1A], BMS-986178 in combination with nivolumab [Part 2A], and BMS-986178 in 
combination with ipilimumab [Part 3A]) for a combined total of approximately 90 subjects in Parts 1A, 2A and 3A. 
Initially, approximately 3 subjects will be treated at the starting dose levels of BMS-986178 or BMS-986178 in 
combination with nivolumab or ipilimumab. Additional cohorts of approximately 3 evaluable subjects will be treated 
at recommended dose levels per BLRM (-Copula) recommendations during the dose escalation phase. At least 
6 DLT-evaluable subjects will be treated at the MTD.
Schedule and Dose Exploration (Parts 4, 5, 8, and 9):
Approximately 6 to 12 subjects are expected to be treated during each schedule and dose exploration part 
(BMS-986178 in combination with nivolumab [Part 4] and BMS-986178 in combination with ipilimumab [Part 5] for 
a combined total of approximately 12 to 24 subjects in Parts 4 and 5).
Approximately 20 evaluable subjects per dose cohort will be treated in Part 8 of the study, BMS-986178 in 
combination with nivolumab (Cohort 1-3) and monotherapy nivolumab (Cohort 4). Total number of subjects in this 
Part 8 will be approximately 80.
In Part 9, subjects will be treated with DPV-001 vaccine, single dose cyclophosphamide and nivolumab with/without 
BMS 986178. There will be a total of approximately 18 subjects combined in Cohorts 1 and 2 of Part 9, with a 
possibility of 20% over enrollment. Part 9 may be further expanded to 24 subjects for Cohort 1 and 12 subjects for 
Cohort 2.
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
1.2
Research Hypothesis 
It is anticipated that anti-OX40 agonist antibody (BMS-986178), administered as a single agent or 
in combination with anti-PD-1 antibody (nivolumab) or anti-CTLA-4 (ipilimumab) or DPV-001,
will demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile, to 
support further clinical testing. No prospective hypotheses are being formally evaluated.
1.3
Objectives(s))
1.3.1
Primary Objective
The primary objective is to determine the safety, tolerability, DLTs, and MTD/RP2D of BMS-
986178 administered alone or in combination with nivolumab and/or ipilimumab or DPV-001 in 
subjects with advanced solid tumors.
1.3.2
Secondary Objectives
Secondary Objectives for Parts 1-8
•
To investigate the preliminary anti-tumor activity of BMS-986178 administered alone or in 
combination with nivolumab and/or ipilimumab,  in subjects with advanced solid tumors
•
To characterize the PK of BMS-986178 administered alone or in combination with nivolumab 
and/or ipilimumab
•
To characterize the immunogenicity of BMS-986178 administered alone or in combination 
with nivolumab and/or ipilimumab, and the immunogenicity of nivolumab or ipilimumab 
administered with BMS-986178
•
To assess the proportion of subjects showing a change in peripheral pharmacodynamic 
biomarkers such as soluble OX40 and peripheral OX40 receptor occupancy along with tumor 
pharmacodynamic of BMS-986178 in combination with nivolumab or nivolumab 
monotherapy (Part 8).
Secondary Objectives for Part 9
•
To investigate the preliminary anti-tumor activity of BMS 986178 in combination with 
nivolumab and DPV-001 and nivolumab in combination with DPV-001 in subjects with TNBC
and ER-low positive breast cancer.
•
To characterize the pharmacokinetics (PK) of BMS 986178 in combination with nivolumab 
and DPV-001
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The overall safety profile of ipilimumab is well characterized and consists mainly of 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
ICH and in accordance with the ethical principles underlying European Union Directive 
2001/20/EC and the US Code of Federal Regulations, Title 21, Part 50 (21CFR50).
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the subject informed consent will receive Institutional Review Board/Independent Ethics 
Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.
All potential serious breaches must be reported to BMS immediately. A serious breach is a breach 
of the conditions and principles of GCP in connection with the study or the protocol, which is 
likely to affect, to a significant degree, the safety or physical or mental integrity of the subjects of 
the study or the scientific value of the study.
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment). 
2.2
Institutional Review Board/Independent Ethics Committee
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, subject recruitment materials 
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(eg, advertisements), and any other written information to be provided to subjects. The investigator 
or BMS should also provide the IRB/IEC with a copy of the IB or product labeling information to 
be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other information 
(eg, expedited safety reports, amendments, and administrative letters) according to regulatory 
requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives (as 
per country guidelines) are clearly and fully informed about the purpose, potential risks, and other 
critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form(s) which will include all elements required by ICH, GCP, and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
•
Provide a copy of the consent form(s) and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 
•
Allow time necessary for subject or subject’s legally acceptable representative to inquire about 
the details of the study.
•
Obtain an informed consent signed and personally dated by the subject or the subject’s legally 
acceptable representative and by the person who conducted the informed consent discussion. 
•
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects, prior to the beginning of the study, 
and after any revisions are completed for new information.
•
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject.
•
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject’s consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject’s legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject’s willingness to continue participation in the study. This communication should be 
documented. 
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The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects’ signed ICF and, in 
the US, the subjects’ signed HIPAA Authorization.
The consent form(s) must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to refuse 
participation in, or to be withdrawn from, the clinical study at any time should be considered by 
the investigator. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a Phase 1/2a, open-label study of BMS-986178 in subjects with advanced solid tumors that 
integrates initial BMS-986178 monotherapy with subsequent nivolumab and/or ipilimumab or 
nivolumab and DPV-001 combination therapy (see Figure 3.1-1). Study sections (dose escalation 
and dose expansion) will proceed in a phased approach that is based upon study-emergent safety, 
PK, and PD data. The first section of the study will begin with BMS-986178 monotherapy dose 
escalation cohorts. The clinical data from the first 3 monotherapy dose cohorts will serve as a 
foundation for initiating dose escalation of BMS-986178 in combination with nivolumab. The 
clinical data from the first 3 monotherapy dose cohorts in addition to the clinical data from the first 
cohort of BMS-986178 in combination with nivolumab will then serve as a foundation for 
initiating dose escalation of BMS-986178 in combination with ipilimumab. The clinical data for 
BMS-986178 in combination with nivolumab and BMS-986178 in combination with ipilimumab 
will serve as the foundation for initiating combination therapy of BMS-986178 with nivolumab 
and ipilimumab in Parts 6 and 7. After establishment of a tolerable and pharmacologically active 
MTD/RP2D of BMS-986178 in the dose escalation and schedule and dose exploration sections, 
dose expansion in specific tumor cohorts will be initiated. Recent preclinical and clinical data will 
serve as the foundation for focusing on further optimizing the dose of BMS-986178 in combination 
with nivolumab.
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Figure 3.1-1:
Study Design Schematic (Parts 1 to 9)
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Dose levels are specific for each part. Dose expansion will begin only after MTD/RP2D determination in the 
corresponding dose escalation phases of the study.
Abbreviations: MTD = maximum tolerated dose; RP2D = recommended Phase 2 dose.
3.1.1
Study Outline (All Parts)
3.1.2
Dose Escalation (Parts 1A, 2A, and 3A)
The dose escalation part of the study will evaluate the safety and tolerability of BMS-986178 alone 
or in combination with nivolumab or ipilimumab in subjects with advanced solid tumors (listed in 
Section 3.3.1 [Inclusion criteria 2]).
The initial dose level of BMS-986178 planned for this study is 20 mg. Dose escalation decisions 
for subsequent doses will be based on DLTs using a BLRM (for BMS-986178 monotherapy) or a 
BLRM (-Copula) model (for BMS-986178 in combination with nivolumab or ipilimumab). The 
DLT period is 28 days for both monotherapy and combination therapy dose escalation parts. The 
DLT rate will be determined based on the incidence, severity, and duration of AEs that occur 
within the DLT period and for which no alternative cause can be identified. Dose selection for the 
next monotherapy cohort/dose level will take into account the BLRM (-Copula) recommendation 
(Section 3.1.2.4) in conjunction with clinical recommendation and all available PK, PD, 
Part 8:
Cohort 1:
20 mg q12w/Nivo. 480 mg q4w
Combination Therapy: BMS-986178 + Nivolumab
Dose Regimen Exploration
Dose Exploration
Cohort 4:
Nivo. Mono. 480 mg q4w
Cohort 2:
40 mg q12w/Nivo. 480 mg q4w
Cohort 3:
80 mg q12w/Nivo. 480 mg q4w
Part 9:
Cohort 1:
BMS-986178 40 mg/Nivo 480 mg q4w/DPV-001 1 mg
Combination Therapy: DPV-001 + BMS-986178 + Nivolumab or DPV-
001 + Nivolumab Monotherapy Dose Regimen Exploration
Cohort 2:
Nivo 480 mg q4w/DPV-001 1 mg
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immunogenicity, and clinical and laboratory safety data from all treated subjects. Starting dose 
selection of BMS-986178 for Part 2A will be determined using data available from Part 1A, 
including clinical and laboratory safety assessments, PK/PD data, immunogenicity, and modeling 
recommendation within Bayesian modeling framework by incorporating single-agent toxicity 
profiles of both BMS-986178 (Part 1A) and nivolumab (CA209003). Starting dose selection of 
BMS-986178 for Part 3A will be determined using data available from Parts 1A and 2A, including 
clinical and laboratory safety assessments, PK/PD data, and modeling recommendation within 
Bayesian modeling framework by incorporating single-agent toxicity profiles of both 
BMS-986178 (Part 1A) and ipilimumab (CA184022). The final dose escalation decision will be 
made after discussion and agreement between the investigators and the BMS Medical Monitor. 
Actual doses can be modified per the BLRM (-Copula) but will not exceed doubling of the 
previously tested dose. In Parts 2A and 3A, doses intermediate to previously tested doses or doses 
lower than the starting dose may be explored to further characterize the dose response for safety, 
PK, or PD as appropriate based on clinical data collected.
During dose escalation for all dose cohorts, the initial subject (sentinel subject) will be observed 
for 5 days before additional subjects in that cohort are treated with study drug. 
All safety signals throughout the conduct of the study will be reviewed by the BMS-986178 
Medical Surveillance Team (MST). If unexpected safety findings are identified between scheduled 
MST meetings, an ad hoc meeting will be convened, as appropriate.
Approximately 30 subjects will be enrolled in each dose escalation part. The number of subjects 
in each dose escalation cohort may vary depending on the BLRM (-Copula) recommendations. 
Initially, approximately 3 subjects will be treated at the starting dose levels of BMS-986178 or 
BMS-986178 in combination with nivolumab or ipilimumab. Additional cohorts of approximately 
3 evaluable subjects will be treated at recommended dose levels per BLRM (-Copula) during the 
dose escalation phase. At least 6 DLT-evaluable subjects will be treated at the MTD.
3.1.2.1
Part 1A: Monotherapy Dose Escalation
Part 1A is BMS-986178 monotherapy dose escalation. The initial dose of BMS-986178 for Part 1A 
will be 20 mg with expected subsequent doses of 40, 80, 160, and 320 mg. Dosing of BMS-986178 
will begin on Day 1 of each cycle and will be administered q2w for up to 12 cycles.
3.1.2.2
Part 2A: Combination with Nivolumab Dose Escalation
Part 2A is the combination arm of BMS-986178 with nivolumab that will be initiated only after at 
least 3 dose levels in the monotherapy dose escalation have been found to be tolerated or an 
MTD/RP2D has been determined in the monotherapy dose escalation (Part 1A). The starting dose 
of BMS-986178 in Part 2A will be at least 1 dose level below a dose that was demonstrated to be 
tolerated in Part 1A to ensure further safety of the combination. At no time will the dose for 
BMS-986178 in Part 2A exceed the highest tolerated dose in Part 1A. Nivolumab will be 
administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study 
drugs will be administered q2w starting on Day 1 of each cycle for up to 12 cycles.
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3.1.2.3
Part 3A: Combination with Ipilimumab Dose Escalation
Part 3A is the combination arm of BMS-986178 with ipilimumab that will be initiated only after 
at least 3 dose levels in the monotherapy dose escalation have been found to be tolerated or an 
MTD/RP2D has been determined in the monotherapy dose escalation (Part 1A) and at least 1 dose 
cohort has been found to be tolerated in the BMS-986178 with nivolumab dose escalation part 
(Part 2A). The starting dose of BMS-986178 in Part 3A will be at least 1 dose level below a dose 
that was demonstrated to be tolerated in Part 1A. At no time will the dose for BMS-986178 in 
Part 3A exceed the highest tolerated dose in Part 1A to further ensure safety of the combination 
doses in treated subjects. Ipilimumab will be administered at a dose of 1 mg/kg. Each treatment 
cycle will be 3 weeks in length. BMS-986178 will be administered q3w starting on Cycle 1 Day 1, 
up to and including 8 cycles, and ipilimumab will be administered q3w starting on Day 1 for 
4 cycles. Only BMS-986178 will be administered in the last 4 cycles.
3.1.2.4
BLRM Dose Escalation and Stopping Rules
In Parts 1A, 2A, and 3A, the BLRM and BLRM (-Copula) models (Section 1.1.15) will be utilized 
for dose escalation recommendations after DLT information becomes available for each cohort of 
subjects. BMS-986178 dose selection for the next cohort/dose level will take into account the 
BLRM (-Copula) recommendation in conjunction with clinical recommendation and all available 
PK, PD, and clinical and laboratory safety data from all treated subjects. The final dose escalation 
decision will be made after discussion and agreement between investigators and the BMS Medical 
Monitor. 
BLRM Dose Escalation Rules (Parts 1A, 2A, and 3A)
Cohort tolerability assessment and subsequent dose recommendation will occur when 2 evaluable 
subjects within a dose cohort have completed the 28-day DLT period. If the potential DLT 
occurring in the third evaluable subject at a specific dose level does not influence the dose 
recommendation by BLRM (-Copula), the BLRM (-Copula)-recommended next dose level may 
proceed without waiting for the third subject to complete the corresponding DLT observation 
period after discussion and agreement between the Sponsor and investigators. While waiting for 
the DLT information of those 2 or 3 subjects, if additional subjects are available, these subjects 
could be enrolled to the current dose level. Continuous re-assessment of dose recommendation by 
BLRM (-Copula) will be carried out at every dose level of each cohort of subjects, taking into 
consideration all available DLT information.
The BLRM (-Copula) model will first exclude doses that are intolerable (with overdosing 
probabilities > 25%). Among those qualified candidate doses that are considered “safe”, the model 
will select the dose that maximizes the probability of being within the target toxicity range (DLT 
rate of 16% to up to 33%). 
•
Dose levels for the next cohort will be based on evaluating 4 potential recommendations: 
escalate, de-escalate, stay at same dose level, or stop and select a new dose other than pre-
specified doses.
•
Escalation by more than 1 dose level (dose skipping) is not permitted. 
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•
Based on model suggestions and a review of the available safety, PK, and PD data in 
combination with clinical recommendation, lower doses of BMS-986178 may be tested if none 
of the planned doses are found to be tolerated as monotherapy or in combination with 
nivolumab or ipilimumab. Such decisions will be made after discussion and agreement 
between the investigators and the BMS Medical Monitor.
•
No intra-subject dose escalation of BMS-986178 is allowed at any dose level.
•
Dose de-escalation can be recommended by the model, and the final decision will be made 
based on clinical recommendation.
BLRM Stopping Rules during Dose Escalation (Parts 1A, 2A, and 3A)
•
If all of the current pre-specified doses are considered intolerable according to the pre-specified 
cutoff, then the model will recommend stopping the current dose level and a new dose level 
lower than the current lowest dose level will need to be identified (EWOC stopping). 
•
The maximum number of subjects in a dose level will be 12. This limit is set to avoid instances 
in which the model could recommend adding subjects indefinitely to a specific dose level due 
to uncertainty in the tolerability profile. 
•
If, for a specific dose level, 6 subjects have been treated and the chance of determining that 
dose level to be the “target” dose is > 50%, then the model will suggest to stop the arm and 
declare the current dose level to be MTD.
Appendix 1 provides further detailed explanation along with an illustration of the BLRM dose 
escalation design.
3.1.2.5
Dose-Limiting Toxicity in Dose Escalation Parts
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, severity, 
and duration of AEs for which no clear alternative cause is identified. The DLT period will be 
28 days after initial dosing in monotherapy and combination parts of dose escalation. 
For the purpose of defining MTD/RP2D, the incidence of DLTs during the DLT period will be 
used. AEs occurring after the DLT period will be considered for the purposes of defining the RP2D 
upon agreement between the Sponsor, Medical Monitor, and investigators, if they are determined 
to have no clear alternative cause and are not related to disease progression.
For the purpose of subject management, any AE that meets DLT criteria, regardless of the cycle 
in which it occurs, will lead to discontinuation of study drug. Subjects experiencing a DLT will 
not be retreated with study drug(s) and will enter the Safety Follow-up period of the study for up 
to 100 days from the last administration of the study drug(s). Subjects who withdraw from the 
study during the DLT evaluation interval for reasons other than a DLT may be replaced with a 
new subject at the same dose level.
Further details on DLTs are included in Section 4.5.1.
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3.1.3
Schedule and Dose Exploration
3.1.3.1
Part 4: Combination with Nivolumab on a 4-week Schedule
Part 4 is the combination arm of BMS-986178 with nivolumab (480 mg) to be administered q4w. 
The dose of BMS-986178 will be a dose previously evaluated in Part 2A that has been found to 
have a manageable safety profile. If the starting dose of BMS-986178 is not tolerated or to further 
characterize the dose response for safety, PK, or PD as appropriate based on clinical data collected, 
a dose(s) lower or higher than the previously administered dose in this part may be explored. To 
further ensure safety of the combination, at no time will the dose for BMS-986178 in Part 4 exceed 
the highest tolerated dose in Part 2A, in which q2w dosing is explored. Approximately 6 to 
12 subjects will be treated in this schedule and dose exploration cohort.
3.1.3.2
Part 5: Combination with Ipilimumab at 3 mg/kg
Part 5 is the combination arm of BMS-986178 with ipilimumab 3 mg/kg q3w for 4 doses, followed 
by monotherapy with BMS-986178 (maintenance therapy). The dose of BMS-986178 will be a 
dose previously evaluated in Part 3A that has been found to have a manageable safety profile. If 
the starting dose of BMS-986178 is not tolerated or to further characterize the dose response for 
safety, PK, or PD as appropriate based on clinical data collected, a dose(s) lower or higher than 
the previously administered dose in this part may be explored. To further ensure safety of the 
combination, at no time will the dose for BMS-986178 in Part 5 exceed the highest tolerated dose 
in Part 3A. Approximately 6 to 12 subjects will be treated in this schedule and dose exploration 
cohort.
3.1.3.3
Part 8: Dose Regimen Exploration of Combination with Nivolumab in 
Bladder Cancer
Part 8 is a dose regimen exploration of BMS-986178 in combination with nivolumab or nivolumab 
monotherapy. Nivolumab will be administered at a flat dose of 480 mg to be administered every 4 
weeks.
Approximately 20 evaluable subjects per cohort will be treated in Part 8.
Part 8 Cohort 1-3: BMS-986178 will be administered as a flat dose of either 20 mg, 40 mg, or 
80 mg q12w in combination with nivolumab flat dose (480 mg; q4w). Each treatment cycle will 
be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 
24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with 
the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of 
nivolumab and BMS-986178.
Part 8 Cohort 4: Nivolumab monotherapy will be administered as a flat dose of 480 mg (q4w). 
Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months 
of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. A tetanus vaccine (Tdap 
preferred, Td or equivalent after discussion with the medical monitor) will be administered first 
on Cycle 1 Day 1 prior to administration of nivolumab monotherapy.
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3.1.3.4
Part 9 Combination BMS-986178, Nivolumab, and DPV-001 
In part 9, subjects will be randomized in a 2:1 ratio to cohort 1 or cohort 2.
Part 9 Cohort 1
Cohort 1 is a combination of BMS-986178, nivolumab, DPV-001 (UbiLT3 and UbiLT6) vaccine, 
and single dose cyclophosphamide. Single-dose cyclophosphamide 300 mg/m2 is to be 
administered IV over a 30 to 60 minute infusion, 3 days prior to C1D1. On C1D1 the subjects will 
receive both UbiLT3 and UbiLT6 IN by ultrasound guidance. DPV-001 on C1D1 will consist of 
both UbiLT3 and UbiLT6 vaccine (total of 1.0 mL suspension, 0.5 mL suspension UbiLT3 into 1
lymph node and 0.5 mL of UbiLT6 into another lymph node). After the DPV-001 is administered 
on C1D1, the subject will be administered BMS-986178, as a flat dose of 40 mg (q4w) over a 
30-minute infusion. The order of dose administration is DPV-001 then BMS-986178 for C1D1. 
On day C1D8, the subject will be administered both UbiLT3 and UbiLT6, at the same dose listed 
on C1D1, but it will be administered ID.
On C1D15, the subject with be administered UbiLT3 ID which will then commence alternating 
between UbiLT3 and UbiLT6 on subsequent doses, then the subject will be administered 
nivolumab at 240 mg infusion over 30 minutes. BMS-986178 will only be given on day 1 of cycles 
1-6, 9, and 12.
DPV-001 vaccine will be given as a total of 1 mg flat dose at each administration. Vaccine may 
be given as multiple injections due to volume, according to institutional policy.
Subsequent doses of DPV-001 are delivered ID q2w (1.0 mL suspension ID rotating between 
UbiLT3 and UbiLT6 on alternate vaccinations, starting with UbiLT3) which starts at C1D15 for a 
total of 4 doses. From C3D1 to C6D1, subjects will receive this vaccine q4w, (still alternating
between the UbiLT3 and UbiLT6). After cycle 6, the vaccine will be given 2 more times, at C9D1 
and C12D1 (still alternating between the UbiLT3 and UbiLT6).
From C2D1 through C6D1, nivolumab will be administered as a 480 mg flat dose q4w. It will be 
administered as an infusion over a 30-minute period, after DPV-001 is given. BMS-986178 will 
be administered following a 30-minute waiting period after the nivolumab dosing. Nivolumab will 
continue to be administered as a 480 mg flat dose q4w. At C7D1, C8D1, C10D1, C11D1 and 
C13D1 to C26D1, nivolumab will be given as a monotherapy dose.
Approximately 12 subjects will be treated in this cohort. All cycles will be 4 weeks in length. 
Part 9 Cohort 2
Cohort 2 is a combination of nivolumab, DPV-001 (UbiLT3 and UbiLT6) vaccine, and single dose 
cyclophosphamide. Single-dose cyclophosphamide 300 mg/m2 is to be administered IV over a 30
to 60 minute infusion, 3 days prior to C1D1. On C1D1 the subjects will receive DPV-001 IN by 
ultrasound guidance. DPV-001 on C1D1 will consist of both UbiLT3 and UbiLT6 vaccine (total 
of 1.0 mL suspension, 0.5 mL suspension UbiLT3 into one lymph node and 0.5 mL of UbiLT6 
into another lymph node). 
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On day C1D8, the subject will be administered both UbiLT3 and UbiLT6, at the same dose level 
above, but it will be administered ID.
On C1D15, the subject will be administered UbiLT3 ID which will then commence alternating 
between UbiLT3 and UbiLT6 on subsequent doses. Then the subject will be administered 
nivolumab at 240 mg infusion over 30 minutes on C1D15.
DPV-001 vaccine will be given as a total of 1 mg flat dose at each administration.  Vaccine may 
be given as multiple injections due to volume, according to institutional policy.
Subsequent doses of DPV-001 are delivered ID q2w (1.0 mL suspension ID rotating between 
UbiLT3 and UbiLT6 on alternate vaccinations, starting with UbiLT3), which starts at C1D15 for 
a total of 4 doses. From C3D1 to C6D1, subjects will receive this vaccine q4w, still alternating 
between the UbiLT3 and UbiLT6). After cycle 6, the vaccine will be given 2 more times, at C9D1 
and C12D1. 
Beginning at C2D1 through C26D1, nivolumab will be administered as a 480 mg flat dose q4w on 
Day 1 of each cycle, as an infusion over a 30-minute period. When nivolumab and DPV-001 are 
given together, DPV-001 will be given first.
Approximately 6 subjects will be treated in this cohort. All cycles will be 4 weeks in length. 
One sentinel subject will be dosed initially in each cohort in Part 9, prior to dosing of subsequent 
subjects. The sentinel subject will be observed for 5 days before the next subject is dosed. If 
cytokine release syndrome or unexpected toxicity occurs in the first treated subject during the 
sentinel observation period, subsequently 2 subjects will be treated sequentially, with an interval 
period of at least 5 days between the beginning of treatment for patient 2 and 3. If cytokine release 
syndrome is observed in 2 of the first 3 treated subjects, then the regimen and/or schedule will be 
re-evaluated, with consideration for lower doses of study drug(s) before additional subjects are 
enrolled. 
3.1.4
Safety Cohorts
3.1.4.1
Part 6A: Combination with Nivolumab and Ipilimumab in RCC
Part 6A is the safety cohort for the combination of BMS-986178 with ipilimumab and nivolumab 
in subjects with RCC. BMS-986178 will be administered at a flat dose of 40 mg in combination 
with nivolumab (240 mg) and ipilimumab (1 mg/kg) q3w during Cycles 1 to 4, followed by 
maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab 
(480 mg) will be administered q4w. Study drugs will be administered accordingly starting on 
Day 1 of each cycle. If the starting dose of BMS-986178 is not tolerated or to further characterize 
the dose response for safety, PK, or PD as appropriate based on clinical data collected, a dose(s) 
lower than the previously administered dose in this part may be explored. Approximately 6 to 12 
subjects will be treated in this safety cohort.
3.1.4.2
Part 7A: Combination with Nivolumab and Ipilimumab in NSCLC 
Part 7A is the safety cohort for the combination of BMS-986178 with ipilimumab and nivolumab 
in subjects with NSCLC. BMS-986178 will be administered at a flat dose of 40 mg (q2w) in 
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combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week 
cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If the starting 
dose of BMS-986178 is not tolerated or to further characterize the dose response for safety, PK, 
or PD as appropriate based on clinical data collected, a dose(s) lower than the previously 
administered dose in this part may be explored. If subjects continue for additional cycles, past 
cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles. 
Approximately 6 to 12 subjects will be treated in this safety cohort.
3.1.5
Dose Expansion Parts (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B, 7B)
Treatment in the dose expansion cohorts will be initiated when the MTD/RP2D(s) has been 
determined based on the evaluation of totality of available clinical safety (DLTs, AEs occurring 
after the DLT period), PK, PD, immunogenicity, and modeling data from the dose escalation parts 
(1A, 2A, and 3A) or schedule and dose exploration parts (4 and 5). Mandatory pre- and on-
treatment biopsies of tumor will be obtained for all study subjects.
3.1.5.1
Part 2B: Combination with Nivolumab Dose Expansion in Colorectal 
Cancer
Part 2B is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with CRC at the MTD/RP2D(s) determined in Parts 2A or 4. Nivolumab will be administered at a 
flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in 
length and study drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for 
up to 12 or 6 cycles, respectively. Approximately 35 subjects will be treated in this expansion 
cohort.
3.1.5.2
Part 2C: Combination with Nivolumab Dose Expansion in Bladder 
Cancer
Part 2C is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with BC at the MTD/RP2D(s) determined in Parts 2A or 4. Nivolumab will be administered at a 
flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in 
length and study drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for 
up to 12 or 6 cycles, respectively. Approximately 27 subjects will be treated in this expansion 
cohort.
3.1.5.3
Part 2D: Combination with Nivolumab Dose Expansion in Cancer of the 
Cervix 
Part 2D is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with cervical cancer at the MTD/RP2D(s) determined in Part 2A or 4. Nivolumab will be 
administered at a flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 
4 (480 mg) weeks in length and study drugs will be administered every 2 or 4 weeks starting on 
Day 1 of each cycle for up to 12 or 6 cycles, respectively. Approximately 37 subjects will be 
treated in this expansion cohort.
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3.1.5.4
Part 2E: Combination with Nivolumab Dose Expansion in Other Tumors 
for Signal Finding
Part 2E is the combination therapy (BMS-986178 with nivolumab) dose expansion part at the 
MTD/RP2D(s) determined in Part 2A or 4. Nivolumab will be administered at a flat dose of 240 
or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in length and study 
drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for up to 12 or 6 
cycles, respectively. Approximately 40 subjects will be treated in this expansion cohort. 
Tumor types for this cohort will be selected by Sponsor from those permitted in dose escalation 
which do not have a dedicated expansion cohort or plans for evaluation in other studies and those 
tumors selected will be communicated to the investigators. This cohort will allow for further 
exploration of early signs of clinical activity observed in tumors during the dose escalation phase 
of the trial as well as potential signals arising from ongoing trials of other anti-OX40 agonists in 
combination with anti-PD(L)-1. Subjects enrolled in this cohort must be refractory to or intolerant 
of established therapy known to provide clinical benefit for their condition, i.e., subjects must not 
be candidates for regimens known to provide clinical benefit.
3.1.5.5
Part 3B: Combination with Ipilimumab Dose Expansion in Ovarian 
Cancer
Part 3B is the combination therapy (BMS-986178 with ipilimumab) dose expansion part in 
subjects with OC at the MTD/RP2D(s) determined in Part 3A or 5. Each treatment cycle will be 
3 weeks in length. Ipilimumab will be administered in the initial 4 cycles in combination with 
BMS-986178. Then the subject will continue on BMS-986178 monotherapy for up to an additional 
4 cycles for a total of up to 24 weeks (8 cycles) of treatment. Approximately 35 subjects with OC 
will be treated in this expansion cohort.
3.1.5.6
Part 3C: Combination with Ipilimumab Dose Expansion in Other Tumors 
for Signal Finding
Part 3C is the combination therapy (BMS-986178 with ipilimumab) dose expansion part in 
subjects with other tumors from dose escalation for signal finding at the MTD/RP2D(s) determined 
in Part 3A or 5. Each treatment cycle will be 3 weeks in length. Ipilimumab will be administered 
in the initial 4 cycles in combination with BMS-986178. Then the subject will continue on 
BMS-986178 monotherapy for up to an additional 4 cycles for a total of up to 24 weeks (8 cycles) 
of treatment. Approximately 40 subjects will be treated in this expansion cohort.
Tumor types for this cohort will be selected by Sponsor from those permitted in dose escalation 
which do not have a dedicated expansion cohort or plans for evaluation in other studies and those 
selected tumors will be communicated to the investigators. This cohort will allow for further 
exploration of early signs of clinical activity observed in tumors during the dose escalation phase 
of the trial as well as potential signals arising from ongoing trials of other anti-OX40 agonists in 
combination with anti-CTLA-4. Subjects enrolled in this cohort must be refractory to or intolerant 
of established therapy known to provide clinical benefit for their condition, i.e., subjects must not 
be candidates for regimens known to provide clinical benefit.
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3.1.5.7
Part 6B: Combination with Nivolumab and Ipilimumab in Renal Cell 
Carcinoma
Part 6B is the combination therapy (BMS-986178, nivolumab, and ipilimumab) dose expansion 
part in subjects with RCC at a dose determined to be tolerated in Part 6A. BMS-986178 will be 
administered at the RP2D(s) in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) 
q3w during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which 
BMS-986178 and nivolumab (480 mg) will be administered q4w. Study drugs will be administered 
accordingly starting on Day 1 of each cycle. Approximately 40 subjects will be treated in this 
expansion cohort.
3.1.5.8
Part 7B: Combination with Nivolumab and Ipilimumab in Non-small Cell 
Lung Cancer
Part 7B is the combination therapy (BMS-986178, nivolumab, and ipilimumab) dose expansion 
part in subjects with NSCLC at a dose determined to be tolerated in Part 7A. BMS-986178 will be 
administered at the RP2D(s) (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab 
(1 mg/kg; q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on 
Day 1 of each cycle. If subjects continue for additional cycles, past Cycle 4, all study drugs 
(BMS-986178/nivolumab/ipilimumab) will continue for all cycles. Approximately 40 subjects will 
be treated in this expansion cohort.
3.1.5.9
Stopping Rules during Dose Expansion
•
Evaluation of toxicity will be performed throughout enrollment in the dose expansion cohorts. 
•
If the rate of DLTs exceeds 33% in any cohort, the findings will be discussed between the 
investigators and Sponsor, and further enrollment may be interrupted in that expansion cohort. 
•
If an expansion cohort is discontinued due to toxicity, a new cohort at a previously tested lower 
dose level may be considered based on the aggregate safety experience and in consultation and 
agreement between the investigators and Sponsor.
•
During dose expansion, a specific cohort may be stopped due to lack of efficacy per Simon 
2-stage design recommendation.176,177 Due to the heterogeneous nature of tumor responses 
seen with immunotherapy (eg, late responses), such a decision would not be strictly based on 
the number of responses but would include all available efficacy data.
•
The non-binding nature of stopping boundaries allows for flexibility of examination on the 
totality of data to determine the risk/benefit ratio.
3.1.6
Study Schedule
In all cohorts, subjects will complete: Screening (up to 28 days), Treatment (up to 24 weeks [Parts
1-7], until meeting protocol-specified discontinuation criteria), and Safety Follow-up 
(approximately 100 days), as described below. Screening and the Treatment period are calculated 
relative to the first dose of study drug, while Safety Follow-up periods are calculated relative to 
the last dose. The study visit schematic is presented in Figure 3.1.6-1. The study will end when the 
last subject completes their last study visit, which is planned to be about 4 years after the start of 
the study. Parts 8 and 9 subjects will receive treatment up to 24 months (the maximum treatment 
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allowed for any subject is 2 years from the first dose of study treatment regardless of dose delays). 
Safety Follow-up period will be approximately 100 days from the end of treatment.
Figure 3.1.6-1:
Study Visit Schematic
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3.1.6.2
Treatment Period
Eligible subjects will be assigned to the open parts/cohorts by IRT (see Section 4.4). Subjects must 
meet all eligibility criteria at time of treatment initiation.
The treatment period consists of up to 24 weeks of dosing for Parts 1-7. Parts 8 and 9 will have a 
treatment period up to a maximum of 24 months of dosing from first dose regardless of treatment 
delays.
Following each treatment cycle, the decision to treat a subject with the next cycle of study therapy, 
up to 24 weeks of treatment or in Parts 8 and 9 up to 24 months, will be based on risk/benefit and 
tumor assessments. Tumor assessments will be performed every 8 weeks for Parts 1-7 and 9 or 
every 12 weeks for Part 8 (± 1 week). Assessments of partial response (PR) and complete response 
(CR) must be confirmed at least 4 weeks following initial assessment. Tumor progression or 
response endpoints will be assessed using Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 (Appendix 3).
Subjects with a response of SD, PR, or CR at the end of a given cycle will continue to the next 
treatment cycle. Subjects will generally be allowed to continue study therapy until the first 
occurrence of one of the following: 1) completion of the maximum number of cycles; 2) PD; 
3) clinical deterioration suggesting that no further benefit from treatment is likely; 4) intolerability 
to therapy; or 5) the subject meets criteria for discontinuation of study therapy as outlined in 
Section 4.5.6. Individual subjects with confirmed CR will be given the option to discontinue study 
therapy on a case-by-case basis after specific consultation and agreement between the investigator 
and BMS Medical Monitor in settings where risk/benefit justify discontinuation of study therapy.
Approximately 642 subjects will be enrolled, and approximately 545 subjects will be treated in the 
study.
3.1.6.3
Safety Follow-up
Upon completion of study therapy, subjects will enter the Safety Follow-up period.
After the end of treatment (EOT) visit, subjects will be evaluated for any new AEs for at least 
100 days after the last dose of therapy. Follow-up visits should occur at Days 30, 60, and 100 after 
the last dose or the date of discontinuation. Subjects (except those who withdraw consent for study 
participation) are expected to complete the 3 clinical Safety Follow-up visits regardless of whether 
they start new anti-cancer therapy.
For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the 
last scheduled and completed on-treatment visit, and the start of Week 1 Safety Follow-up visit. 
For subjects 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); the visit does not need to be 
repeated and will be considered the start of the Safety Follow-up period.
3.1.7
Treatment with Additional Cycles
Parts 1-7 subjects will be treated for 24 weeks unless criteria for study drug discontinuation are 
met earlier (Section 4.5.6). Subjects in Parts 2, 4, 6, and 7 completing approximately 24 weeks of 
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treatment with ongoing disease control (CR, PR, or SD) may be eligible for an additional 
18 months of study therapy beyond the initial 24 weeks, on a case-by-case basis, after discussion 
and agreement with the BMS Medical Monitor that the risk/benefit assessment favors continued 
administration of study therapy. Upon completion of the additional 18 months of study therapy,
subjects will enter Safety Follow-up period. Parts 8 and 9 subjects will not be eligible for treatment 
with additional cycles. The maximum treatment allowed for any subject is 2 years from the first 
dose of study treatment regardless of dose delays.
Parts 3 and 5 subjects completing approximately 24 weeks of treatment with ongoing disease 
control (CR, PR, or SD) may be eligible for an additional 24 weeks of study therapy beyond the 
initial 24 weeks, on a case-by-case basis, after discussion and agreement with the BMS Medical 
Monitor that the risk/benefit assessment favors continued administration of study therapy. Upon 
completion of the additional 24 weeks of study therapy, subjects will enter Safety Follow-up 
period.
3.1.8
Treatment Beyond Progression
Treatment beyond progression may be allowed in select subjects with initial RECIST v1.1-defined 
progressive disease after discussion and agreement with the BMS Medical Monitor that the 
benefit/risk assessment favors continued administration of study therapy (eg, subjects are 
continuing to experience clinical benefit as assessed by the investigator, tolerating treatment, and 
meeting other criteria specified in Section 3.5.1.
Subjects must be re-consented with an Informed Consent Form addendum to continue treatment 
beyond progression.
3.2
Post-study Access to Therapy
At the end of the study, BMS will not continue to provide BMS-supplied study drug to subjects 
and investigators unless BMS chooses to extend the study. The investigator should ensure that the 
subject receives appropriate SOC to treat the condition under study.
3.3
Study Population
For entry into the study, the following criteria MUST be met prior to dosing on Day 1. No 
exceptions will be granted.
3.3.1
Inclusion Criteria
1) Signed Written Informed Consent
a) Participants or their legally acceptable representative, must have signed and dated an 
IRB/IEC approved written informed consent form in accordance with regulatory and 
institutional guidelines. This must be obtained before the performance of any protocol-
related procedures that are not part of normal patient care.
b) Consent for tumor biopsy samples (mandatory pre- and on-treatment biopsies) are required 
for all subjects enrolled.
c) Participants must be willing and able to comply with scheduled visits, treatment schedule, 
laboratory testing, and other requirements of the study.
2) Type of Participant and Target Disease Characteristics
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Subjects must be at least 18 years old and have histologic or cytologic confirmation of a 
malignancy that is advanced (metastatic, recurrent, refractory, and/or unresectable) with 
measurable disease per RECIST v1.1 (see Appendix 3).
1) Dose Escalation/Schedule and Dose Exploration/Safety Cohorts/Dose Expansion 
(Part 2E/3C) Subjects must be refractory to or intolerant of established therapy known to 
provide clinical benefit for their condition, i.e., subjects must not be candidates for 
regimens known to provide clinical benefit.
The following tumor histologies will be permitted except for subjects with primary central 
nervous system (CNS) tumors, or with CNS metastases as the only site of active disease.
Parts 1A, 2A, 2E, 3A, 3C, 4, and 5
(i) Melanoma: BRAF mutation status must be documented if known
(ii) NSCLC: EGFR, anaplastic lymphoma kinase (ALK), KRAS, and ROS1 
mutational status must be documented if known
(iii)Head and neck cancer restricted to squamous cell carcinoma: HPV status 
must be documented if known
(iv)Transitional cell carcinoma of the genitourinary tract
(v) Renal cell carcinoma
(vi)Pancreatic adenocarcinoma
(vii)
CRC: MSI, KRAS, and BRAF status must be documented if known
(viii)
Cervical cancer: HPV status must be documented if known
(ix)Triple negative breast cancer HER2, ER, and PgR status must be 
documented
(x) Adenocarcinoma of the endometrium
(xi)Ovarian cancer
(xii)
Prostate adenocarcinoma
(xiii)
Hepatocellular cancer-Child Pugh A only
(xiv)
Small cell lung cancer
(xv)
Gastric and gastric esophageal junction cancer: HER2 status must 
be documented if known
(xvi)
Thyroid cancer
Part 6A (RCC)
(xvii)
Subjects with histological confirmation of RCC with a clear-cell 
component
(xviii)
Subjects must have received at least 1, but no more than 2, prior 
systemic therapies in the advanced/metastatic setting.
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Part 7A (NSCLC)
Subjects must have histologic or cytologic confirmation of NSCLC (per the seventh 
International Association for the Study of Lung Cancer [IASLC]178) with squamous or 
nonsquamous histology that is advanced (metastatic and/or unresectable).
(xix)
Subjects must have had at least 1, but no more than 2, prior systemic 
therapies 
for 
NSCLC. 
Maintenance, 
adjuvant, 
or 
neoadjuvant 
(chemotherapy or chemoradiation) therapy does not count as an additional 
line of treatment.
(xx)
Subjects should have been offered a platinum-based chemotherapy 
for NSCLC. The platinum-based chemotherapy may have been in the 
adjuvant, neoadjuvant, or recurrent setting. Prior adjuvant or neoadjuvant 
chemotherapy is permitted as long as the last administration of the prior 
regimen occurred at least 4 weeks prior to enrollment.
(xxi)
Prior definitive chemoradiation for locally advanced disease is also 
permitted as long as the last administration of chemotherapy or radiotherapy 
(whichever was given last) occurred at least 4 weeks prior to enrollment.
(xxii)
Subjects with known EGFR mutations or ALK rearrangements must 
have received EGFR or ALK inhibitors, respectively.
(xxiii)
EGFR, ALK, KRAS, ROS1 mutational status must be documented 
if known.
2) Dose Expansion: Parts 2B, 2C, 2D, 3B, 6B, 7B, 8, and 9
The following tumor types will be permitted:
(a) Cervical Cancer - Part 2D
(i) Histologically confirmed cervical cancer that is unresectable, metastatic, or 
recurrent with documented disease progression
(ii) Document tumor HPV status if known. If tumor HPV status is unknown, 
subjects must consent to allow their submitted archived tumor tissue sample 
(block or unstained slides) to be tested.
(iii)Prior therapy requirement:
Subjects must have been offered and/or have received or refused at 
least 1 prior platinum-based therapy for metastatic and/or 
unresectable disease. Subjects must have not received more than 2 
prior systemic therapies. Reason(s) for refusal should be 
documented. Concurrent chemotherapy administered with primary 
radiation and adjuvant chemotherapy given following completion of 
radiation therapy do not count as systemic therapies, though patients 
who progressed less than 6 months from primary platinum-based 
therapy are eligible.
(b) Colorectal Cancer - Part 2B 
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(i) Histologically confirmed CRC that is metastatic or recurrent with 
documented disease progression
(ii) Document MSI, MMR, KRAS, and BRAF status if known. If unknown, 
subjects must consent to allow their submitted archived tumor tissue sample 
(block or unstained slides) to be tested.
(iii)Prior therapy requirement:
Subjects must have received at least 1, but no more than 3, prior 
systemic therapies for metastatic and/or unresectable disease (or have 
progressed within 6 months of adjuvant therapy).
(c) Bladder Cancer - Part 2C 
(i) Histologically or cytologically confirmed urothelial carcinoma (including 
mixed histologies of urothelial carcinoma with elements of other subtypes) 
of the renal pelvis, ureter, bladder, or urethra with progression or refractory 
disease
(ii) Prior therapy requirement:
Subjects must have been offered and/or have received or refused 1 prior 
platinum-based therapy for the treatment of metastatic or locally 
advanced unresectable disease. Subjects must have not received more 
than 2 prior systemic therapies. Reason(s) for refusal should be 
documented. 
(d) Ovarian - Part 3B
(i) Histologically or cytologically confirmed ovarian carcinoma (including 
epithelial OC, primary peritoneal, or fallopian tube carcinoma) with 
documented disease progression
(ii) Documented germline BRCA mutation status, if known. If unknown, 
subjects must consent to allow their submitted archived tumor tissue sample 
(block or unstained slides) to be tested.
(iii)Prior therapy requirement: 
Subjects must have received no more than 3 prior systemic therapies. 
One regimen must have been a prior platinum-based chemotherapy 
regimen for primary disease, possibly including intra-peritoneal therapy 
consolidation, biologic/targeted (non-cytotoxic) agents, or extended 
therapy (maintenance/consolidation) administered after surgical or 
non-surgical assessment. Patients must have progressed less than 
12 months after completion of their last platinum-based chemotherapy. 
The number of months (platinum-free interval) should be calculated 
from the date of the last administered dose of platinum therapy to the 
date of the documentation of progression.
(e) RCC (Part 6B)
(i) Subjects with histologically confirmed RCC with a clear-cell component 
(ii) Advanced (not amenable to curative surgery or radiation therapy) or 
metastatic (AJCC Stage IV) RCC
(iii)No prior systemic therapy for RCC with the following exception:
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One prior adjuvant or neoadjuvant therapy for completely resectable 
RCC if such therapy did not include an agent that targets VEGF or 
VEGF receptors and if recurrence occurred at least 6 months after the 
last dose of adjuvant or neoadjuvant therapy.
(iv)Subjects with favorable-, intermediate-, and poor-risk categories will be 
eligible for the study. Subjects must be categorized according to favorable-
versus intermediate-/poor-risk status at registration according to the 
International Metastatic RCC Database Consortium (IMDC) criteria 
(Appendix 5).
(f) NSCLC (Part 7B)
(i) Subjects with histologically confirmed Stage IV or recurrent NSCLC (per 
the 7th IASLC) squamous or nonsquamous histology, with no prior 
systemic anticancer therapy (including EGFR and ALK inhibitors) given as 
primary therapy for advanced or metastatic disease. 
(ii) Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last 
administration of the prior regimen occurred at least 6 months prior to 
enrollment. 
(iii)Prior definitive chemoradiation for locally advanced disease is also 
permitted as long as the last administration of chemotherapy or radiotherapy 
(which ever was given last) occurred at least 6 months prior to enrollment.
(g) Bladder (Part 8)
(i) Histologically or cytologically confirmed urothelial carcinoma (including 
mixed histologies of urothelial carcinoma with elements of other subtypes) 
of the renal pelvis, ureter, bladder, or urethra with progression or refractory 
disease.
(ii) Subjects will need to have a pre-treatment and 2 on-treatment biopsies.
(iii)Prior therapy requirement:
Subjects must have been offered and/or have received or refused 1 prior 
platinum-based therapy for the treatment of metastatic or locally 
advanced unresectable disease. Subjects must have not received more 
than 1 prior systemic therapy. Reason(s) for refusal should be 
documented.
Subjects must be immunotherapy treatment naïve (eg, no prior therapy 
with experimental anti-tumor vaccines; any T-cell co-stimulation or 
checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-
CD137, or anti-CTLA-4 antibody, including ipilimumab; or other 
medicines specifically targeting T-cells).
(iv)Within 12 months of peri-operative (neo-adjuvant or adjuvant) treatment 
with a platinum agent in the setting of cystectomy for localized muscle-
invasive urothelial cancer.
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(v) Sequential chemotherapy given as a planned sequence to optimize response 
will count as 1 regimen.
(vi)Vaccines for infectious disease (e.g., influenza) allowed, provided they are 
administered ≥2 weeks prior to or ≥2 weeks after study treatment/vaccine.
(h) TNBC and ER-Low Positive Breast Cancer (Part 9)
(i) Not applicable per site-specific Protocol Amendment 04. See 2) (h) (vi).
Histologically confirmed breast cancer [per local laboratory, ER<1 (Allred 
score) by American Society of Clinical Oncology/College of American 
Pathologists (ASCO/CAP), PR<1 (Allred score) by ASCO/CAP, and 
HER2-negative per current NCCN guidelines (www.nccn.org)].179
(ii) Subjects need to have 1 pre-treatment and 1 on-treatment biopsy. For the 
pre-treatment biopsy, archived material is acceptable if at least 2 tumor-
bearing cores are available, and the material is obtained in the 
advanced/metastatic setting within 3 months of enrollment, with no 
intervening anti-neoplastic systemic therapies. 
(iii)Not applicable per site-specific Protocol Amendment 04. See 2) (h) 
(viii). Stage IV metastatic or unresectable disease with zero or one prior 
systemic therapies in the advanced/metastatic setting. Subjects with < 12 
months from receipt of last curative-intent chemotherapy are allowed; 
curative chemotherapy will be considered first-line therapy. Prior receipt of 
chemotherapy in the (neo)adjuvant setting is acceptable, as long as 
completed greater than 6 months from start of treatment. 
(iv)Not applicable per site-specific Protocol Amendment 04. See 2) (h) (x). 
Vaccines for infectious disease (e.g., influenza) allowed, provided they are 
administered ≥2 weeks prior to or ≥2 weeks after study treatment/vaccine. 
Part 9 will allow the DRibbleDRibbles vaccine as part of subject treatment.
(v) Not applicable per site-specific Protocol Amendment 04. See 2) (h) (ix).
Subjects must be immunotherapy treatment naïve (eg, no prior therapy with 
experimental anti-tumor vaccines; any T-cell co-stimulation or checkpoint 
pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-
CTLA-4 antibody, including ipilimumab; or other medicines specifically 
targeting T-cells). Prior receipt of intralymphatic cytokine therapy (IRX-2) 
is acceptable.
(vi)Histologically confirmed breast cancer [per local laboratory, ER < 1% 
expression by IHC staining for triple negative breast cancer and ER 1% 
through 10% for ER-low positive breast cancer by American Society of 
Clinical Oncology/College of American Pathologists (ASCO/CAP), PgR <
1% for triple negative breast cancer by ASCO/CAP, and HER2-negative 
per current NCCN guidelines (www.nccn.org)].180
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(vii)
Prior endocrine therapy in ER-low positive participants is permitted.
(viii)
Stage IV metastatic or unresectable disease with 0 through 2 prior 
chemotherapy-containing regimens in the advanced/metastatic setting of 
which no more than 1 prior line may include an anti-PD-1 or an anti-PD-L1 
checkpoint inhibitor. Subjects with < 12 months from receipt of last 
curative-intent chemotherapy are allowed; curative chemotherapy will be 
considered first-line therapy. Prior receipt of chemotherapy in the 
(neo)adjuvant setting is acceptable, as long as completed greater than 6 
months from start of treatment. 
(ix)Anti-PD-1 or anti-PD-L1 antibody is permitted after a washout period of 
any time greater than 4 weeks from the last treatment.
(x) Approved or authorized vaccines for infectious disease (eg, influenza and 
SARS-CoV-2) are allowed, provided they are administered ≥10 days prior 
to or ≥10 days after study treatment/vaccine. Part 9 will allow the DRibbles 
(DPV-001) vaccine as part of subject treatment. Any vaccine(s) other than 
Fluzone® or the study vaccine DPV-001 must first be discussed with the 
BMS medical monitor.
3) Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
4) Presence of at least 1 lesion with measurable disease as defined by RECIST v1.1 for 
response assessment. Subjects with lesions in a previously irradiated field as the sole site of 
measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear 
progression and can be measured accurately. 
5) All subjects require a fresh tumor biopsy, these subjects must have at least one lesion 
accessible for pre- and on-treatment biopsy, in addition to the minimum one RECIST v1.1 
measureable lesion required for response assessment. This lesion needs to be distinct from 
index lesion(s) being evaluated for radiological response.
6) Parts 1-7 subjects with prior exposure to therapy with any agent specifically targeting 
checkpoint pathway inhibition (such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-LAG-3, and 
anti-CTLA-4 antibody) are permitted after a washout period of any time greater than 4 weeks 
from the last treatment.
Note: (i) Subjects who experienced prior Grade 1 to 2 checkpoint therapy-related immune-
mediated AEs must have confirmed recovery from these events at the time of study entry, 
other than endocrinopathies treated with supplementation, as documented by resolution 
of all related clinical symptoms, abnormal findings on physical examination, and/or 
associated laboratory abnormalities. Where applicable, these subjects must also have
completed steroid tapers for treatment of these AEs by a minimum of 14 days prior to 
commencing treatment with study therapy.
(ii) Eligibility of subjects with prior ≥Grade 3 checkpoint therapy-related immune AEs, 
will be considered on a case-by-case basis after discussion and agreement between the 
investigators and the medical monitor (eg, asymptomatic isolated Grade 3 lipase 
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elevations without clinical or radiological features of pancreatitis will be permitted to 
enroll).
7) Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose 
of study drug. Subjects with symptomatic tumor lesions at baseline that may require palliative 
radiotherapy within 4 weeks of first dose of study drug are strongly encouraged to receive 
palliative radiotherapy prior to enrollment.
8) All Subjects must consent to the acquisition of pre- and on-treatment tumor biopsies for 
performance of correlative biomarker studies. Archival specimens may not be substituted for 
fresh baseline specimens (except for Part 9) but can be submitted to help understand the 
evolution of the tumor (ie, PD-L1 expression changes over time) for performance of correlative 
studies. Subjects who either do not consent to a pre-treatment tumor biopsy or do not have 
accessible lesions are not eligible. (However, subjects whose pre-treatment biopsy yields 
inadequate tissue quantity or quality will not be ineligible on this basis alone). For Part 9, 
please refer to above inclusion criteria.
9) All Subjects enrolled will be required to undergo mandatory pre- and on-treatment 
biopsies at acceptable clinical risk as judged by the investigator.
(a) The solid tumor tissue specimen must be a core needle, excisional, or incisional 
biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, or 
punch biopsies are not considered adequate for biomarker review. Biopsies of 
bone lesions that do not have a soft tissue component or decalcified bone tumor 
samples are also not acceptable. 
(b) Biopsied lesions should be distinct from index lesion(s) being evaluated for 
radiological response
10) Adequate organ function for subjects as defined by the following:
(a) Neutrophils ≥1500/μL
(b) Platelets ≥80 × 103/μL (transfusion to achieve this level is not permitted within 
2 weeks of first study drug administration)
(c) Hemoglobin ≥8 g/dL (transfusion to achieve this level is not permitted within 
2 weeks of first study drug administration)
(d) ALT and AST ≤3× upper limit of normal (ULN)
(e) Total bilirubin ≤1.5 × ULN (except subjects with Gilbert’s Syndrome who 
must have normal direct bilirubin)
(f) Normal thyroid function or stable on hormone supplementation, per 
investigator assessment
(g) Albumin ≥2 g/dL
(h) Serum creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥40 mL/min 
(measured using the Cockcroft-Gault formula below):
Female CrCl = 
(140 - age in years) × weight in kg × 0.85
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72 × serum creatinine in mg/dL
Male CrCl =
(140 - age in years) × weight in kg × 1.00 
72 × serum creatinine in mg/dL
11) Ability to comply with treatment, PK, and PD sample collection and required study follow-
up
Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the 
study as a pre-treatment failure (eg, subject has not been treated). If re-enrolled, the subject must 
be re-consented.
3) Age and Reproductive Status
a) Men and women, ages ≥18 years at the time of informed consent
b) Women of childbearing potential (WOCBP) must have a negative serum or urine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic 
gonadotrophin [hCG]) within 24 hours prior to the start of study drug.
c) Women must not be breastfeeding
d) For Parts 1-8, WOCBP must agree to follow instructions for method(s) of contraception 
for the duration of treatment with study drug BMS-986178 plus 5 half-lives of study drug 
plus 30 days as defined below. This duration should be 12 weeks for Parts 1 and 3 subjects 
(50 days plus 30 days) or 5 months for Part 2 subjects (130 days plus 30 days [duration of 
ovulatory cycle]), for a total of up to 160 days post-treatment completion. For Part 9, 
WOCBP must agree to follow instructions for method(s) of contraception for duration of 
study therapy plus 1 year after last dose of study therapy as defined below.
e) For Parts 1-8, males who are sexually active with WOCBP must agree to follow 
instructions for method(s) of contraception for the duration of treatment with study drug 
BMS-986178 plus 5 half-lives of the study drug plus 90 days. The duration should be 20 
weeks for Parts 1 and 3 subjects (50 days plus 90 days) or 7 months for Part 2 subjects (130 
days plus 90 days [duration of sperm turnover]), for a total of up to 220 days post-treatment 
completion. For Part 9, males who are sexually active must agree to follow instructions for 
method(s) of contraception for the duration of treatment plus 4 months after the last dose 
of study therapy. For Parts 1-9, male subjects must be willing to refrain from sperm 
donation during this time.
f)
For Parts 1-8, azoospermic males are exempt from contraceptive requirements. For Part 9, 
azoospermic males are not exempt from contraceptive requirements and will be required 
to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, 
anal, oral) with WOCBP, even if the participant has undergone a successful vasectomy or 
if the partner is pregnant. For Parts 1-9, WOCBP who are continuously not heterosexually 
active are also exempt from contraceptive requirements, but must still undergo pregnancy 
testing as described in this section.
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Investigators shall counsel women of child bearing potential (WOCBP) and male participants (as 
defined below), 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.
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Highly effective methods of contraception have a failure rate of < 1% when used consistently and 
correctly. WOCBP must use a highly effective method of contraception (listed below). WOCBP 
partners of male subjects must use a highly effective method of contraception. Local laws and 
regulations may require use of alternative and/or additional contraception methods. Male subjects 
must inform their female partners who are WOCBP of the contraceptive requirements of the 
protocol and are expected to adhere to using contraception with their partner. Male subjects are 
expected to use a condom, in addition to a highly effective method as noted in the list below:
1) Progestogen only hormonal contraception associated with inhibition of ovulation
2) Hormonal methods of contraception including oral contraceptive pills containing 
combined estrogen and progesterone, vaginal ring, injectables, implants, and 
intrauterine devices (IUDs) such as Mirena®
3) Nonhormonal IUDs, such as ParaGard®
4) Bilateral tubal occlusion
5) Vasectomized partner with documented azoospermia 90 days after procedure
•
Vasectomy is a highly effective birth control method provided that the partner 
is the sole sexual partner of the WOCBP trial participant and that the 
vasectomized partner has received medical assessment of the surgical success.
6) Intrauterine hormone-releasing system
7) Complete abstinence
•
Complete abstinence is defined as the complete avoidance of heterosexual 
intercourse (refer to Glossary of Terms)
•
Complete abstinence is an acceptable form of contraception for all study drugs 
and must be used at least 30 days prior to first dose of study drug and throughout 
the duration of the study treatment (plus 5 half-lives of the study drug(s) plus 
30 days).
•
It is not necessary to use any other method of contraception when complete 
abstinence is elected.
•
Subjects who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 5.1.
•
Acceptable alternate methods of highly effective contraception must be 
discussed in the event that the subject chooses to forego complete abstinence.
•
The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the subject.
8) Use a condom in male subjects with female partners.
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UNACCEPTABLE METHODS OF CONTRACEPTION
1) Periodic abstinence (calendar, symptothermal, and/or post-ovulation methods)
2) Withdrawal (coitus interruptus)
3) Spermicide only
4) Lactation amenorrhea method
5) Diaphragm with spermicide
6) Cervical cap with spermicide
7) Vaginal sponge with spermicide
8) Male or female condom with or without spermicide*
9) Progestogen-only oral hormonal contraception by WOCBP, where inhibition of 
ovulation is not the primary mode of action or male subject’s WOCBP partner
* A male and a female condom must not be used together.
3.3.2
Exclusion Criteria
1) Target Disease Exceptions
a) Subjects with known or suspected CNS metastases or untreated CNS metastases, 
or with the CNS as the only site of disease, are excluded. However, subjects with 
controlled brain metastases will be allowed to enroll. For Parts 1-8, controlled brain 
metastases are defined as no radiographic progression for at least 4 weeks following 
radiation and/or surgical treatment (or 4 weeks of observation if no intervention is 
clinically indicated), and off of steroids for at least 2 weeks, and no new or 
progressive neurological signs and symptoms. For Part 9 only, participants are 
eligible if CNS metastases have been treated and participants have neurologically 
returned to baseline (except for residual signs or symptoms related to CNS 
treatment). In addition, participants must have been either off corticosteroids for at 
least 2 weeks prior to randomization. Imaging performed within 28 days prior to 
randomization must document radiographic stability of CNS lesions and be 
performed after completion of any CNS-directed therapy.
b) Subjects with carcinomatous meningitis
c) For ovarian cancer (Part 3B):
i)
Ovarian cancer subjects with history of bowel obstruction in the prior 6 months 
or with intraperitoneal catheter (eg Tenckhoff) will be excluded. 
ii)
Not applicable
d) For NSCLC (Part 7B)
i)
Subjects with known EGFR mutations, which are sensitive to available targeted 
inhibitor therapy (including, but not limited to, deletions in exon 19 and exon 
21 [L858R] substitution mutations), are excluded. All subjects with non-
squamous histology must have been tested for EGFR mutation status; use of an 
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FDA-approved test is strongly encouraged. Subjects with non-squamous 
histology and unknown or indeterminate EGFR status are excluded.
ii) Subjects with known ALK translocations, which are sensitive to available 
targeted inhibitor therapy, are excluded. If tested, the use of an FDA-approved 
test is strongly encouraged. Subjects with unknown or indeterminate ALK 
status may be enrolled.
e) For Bladder Cancer (Part 8)
i)
Prior therapy with experimental anti-tumor vaccines, any T-cell co-stimulation 
or checkpoint pathways, such as anti-PD1, anti-PD-L1, anti-PD-L2, anti-
CD137, or anti-CTLA-4 antibody, including ipilimumab, or other medicines 
specifically targeting T-cells is also prohibited in this part of the study.
ii) No prior adverse reaction to tetanus toxoid-containing vaccines.
iii) Subjects with known allergies to egg products, neomycin, or tetanus toxoid are 
also considered ineligible.
f)
For TNBC and ER-Low Positive Breast Cancer (Part 9)
i)
Not applicable per site-specific Protocol Amendment 04. See f) ii). Prior 
treatment with experimental anti-tumor vaccines; any T-cell co-stimulation or 
checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, 
or anti-CTLA-4 antibody, including ipilimumab; or other medicines 
specifically targeting T-cells. Prior receipt of intralymphatic cytokine therapy 
(IRX-2) is acceptable.
ii) Prior treatment with experimental anti-tumor vaccines; any T-cell co-
stimulation or checkpoint pathways (other than anti-PD-1/anti-PD-L1), such as 
anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including ipilimumab; or 
other medicines specifically targeting T-cells. Prior receipt of intralymphatic 
cytokine therapy (IRX-2) and anti-PD-1/anti-PD-L1 antibody is acceptable.
2) Medical History and Concurrent Diseases
a) Subjects with a prior malignancy, different from the one used for enrollment in this 
study, diagnosed within less than 2 years prior to study entry are excluded (except 
non-melanoma skin cancers and in situ cancers such as bladder, colon, 
cervical/dysplasia, melanoma, or breast). In addition, subjects with other second 
malignancies diagnosed more than 2 years ago who have received therapy with 
curative intent with no evidence of disease during the interval who are considered 
by the investigator to present a low risk for recurrence will be eligible.
b) Subjects with other active malignancy requiring concurrent intervention are 
excluded.
c) Prior organ allograft
d) Previous treatment:
i)
Prior anti-cancer treatments are permitted (ie, chemotherapy, radiotherapy, 
hormonal,
or immunotherapy) except in Parts 6B (Inclusion criteria 
1.a)(1)2)(e)) and 7B (Inclusion criteria 1.a)(1)2)(f)). 
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ii) Toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery 
must either have resolved, returned to baseline or Grade 1, or have been deemed 
irreversible.
iii) For cytotoxic agents, at least 4 weeks or 5 half-lives (whichever is shorter) must 
have elapsed between the last dose of prior anti-cancer therapy and initiation of 
study therapy.
iv) For non-cytotoxic agents, at least 4 weeks or 5 half-lives (whichever is shorter) 
must have elapsed from last dose of prior anti-cancer therapy and the initiation 
of study therapy. If 5 half-lives is shorter than 4 weeks, agreement with 
Sponsor/medical monitor is mandatory. 
e) Subjects with prior therapy with any agent specifically targeting T-cell 
co-stimulation pathways such as anti-OX40 antibody, anti-CD137, anti-GITR 
antibody, and anti-CD27 are excluded.
f)
Subjects with active, known, or suspected autoimmune disease are excluded. 
Subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to 
autoimmune condition only requiring hormone replacement, euthyroid subjects 
with a history of Grave’s disease (subjects with suspected autoimmune thyroid 
disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and 
thyroid stimulating immunoglobulin prior to first dose of study drug), psoriasis not 
requiring systemic treatment, or conditions not expected to recur in the absence of 
an external trigger are permitted to enroll. Subjects with well controlled asthma 
and/or mild allergic rhinitis (seasonal allergies) are eligible.
g) Subjects with history of life-threatening toxicity related to prior immune therapy 
(eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug 
specifically targeting T-cell co-stimulation or immune checkpoint pathways) 
except those that are unlikely to re-occur with standard countermeasures (eg, 
hormone replacement after adrenal crisis)
h) Subjects with interstitial lung disease that is symptomatic or that may interfere with 
the detection or management of suspected drug-related pulmonary toxicity
i)
Subjects with a condition requiring systemic treatment with either corticosteroids 
(> 10 mg daily prednisone equivalents) or other immunosuppressive medications 
within 14 days of study drug administration except for adrenal replacement steroid 
doses > 10 mg daily prednisone equivalent in the absence of active autoimmune 
disease. Note: Treatment with a short course of steroids (< 5 days) up to 7 days 
prior to initiating study drug is permitted.
j)
Uncontrolled or significant cardiovascular disease, including but not limited to any 
of the following:
i)
Myocardial infarction or stroke/transient ischemic attack within the past 6 
months
ii) Uncontrolled angina within the past 3 months
iii) Any history of clinically significant arrhythmias (such as ventricular 
tachycardia, ventricular fibrillation, or torsades de pointes)
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iv) History of other clinically significant heart disease (eg, cardiomyopathy, 
myocarditis, congestive heart failure with New York Heart Association 
functional classification III-IV, pericarditis, significant pericardial effusion)
v) Cardiovascular disease-related requirement for daily supplemental oxygen 
therapy
vi) QT interval corrected for heart rate using Fridericia’s formula (QTcF) 
prolongation > 480 msec
k) History of any chronic hepatitis as evidenced by the following:
i)
Positive test for hepatitis B surface antigen
ii) Positive test for qualitative hepatitis C viral load (by polymerase chain reaction 
[PCR])
Note: Subjects with positive hepatitis C antibody and negative quantitative 
hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection 
is not an exclusion criterion.
Additional testing or substitute testing per institutional guidelines to rule out 
infection is permitted.
l)
Evidence of active infection that requires systemic antibacterial, antiviral, or 
antifungal therapy ≤7 days prior to initiation of study drug therapy (does not apply 
to viral infections that are presumed to be associated with the underlying tumor type 
required for study entry).
m) Known history of testing positive for HIV or known acquired immunodeficiency 
syndrome. Note: Testing for HIV must be performed at sites where mandated by 
local requirements.
n) Not applicable per site-specific Protocol Amendment 04. See 2) r). Any major 
surgery within 4 weeks of study drug administration. Subjects must have recovered 
from the effects of major surgery or significant traumatic injury at least 14 days 
before the first dose of study drug.
o) Use of non-oncology vaccines containing live/attenuated virus for prevention of 
infectious diseases within 4 weeks prior to study drug. The use of inactivated 
seasonal influenza vaccines, eg, Fluzone®, will be permitted on study without 
restriction, however, for subjects treated in Part 9, any vaccine (including 
inactivated) must first be discussed with the BMS medical monitor. Previous 
SARS-CoV-2 vaccines less than 10 days prior to start of study drug. For vaccines 
requiring more than 1 dose, the full series (eg, both doses of a 2-dose series) should 
be completed prior to start of study treatment when feasible and when a delay in 
enrollment would not put the study subject at risk.
p) Use of packed red blood cell or platelet transfusion within 2 weeks prior to the first 
dose of study drug
q) A known or underlying medical or psychiatric condition and/or social reason that, 
in the opinion of the investigator or Sponsor, could make the administration of 
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study drug hazardous to the subject or could adversely affect the ability of the 
subject to comply with or tolerate the study.
r)
Any major surgery within 2 weeks of study drug administration. Subjects must have 
recovered from the effects of major surgery or significant traumatic injury at least 
14 days and have adequate wound healing before the first dose of study drug.
s) Participant has any condition, including active or uncontrolled infection, or the 
presence of laboratory abnormalities, which places the subject at unacceptable risk 
if he/she were to participate in the study. Previous SARS-CoV-2 infection within 
10 days for mild or asymptomatic infections or 20 days for severe/critical illness 
prior to first dose of study drug. Acute symptoms must have resolved and based on 
investigator assessment in consultation with the medical monitor, there are no 
sequelae that would place the participant at a higher risk of receiving study 
treatment.
t)
Subjects who are pregnant and/or breastfeeding.
3) Allergies and Adverse Drug Reaction
a) History of allergy to nivolumab or ipilimumab (Parts 2, 4, and 9 or 3 and 5,
respectively) or history of allergy to the combination of nivolumab and ipilimumab 
(Parts 6 and 7)
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) to 
prior anti-cancer immune modulating therapies (eg, checkpoint inhibitors, T-cell 
co-stimulatory antibodies)
4) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain 
specific circumstances, a person who has been imprisoned may be included or
permitted to continue as a subject. Strict conditions apply, and BMS approval is 
required.)
b) Subjects who are compulsorily detained for the treatment of either psychiatric or 
physical (eg, infectious disease) illness
c) Inability to comply with restrictions and prohibited activities/treatments as listed in 
Section 3.4
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet all 
eligibility criteria.
3.3.3
Women of Childbearing Potential
WOCBP is defined as any female who has experienced menarche and who has not undergone 
surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. 
Menopause 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 
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•
Documented disease progression as defined by RECIST (see Appendix 3) unless the subject 
meets the criteria for treatment beyond progression (Section 3.5.1)
•
Clinical deterioration while receiving active study therapy that, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
subject
•
Inability to comply with protocol requirements
•
Discretion of the investigator
•
Protocol-defined reasons for discontinuation (see Section 4.5.6)
In case of pregnancy, the investigator must immediately notify the BMS medical monitor/designee 
of this event. In the event that a female subject becomes pregnant during a clinical trial, the study 
drug must be discontinued immediately. Please call the BMS medical monitor within 24 hours of 
awareness of the pregnancy (Section 6.4). 
All subjects who discontinue the investigational product should comply with the protocol-specified 
follow-up procedures outlined in Table 5.1-9. The only exception to this requirement is when a 
subject withdraws consent for all study procedures including post-treatment study follow-up or 
loses the ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment 
of a psychiatric or physical illness).
If the study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate CRF page.
3.5.1
Treatment Beyond Disease Progression
As described in Section 1.1.20 accumulating evidence indicates that a minority of subjects with 
solid tumors treated with immunotherapy may derive clinical benefit despite initial evidence of 
progressive disease. Subjects will be permitted to continue on treatment beyond initial 
RECIST v1.1 (see Appendix 3)-defined progressive disease as long as they meet the following 
criteria:
•
Investigator-assessed clinical benefit and without rapid disease progression
•
Continue to meet all other study protocol eligibility criteria
•
Subject tolerates study drug
•
Subject has stable performance status
•
Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (eg, CNS metastases).
•
Subject provides written informed consent prior to receiving any additional BMS-986178, 
nivolumab, and/or ipilimumab treatment using an ICF describing any reasonably foreseeable 
risks or discomforts or other alternative treatment options.
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The assessment of clinical benefit should take into account whether the subject is clinically 
deteriorating and unlikely to receive further benefit from continued treatment. As described in 
Section 3.1.8, all decisions to continue treatment beyond initial progression must be discussed with 
the BMS Medical Monitor, and an assessment of the risk/benefit of continuing with study therapy 
must be documented in the study records. Subjects will be re-consented to explain the rationale for 
this ongoing treatment. 
3.5.1.1
Discontinuation due to Further Progression 
Subjects should discontinue study therapy upon further evidence of further progression, defined 
as an additional 10% or greater increase in tumor burden volume from the time of initial 
progression (including all target lesions and new measurable lesions). 
The tumor burden volume from the time of initial progression should be used as the reference 
baseline for comparison with the postprogression assessment.
Any new lesion considered non-measurable at the time of initial progression may become 
measurable, and therefore, must be included in the tumor burden measurement as follows:
For solid tumors: New lesions are considered measurable at the time of initial progression if the 
longest diameter is at least 10 mm (except for pathological lymph nodes, which must have a short 
axis of at least 15 mm). 
For statistical analyses that include the investigator-assessed progression date, subjects who 
continue treatment beyond the initial investigator-assessed, RECIST v1.1-defined progression will 
be considered to have investigator-assessed progressive disease at the time of the initial 
progression event.
3.5.1.2
Assessment Schedule for Subjects with Post-progression Treatment
Subjects should continue to receive monitoring according to the on-treatment assessments in Table 
5.1-2, Table 5.1-3, Table 5.1-4, Table 5.1-5, Table 5.1-6, Table 5.1-8, and Table 5.1-9.
Radiographic assessment by computed tomography (CT) (preferred) or MRI described in Section
5.1 and Appendix 3 is required when subjects continue post-progression treatment. For subjects 
that discontinue postprogression treatment with study therapy, no additional radiographic 
assessments will be required.
3.6
Post-study Drug Follow-up
Post-study follow-up is of critical importance and is essential to preserving subject safety and the 
integrity of the study. Subjects who discontinue study drug must continue to be followed per the 
Safety Follow-up (approximately 100 days).
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug 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 subject 
specifically withdraws consent for any further contact with him/her or persons previously 
authorized by the subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
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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 drug 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 subject 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.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing status. 
This includes follow-up with persons authorized by the subject as noted above. Lost to follow-up 
is defined by the inability to reach the subject after a minimum of 3 documented phone calls, faxes, 
texts, or emails as well as lack of response by the subject to 1 registered mail letter. All attempts 
should be documented in the subject’s medical records. If it is determined that the subject has died, 
the site will use permissible local methods to obtain the 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 subject’s informed consent, then the investigator may use a 
Sponsor-retained third-party representative to assist site staff with obtaining subject’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 subject remains lost to follow-up, then the last known alive date as determined by the 
investigator should be reported and documented in the subject’s medical records.
4
STUDY DRUG
In this study, all drugs will be considered investigational products: BMS-986178, nivolumab, 
ipilimumab, tetanus vaccine, and UbiLT3 and UbiLT6 (Table 4-1).
Product description and storage information are described in Table 4-1.
Table 4-1:
Study Drugs for CA012004
Product Description 
Class and Dosage 
Form
Potency
IP/Non-IP
Blinded or 
Open Label
Packaging/Appe
arance
Storage 
Conditions
(per label)
BMS-986178 Injection
25 mg/mL
(80 mg/vial)
IP
Open Label
Vial
Store at 2°C to 
8°C; do not 
freeze; 
protected from 
light.
Nivolumab Injection
10 mg/mL
(100 mg/vial)
IP
Open Label
Vial
Store at 2°C to 
8°C; store in 
original 
package; do not 
freeze; 
protected from 
light.
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Table 4-1:
Study Drugs for CA012004
Product Description 
Class and Dosage 
Form
Potency
IP/Non-IP
Blinded or 
Open Label
Packaging/Appe
arance
Storage 
Conditions
(per label)
Ipilimumab Injection
5 mg/mL
(200 mg/vial)
IP
Open Label
Vial
Store at 2°C to 
8°C; do not 
freeze; 
protected from 
light.
Tetanus vaccine
Per locala
IP
Open Label
Various 
packaging 
configurations
Refer to the 
label on 
container and/or 
package insert
UbiLT3 and UbiLT6 
vaccineb
1 mg/mL and as 
per Pharmacy 
Manual
IP
Open Label
Vial and various 
packaging 
configurations
Refer to label 
on container 
and/or package 
insert or 
pharmacy 
manual.
Abbreviations: IB = Investigator Brochure; IP = investigational product
a Tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be obtained as 
local commercial product in countries if allowed by local regulations or through investigating sites standard 
prescribing procedures.
b DPV-001 (UbiLT3 and UbiLT6) will be provided by Ubivac.
4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined as a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already with a marketing authorization but used 
or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that the investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations. 
In this protocol, the investigational products are BMS-986178, nivolumab, ipilimumab, UbiLT3 
and UbiLT6, and tetanus vaccine.
4.2
Non-Investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the SOC for a given diagnosis, may be considered as non-investigational 
products.
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Cyclophosphamide is a non-investigational product(s) in this protocol. BMS will not supply, as 
cyclophosphamide will be sourced locally by sites through investigating sites standard prescribing 
procedures.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug 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 drug arise, the study drug should not be dispensed 
and contact BMS immediately.
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets). Please 
refer to Section 9.2.2 for guidance on IP records and documentation.
BMS-986178 Preparation
Calculated dosages for solutions for infusion may be mixed in a D5W bag or normal saline (0.9% 
NaCl) bag to a recommended concentration. Further details with regard to specific concentrations 
for drug dilution and administration will be provided in the pharmacy dosing manual for 
BMS-986178.
BMS-986178 Administration
The administration of the entire bag or syringe (if syringe pump is used) contents should be infused 
over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion 
line), through an IV infusion set (sterile, non-pyrogenic diethylhexyl phthalate [DEHP]-free and 
non-DEHP free components, low protein binding, polyethersulfone or nylon 0.2-μm in line filter, 
which will be supplied by the site). Care must be taken to ensure the sterility of the prepared 
solution, as the drug product does not contain antimicrobial preservatives or bacteriostatic agents. 
Equilibration to room temperature is recommended for the drug product, infusion fluid, and their 
combination prior to administration.
Diluted solutions of BMS-986178 for injection are stable for up to 24 hours, at either refrigerated 
conditions, 2° to 8°C (36° to 46°F), and light protected; 4 hours of which can be under ambient 
temperature 15 to 25°C (59° to 77°F), and ambient light conditions. The diluted bag should not be 
shaken. Infusion of BMS-986178 injection must be completed within 24 hours of dilution. The 
start of drug infusion equals zero (0) hour.
For treatment visits in which both BMS-986178 and nivolumab are administered, nivolumab will 
be administered first followed by BMS-986178 after a minimum of 30 minutes following 
completion of the nivolumab infusion and flush. Further details regarding preparation and 
administration will be provided separately in site/pharmacy training materials and Investigator’s 
Brochure for BMS-986178.170
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For treatment visits in which both BMS-986178 and ipilimumab are administered, ipilimumab will 
be administered first followed by BMS-986178 after a minimum of 30 minutes following 
completion of the ipilimumab infusion and flush. Further details regarding preparation and 
administration will be provided separately in site/pharmacy training materials and Investigator’s 
Brochure for BMS-986178.170
For treatment visits in which BMS-986178, nivolumab, and ipilimumab are administered, 
nivolumab will be administered first followed by ipilimumab then BMS-986178. After each 
30-minute infusion, there will be a 30-minute waiting period and a flush before starting the next 
study drug infusion. Further details regarding preparation and administration will be provided 
separately in site/pharmacy manual and Investigator’s Brochure for BMS-986178.170
DRibbles Vaccine Preparation 
DPV-001 Storage and Handling
UbiLT3 and UbiLT6 DRibble vaccine is shipped under liquid nitrogen conditions and stored 
frozen at -60 ºC to -90 ºC. 
The vaccine consists of a cellular product that is enriched for autophagosomes from the UbiLT3 
and UbiLT6 cell lines and is cryopreserved in hetastarch. Packaging consists of a 1.5 mL cryovial. 
DPV-001 Preparation
The vial of UbiLT3 and/or UbiLT6 will be thawed in a 37oC (± 2oC) water bath, vortexed, loaded 
into a syringe, kept on ice and administered within 4 hours of thawing (refer to pharmacy manual 
for additional information). DPV-001 for injection should be withdrawn from vials by syringe to 
required volume, 1 mg flat dose (0.5 mg each when both UbiLT3 and UbiLT6 are given). Vaccine 
may be given as multiple injections due to volume, according to institutional policy.
Further details with regard to specific drug dispensing and administration will be provided in the 
package insert, pharmacy manual, or DPV-001 IB.53
DPV-001 Administration
The first vaccination of UbiLT3 and UbiLT6 (components of DPV-001) is administered IN under 
ultrasound guidance. 
The second vaccination of UbiLT3 and UbiLT6 is administered ID on C1D8.
On C1D15, the subjects will receive DPV-001 followed by nivolumab. DPV-001 will consist of 
only UbiLT3 1 mg ID. After the administration of UbiLT3, the subject will be administered 
nivolumab at 240 mg infusion over 30 minutes. Alternating of DPV-001 vaccine components is a 
heterologous prime-boost strategy. 
Starting at cycle 2, nivolumab will be given on day1 of each cycle as a 480 mg flat dose (q4w) 
infusion over 30 minutes. DPV-001 1 mg ID will alternate between either UbiLT3 or UbiLT6. 
UbiLT6 will be given on C2D1, C3D1, C5D1, and C9D1. UbiLT3 1 mg ID will be given on 
C2D15, C4D1, C6D1, and C12D1.
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For treatment with DPV-001, nivolumab, with or without BMS-986178, there will be a waiting 
period after DPV-001 administration of 60 minutes on C1D1 and 30 minutes for all subsequent 
doses. After the waiting period, nivolumab will then be infused over 30 minutes, followed by a 30 
minutes waiting period before BMS-986178 can be given. DPV-001 will be administered 
intranodally under ultrasound guidance on C1D1, then intradermally on C1D8 and beyond. Further 
details regarding preparation and administration will be provided separately in site/pharmacy 
manual and Investigator’s Brochure for DPV-001.53
Cyclophosphamide Administration
Commercial cyclophosphamide will be sourced locally per site prescribing procedures and 
administered IV at 300 mg/m2 over a 30 to 60 minute infusion on day -3. 
4.4
Method of Assigning Subject Identification
This is an open-label study. All enrolled subjects, including those not dosed, will be assigned 
sequential subject numbers starting with 00001, (eg, 00001, 00002, 00003... 00010). Those 
enrolled subjects meeting the inclusion and exclusion criteria will be eligible to be dosed.
Once informed consent has been obtained, the investigator (or designee) will register the subject 
by an IRT.
The following information is required for registration:
•
Gender
•
Diagnosis (if applicable)
•
Statement that subject is eligible
•
Date of informed consent
•
Date of Birth
Based on the rate of subject enrollment, the Sponsor will implement an IRT to assign subject 
numbers, study part and dose level as well as manage drug supply. IRT instructions will be 
provided to the sites in a separate instruction manual.
Treatment group/dose level will be provided to the site study team through the IRT after the subject 
has been deemed eligible and is assigned for the study. Site personnel/investigator will receive a 
receipt confirming the treatment assignment. A copy of this documentation should remain in the 
subject’s chart. Because of the nature of the study design, limited early access to the assignment 
information will be granted to the study team.
Once it is determined that the subject meets the eligibility criteria, the investigative site will register 
the subject through IRT prior to the first study drug administration. 
Subjects will be assigned to a part or a cohort within a part by IRT. Details about how the subjects 
will be assigned to a specific part/cohort will be provided in IRT training documentation.
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In the dose escalation phases, if a subject discontinues treatment with either BMS-986178, 
nivolumab, or ipilimumab during the DLT period for reasons other than a DLT, the subject may 
be replaced with a new subject, if necessary, for safety assessments. Replacement subjects will 
receive the same treatment but will be assigned a new subject number.
Additional subjects may be added to expansion cohorts and Part 8 if adequate paired pre-treatment 
and on-treatment biopsy specimens are not obtained from previously assigned subjects. The 
additional subjects will receive the same treatment as the subjects being replaced, but new subject 
numbers will be assigned.
Subjects may be permitted to rescreen for the study following agreement between the investigator 
and the Sponsor/medical monitor.
Part 9
All Part 9 participants will be randomized in a 2:1 ratio to receive either combination of BMS-
986178, nivolumab, DPV-001 vaccine, single dose cyclophosphamide (cohort 1) or combination 
of nivolumab, DPV-001 vaccine, and single dose cyclophosphamide (cohort 2).
4.5
Selection and Timing of Dose for Each Subject
Each subject will be assigned to a specific dose level as listed in Section 4.4 during dose escalation. 
Subjects in the dose expansion will be treated at the MTD, or at the RP2D, as agreed upon by the 
investigators and the Sponsor.
Nivolumab will be administered as flat doses. There will be no dose escalations or reductions of 
nivolumab allowed once assigned. There are no premedications recommended for nivolumab on 
the first cycle. If an acute infusion reaction is noted, the subjects should be managed according to 
Section 4.5.7.
Ipilimumab will be administered at 1 or 3 mg/kg. There will be no dose escalations or reductions 
of ipilimumab allowed once assigned. There are no premedications recommended for ipilimumab 
on the first cycle. If an acute infusion reaction is noted, the subjects should be managed according 
to Section 4.5.7.
There will be no dose escalations or reductions of DPV-001 allowed once assigned.
There will be no dose escalations or reductions of BMS-986178 allowed once assigned.
4.5.1
Dose Limiting Toxicity
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence, severity, 
and duration of AEs, for which no clear alternative cause is identified and that occur within 28 days
of initiation of study drug(s). AEs will be graded according to the NCI CTCAE v4.03.
For the purpose of subject management, potential DLTs that occur at any time, whether during 
dose escalation or dose expansion, will result in all study drug(s) being held pending evaluation of
the event’s relatedness to study drug, severity, duration, and in accordance with Section 4.5.4. 
Subjects must meet criteria for treatment prior to re-initiation of study treatment (see 
Section 4.5.5).
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For the purpose of subject management, an AE that meets the DLT criteria, regardless of the cycle 
in which it occurs, will lead to discontinuation of study drug(s) except for exceptions as outlined 
in Section 4.5.6. Such subjects will not be retreated with study drug(s) and will enter the Safety 
Follow-up period of the study.
Subjects who withdraw from the study during the DLT evaluation interval for reasons other than 
a DLT may be replaced with a new subject at the same dose level. The incidence of DLT(s) during 
the DLT evaluation period will be used in dose escalation decisions and to define the MTD. All 
AEs for which no clear alternative cause is identified occurring after the 28-day DLT period may 
be considered to represent DLTs for the purposes of defining the RP2D upon agreement between 
the Sponsor, medical monitor, and investigators, if they are determined to have no clear alternative 
cause and not related to disease progression. DLT criteria will be utilized for the evaluation of a 
manageable and tolerable dose in the schedule and dose exploration parts (Parts 4, 5, and 8) and 
safety cohorts (Parts 6A and 7A).
Any one of the following events for which an alternative cause cannot be identified will be 
considered a DLT:
A. Hepatic DLT
•
Any ≥Grade 3 elevation of AST, ALT, or total bilirubin
•
Grade 2 AST or ALT with symptomatic liver inflammation (eg, right upper quadrant 
tenderness, jaundice, pruritus)
•
AST or ALT > 3 × ULN and concurrent total bilirubin > 2 × ULN without initial findings of 
cholestasis (elevated serum alkaline phosphatase (eg, findings consistent with Hy’s law or 
FDA definition of potential drug-induced liver injury [pDILI]) (Note that this special category 
of DLT uses ULN rather than CTC Grade for definition.)
B. Non-hepatic DLT
•
Grade 2 or greater uveitis, episcleritis, or iritis
•
Any other Grade 2 eye pain or blurred vision that does not respond to topical therapy and does 
not improve to Grade 1 severity within 2 weeks OR requires systemic treatment 
•
Grade 3 or greater pneumonitis, bronchospasm, neurologic toxicity, hypersensitivity reaction, 
or infusion reaction 
•
Any Grade 3 or greater non-dermatologic, non-hepatic toxicity will be considered a DLT with 
the following specific EXCEPTIONS:
♦Grade 3 or Grade 4 electrolyte abnormalities that are not complicated by associated 
clinical adverse experiences, last less than 72 hours, and either resolve spontaneously 
or respond to conventional medical intervention
♦Grade 3 nausea, vomiting, or diarrhea that lasts less than 72 hours, and either resolves 
spontaneously or responds to conventional medical intervention
♦Grade 3 or 4 elevation of amylase or lipase not associated with clinical or radiographic 
evidence of pancreatitis
♦Isolated 
Grade 
3 
fever 
not 
associated 
with 
hemodynamic 
compromise 
(eg, hypotension, clinical, or laboratory evidence of impaired end-organ perfusion)
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♦Grade 3 endocrinopathy that is well controlled by hormone replacement
♦Grade 3 tumor flare (defined as pain, irritation, or rash that localizes to sites of known 
or suspected tumor)
♦Grade 3 fatigue for ≤7 days
♦Grade 3 infusion reaction that returns to Grade 1 in less than 6 hours
C. Dermatologic DLT
•
Grade 4 rash
•
Grade 3 rash if no improvement (ie, resolution to ≤Grade 1) after a 1- to 2-week infusion 
delay. Subjects who have not experienced a Grade 3 skin AE may resume treatment in the 
presence of Grade 2 skin toxicity.
D. Hematologic DLT
•
Grade 4 neutropenia ≥7 days in duration
•
Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant bleeding, 
or any requirement for platelet transfusion
•
Grade 4 anemia not explained by underlying disease
•
Grade ≥3 febrile neutropenia
•
≥Grade 3 hemolysis (ie, requiring transfusion or medical intervention such as steroids)
4.5.2
Management Algorithms for Immuno-Oncology Agents
IO agents are associated with AEs that can differ in severity and duration from AEs caused by 
other therapeutic classes. Nivolumab, ipilimumab, and BMS-986178 are considered IO agents in 
this protocol. Early recognition and management of AEs associated with IO agents may mitigate 
severe toxicity. Management algorithms in Appendix 2 have been developed from extensive 
experience with nivolumab and ipilimumab to assist investigators in assessing and managing the 
following groups of AEs:
•
Gastrointestinal
•
Renal
•
Pulmonary
•
Hepatic
•
Endocrinopathies
•
Skin
•
Neurological
•
Myocarditis
•
The clinical nature of AEs noted with BMS-986178 will determine the role of the above 
algorithms for use in toxicities related to its use in this study. 
The algorithms recommended for utilization in this protocol are included in Appendix 2.
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4.5.3
Guidelines for Dose Modification
Intra-subject dose escalation or reduction of BMS-986178, nivolumab, ipilimumab, or DPV-001
is not permitted in this study in order to allow better evaluation of the extended safety and efficacy 
at individual dose levels and schedules.
4.5.4
Dose Delays due to Toxicity 
Subjects who experience the following must have all study drug(s) held:
•
Potential DLTs, until DLT relatedness is defined.
•
Select AEs and laboratory abnormalities: 
−
≥Grade 1 pneumonitis
−
≥Grade 2 abnormality in AST, ALT, total bilirubin 
−
≥Grade 2 creatinine
−
≥Grade 2 non-skin, drug related AE, with the exception of fatigue
−
≥Grade 2 diarrhea or colitis
−
≥Grade 2 neurological AE 
−
Grade 2 myocarditis
−
Grade 4 amylase and/or lipase abnormalities regardless of symptoms or clinical 
manifestation. (Grade 3 amylase or lipase increase that is not associated with symptoms or 
clinical manifestations of pancreatitis does not require dose delay)
•
AE, laboratory abnormality, or concurrent illness that, in the judgment of the Investigator, 
warrants delaying the dose of study drug.
•
Confirmed SARS-CoV-2 infection.
If a dose delay is necessary for subjects who are receiving study treatment, all study drugs must 
be held. Dosing visits are to be delayed but not skipped to ensure that subjects will receive all 
scheduled treatment cycles if toxicity allows. During treatment, dosing will be as follows:
•
Part 2 subjects will receive 12 doses (12 cycles) of q2w BMS-986178 and nivolumab 
combination therapy.
•
Parts 3 and 5 subjects will receive up to 4 doses of q3w BMS-986178 and ipilimumab 
combination therapy and 4 doses of q3w BMS-986178 monotherapy during maintenance.
•
Part 4 subjects will receive 6 doses (6 cycles) of q4w BMS-986178 and nivolumab 
combination therapy.
•
Part 6 subjects will receive 4 doses of q3w BMS-986178, nivolumab, and ipilimumab 
combination therapy and 3 doses of q4w BMS-986178 and nivolumab during maintenance.
•
Part 7 subjects will receive 4 cycles (1 cycle = 6 weeks) of q2w BMS-986178 and nivolumab 
and q6w ipilimumab combination therapy.
•
Part 8
−
Cohorts 1-3 subjects will receive 9 doses of BMS-986178 (q12w) and 27 doses of 
nivolumab (q4w) combination therapy.
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Cohort 4 subjects will receive 27 doses of nivolumab (q4w) monotherapy.
•
Part 9
−
Cohort 1 subjects will receive 8 doses of BMS-986178 on Day 1 of Cycle 1-6, Cycle 9, 
and Cycle 12; 26 doses of nivolumab (Cycle 1 flat dose, q4w starting at Cycle 2); 11 doses 
of DPV-001 (UbiLT3 and/or UbiLT6), and a single dose of cyclophosphamide.
−
Cohort 2 subjects will receive 26 doses of nivolumab (Cycle 1 flat dose, q4w starting at 
Cycle 2); 11 doses of DPV-001 (UbiLT3 and/or UbiLT6), and a single dose of 
cyclophosphamide.
Subjects receiving BMS-986178 in combination with nivolumab, nivolumab and ipilimumab, or 
nivolumab and DPV-001 who have study treatment-related toxicities that meet the criteria for a 
dose delay should have all study drugs held until the criteria to resume treatment are met (see 
Section 4.5.5). Subjects who require a dose delay should be re-evaluated weekly, or more 
frequently if clinically indicated, and resume treatment when criteria are met. Continue tumor 
assessments per protocol even if dosing is delayed. Because nivolumab-, ipilimumab- and/or 
BMS-986178-related AEs require early recognition and prompt intervention, management 
algorithms have been developed for suspected pulmonary toxicity, gastrointestinal toxicity, 
hepatotoxicity, endocrinopathy, skin toxicity, neurological toxicity, and renal toxicity (algorithms 
are provided in Appendix 2).
For subjects who have dose delays in Parts 1-7, the total study treatment period should not exceed 
36 weeks, unless approved by the BMS Medical Monitor (or designee). Parts 8 and 9 will have a 
treatment period up to a maximum of 24 months of dosing from first dose regardless of treatment 
delays. Extensions to the period of dose delays may be granted for individual subjects on a case 
by case basis after specific consultation and agreement between the investigator and BMS medical 
monitor in settings where risk/benefit may justify continued study therapy (eg, subject deriving 
clinical benefit who requires prolonged steroid taper for the management of non-DLT drug-related 
AEs, or experiences delays for the management of a non-drug-related AE).
The end of cycle tumor assessments (ie, CT/MRI, etc) will continue every 8 weeks Parts 1-7 and 
9 or every 12 weeks Part 8 (± 1 week) relative to the subject’s first dose of BMS-986178, regardless 
of any treatment delay incurred.
4.5.5
Criteria to Resume Treatment
4.5.5.1
Criteria to Resume Treatment in Subjects with a Dose Delay
If a dose delay is necessary for subjects who are receiving study treatment, all study drugs must 
be held.
Subsequent dosing with study therapy may resume once non-DLT AEs resolve to Grade 1 or 
baseline. 
Subjects experiencing AEs not meeting the criteria for permanent discontinuation as outlined in 
Section 4.5.6 may resume treatment with study medication under the following criteria:
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•
Subjects may resume treatment with study drug when the AE(s) resolve to Grade ≤1 or 
baseline value with the following exceptions:
−
Subjects may resume treatment in the presence of Grade 2 fatigue.
−
Subjects who have not experienced a Grade 3 skin AE may resume treatment in the 
presence of Grade 2 skin toxicity.
−
Subjects with Grade 2 eye pain or blurred vision not meeting DLT criteria (Section 4.5.1) 
must resolve to baseline prior to resuming study therapy.
−
Any pulmonary toxicity, diarrhea, or colitis must have resolved to baseline before 
treatment is resumed. Subjects with persistent Grade 1 pneumonitis after completion of a 
steroid taper over at least 1 month may be eligible for resumption of treatment if discussed 
with and approved by BMS Medical Monitor (or designee).
−
Subjects with endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment after consultation with the BMS Medical Monitor (or 
designee). Adrenal insufficiency requires discontinuation regardless of control with 
hormone replacement.
−
For subjects with Grade 2 AST, ALT and/or total bilirubin abnormalities, dosing may 
resume when laboratory values return to baseline and management with corticosteroids, if 
needed, is complete.
−
Subjects with a Grade 4 amylase or lipase increase that is not associated with symptoms or 
clinical manifestations of pancreatitis can be restarted on therapy once the levels have 
decreased to Grade 3 or lesser - and after consultation with the BMS Medical Monitor.
•
If study treatment is delayed past the scheduled dosing visit per protocol, the scheduled study 
treatment administration will be delayed, but not skipped, until dosing resumes to ensure that 
subjects will receive all scheduled treatment cycles if toxicity allows.
•
The consideration to re-initiate study therapy under these exceptions will be made on a case 
by case basis after considering the overall risk/benefit profile and in consultation between the 
investigator and the study Sponsor. Any AE with clinical risk will be assessed on a case by 
case basis with the investigator and the BMS Medical Monitor to determine the risks and 
benefits of continuing on therapy following resolution versus discontinuing therapy 
permanently. 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.
•
If dosing is delayed ≥9 weeks, the subject must be permanently discontinued from study 
treatment, except as specified in Section 4.5.6. Extensions to the period of dose delays may be 
granted for individual subjects on a case by case basis after specific consultation and agreement 
between the investigator and BMS medical monitor in settings where risk/benefit may justify 
continued study therapy (eg, subject deriving clinical benefit who requires prolonged steroid 
taper for the management of non-DLT immune-related AEs, or experiences delays for 
management of a non-drug-related AE).
•
Dosing delays to allow prolonged steroid tapers to manage AEs are allowed. Additionally, 
dosing delays ≥9 weeks (as noted above) that occur for non-drug-related reasons may be 
allowed if approved by the BMS Medical Monitor.
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If the toxicity resolves to ≤Grade 1 or baseline > 9 weeks after the last dose, the subject does 
not meet the criteria for permanent discontinuation (see Section 4.5.6), and the investigator 
believes that the subject is deriving clinical benefit, the subject may be eligible to resume study 
treatment(s) following approval from the BMS Medical Monitor (or designee).
•
Tumor assessments should continue as per protocol even if dosing is delayed.
•
Participants with confirmed SARS-CoV-2 infection may resume treatment after 1) at least 10 
days (20 days for severe/critical illness) have passed since symptoms first appeared, positive 
RT-PCR test result, or positive viral antigen test result, 2) resolution of acute symptoms 
(including at least 24 hours has passed since last fever without fever reducing medications), 3) 
evaluation by the investigator with confirmation that there are no sequelae that would place 
the participant at a higher risk of receiving investigational treatment, and 4) consultation by 
the medical monitor. For suspected cases, treatment may also resume if SARS-CoV-2 infection
is ruled out and other criteria to resume treatment are met.
•
Prior to re-initiating on-study treatment in a subject with a dosing delay due to SARS-CoV-2 
infection, the medical monitor must be consulted.
4.5.5.2
Criteria for Resuming Treatment in Subjects with an Infusion Reaction
In subjects experiencing an infusion reaction with study drug administration, the following 
guidelines for dose delay and criteria to resume treatment are to be followed:
•
Parts 2, 4, 6, 7, 8, and 9 on days with administration of BMS-986178 and nivolumab only: If 
a nivolumab-related infusion reaction prevents subsequent infusion of BMS-986178 on the 
same day, the dose of BMS-986178 should be replaced as soon as possible. In such instances, 
at least 12 days must elapse between the replacement dose of BMS-986178 and the 
administration of the next dose of nivolumab combined with BMS-986178.
•
Parts 3 and 5: If an ipilimumab-related infusion reaction prevents subsequent infusion of 
BMS-986178 on the same day, the dose of BMS-986178 should be replaced as soon as 
possible. In such instances, at least 19 days must elapse between the replacement dose of 
BMS-986178 and the administration of the next dose of ipilimumab combined with 
BMS-986178 on a q3w schedule.
•
Parts 6 or 7: If a nivolumab-related infusion reaction prevents subsequent infusion of 
ipilimumab and/or BMS-986178 on the same day, the dose of ipilimumab and BMS-986178 
should be replaced as soon as possible. In such instances, at least 19 days must elapse between 
the replacement dose of ipilimumab and the administration of the next dose of BMS-986178 
and nivolumab combined with ipilimumab on a q3w schedule. However, if an ipilimumab-
related infusion reaction prevents subsequent infusion of BMS-986178 on the same day, the 
dose of BMS-986178 should be replaced as soon as possible. In such instances, at least 19 days 
must elapse between the replacement dose of BMS-986178 and the administration of the next 
dose of BMS-986178 and nivolumab combined with ipilimumab.
Guidelines for management of an infusion reaction during study drug administration are included 
in Section 4.5.7.
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4.5.6
Guidelines for Permanent Discontinuation
Subjects will be required to permanently discontinue all study drugs for the following AEs:
•
Progressive Disease (see also Section 3.5.1 for details regarding continuing treatment beyond 
disease progression)
•
Clinical deterioration, as assessed by the investigator
•
Grade 3 infusion reaction that does not return to Grade 1 in less than 6 hours
•
Grade 3 or greater pneumonitis, bronchospasm, myocarditis, neurologic toxicity, or cytokine 
release syndrome (i.e. systemic inflammatory response syndrome)
•
Life-threatening skin toxicity (toxic epidermal necrolysis)
•
Grade 2 or greater episcleritis, or iritis. Any Grade 2 or greater drug-related uveitis, eye pain 
or blurred vision that does not respond to topical therapy and does not improve to Grade 1 
severity within the re-treatment period OR requires systemic treatment.
•
Any Grade 4 AE; however, an exception may be made for the following upon consultation 
between the investigator and BMS medical monitor:
−
Grade 4 electrolyte abnormalities ≤72 hours in duration
−
Grade 4 neutropenia ≤7 days in duration
−
Grade 4 lymphopenia or leukopenia.
−
Grade 4 increase in amylase or lipase that is not associated with clinical or radiographic 
evidence of pancreatitis
−
Grade 4 drug-related endocrinopathy adverse events, such as, hyper- or hypothyroidism, 
or glucose intolerance, which resolve or are adequately controlled with physiologic 
hormone replacement (corticosteroids, thyroid hormones) or glucose-controlling agents, 
respectively, may not require discontinuation after discussion with and approval from the 
BMS Medical Monitor.
•
Any toxicity that meets DLT criteria as defined in Section 4.5.1; however, an exception may 
be made on a case-by-case basis upon consultation between the investigator and BMS medical 
monitor:
−
Grade 3 diarrhea, nausea, vomiting, or abdominal pain that returns to Grade 1 or baseline 
within 3 days with medical intervention
−
AST or ALT > 5× and < 8× institutional ULN for < 2 weeks
−
Grade 3 pruritus or rash that returns to Grade 1 or baseline within 7 days with medical 
intervention
The consideration to re-initiate study therapy under these exceptions will be made on a 
case-by-case basis after considering the overall risk/benefit profile and in consultation 
between the investigator and the Sponsor.
•
Confirmed CR
•
Completion of 24 weeks of treatment (Parts 1-7) or 24 months for Parts 8 and 9. Subjects in 
Part 2, 4 6, or 7 that continue for additional cycles up to 24 months of treatment.
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All subjects who discontinue study drug(s) should comply with protocol-specified follow-up 
procedures as outlined in Section 5.1. The only exception to this requirement is when a subject 
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 a 
psychiatric or physical illness).
If study treatment is discontinued prior to the subject’s completion of treatment, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate CRF page.
4.5.7
Treatment of Drug-Related Infusion Reactions
Since BMS-986178, nivolumab, and ipilimumab contain only human immunoglobulin protein 
sequences, they are unlikely to be immunogenic and induce infusion or hypersensitivity reactions.
However, if an infusion reaction or a hypersensitivity reaction were to occur, it might manifest 
with fever, chills, rigors, headache, rash, pruritus, arthralgias, hypo- or hypertension, 
bronchospasm, or other symptoms. All Grade 3 or 4 infusion reactions should be reported within 
24 hours to the BMS Medical Monitor and reported as an SAE if criteria are met. Infusion reactions 
should be graded according to NCI CTCAE v4.03 guidelines and reported on the appropriate CRF.
Treatment recommendations are provided below and may be modified based on local treatment 
standards and guidelines as appropriate:
For Grade 1 symptoms: Mild reaction; infusion interruption not indicated; intervention not
indicated.
•
Remain at bedside and monitor subject until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg, to be given at least 
30 minutes before additional study drug administrations.
For Grade 2 symptoms: Moderate reaction; requires therapy or infusion interruption but 
responds promptly to symptomatic treatment [eg, antihistamines, non-steroidal 
anti-inflammatory 
drugs, 
narcotics, 
corticosteroids, 
bronchodilators, 
IV 
fluids]; 
prophylactic medications indicated for ≤24 hours.
•
Stop the drug being infused (either BMS-986178, nivolumab, or ipilimumab infusion), begin 
an IV infusion of normal saline, and treat the subject with diphenhydramine 50 mg IV (or 
equivalent) and/or paracetamol 325 to 1000 mg (acetaminophen); monitor subject until 
resolution of symptoms.
•
Bronchodilator or corticosteroid therapy may also be administered as appropriate.
•
The infusion may be restarted at 50% of the original infusion rate when symptoms resolve; if 
no further complications ensue after 30 minutes, the rate may be increased to 100% of the 
original infusion rate. Monitor subject closely.
•
The amount of study drug infused must be recorded on the CRF.
•
If symptoms recur, then no further dosing with the relevant drug and/or subsequent drug, as 
the case may be, will be administered at that visit.
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•
The following prophylactic premedications are recommended for future infusions: 
diphenhydramine 50 mg (or equivalent) and/or paracetamol 325 to 1000 mg (acetaminophen) 
should be administered at least 30 minutes before additional BMS-986178, nivolumab, or 
ipilimumab administrations (whichever caused the reaction). If necessary, corticosteroids (up 
to 25 mg of SoluCortef or equivalent) may be used.
For Grade 3 or Grade 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 other clinical sequelae 
[eg, renal impairment, pulmonary infiltrates]. Grade 4: life-threatening; pressor or 
ventilatory support indicated. 
•
Immediately discontinue study drug infusion. Begin an IV infusion of normal saline and treat 
the subject as follows. Recommend bronchodilators, epinephrine 0.2 to 0.5 mg 
(1:1,000 solution) for intramuscular administration or 0.1 to 0.25 mg (1:10,000 solution) 
injected slowly for IV administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed. Subject should be monitored until 
the investigator is comfortable that the symptoms will not recur. Study drug(s) will be 
permanently discontinued. Investigators should follow their institutional guidelines for the 
treatment of anaphylaxis. Remain at bedside and monitor subject until recovery from 
symptoms. In the 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).
Late-occurring Symptoms:
In the 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).
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Study drug will be administered in the clinical facility by trained medical personnel. The 
investigator and the study personnel will ensure that each subject receives the prescribed dose of 
study drug. Treatment compliance will be monitored by drug accountability as well as by recording 
BMS-986178, nivolumab, and/or ipilimumab administration in subjects’ medical records and 
CRFs.
Drug supplies will be inventoried and accounted for throughout the study. The Drug 
Accountability Log will be reviewed by the study monitor during site visits and at the completion 
of the study. Any discrepancy should be brought to the attention of the Sponsor.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as partially 
used study drug containers, vials, and syringes may be destroyed on site.
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Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible BMS study monitor unless study drug containers must be immediately destroyed as 
required for safety or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:
•
On-site disposal practices must not expose humans to risks from the drug.
•
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
•
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s standard operating procedures (SOPs) and a copy provided to BMS upon 
request.
•
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, (ie, incinerator, licensed sanitary landfill, or licensed waste disposal 
vendor) must be documented.
•
Accountability and disposal records are complete, up-to-date, and available for the monitor to 
review throughout the clinical trial period.
If conditions for on-site destruction cannot be met, the responsible BMS study monitor will make 
arrangements for the return of study drug to the Sponsor.
It is the investigator’s responsibility to arrange for disposal of all empty containers, 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.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused and/or 
partially used study drug that was supplied by BMS must be returned to BMS. The return of study 
drug will be arranged by the responsible study monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, 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. 
4.10
Retained Samples for Bioavailability/Bioequivalence
Not Applicable.
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Study assessments and procedures are presented in Table 5.1-1, Table 5.1-2, Table 5.1-3, Table 
5.1-4, Table 5.1-5, Table 5.1-6, Table 5.1-7, Table 5.1-8, and Table 5.1-9. In limited instances, 
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scheduled events can occur outside of the indicated timeframes; BMS should be notified of these 
instances.
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Table 5.1-1:
Screening Procedural Outline (CA012004) - Parts 1 - 9
Procedure
Screening
Visit
(-28 day 
to -1 Visit)
D -14 to -1
Visit
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed consent is 
signed. Must be obtained prior to performing any screening procedures.
Inclusion/Exclusion Criteria
X
Must be confirmed prior to randomization or treatment assignment.
Medical History
X
Include any toxicities or allergy related to previous treatments.
Prior Cancer Therapies
X
ECOG Performance Status
X
See Appendix 4.
Archived Tumor Tissue Sample
X
An archival, FFPE tumor tissue block, or slide samples (a minimum of 15 unstained 
slides [25 preferred]), may be provided by all subjects. Samples should be shipped to 
the central laboratory. 
Fresh Pre-treatment Tumor Biopsy
X
All subjects require a mandatory pre- and on-treatment biopsy.
Archival specimens may not be substituted for fresh baseline specimens but can be 
submitted to help understand the evolution of the tumor (ie, PD-L1 expression 
changes over time). For part 9, please refer to section 3.3.1-2)-2)(h)(ii)
Fecal Microbiome (Part 9 Only)
X
Subjects will receive kit during visit, collect sample at home and return to site.
Blood PD, Blood Genotype, and 
Blood TCR
X
Safety Assessments
Physical Examination (PE)
X
If the screening PE is performed within 24 hours prior to dosing on D1, then a single 
exam may count as both the screening and predose evaluations.
Physical Measurements
X
Includes height and weight.
Vital Signs
X
Includes body temperature, respiratory rate, seated blood pressure, and heart rate. 
Oxygen Saturation
X
Pulse oximetry collected at rest.
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anti-OX40 mAb
Table 5.1-1:
Screening Procedural Outline (CA012004) - Parts 1 - 9
Procedure
Screening
Visit
(-28 day 
to -1 Visit)
D -14 to -1
Visit
Notes
Electrocardiogram (ECGs)
X
ECGs should be recorded after the subject has been supine for at least 5 minutes.
All ECG tests should be performed as a single measurement. 
Laboratory Tests
Laboratory tests listed below must be completed within 2 weeks of D1 unless otherwise noted.
Serology
X
Within 28 days of dosing, if required: Hep B surface antigen, and Hep C antibody (if 
Hep C antibody is positive reflex to Hep C RNA), or Hep C RNA.
Note: Testing for HIV-1 and HIV-2 must be performed at sites where mandated by 
local requirements.
Chemistry (Excluding LFTs)
X
See Section 5.3.2. Includes assessments for sodium, potassium, chloride, total serum 
calcium, magnesium, carbon dioxide, phosphorus, BUN, creatinine, creatinine 
clearance, fasting glucose, total protein, albumin, amylase, lipase, uric acid, ferritin, 
CRP, and LDH.
CBC with Differential and Platelets
X
LFT Assessment
X
See Section 5.3.2.
Urinalysis
X
See Section 5.3.2.
Thyroid Function Tests (TFTs)
X
TSH with free T3 and free T4.
Genetic Mutations
X
See Section 5.7. Collected as part of the medical history on appropriate CRF
Tumor Markers (Serum)
X
CA125, AFP, CEA, CA19-9, and PSA for all subjects
Pregnancy Test
X
For WOCBP only; serum will be collected at screening and within 24 hours prior to 
dosing. The serum pregnancy test may be completed on the first day of treatment, 
provided the results are available before the start of study therapy.
If performed within 24 hours of dosing on C1D1, then C1D1 pregnancy test is not 
required.
Follicle Stimulating Hormone (FSH)
X
If needed to document post-menopausal status as defined in Section 3.3.3.
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anti-OX40 mAb
Table 5.1-1:
Screening Procedural Outline (CA012004) - Parts 1 - 9
Procedure
Screening
Visit
(-28 day 
to -1 Visit)
D -14 to -1
Visit
Notes
Adverse Event Reporting
Clinical Complaints
X
Collected during the 2 weeks prior to C1D1.
Monitor for Serious Adverse Events
and any AEs (SAEs or non-serious 
AEs) associated with SARS-CoV-2 
infection
X
All SAEs must be collected from the date of the subject’s written consent until 100 days
of discontinuation of dosing. SAEs should be approved in eCRF directly within 5 
business days of entry.
Efficacy Assessments
Tumor Assessments
X
CT with contrast is the preferred modality (MRI if CT is not feasible). Assessment 
should include the chest/abdomen/pelvis at a minimum and should include other 
anatomic regions as indicated by individual subject disease histories.
Brain Imaging
X
Brain imaging (CT/MRI) for subjects with history or symptoms of brain metastases and 
who have not had brain imaging within 30 days of anticipated first study drug 
administration.
Bone Scan
X
As clinically indicated (eg, subjects with history or symptoms of bone metastases), but 
bone scans will not be considered a modality for the assessment for measurable disease.
IRT Subject Assignment/ Treatment 
Assignment
X
X
After the subject consents, the sites will use the IRT to have the subject number 
assigned. After the subject has completed all screening procedures, IRT will be used for 
treatment assignment or discontinuing the subject. Subsequent visits will need to be 
registered into the IRT system for drug supply. Participant must receive the first dose of 
study medication within 3 calendar days from treatment/cohort assignment.
Abbreviations: AFP = alpha fetal protein; BUN = blood urea nitrogen; C = Cycle; CEA = carcinoembryonic antigen; CBC = complete blood count; CRC = 
colorectal cancer; CRF = case report form; CRP = C-reactive protein; CT = computed tomography; D = Day; ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group; FFPE = formalin-fixed, paraffin-embedded; HIV = human immunodeficiency virus; HPV = Human papillomavirus; IRT = 
Interactive Response Technology; LDH = lactic acid dehydrogenase; LFT =liver function test; MSI = microsatellite instability; MRI = magnetic resonance imaging; 
PD = pharmacodynamic; PSA = Prostate-Specific Antigen; RNA = ribonucleic acid; T3 =triiodothyronine; T4 = thyroxine; TCR = T-cell receptor; TSH = thyroid-
stimulating hormone; WOCBP = women of child bearing potential.
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Table 5.1-2:
On Treatment Procedural Outline Parts 1 and 2 (CA012004 - q2w Dosing)
(C1-C12, 
Additional Cycles)
Cycle = 2 Weeks
C1
C2-C8 
C9 
C10 - beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D1
D1
D1
EOTa,b,c
Notesd
Safety Assessments
Physical 
Examination (PE)
X
X
Predose (C1 only); See note in screening.
Symptom-directed 
PE
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only
Vital Signs 
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion 
C1D1 and C2D1
12-Lead 
Electrocardiogram 
(ECG) 
X
X
All ECG tests should be performed as a 
single measurement.
ECGs will be done at both predose and 4 
hours when BMS-986178 PK sample is 
collected (ECGs should be done prior to the 
PK sample) at C1D1 and C9D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
Collect on C1D1, C1D2 and C1D8 and 
every cycle D1
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
LFT Assessment
X
X
X
X
X
X
X
AST, ALT, ALP, and T. Bilirubin. Direct 
Bilirubin (only if T. Bilirubin is elevated); 
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anti-OX40 mAb
Table 5.1-2:
On Treatment Procedural Outline Parts 1 and 2 (CA012004 - q2w Dosing)
(C1-C12, 
Additional Cycles)
Cycle = 2 Weeks
C1
C2-C8 
C9 
C10 - beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D1
D1
D1
EOTa,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-1 for specific samples at each cycle during the study
Serial Serum PK 
Sampling for BMS-
986178 
See Table 5.5.1-1for specific samples at each cycle during the study.
BMS-986178 ADA 
Sample
See Table 5.5.1-1 for specific samples at each cycle during the study
Serial Serum PK 
Sampling for 
Nivolumab (Part 2 
Only) 
See Table 5.5.1-1 for specific samples at each cycle during the study
Nivolumab ADA 
Sample (Part 2 Only)
See Table 5.5.1-1 for specific samples at each cycle during the study
Biomarker 
Assessments
See Table 5.6-1 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-1 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-1 for specific samples at each cycle during the study.
PBMC
See Table 5.6-1 for specific samples at each cycle during the study.
Blood 
Multiparameter Flow
See Table 5.6-1 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-1 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-1 for specific samples at each cycle during the study.
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Table 5.1-2:
On Treatment Procedural Outline Parts 1 and 2 (CA012004 - q2w Dosing)
(C1-C12, 
Additional Cycles)
Cycle = 2 Weeks
C1
C2-C8 
C9 
C10 - beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D1
D1
D1
EOTa,b,c
Notesd
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-1 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-1 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. Same modality 
should be used for all assessments. Assessed 
by RECIST v1.1; see Appendix 3.
Assessment to be performed prior to 
initiating next cycle of treatment.
An unconfirmed PR or unconfirmed CR 
must be confirmed at least 4 weeks after 
initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
Parts 1 and 2
BMS-986178
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Part 2 ONLY
Nivolumab (240 mg 
Flat Dose)
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
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= Prostate-Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; 
T4 = thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C12D14) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For these treatment groups, 1 cycle = 2 weeks, up to 12 cycles of dosing. Subjects who 
have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). For nivolumab, vital signs will be obtained before 
the infusion and then every 30 minutes (± 10 minutes) until the start of BMS-986178 infusion or per institution guidelines for administration of nivolumab. The 
30-minute post nivolumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event BMS-986178 administration is delayed, nivolumab 
vital signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, 
the subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
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Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Safety Assessments
Physical 
Examination (PE)
X
X
Predose (C1 Only)
See note in screening
Symptom-directed 
PE
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only 
Vital Signs
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion 
C1D1 and C2D1 
12-Lead 
Electrocardiogram 
(ECGs)
X
X
All ECG tests should be performed as a 
single measurement. 
ECGs will be done at both predose and 4 
hours when BMS-986178 PK sample is 
collected (ECGs should be done prior to the 
PK sample) at C1D1 and C4D1. 
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
Collect on C1D1, C1D2, C1D8, and C1D15, 
and every cycle D1
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
LFT Assessment
X
X
X
X
X
X
X
X
AST, ALT, ALP, and T. Bilirubin. Direct 
Bilirubin (only if T. Bilirubin is elevated); 
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-3
Serial Serum PK 
Sampling 
BMS-986178 
Refer to Table 5.5.1-3.
BMS-986178 ADA 
Sampling
Refer to Table 5.5.1-3.
Serial Serum PK 
Sampling for 
Ipilimumab 
Refer to Table 5.5.1-3.
Ipilimumab ADA 
sampling 
Refer to Table 5.5.1-3.
Biomarker 
Assessments
See Table 5.6-2 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-2 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-2 for specific samples at each cycle during the study.
PBMC
See Table 5.6-2 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow
See Table 5.6-2 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-2 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-2 for specific samples at each cycle during the study.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-2 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-2 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor Assessments 
Every 8 weeks (± 1 week)
Note: If subject completes 24 weeks of dosing, C8D21 will be the last
cycle visit (EOT), this will be at Week 25, and the 27-week scan should 
be done at this time.
X
By methods used at baseline. Same modality 
should be used for all assessments孱Assessed 
by RECIST v1.1; see Appendix 3. 
Assessment to be performed prior to 
initiating next cycle of treatment.
An unconfirmed PR or unconfirmed CR 
must be confirmed at least 4 weeks after 
initial assessment. 
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
X
X
X
X
All subjects
Supplied by BMS
Use vials assigned per IRT
Part 3
Ipilimumab 
(1 mg/kg)
X
X
X
Supplied by BMS
Use vials assigned per IRT 
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-3:
On Treatment Procedural Outline Parts 3 and 5 (CA012004 - q3w Dosing)
(C1-C8, Additional 
Cycles)
Cycle = 3 weeks
C1 
C2-C3
C4
C5-
beyond 
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
EOTa,b,c
Notesd
Part 5
Ipilimumab 
(3 mg/kg)
X
X
X
Supplied by BMS
Use vials assigned per IRT 
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; BMS = Bristol-Myers Squibb; C=Cycle; CBC = complete blood count; CEA = 
carcinoembryonic antigen; CR = complete response; CRC = colorectal cancer; D = Day; ECG = electrocardiogram; EOT = end of treatment; LFT = liver function 
test; IRT = Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; 
PSA = Prostate-Specific Antigen; RNA = ribonucleic acid; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; VS 
= vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C8D21) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For these treatment groups 1 cycle = 3 weeks, up to 8 cycles of dosing. Subjects who 
have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
then every 30 minutes (± 10 minutes) until the start of BMS-986178 infusion or per institution guidelines for administration of ipilimumab. The 30-minute post 
ipilimumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event BMS-986178 administration is delayed, ipilimumab vital signs will 
be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the subject must 
be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-4:
On Treatment Procedural Outline Part 4, (CA012004 - q4w Dosing)
(C1-C6, 
Additional Cycles)
Cycle = 4 weeks
C1 
C2-C4
C5
C6-
beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D15
D1
D1
EOTa,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
Predose (C1 only). See note in screening.
Symptom-directed 
PE
X
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion C1D1 and 
C2D1 
12-Lead 
Electrocardiogram 
(ECGs)
X
X
All ECG tests should be performed as a single 
measurement.
ECGs will be done at both predose and 4 hours 
when BMS-986178 PK sample is collected (ECGs 
should be done prior to the PK sample) at C1D1 and 
C5D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
X
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-4:
On Treatment Procedural Outline Part 4, (CA012004 - q4w Dosing)
(C1-C6, 
Additional Cycles)
Cycle = 4 weeks
C1 
C2-C4
C5
C6-
beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D15
D1
D1
EOTa,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-2 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling 
BMS-986178
See Table 5.5.1-2 for specific samples at each cycle during the study.
BMS-986178 ADA 
Sample
See Table 5.5.1-2 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab
See Table 5.5.1-2 for specific samples at each cycle during the study.
Nivolumab ADA 
Sampling
See Table 5.5.1-2 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-3 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-3 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-3 for specific samples at each cycle during the study.
PBMC
See Table 5.6-3 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow 
See Table 5.6-3 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-3 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-3 for specific samples at each cycle during the study.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-4:
On Treatment Procedural Outline Part 4, (CA012004 - q4w Dosing)
(C1-C6, 
Additional Cycles)
Cycle = 4 weeks
C1 
C2-C4
C5
C6-
beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D15
D1
D1
EOTa,b,c
Notesd
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-3 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-3 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor 
Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. Same modality should 
be used for all assessments孱Assessed by RECIST 
v1.1; see Appendix 3.
Assessment to be performed prior to initiating next 
cycle of treatment.
An unconfirmed PR or unconfirmed CR must be 
confirmed at least 4 weeks after initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Nivolumab
X
X
X
X
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = 
carcinoembryonic antigen; CR = complete response; CRC = colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; IRT = Interactive 
Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA = Prostate-
Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = 
thyroxine; VS = vital signs.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C6D28) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For these treatment groups 1 cycle = 4 weeks, up to 6 cycles of dosing. Subjects who 
have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). For nivolumab, vital signs will be obtained before 
the infusion and then every 30 minutes (± 10 minutes) until the start of BMS-986178 infusion or per institution guidelines for administration of nivolumab. The 
30-minute post nivolumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event BMS-986178 administration is delayed, nivolumab 
vital signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, 
the subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
164
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
Predose (C1 Only)
See note in screening
Symptom-directed 
PE
X
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements 
X
X
X
X
Weight only
Vital Signs
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours post-infusion C1D1 and 
C2D1 
12-Lead 
Electrocardiogram 
(ECGs)
X
X
All ECG tests should be performed as a single 
measurement.
ECGs will be done at both predose and 4 hours 
when BMS-986178 PK sample is collected (ECGs 
should be done prior to the PK sample) on C1D1 
and C4D1. 
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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5.0
v




Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Monitor for Non-
Serious Adverse 
Events
Non-serious AEs will be collected starting with the first dose of study medication 
and through 100 days after discontinuation of dosing.
Monitor for 
Serious Adverse 
Events
See note in screening procedures (Table 5.1-1)
Pharmacokinetic 
Assessments
See Table 5.5.1-4 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling 
BMS-986178 
See Table 5.5.1-4 for specific samples at each cycle during the study.
BMS-986178 ADA 
Sampling 
See Table 5.5.1-4 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab
See Table 5.5.1-4 for specific samples at each cycle during the study.
Nivolumab ADA 
Sampling
See Table 5.5.1-4 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Ipilimumab 
See Table 5.5.1-4 for specific samples at each cycle during the study.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
167
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Ipilimumab ADA 
sampling
See Table 5.5.1-4 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-2 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-2 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-2 for specific samples at each cycle during the study.
PBMC
See Table 5.6-2 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow 
See Table 5.6-2 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-2 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-2 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-2 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-2 for specific samples at each cycle during the study.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
168
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Efficacy 
Assessments
Tumor 
Assessments
Every 8 weeks (± 1 week)
Note: If subject completes 24 weeks of dosing, C7D21 will be the last cycle visit 
(EOT), this will be at Week 24, and the 27 week scan should be done at this time.
By methods used at baseline. Same modality should 
be used for all assessments孱Assessed by RECIST 
v1.1; see Appendix 3.
Assessment to be performed prior to initiating next 
cycle of treatment.
An unconfirmed PR or unconfirmed CR must be 
confirmed at least 4 weeks after initial assessment. 
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
(C1-C4, q3w; C5
and beyond, q4w)
Dosing will be on C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, and 
C7D1, which corresponds to Weeks 1, 4, 7, 10, 13, 17, and 21
Supplied by BMS
Use vials assigned per IRT
Nivolumab 
(240 mg flat dose)
(C1-C4, q3w)
Dosing will be on C1D1, C2D1, C3D1, and C4D1, 
which corresponds to Weeks 1, 4, 7, and 10
Supplied by BMS
Use vials assigned per IRT
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
169
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-5:
On Treatment Procedural Outline Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with RCC)
(C1-C7, 
Additional 
Cycles)
Cycle = 3 weeks 
for C1-C4
Cycle = 4 weeks 
for C5 and 
beyond 
C1 
C2-C3
C4
C5-
Beyond
Window (± 2 days)
Procedure
D1
D2
D8
D15
D1
D1
D1
D15
EOTa,b,c
Notesd
Nivolumab 
(480 mg flat dose)
(C5 and beyond, 
q4w)
Dosing will be on C5D1, C6D1, and C7D1, 
which corresponds to Weeks 13, 17, and 21
Supplied by BMS
Use vials assigned per IRT
Ipilimumab 
(1 mg/kg)
(C1-C4, q3w)
Dosing will be on C1D1, C2D1, C3D1, and C4D1, 
which corresponds to Weeks 1, 4, 7, and 10
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = 
carcinoembryonic antigen; CR = complete response; CRC = colorectal cancer; D = Day; ECG = electrocardiogram; EOT = end of treatment; LFT = liver function 
test; IRT = Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; 
PSA = Prostate-Specific Antigen; RNA = ribonucleic acid; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; VS 
= vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C7D21) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. For C1 to C4, 1 cycle = 3 weeks, and for C5 and beyond, 1 cycle = 4 weeks. Subjects 
who have additional cycles will follow this same time and events table.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion, 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
170
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
then every 30 minutes (± 10 minutes) until the start of the next study drug infusion or per institution guidelines for administration of ipilimumab and/or 
nivolumab. The 30-minute post nivolumab infusion VS may correspond to the pre-infusion ipilimumab or BMS-986178 VS and the 30-minute post ipilimumab 
infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event the next study drug administration is delayed, nivolumab and/or ipilimumab vital 
signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the 
subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
171
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
Predose (C1 only); See note in 
screening.
Symptom-directed 
PE
X
X
X
X
X
X
X
X
X
To include signs and symptoms
Physical 
Measurements
X
X
X
X
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours 
post-infusion C1D1 and C2D1
12-Lead 
Electrocardiogram 
(ECG) 
X
X
All ECG tests should be performed 
as a single measurement.
ECGs will be done at both predose 
and 4 hours when BMS-986178 PK 
sample is collected (ECGs should be 
done prior to the PK sample) at 
C1D1 and C4D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on D1.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
X
X
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
X
X
X
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Serial Serum PK 
Sampling for 
BMS-986178 
See Table 5.5.1-5 for specific samples at each cycle during the study.
BMS-986178 ADA 
Sample
See Table 5.5.1-5 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab 
See Table 5.5.1-5 for specific samples at each cycle during the study.
Nivolumab ADA 
Sample 
See Table 5.5.1-5 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Ipilimumab
See Table 5.5.1-5 for specific samples at each cycle during the study.
Ipilimumab ADA 
Sample
See Table 5.5.1-5 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-4 for specific samples at each cycle during the study.
Blood RNA, Blood 
RO
See Table 5.6-4 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-4 for specific samples at each cycle during the study.
PBMC
See Table 5.6-4 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow
See Table 5.6-4 for specific samples at each cycle during the study.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Serum Factors
See Table 5.6-4 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-4 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-4 for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-4 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor 
Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. Same 
modality/ should be used for all 
assessments. Assessed by 
RECIST v1.1; see Appendix 3.
Assessment to be performed prior to 
initiating next cycle of treatment.
An unconfirmed PR or unconfirmed 
CR must be confirmed at least 4 
weeks after initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178
(q2w)
Dosing will be on C1D1, C1D15, C1D29, C2D1, C2D15, 
C2D29, C3D1, C3D15, C3D29, C4D1, C4D15, and C4D29, 
which corresponds to Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 
21, and 23
X
X
X
Supplied by BMS
Use vials assigned per IRT
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-6:
On Treatment Procedural Outline Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in 
Subjects with NSCLC)
(C1-C4, 
Additional Cycles)
(Cycle = 6 weeks)
C1
C2-C4
C5-Beyond
Window (± 2 Days)
Procedure
D1
D2
D8
D15
D22
D29
D1
D15
D29
D1
D15
D29
EOT
a,b,c
Notesd
Nivolumab 
(240 mg q2w Flat 
Dose)
Dosing will be on C1D1, C1D15, C1D29, C2D1, C2D15, 
C2D29, C3D1, C3D15, C3D29, C4D1, C4D15, and C4D29, 
which corresponds to Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 
21, and 23
X
X
X
Supplied by BMS
Use vials assigned per IRT
Ipilimumab 
(1 mg/kg q6w) 
Dosing will be on Day 1 of each cycle, 
X
Supplied by BMS
Use vials assigned per IRT
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
= Prostate-Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; 
T4 = thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C4D35) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. One cycle = 6 weeks. Subjects who have additional cycles will follow this same time 
and events table. BMS-986178, nivolumab, and ipilimumab will continue for all additional cycles.
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (± 5 minutes) until 60 minutes after completion of the infusion, 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
then every 30 minutes (± 10 minutes) until the start of the next study drug infusion or per institution guidelines for administration of ipilimumab and nivolumab. 
The 30-minute post nivolumab infusion VS may correspond to the pre-infusion ipilimumab VS and the 30-minute post ipilimumab infusion VS may correspond 
to the pre-infusion BMS-986178 VS. In the event the next study drug administration is delayed, nivolumab and/or ipilimumab vital signs will be obtained until 
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the subject must be observed 
further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
Safety 
Assessments
Physical 
Examination (PE)
X
X
X
Predose (C1 only); See note in 
screening.
Symptom-directed 
PE
X
X
X
X
X
X
X
To include signs and symptoms; 
Physical 
Measurements
X
X
X
X
X
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
X
X
X
See note in screening.e
Observe subjects 4 hours 
post-infusion C1D1 and C2D1
12-Lead 
Electrocardiogram 
(ECG) 
X
All ECG tests should be performed 
as a single measurement.
ECGs will be done at both predose 
and 4 hours when BMS-986178 PK 
sample is collected (ECGs should 
be done prior to the PK sample) at 
C1D1 and C2D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on all dosing days
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
X
X
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
X
X
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
Pharmacokinetic 
Assessments
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
BMS-986178 
(cohort 1-3 only)
See Table 5.5.1-6 for specific samples at each cycle during the study.
BMS-986178 
ADA Sample
(cohort 1-3 only)
See Table 5.5.1-6 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab 
See Table 5.5.1-6 for specific samples at each cycle during the study.
Nivolumab ADA 
Sample 
See Table 5.5.1-6 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-5 for specific samples at each cycle during the study.
Blood RNA, 
Blood RO
See Table 5.6-5 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-5 for specific samples at each cycle during the study.
PBMC
See Table 5.6-5 for specific samples at each cycle during the study.
Blood 
Multiparameter 
Flow
See Table 5.6-5 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-5 for specific samples at each cycle during the study.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
PD Plasma
See Table 5.6-5 for specific samples at each cycle during the study.
ctDNA
See Table 5.6-5 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-5 for specific samples at each cycle during the study.
On treatment C1D15 and C1D78
Blood TCR
See Table 5.6-5 for specific samples at each cycle during the study.
Efficacy 
Assessments
Tumor 
Assessments 
Every 12 weeks (± 1 week)
X
By methods used at baseline. Same 
modality/ should be used for all
assessments. Assessed by 
RECIST v1.1; see Appendix 3.
Assessment to be performed prior 
to initiating next cycle of treatment.
An unconfirmed PR or 
unconfirmed CR must be 
confirmed at least 6 weeks after 
initial assessment.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-7:
On Treatment Procedural Outline Part 8 (CA012004 - q12w Dosing)
(C1-C8)
(Cycle = 12 
weeks)
C1-C2
C3-beyond
Window (± 2 Days)
Procedure
D1
D8
D15
D29
D57
D1
D15
D29
D57
EOT
a,b,c
Notesd
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug 
Supplies
BMS-986178 
(q12w) Cohort 1-
3 Only
Dosing on Day 1 of each cycle 
Supplied by BMS
Use vials assigned per IRT
Nivolumab 
(480 mg Flat 
Dose q4w)
Dosing on Day 1, 29, and 57 of each cycle 
Supplied by BMS
Use vials assigned per IRT
Tetanus Vaccine
C1D1 Only
Locally Sourced
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
= Prostate-Specific Antigen; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; 
T4 = thyroxine; VS = vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C9D78) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. One cycle = 12 weeks. 
e For BMS-986178, vital signs will be obtained before the infusion and then every 15 minutes (±5 minutes) until 60 minutes after completion of the infusion, 
except for C1D1 and C2D1 (where vital signs will be obtained every 30 minutes until 4 hours post infusion). Vital signs will be obtained before the infusion and 
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
then every 30 minutes (±10 minutes) until the start of the next study drug infusion or per institution guidelines for administration of nivolumab. The 30-minute 
post nivolumab infusion VS may correspond to the pre-infusion BMS-986178 VS. In the event the next study drug administration is delayed, nivolumab vital 
signs will be obtained until 60 minutes after completion of the infusion. If any vital sign is abnormal (based upon clinician assessment) at the final check, the 
subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-8:
On Treatment Procedural Outline Part 9 (CA012004 - q4w Dosing)
(C1-C26)
(Cycle = 4 weeks)
C1 
C2-beyond
Window (± 2 Days)
Procedure
D-3
D1
D8
D15
D1
C2D15 
Only
EOT
a,b,c
Notesd
Safety Assessments
Physical Examination 
(PE)
X
X
Predose (C1 only); See note in 
screening.
Symptom-directed PE
X
X
X
X
To include signs and symptoms 
Physical Measurements
X
X
X
Weight only 
Vital Signs 
X
X
X
X
X
X
See note in screening.e
12-Lead 
Electrocardiogram 
(ECG) 
X
X (C5D1 
only)
All ECG tests should be 
performed as a single 
measurement.
ECGs will be done at predose at 
C1D1 and C5D1.
Laboratory Tests
See note in screening procedures and Section 5.3.2. Predose on all dosing days
Chemistry (Excluding 
LFTs)
X
X
X
X
X
X
CBC with Differential 
and Platelets
X
X
X
X
X
X
X
LFT Assessment
X
X
X
X
X
X
AST, ALT, ALP, and T. 
Bilirubin. Direct Bilirubin (only 
if T. Bilirubin is elevated); 
GGT (if ALP increase is 
clinically significant)
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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v




Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-8:
On Treatment Procedural Outline Part 9 (CA012004 - q4w Dosing)
(C1-C26)
(Cycle = 4 weeks)
C1 
C2-beyond
Window (± 2 Days)
Procedure
D-3
D1
D8
D15
D1
C2D15 
Only
EOT
a,b,c
Notesd
BMS-986178 ADA 
Sample
See Table Table 5.5.1-7 for specific samples at each cycle during the study.
Serial Serum PK 
Sampling for 
Nivolumab 
See Table Table 5.5.1-7 for specific samples at each cycle during the study.
Nivolumab ADA 
Sample 
See Table Table 5.5.1-7 for specific samples at each cycle during the study.
Biomarker 
Assessments
See Table 5.6-6 for specific samples at each cycle during the study.
Fecal Microbiome
See Table 5.6-6 for specific samples at each cycle during the study.
Blood RNA
See Table 5.6-6 for specific samples at each cycle during the study.
Blood PD
See Table 5.6-6 for specific samples at each cycle during the study.
PBMC
See Table 5.6-6 for specific samples at each cycle during the study.
Blood Multiparameter 
Flow
See Table 5.6-6 for specific samples at each cycle during the study.
Serum Factors
See Table 5.6-6 for specific samples at each cycle during the study.
PD Plasma
See Table 5.6-6 for specific samples at each cycle during the study.
Mandatory Fresh 
Tumor Biopsy
See Table 5.6-6  for specific samples at each cycle during the study.
Blood TCR
See Table 5.6-6 for specific samples at each cycle during the study.
Efficacy Assessments
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-8:
On Treatment Procedural Outline Part 9 (CA012004 - q4w Dosing)
(C1-C26)
(Cycle = 4 weeks)
C1 
C2-beyond
Window (± 2 Days)
Procedure
D-3
D1
D8
D15
D1
C2D15 
Only
EOT
a,b,c
Notesd
Tumor Assessments 
Every 8 weeks (± 1 week)
X
By methods used at baseline. 
Same modality/ should be used 
for all assessments. Assessed 
by RECIST v1.1; see Appendix 
3.
Assessment to be performed 
prior to initiating next cycle of 
treatment.
An unconfirmed PR or 
unconfirmed CR must be 
confirmed at least 6 weeks after 
initial assessment.
Brain Imaging
As clinically indicated
Bone Scan
As clinically indicated
Clinical Drug Supplies
BMS986178 
40 mg flat dose (q4w) 
Cohort 1:  Dosing on Day 1 of C1 through C6, C9, C12 
Cohort 2:  Not applicable
Supplied by BMS
Use vials assigned per IRT
Nivolumab 
(240 mg Flat Dose)
(480 mg Flat Dose q4w)
C1D15 as a 240 mg flat dose (initial dose)
Starting on C2D1 as 480 mg flat dose q4w
Supplied by BMS
Use vials assigned per IRT
Cyclophosphamide
(300 mg/m2)
Day -3 prior to C1D1 only
Sourced locally
UbiLT3 and/or UbiLT6
(0.5 mg or 1 mg)
C1D1 0.5 mg UbiLT3 and 0.5 mg UbiLT6 Intranodally (2 different lymph nodes)
C1D8 0.5 mg UbiLT3 and 0.5 mg UbiLT6 Intradermal
Sourced by BMS
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-8:
On Treatment Procedural Outline Part 9 (CA012004 - q4w Dosing)
(C1-C26)
(Cycle = 4 weeks)
C1 
C2-beyond
Window (± 2 Days)
Procedure
D-3
D1
D8
D15
D1
C2D15 
Only
EOT
a,b,c
Notesd
Starting at C1D15, alternating 1 mg UbiLT3 or 1 mg UbiLT6 will be given Intradermal q2w, for 
up to a total of 4 doses, starting with UbiLT3.
At C4D1 until C6D1, vaccine will be given q4w. It will be given again at C9D1 and C12D1 (See 
Figure 3.1.6-1)  
Abbreviations: ADA = anti-drug antibody; AFP = alpha fetal protein; ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate 
aminotransferase; BMS = Bristol-Myers Squibb; C = Cycle; CBC = complete blood count; CEA = carcinoembryonic antigen; CR = complete response; CRC = 
colorectal cancer; D = Day; EOT = end of treatment; LFT = liver function test; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IRT 
= Interactive Response Technology; LFT = liver function test; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamic; PR = partial response; PSA 
= Prostate-Specific Antigen; RNA = ribonucleic acid; TCR = T-cell receptor; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; VS = 
vital signs.
a EOT is defined as the visit where the decision is made to discontinue the subject from treatment.
b For subjects who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, C26D28) 
and the start of the Week 1 Safety Follow-up visit.
c For subjects who do not complete all scheduled cycles of therapy, the EOT visit will be the most recent on-treatment visit (with all available safety and response 
data) and does not need to be repeated and will be considered the start of the Week 1 Safety Follow-up visit.
d Subjects will have procedures listed in this table completed at all cycles. One cycle =  4 weeks.
e For DPV-001, on C1D1, vital signs will be collected at pre-dose and then every 15 minutes (± 5 minutes) until 1 hour post dose; on C1D8 and beyond, vital signs 
will be obtained at pre-dose and then every 15 minutes (± 5 minutes) until 30 minutes post dose. For nivolumab, vital signs will be collected before the infusion
and
then every 30 minutes (± 10 minutes) until the start of the next study drug infusion or per institution guidelines. The 30-minute post nivolumab infusion 
vital sign may correspond to the pre-infusion BMS-986178 vital sign. In the event the next study drug administration is delayed, nivolumab vital signs will be
obtained until 60 minutes after completion of the infusion. For BMS-986178, on C1D1 and C2D1, vital signs will be obtained before the infusion and then
every 30 minutes until 4 hours post infusion; on C3D1 and beyond, vital signs will be taken every 15 minutes (± 5 minutes) until 60 minutes post infusion. If
any vital sign is abnormal (based upon clinician assessment) at the final check, the subject must be observed further for a period of time, as clinically indicated.
f Serum or urine pregnancy test must be performed (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to 
administration of study drug. If the pregnancy test is positive, hold all study drugs and perform confirmatory testing. If pregnancy is confirmed, permanently 
discontinue and immediately notify the BMS Medical Monitor/designee per Section 6.4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
188
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5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.1-9:
Follow-up Procedural Outline Parts 1 - 9 (CA012004)
Procedure
Safety Follow-up
FU 1
30 Daysa
(± 7 days) 
FU 2
60 Days 
(± 7 days)
FU 3
100 Days 
(± 10 days)
Notes
Safety Assessments
Physical Examination (PE)
X
X
X
Vital Signs
X
X
X
Includes body temperature, seated blood pressure, and heart rate. 
Laboratory Tests
Chemistry (excluding LFTs)
X
X
X
See Section 5.3.2.
CBC with Differential and 
Platelets
X
X
X
LFT Assessment
X
X
X
LFTs will be monitored following the last dose of BMS-986178. Includes 
AST, ALT, total bilirubin, direct bilirubin (only if total bilirubin is elevated) 
alkaline phosphatase, and GGT (if ALP increase is clinically significant).
Urinalysis
As clinically indicated. See Section 5.3.2.
Pregnancy Test
X
X
X
For WOCBP; serum or urine pregnancy test may be performed (clinic urine 
pregnancy test: minimum sensitivity 25 IU/L or equivalent units of hCG).
If positive, perform confirmatory testing. If pregnancy is confirmed, 
immediately notify the BMS Medical Monitor/designee per Section 6.4.
Adverse Event Reporting
Monitor for Non-Serious 
Adverse Events
Xb
Xb
Xc
Non-serious AEs will be collected starting with the first dose of study 
medication and through 100 days after discontinuation of dosing.
Monitor for Serious Adverse 
Events and any AEs (SAEs or 
non-serious AEs) associated 
with SARS-CoV-2 infections
Xb
Xb
Xc
See note in screening procedures (Table 5.1-1). Participants will be followed 
for all AEs (SAEs and non-serious AEs) associated with confirmed or 
suspected SARS-CoV-2 infection until resolution, the condition stabilizes, the 
event is otherwise explained, the event is deemed irreversible, the particpants 
is lost to follow-up (as defined in Section 3.6.2), or for suspected cases, until 
SARS-CoV-2 infection is ruled out.
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b Record at each visit. Collect continuously throughout the treatment period and for a minimum of 100 days following discontinuation of dosing.
c  Beyond 100 days from the last dose of study therapy, participants will be followed for drug-related AEs/SAEs until resolution, returns to baseline, or is deemed 
irreversible, or until the participant is lost to follow-up or withdraws study consent.
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In the event that multiple procedures are required at a single time point, the following is a list of 
procedures from highest to lowest priority:
1) PK Sampling
2) Safety (ECG)
3) Safety (clinical laboratories)
5.1.1
Retesting During Screening 
Retesting of laboratory parameters and/or other assessments within any single screening will be 
permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (ie, the most current result prior to Randomization) 
and is the value by which study inclusion will be assessed, as it represents the subject’s most 
current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1 may be repeated in an 
effort to find all possible well-qualified subjects. Consultation with the Medical Monitor (or 
designee) may be needed to identify whether repeat testing of any particular parameter is clinically 
relevant.
Testing for asymptomatic SARS-CoV-2 infection by RT-PCR or viral antigen is not required. 
However, some subjects 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, subjects may be considered eligible for the study after meeting all 
inclusion/exclusion criteria related to active infection, and after meeting all of 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 SARS-CoV-2 sequelae that may place the 
participant at a higher risk of receiving investigational treatment.
5.2
Study Materials
The site will provide all required materials for the tests performed locally (ie, relevant clinical
laboratory tests and urine drug screens). The site will have a well-calibrated scale available for 
recording body weight, a 12-lead ECG machine, and a calibrated sphygmomanometer, a syringe 
pump, 0.2-μm filter infusion sets, and a thermometer for vital signs assessments. A current and 
fully stocked advanced cardiac life support cart will be immediately available on the premises. The 
site will have a refrigerated centrifuge, a monitored and alarmed refrigerator, and freezer (-70°C 
preferred, -20°C acceptable), as well as containers and dry ice for shipment and storage of blood 
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samples. The site will provide all materials required for accurate source documentation of study 
activities and for housing the subjects during the study. The site will source marketed product from 
a single commercial lot.
BMS will provide a Sponsor-approved protocol and any amendments or administrative letters (if 
required) and an IB. CRFs (electronic or hard copy) will be provided by BMS. BMS/central 
laboratory will provide labels and tubes for the collection of blood samples for PK/PD and for 
genotyping analysis.
5.3
Safety Assessments
AEs will be assessed during the study and for 100 days after the last treatment. AEs will be 
evaluated according to NCI CTCAE v4.03 and should be followed per requirements in Section 6.1
and Section 6.2. AEs will be coded using the most current version of Medical Dictionary for 
Regulatory Activities and reviewed for potential significance and importance. Subjects should be 
followed until all treatment-related AEs have recovered to baseline or are deemed irreversible by 
the investigator.
Protocol-specified assessments are described in Table 5.1-1 (Screening), Table 5.1-2 (On 
Treatment - Parts 1 and 2), Table 5.1-3 (On Treatment - Parts 3 and 5), Table 5.1-4 (On Treatment 
- Part 4), Table 5.1-5 (On Treatment - Part 6), Table 5.1-6 (On Treatment - Part 7), Table 5.1-7
(On Treatment - Part 8), Table 5.1-8 (On Treatment - Part 9), and Table 5.1-9 (Follow-up -
Parts 1-9).
5.3.1
Imaging Assessment for the Study
1) CT/MRI
a) Contrast-enhanced CT scans acquired on dedicated CT equipment is preferred for 
this study. CT with contrast of the chest, abdomen, and pelvis are to be performed 
for tumor assessments. CT scans should be acquired with 5-mm slices and no 
intervening gap (contiguous).
(1) Should a subject have a contraindication for CT IV contrast, a non-
contrast CT of the chest and a contrast-enhanced MRI of the abdomen 
and pelvis may be obtained. MRIs should be acquired with slice 
thickness of < 5 mm with no gap (contiguous). 
(2) Every attempt should be made to image each subject using an identical 
acquisition protocol on the same scanner for all imaging time points.
(3) Note on the use of the CT component of a positron emission tomography
(PET)/CT scanner:
Combined modality scanning such as with fluorodeoxyglucose (FDG)-PET/CT is 
increasingly used in clinical care and is a modality/technology that is in rapid evolution; 
therefore, the recommendations outlined here may change rather quickly with time. At 
present, low-dose or attenuation-correction CT portions of a combined FDG-PET/CT 
are of limited use in anatomically based efficacy assessments; it is therefore suggested 
that they should not be substituted for dedicated diagnostic contrast-enhanced CT scans 
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for anatomically based RECIST measurements. However, if a site can document that 
the CT performed as part of a FDG-PET/CT is of identical diagnostic quality to a 
diagnostic CT (with IV and oral contrast), then the CT portion of the FDG-PET/CT can 
be used for RECIST 1.1 measurements. Note, however, that the FDG-PET portion of 
the CT introduces additional data that may bias an investigator if it is not routinely or 
serially performed.
2) Brain MRI
a) MRI of the brain is required at screening if subject is symptomatic or has a history 
of brain metastasis. Subjects with a history of brain metastasis should have 
surveillance MRI approximately every 12 weeks or sooner, if clinically indicated.
b) MRI brain scans during on-study treatment and follow-up periods are required only
if there is a prior history of lesions present at Screening, or as clinically indicated 
for new signs and symptoms that suggest central nervous system (CNS) 
involvement.
3) Bone Scan
a) Bone scans can be used to evaluate metastatic disease.
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the Study Investigator as per 
standard medical/clinical judgment.
5.3.2
Laboratory Test Assessments
Each site’s local laboratory will perform the analyses and will provide reference ranges for these 
tests.
Results of clinical laboratory tests performed on Day -3 and Day 1 must be available prior to 
dosing.
The following clinical laboratory tests will be performed:
Hematology
Hemoglobin
Hematocrit
Platelet count
Total leukocyte count, including differential
CBC and differential results will be monitored on an ongoing basis and should be sent to the 
local laboratory data service upon receipt of the results. Others will be sent to the local 
laboratory data service.
Serum Chemistry
AST
ALT
Amylase
Total bilirubin
Total protein
Albumin
Sodium
Potassium
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Direct bilirubin (only as reflex when T 
bilirubin elevated)
ALP
Lactate dehydrogenase
Lipase
Creatinine 
Blood urea nitrogen
Uric acid (at screening only)
Glucose (fasting at screening)
Gamma-glutamyl transferase (only as reflex 
when ALP increase is clinically significant)
Chloride
Calcium
C-reactive protein
Ferritin
Carbon dioxide
Phosphorus
Magnesium
CrCL(screening only)
Thyroid Laboratories
Thyroid-stimulating hormone (TSH)
Free T3 and free T4 (at screening and reflex when TSH abnormal)
Urinalysis
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein, or leukocytes esterase are positive 
Serology
Hepatitis B surface antigen
Serum for hepatitis C antibody(if Hep C Ab is positive reflex to Hep C RNA) or Hep C RNA, 
HIV-1 and -2 antibody (testing for HIV-1 and HIV-2 must be performed at sites where 
mandated by local requirements).
Other Analyses
Pregnancy test (WOCBP only: serum testing at screening and within 24 hours prior to dosing; 
urine or serum at all other time points).
FSH (screening only for women only) 
Tumor Specific Serum Markers
CA125 testing for all subjects with OC
Alpha fetal protein (AFP) testing for all subjects with hepatocellular carcinoma
Carcinoembryonic antigen (CEA) testing for all subjects with CRC
CA19-9 testing for all subjects with pancreatic cancer
Prostate-Specific Antigen test for all subjects with prostate cancer
CA15.3 and CEA for all Part 9 subjects, with TNBC and ER-low positive breast cancer (at 
baseline, and subsequently if baseline levels are above upper limit of normal).
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Results of all laboratory tests required by this protocol must be provided to BMS, either recorded 
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 (see Section 6.3).
5.4
Efficacy Assessments
Disease assessment with CT and/or MRI as appropriate will be performed at baseline and every 
8 weeks Parts 1-7, and 9 or every 12 weeks for Part 8 (± 1 week) per RECIST v1.1 (see Appendix 
3) until discontinuation of treatment or withdrawal from study. Tumor assessments at other time 
points may be performed if the investigator is concerned about tumor progression. Assessment of 
tumor response will be reported by the investigator for appropriate populations of subjects as 
defined by RECIST v1.1181 (see Appendix 3) for subjects with advanced solid tumors. The same 
modality should be used and the same scanner is preferred for all assessments.
Investigators will also report the number and size of new lesions that appear while on study. The 
time point of tumor assessments will be reported on the CRF based on the investigators’ 
assessment using RECIST criteria. Please refer to Appendix 3 for specifics of RECIST v1.1 
criteria to be utilized in this study.
5.4.1
Primary Efficacy Assessment
Not applicable.
5.4.2
Secondary Efficacy Assessments
The efficacy assessments will include ORR (eg, PR and CR) for Parts 1-9; duration of response 
and progression-free survival rate (PFSR) at time points (eg, 24 weeks) for Parts 1-8, based on 
assessment of tumor response using RECIST v1.1.
5.4.3
Exploratory Efficacy Assessments
OS data will be collected up to 2 years from the start of study drug treatment for Parts 1-8.
5.5
Pharmacokinetic Assessments
Samples for PK and immunogenicity assessments will be collected for subjects receiving 
BMS-986178 alone or in combination with nivolumab and/or ipilimumab, as described in Table 
5.5.1-1 (Parts 1 and 2), Table 5.5.1-2 (Part 4), Table 5.5.1-3 (Parts 3 and 5), Table 5.5.1-4 (Part 6),
Table 5.5.1-5 (Part 7), Table 5.5.1-6 (Part 8), and Table 5.5.1-7 (Part 9). The PK of BMS-986178 
will be characterized by NCA method. Immunogenicity samples will be analyzed for anti-BMS-
986178 antibodies and/or anti-nivolumab antibodies and/or anti-ipilimumab antibodies by 
validated immunoassays.
If data permit, the PK parameters might be assessed following Cycle 1 Day 1 and Cycle 9 Day 1 
for the q2w dosing regimen in monotherapy or in combination therapy, Cycle 4 Day 1 for the q3w 
or q6w dosing regimen in combination therapy with ipilimumab and/or nivolumab combination 
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therapy, Cycle 5 Day 1 for q4w dosing regimen in combination therapy with nivolumab include 
the following:
Cmax
Maximum observed serum concentration
Tmax
Time of maximum observed concentration
AUC(0-t)
Area under the plasma concentration-time curve from time zero to time of
last quantifiable concentration
AUC(TAU)
Area under the concentration-time curve in 1 dosing interval
In addition, the PK parameters listed below may be assessed following dose administration in 
Cycle 9 Day 1 for the q2w or Cycle 5 Day 1 for q4w dosing regimen in monotherapy or in 
combination therapy and Cycle 4 Day 1 for the q3w and q6w dosing regimen in combination 
therapy with ipilimumab and/or nivolumab.
Ctau
The observed concentration at the end of a dosing interval 
CLT
Total body clearance 
Css-avg
Average concentration over a dosing interval (AUC(TAU)/tau) 
AI
Ratio of an exposure measure at steady state (eg, following Cycle 9 Day 1 
dose) to that after the first dose (exposure measure includes AUC(TAU), 
Cmax and Ctau).
T-HALFeff
Effective elimination half-life that explains the degree of accumulation 
observed for a specific exposure measure (exposure measure includes 
AUC(TAU), Cmax and Ctau)
The following PK parameter will be reported as a separate listing, summary, and plot:
Ctrough
Trough observed plasma concentrations (this includes predose 
concentrations (C0) and Ctau)
5.5.1
Pharmacokinetics and Immunogenicity Collection and Processing
Detailed sampling schedules to be followed for the assessment of PK and immunogenicity for 
BMS-986178 monotherapy or in combination therapy are provided in Table 5.5.1-1 (Parts 1 and 
2), Table 5.5.1-2 (Part 4), Table 5.5.1-3 (Parts 3 and 5), Table 5.5.1-4 (Part 6), Table 5.5.1-5 (Part 
7), Table 5.5.1-6 (Part 8) and Table 5.5.1-7 (Part 9). However, if there is a safety concern (e.g. 
Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection would be permissible (using 
an Unscheduled Visit).
All predose samples should be taken within 30 minutes before the start of any dose infusion. All 
postdose PK sampling time points are relative to the start of BMS-986178 administration. 
End-of-infusion samples should be taken just prior to the end of infusion (EOI; preferably within 
2 minutes). Further details of sample collection, processing, and shipment will be provided in the 
laboratory procedure manual. On-treatment PK samples are intended to be drawn relative to actual 
dosing days; if a dose occurs on a different day within the cycle due to delays or minor schedule 
adjustments, PK samples should be adjusted accordingly.
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Table 5.5.1-1:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 Monotherapy or in Combination Therapy - Parts 1 
and 2 (CA012004 - q2w Dosing)
Study Day of 
Sample 
Collection 
(1 Cycle = 
2 Weeks)
Event
Time 
(Relative to 
start of 
BMS-
986178 
Infusion)
Hour: Min
BMS-986178
PK Sample 
(All 
Subjects)
Nivolumab 
PK Sample 
(Part 2)
BMS-986178 
ADA Sample 
(All 
Subjects)
Nivolumab 
ADA Sample 
(Part 2)
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
C3D1
Predosea
00:00a
X
X
X
X
C4D1
Predosea
00:00a
X
X
End of Treatment
Unschedulede
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both nivolumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle.
e Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
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Table 5.5.1-2:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination Therapy - Part 4 (CA012004 - q4w 
Dosing)
Study Day of 
Sample 
Collection 
(1 Cycle = 
4 Weeks)
Event
Time 
(Relative to 
start of BMS-
986178 
Infusion)
Hour: Min
BMS-986178 
PK Sample
Nivolumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA
Sample
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15e
336:00
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
C3D1
Predosea
00:00a
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
End of Treatment
Unscheduledf
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both nivolumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle.
e D15 sample may be taken during D12 to D18 of a cycle.
f Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
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Table 5.5.1-3:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination with Ipilimumab - Parts 3 and 5 
(CA012004 - q3w Dosing)
Study Day of 
Sample 
Collection
(1 Cycle = 
3 Weeks)
Event
Time 
(Relative to 
start of 
BMS-986178 
Infusion)
Hour: Min
BMS-986178
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15d
336:00
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
C3D1
Predosea
00:00a
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C4D2
24:00
X
C4D4c
72:00
X
C4D8d
168:00
X
C4D15d
336:00
X
End of Treatment
Unschedulede
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both ipilimumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed to beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
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c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle; Day 15 sample may be taken during D13 to D17 of a cycle.
e Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled isit).
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Table 5.5.1-4:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with RCC)
Study Day of 
Sample Collection 
(Cycle = 3 Weeks 
for C1 - C4
Cycle = 4 Weeks 
for C5 and 
Beyond)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178 
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15e
336:00
X
C2D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
C3D1
Predosea
00:00a
X
X
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C4D2
24:00
X
C4D4c
72:00
X
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Table 5.5.1-4:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 6 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with RCC)
Study Day of 
Sample Collection 
(Cycle = 3 Weeks 
for C1 - C4
Cycle = 4 Weeks 
for C5 and 
Beyond)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178 
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C4D8d
168:00
X
C4D15e
336:00
X
End of Treatment
Unscheduledf
X
X
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion. 
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for ipilimumab, nivolumab, and BMS-986178 should be collected at the end of the BMS-986178 infusion. The EOI sample should be taken 
immediately prior to stopping the infusion (preferably within 2 minutes prior to the end of infusion). If the end of infusion is delayed to beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly.
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle.
e D15 sample may be taken during D13 to D17 of a cycle.
f Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection would be permissible (using an 
Unscheduled Visit).
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
203
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-5:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with NSCLC)
Study Day of 
Sample Collection 
(1 Cycle = 
6 Weeks)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178 
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C1D2
24:00
X
C1D4c
72:00
X
C1D8d
168:00
X
C1D15e
Predosea
00:00a
X
X
C1D29f
Predosea
00:00a
X
X
C2D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
C3D1
Predosea
00:00a
X
X
X
X
X
X
C4D1
Predosea
00:00a
X
X
X
X
X
X
EOIb
00:30b
X
X
X
04:00
X
C4D2
24:00
X
C4D4c
72:00
X
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
204
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-5:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for BMS-986178 in Combination -
Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with NSCLC)
Study Day of 
Sample Collection 
(1 Cycle = 
6 Weeks)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
BMS-986178 
PK Sample
Nivolumab 
PK Sample
Ipilimumab 
PK Sample
BMS-986178 
ADA Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C4D8d
168:00
X
C4D15e
Predosea
00:00a
X
X
C4D29f
Predosea
00:00a
X
X
End of Treatment
Unscheduledg
X
X
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for ipilimumab, nivolumab, and BMS-986178 should be collected at the end of the BMS-986178 infusion. The EOI sample should be taken 
immediately prior to stopping the infusion (preferably within 2 minutes prior to the end of infusion). If the end of infusion is delayed to beyond the nominal 
infusion duration, the collection of this sample should also be delayed accordingly
c D4 sample may be taken during D3 to D5 of a cycle.
d D8 sample may be taken during D7 to D9 of a cycle. 
e D15 sample may be taken during D13 to D17 of a cycle.
f D29 sample may be taken during D26 to D30 of a cycle.
g Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection would be permissible (using an 
Unscheduled Visit).
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
205
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-6:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination - Part 8 (CA012004 - q12w Dosing)
Study Day of 
Sample 
Collection 
(1 Cycle = 
12 Weeks)
Event
Time 
(Relative to 
start of BMS-
986178 
Infusion)
Hour: Min
BMS-
986178 PK 
Sample
(Cohort 1-
3)
Nivolumab 
PK Sample
BMS-986178 
ADA 
Sample
(Cohort 1-3)
Nivolumab 
ADA 
Sample
C1D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C1D8c
168:00
X
X
C1D15d
336:00
X
X
C1D29e
696:00
X
X
X
X
C2D1
Predosea
00:00a
X
X
X
X
EOIb
00:30b
X
X
04:00
X
C2D8c
168:00
X
X
C2D15d
336:00
X
C2D29e
696:00
X
X
C3D1
Predosea
00:00a
X
X
X
X
End of Treatment
Unscheduledf
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOI = end of infusion.
Note: The time recorded is relative to BMS-986178 infusion.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion.
b EOI samples for both nivolumab and BMS-986178 should be collected at the end of the BMS-986178 infusion. 
The EOI sample should be taken immediately prior to stopping the infusion (preferably within 2 minutes prior to 
the end of infusion). If the end of infusion is delayed beyond the nominal infusion duration, the collection of this 
sample should also be delayed accordingly.
c D8 sample may be taken during D7 to D9 of a cycle.
d D15 sample may be taken during D12 to D18 of a cycle.
e D29 sample may be taken prior nivolumab infusion.
f Unscheduled: If there is a safety concern (e.g. Grade 3 or 4 AE, SAE, etc.), ad hoc PK and ADA sample collection 
would be permissible (using an Unscheduled Visit).
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
206
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.5.1-7:
Pharmacokinetic and Anti-Drug Antibody Sampling Schedule for 
BMS-986178 in Combination Therapy - Part 9 (CA012004 - q4w 
Dosing)
Study Day of 
Sample 
Collection 
(1 Cycle = 
4 Weeks)
Event
Time 
(Relative to 
start of BMS-
986178 
Infusion in 
Cohort 1 or 
Relative to 
Start of 
Nivolumab in 
Cohort 2)
Hour: Min
BMS-986178 
PK Sample
(Cohort 1 
only)
Nivolumab 
PK Sample
BMS-986178 
ADA Sample
(Cohort 1 
only)
Nivolumab 
ADA 
Sample
C1D
Predosea
:00
X
X
C1D8b
168:00d
X
C1D15c
336:00d
X
X
X
C2D1
Predosea
00:00a
X
X
X
X
C3D1
Predosea
00:00a
X
X
C5D1
Predosea
00:00a
X
X
X
X
C6D1
Predosea
00:00a
X
X
X
X
End of Treatment
EOT
EOT
X
X
X
X
Abbreviations: ADA = anti-drug antibody; C = Cycle; D = Day; EOT = end of treatment; FU = Follow-Up.
a Predose: All predose samples for combinations should be collected prior to the start of the first infusion
b D8 sample may be taken during D7 to D9 of a cycle.
c D15 sample may be taken during D12 to D18 of a cycle.
d Relative to start of DPV-001 administration on C1D1 in Cohort 2
5.5.1.1
Pharmacokinetic and Immunogenicity Sample Analyses
The serum samples will be analyzed for drug (BMS-986178 and/or nivolumab and/or ipilimumab) 
and ADA (anti-BMS-986178 antibodies and/or anti-nivolumab antibodies and/or anti-ipilimumab 
antibodies) by validated immunoassays. In addition, selected serum samples may be analyzed by 
an exploratory method that measures BMS-986178, nivolumab, and ipilimumab; or detect ADAs
for technology exploration purposes; exploratory results will not be reported. Serum samples 
designated for PK or biomarker assessments may also be used for immunogenicity analysis if 
required (eg, insufficient volume for complete immunogenicity assessment or to follow up on 
suspected immunogenicity-related AE).
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
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5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
5.5.2
Labeling and Shipping of Biological Samples
Detailed instructions for the PK blood collection, labeling, processing, storage, and shipping will 
be provided to the site in the laboratory procedure manual.
5.6
Biomarker Assessments
To assess the PD effects of BMS-986178 as well as receptor occupancy (RO) in relation to dose 
and PK, whole blood samples (blood PD and blood RO) will be collected at the times indicated in 
Table 5.6-1 (Parts 1 and 2), Table 5.6-2 (Parts 3, 5, and 6), Table 5.6-3 (Part 4), Table 5.6-4
(Part 7), Table 5.6-5 (Part 8), and Table 5.6-6 (Part 9). The sample testing plans associated with 
each are described in Section 5.7. Complete instructions on the collection, processing, handling, 
and shipment of all samples described herein will be provided in a separate laboratory procedure 
manual.
Blood samples for PD assessment will be analyzed by cytometry to determine baseline and serial 
on-treatment alterations in composition and/or activation status of lymphocyte subsets. 
Lymphocyte subsets to be assayed may include, but are not limited to, CD8+ and CD4+ T-cell 
subsets (activated; effector/memory; regulatory) and populations of those cells as defined by the 
expression of proliferation, activation, exhaustion, or signaling markers such as KI67, HLA-DR, 
PD-1, etc. Treatment-induced alterations in blood lymphocyte populations will be analyzed in 
relation to both dose and blood concentrations of BMS-986178.
Receptor occupancy of OX40 by BMS-986178 (RO) on peripheral blood mononuclear cells 
(PBMCs) may also be determined by flow cytometry. RO will be analyzed in relation to PK and 
PD effects. Samples will be collected to determine RO from subjects in Part 1A and 1B in this 
study. For combination cohorts, a blood tube will also be collected for exploratory purposes to 
measure pharmacodynamic endpoints including, but not limited to RO.
Fecal microbiome will be collected prior to treatment for subjects in Part 9.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
208
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-1:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Monotherapy and 
Combination Therapy - Parts 1 and 2 (CA012004 - q2w Dosing)
Study Day of 
Sample Collection 
(1 Cycle = 2 Weeks)
Event
Time 
(Relative to start of 
BMS-986178 
Infusion)
Hour: Min
Blood RNA, 
Blood ROa
Blood PD 
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc 
Section 5.6
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C2D1
Predosef
00:00
X
X
X
Xh
C3D1
Predosef
00:00
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T cell receptor.
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments. Blood RNA samples will be collected from all subjects. Detailed instructions for 
the collection, processing, and shipping of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
209
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
g D8 sample may be taken during D7 to D9 of a cycle.
h C2D1 fresh tumor biopsy may be taken during C1D12-C2D4.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
210
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-2:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Parts 3, 5, and 6 (CA012004)
Study Day of Sample 
Collection (Cycle = 3 Weeks 
for C1 C8 for Parts 3 and 5)
(Cycle = 3 Weeks for C1 C4
Cycle = 4 Weeks for C5 and 
Beyond for Part 6)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
Blood RO, 
Blood RNAa
Blood 
PD
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C1D15h
336:00
X
X
X
X
C2D1
Predosef
00:00
X
X
X
X
C2D8
C3D1
Predosef
00:00
X
X
X
C4D1
Predosef
00:00
X
X
X
X
EOT/Unscheduled/Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RO=Receptor Occupancy RNA = ribonucleic acid; TCR = T cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments from all subjects. Detailed instructions for the collection, processing, and shipping 
of samples will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
211
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D13 to D17 of a cycle.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
212
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-3:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 4 (CA012004 - q4w Dosing)
Study Day of Sample 
Collection (1 Cycle = 
4 Weeks
Event
Time 
(Relative to 
start of BMS-
986178 
Infusion)
Hour: Min
Blood 
RNA, 
Blood 
ROa
Blood 
PD
PBMC, Blood 
Multiparameter Flow, 
Serum Factors, Plasmab
Tumor 
Biopsyc
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C1D15h
336:00
X
X
X
X
C2D1
Predosef
00:00
X
X
X
X
C3D1
Predosef
00:00
X
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments from all subjects. Detailed instructions for the collection, processing, and shipping 
of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point.. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
213
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory manual
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D12 to D18 of a cycle.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
214
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-4:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 7 (CA012004; BMS-986178 with Nivolumab and Ipilimumab in Subjects with NSCLC)
Study Day of 
Sample Collection 
(1 Cycle = 6 Weeks)
Event
Time 
(Relative to start of 
BMS-986178 Infusion)
Hour: Min
Blood RNA, 
Blood ROa
Blood PD 
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc 
Section 5.6
Blood 
Genotype,d
Blood TCR
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
C1D2
24:00
X
C1D8g
168:00
X
X
X
C1D15h
Predosef
00:00
X
X
X
X
C1D29i
Predosef
00:00
X
X
X
C2D1
Predosef
00:00
X
X
X
X
C3D1
Predosef
00:00
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; PD = 
pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
a Separate samples will be collected for blood RNA and blood RO assessments. Blood RNA samples will be collected from all subjects. Detailed instructions for 
the collection, processing, and shipping of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
215
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D13 to D17 of a cycle.
i
D29 sample may be taken during D26 to D30 of a cycle.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
216
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
Table 5.6-5:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 8 (CA012004 - q12w Dosing
Study Day of 
Sample Collection 
(1 Cycle = 
12 Weeks)
Event
Time 
(Relative to start 
of BMS-986178 
Infusion)
Hour: Min
Blood 
RNA, 
Blood ROa
Blood 
PD 
PBMC, Blood 
Multiparamete
r Flow, Serum 
Factors, 
Plasmab
Plasma for 
ctDNAj
Tumor 
Biopsyc, 
Section
5.6
Blood 
Genotype, 
Blood 
TCRd
Archived 
Tumore
Screening
X
X
X
X
C1D1
Predosef
00:00
X
X
X
X
C1D8g
168:00
X
X
X
C1D15h
336:00
X
X
X
X
X
C1D29i
672:00
X
X
X
X
C1D78
1848:00k
X
X
X
X
C2D1
Predosef
00:00
X
X
X
X
X
C2D8g
168:00
X
X
X
C2D15h
336:00
X
X
X
X
C2D29i
672:00
X
X
X
X
C3D1
Predosef
00:00
X
X
X
X
X
C3D8g
168:00
X
X
X
EOT/Unscheduled/ 
Progression
EOT
X
X
X
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; 
PD = pharmacodynamic; RNA = ribonucleic acid; RO = receptor occupancy; TCR = T-cell receptor. 
Note: The time recorded is relative to BMS-986178 infusion.
Protocol Amendment No: 04 Site Specific
Date: 12-May-2021
217
5.0
Approved
930127600
5.0
v


Clinical Protocol
CA012004
BMS-986178
anti-OX40 mAb
a Separate samples will be collected for blood RNA and blood RO assessments. Blood RNA samples will be collected from all subjects. Detailed instructions for 
the collection, processing, and shipping of each sample will be provided in the laboratory procedure manual.
b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor 
at the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional 
biopsies may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D13 to D17 of a cycle. 
i
D29 sample may be taken during D26 to D30 of a cycle.
j
Blood samples to be collected in 2x 9ml Streck tubes.
k C1D78 sample may be taken during D71 to D85.
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Table 5.6-6:
Pharmacodynamic and Exploratory Biomarker Sampling Schedule for BMS-986178 Combination 
Therapy - Part 9 (CA012004 - q4w Dosing)
Study Day of 
Sample Collection 
(1 Cycle = 4 Weeks)
Event
Time
(Relative to Start of 
BMS-986178 Infusion 
in Cohort 1 or Relative 
to Start of Nivolumab 
in Cohort 2)
Hour: Min
Blood 
RNAa
Blood 
PD
PBMC, Blood 
Multiparameter 
Flow, Serum 
Factors, Plasmab
Tumor 
Biopsyc
Section 5.6
Blood 
Genotype, 
Blood TCRd
Archived 
Tumore
Fecal 
Micro-
biome
Screening
X
X
Xi
X
X
X
X
Day -3
Predosef
X
Xi
C1D1
Predosef
00:00
X
X
X
C1D2
X
X
Xi
C1D8g
168:00j
X
X
C1D15h
336:00j
X
X
C2D1
Predosef
00:00
X
X
X
X
C2D15h
336:00
X
X
C3D1
Predosef
00:00
X
X
X
C4- C6D1f
X
X
Xi
EOT/Unscheduled/ 
Progression
EOT
X
X
X
Abbreviations: C = Cycle; D = Day; EOT = end of treatment; FFPE = formalin-fixed, paraffin-embedded; PBMC = peripheral blood mononuclear cell; PD = 
pharmacodynamic; RNA = ribonucleic acid; TCR = T-cell receptor. 
a Blood RNA samples will be collected from all subjects. Detailed instructions for the collection, processing, and shipping of each sample will be provided in the 
laboratory procedure manual
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b Separate samples will be collected for PBMC, blood multiparameter flow, serum factors, and plasma assessments. Detailed instructions for the collection, 
processing, and shipping of each sample will be provided in the laboratory procedure manual.
c Mandatory predose and on-treatment biopsies for all subjects. Additional subjects may be added in the event that some subjects do not have obtainable tumor at 
the on-treatment time point. Subjects obtaining biopsies should have adequate tissue collected as outlined in the laboratory manual. Additional optional biopsies 
may be collected at EOT, time of disease progression, or during another clinically meaningful event (eg, response or adverse event).
d Blood genotype sample to be collected at screening only.
e All subjects may provide an archived tumor specimen. Archival FFPE block or a minimum of 15 slides is required; 25 slides are preferred. See laboratory 
manual.
f Predose: All predose samples for combinations should be taken prior to the start of the first infusion.
g D8 sample may be taken during D7 to D9 of a cycle.
h D15 sample may be taken during D12 to D18 of a cycle.
i
Serum and PBMC sample only.
j
Relative to start of DPV-001 administration on C1D1 in Cohort 2.
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5.8
Outcomes Research Assessments
Not applicable.
 
 
 
5.10
Additional Research Collection
Additional research collections and retention are mandatory for all subjects, except where 
prohibited by local laws or regulations.
This protocol will include residual samples for additional research (AR).
This collection for additional research is intended to expand the translational 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. It may also be used to support health authority 
requests for analysis, and the advancement of pharmacodiagnostic development to better target 
drugs to the right patients. This may also include genetic/genomic exploration aimed at exploring 
disease pathways, progression and response to treatment etc. 
Sample Collection and Storage
All requests for access to samples or data for additional research will be vetted through a diverse 
committee of the study sponsor’s senior leaders in Research and Development (or designee) to 
ensure the research supports appropriate and well-defined scientific research activities.
•
Additionally, residual blood (or blood derivatives such as serum, plasma, PBMCs and 
extracted RNA/DNA) or tumor tissue (archival or fresh biopsy and extracted RNA/DNA) (see 
Table 5.10-1) will also be retained for additional research purposes.
•
Samples will be securely stored by the BMS Biorepository in New Jersey or at a BMS approved 
third party storage management facility. 
•
Samples will be stored in a coded fashion; and no researcher will have access to the key, which 
is securely held at the clinical site, so that there is no direct ability for a researcher to connect 
a sample to a specific individual.
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•
Additional research samples will be retained for 15 years or the maximum allowed by 
applicable law. No additional sampling is required for residual collections. 
Further details of sample collection and processing will be provided to the site in the procedure 
manual.
Table 5.10-1:
Residual Sample Retention for Additional Research Schedule
Sample Type
Time Points for which residual samples will be retained
PK
All
Archived Tumor Block or Slides
Pre-treatment
Fresh Tumor Biopsy
Pre-treatment, on-treatment and/or unscheduled/EOT
PBMC’s
All
Serum
All
Plasma
All
Blood RNA
All
Blood Genotype/Blood TCR
All
6
ADVERSE EVENTS
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess all 
AE. The causal relationship can be one of the following:
Related: There is no clear alternative cause for the AE that can be identified other than study 
treatment (e.g. disease progression, environmental causes, unrelated trauma).
Not related: There is a clear alternative cause identified for the AE other than study 
treatment.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.)
Immune-mediated adverse events are AEs consistent with immune-mediated mechanism or 
immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor 
progression) have been ruled out. Immune-mediated AEs can include events with an alternate 
etiology which were exacerbated by the induction of autoimmunity.
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Sponsor or designee will be reporting AEs to regulatory authorities and ethics committees 
according to local applicable laws including European Directive 2001/20/EC and FDA Code of 
Federal Regulations 21 CFR Parts 312 and 320.
6.1
Serious Adverse Events
An SAE is any untoward medical occurrence that at any dose: 
•
results in death
•
is life-threatening (defined as an event in which the subject 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)
•
results in persistent or significant disability/incapacity
•
is a congenital anomaly/birth defect 
•
is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [e.g., medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above.) Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization.) Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (e.g., pathogenic or nonpathogenic) via the study 
drug is an SAE. 
Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (See Section 6.1.1
for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy (e.g., death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as SAE (See Section 6.1.1 for reporting details).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
•
a visit to the emergency room or other hospital department < 24 hours, that does not result in 
admission (unless considered an important medical or life-threatening event)
•
elective surgery, planned prior to signing consent
•
admissions as per protocol for a planned medical/surgical procedure
•
routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)
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•
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)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the IB represent the Reference Safety Information to determine 
expectedness of SAEs for expedited reporting. Following the subject’s written consent to 
participate in the study, all SAEs, whether related or not related to study drug, must be collected, 
including those thought to be associated with protocol-specified procedures. All SAEs must be 
collected that occur during the screening period and within 100 days of discontinuation of dosing. 
If applicable, SAEs must be collected that relate to any later protocol-specified procedure (eg, a 
follow-up skin biopsy). 
Participants will be followed for all SAEs and all AEs (SAEs and non-serious AEs) associated 
with confirmed or suspected SARS-CoV-2 infection until resolution, the condition stabilizes, the 
event is otherwise explained, the event is deemed irreversible, the participant is lost to follow-up 
(as defined in Section 3.6.2) or for suspected cases, until SARS-CoV-2 infection is ruled out.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure.
An SAE report must be completed for any event where doubt exists regarding its seriousness. 
If the investigator believes that an SAE is not related to study drug, but is potentially related to the 
conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study drug, and pregnancies must be reported to BMS or 
designee within 24 hours of awareness of the event. SAEs must be recorded on the SAE Report 
Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). The preferred 
method for SAE data reporting collection is through the electronic case report form (eCRF). The 
paper SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF 
system is not functioning. In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. In the event the electronic system is unavailable for transmission, 
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paper forms must be used and submitted immediately. When paper forms are used, the original 
paper forms are to remain on site
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS (or 
designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious AE is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug until 100 days 
after discontinuation of dosing. Nonserious AE information should also be collected from the start 
of a placebo lead-in period or other observational period intended to establish a baseline status for 
the subjects. 
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment as 
appropriate. All identified nonserious AEs must be recorded and described on the nonserious AE 
page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities that 
are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (electronic) as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.
•
Any laboratory test result that is clinically significant or meets the definition of an SAE 
•
Any laboratory test result abnormality that required the subject to have study drug discontinued 
or interrupted
•
Any laboratory test result abnormality that required the subject 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 versus low hemoglobin value).
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6.4
Pregnancy
If, following initiation of the investigational product, it is subsequently discovered that a study 
subject is pregnant or may have been pregnant at the time of study exposure, including during at 
least 1 year after product administration, 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 Section 6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner (eg, dose 
tapering if necessary for subject safety). Please call the BMS Medical Monitor within 24 hours of 
awareness of the pregnancy.
The investigator must immediately notify the BMS Medical Monitor or designee of this event and 
complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours of 
awareness of the event and in accordance with SAE reporting procedures described in 
Section 6.1.1. 
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.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 6.1.1for reporting details.).
6.6
Potential Drug-Induced Liver Injury
Specific criteria for identifying pDILI have not been identified for this protocol. Standard medical 
practice in identifying and monitoring hepatic issues should be followed.
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a pDILI event. All occurrences of pDILIs, meeting the defined 
criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
pDILI is defined as: 
1) Aminotransaminases (AT) (ALT or AST) elevation > 3 times ULN
AND 
2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum ALP),
AND 
3) No other immediately apparent possible causes of AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic. 
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Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a pDILI event. All occurrences of pDILIs meeting the defined 
criteria must be reported as SAEs (see Section 6.1.1 for reporting details).
6.7
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, x-ray 
filming, or any other potential safety assessment required or not required by protocol should also 
be recorded as a nonserious or serious AE, as appropriate, and reported accordingly. 
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
8.1.1
Dose Escalation
As a Phase 1 dose escalation trial, the sample size for each dose escalation cohort depends on 
observed toxicity and posterior inference. Approximately 30 subjects are expected to be treated 
during each dose escalation part (BMS-986178 monotherapy [Part 1A], BMS-986178 in 
combination with nivolumab [Part 2A], and BMS-986178 in combination with ipilimumab 
[Part 3A]) for a combined total of approximately 90 subjects in Parts 1A, 2A and 3A. Initially, 
approximately 3 subjects will be treated at the starting dose levels of BMS-986178 or 
BMS-986178 in combination with nivolumab or ipilimumab. Additional cohorts of approximately 
3 evaluable subjects will be treated at recommended dose levels per BLRM (-Copula) 
recommendations during the dose escalation phase. At least 6 DLT-evaluable subjects will be 
treated at the MTD. At most, 12 DLT-evaluable subjects will be treated at each dose level. This 
limit is set to avoid instances in which the model could recommend adding subjects indefinitely to 
a specific dose level due to uncertainty in the tolerability profile. Escalation by more than 1 dose 
level (dose skipping) is not permitted.
As in any dose escalation study, the exact number of subjects in the dose escalation cannot be 
predicted. However, different estimates with the pre-specified parameters of the dose escalation 
design under various scenarios are provided (see Appendix 1). A maximum of 30 subjects is 
pre-specified as one of the simulation parameters (assuming approximately 6 subjects per dose 
level). The simulation provided in Appendix 1 uses combination therapy as an illustration 
(containing 5 dose levels for BMS-986178 and a fixed dose level for nivolumab [240 mg]). The 
simulation estimated a total of 15 to 21 subjects on average under different scenarios. Note the 
following difference between simulation setting and the conduct of the actual trial: 1) dose 
skipping is allowed in the simulation setting whereas in the actual clinical trial, dose skipping is 
not permitted, 2) the clinical team can override BLRM (-Copula) dose recommendation based on 
the totality of data (clinical safety data along with available PK and PD data). Based on these 
factors, there may be more subjects in the dose escalation phase than the number estimated in the 
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simulation. For planning purposes, it is assumed that approximately 30 subjects may be treated in 
each dose escalation part.
8.1.2
Cohort Expansion
The purpose of cohort expansion is to gather additional safety, tolerability, preliminary efficacy, 
PK, and PD information regarding BMS-986178 alone or in combination with nivolumab and/or 
ipilimumab.
In general, the estimated sample size for Parts 2B, 2C, 2D, 3B, 6B, and 7B in expansion phase is 
guided by Simon 2-stage design, which is based on target response rates (target ORR) and the 
ability to identify a signal for such clinical response that is above the SOC (historical ORR). 
Enrollment of subjects at the end of Stage 1 will continue while the initial efficacy evaluation is 
ongoing. Decisions regarding continuing or not continuing enrollment of a specific arm will be 
based on a combination of model guidance, clinical judgment on the totality of data (clinical safety, 
PK, PD, and efficacy), and communication between the Sponsor and investigators. Parts 2E and 
3C include tumors from dose escalation for signal seeking. Due to the heterogeneity of response 
rates of the mixed tumors, approximately 40 subjects is assigned for each part (Part 2E and 
Part 3C). It is not the intent of the study to use Simon 2-stage design for formal hypothesis testing 
for the following reasons:
•
At an early stage, the Sponsor would like to explore primary anti-tumor activity as a proof of 
confidence. According to the exploratory nature of an early phase design, the sample size is 
not large enough to clearly define the patient population. Meanwhile, there are no control arms 
planned as a comparison.
•
In immuno-oncology, it is known that response rate alone does not reflect all potential clinical 
benefits. Factors such as duration of response, the depth of response, and delayed response 
could become evident as potential benefits according to the nature of immunotherapy.
•
Safety is still the primary objective of the study, and if there is evidence of accumulated toxicity 
for a dose cohort, the cohort may be discontinued.
The Simon 2-stage design will be used as a guide for the disease-restricted expansion cohorts in 
Parts 2B, 2C, 2D, 3B, 6B, and 7B.175,177 The total sample size for each expansion cohort will be 
calculated to provide a reasonable false-positive rate (FPR) and false-negative rate (FNR) based 
on assumptions of true (target) and historic ORR for each indication. The sample size and operating 
characteristics of the Simon 2-stage design are provided in Table 8.1.2-1, although this is not used 
for hypothesis testing. Approximately 12 subjects for CRC and OCs, 10 subjects for BC, 17 
subjects for cervical cancer, and 28 subjects for RCC and NSCLC will be treated in Stage 1 for an 
initial evaluation of efficacy. 
This will inform potential early decisions and guide planning/operations or early termination after 
taking into consideration additional data, (eg, duration of response and/or SD and safety). If the 
true response rate is 10% for CRC and OC, the study has a 66% probability of early termination 
of the cohort. If the true response rate is 25% for BC, the study has a 53% probability of early 
termination of the cohort. If the true response rate is 20% for cervical cancer, the study has a 55% 
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probability of early termination of the cohort. If the true response rate is 40% for RCC and NSCLC, 
the study has a 55% probability of early termination of the cohorts.
For an expansion cohort of 35 subjects in CRC and OC and the assumed true response rate of 30%, 
there is a 94% chance of observing at least 7 responses (in other words, the FNR is 6%). If the true 
response rate is only 10% rather than 30%, then there is a 6% chance that there will be at least 
7 responses in 35 subjects (in other words, FPR is 6%). Also, if 7 responses are observed (eg, 20% 
observed response rate), the lower bound of the 80% CI for the ORR is 11% (higher than historical 
ORR of 10%). The CI is calculated using Clopper-Pearson method.
For an expansion cohort of 27 subjects with BC and the assumed true response rate of 50%, there 
is an 88% chance of observing at least 11 responses (in other words, the FNR is 12%). If the true 
response rate is only 25% rather than 50%, then there is a 5% chance that there will be at least 
11 responses in 27 subjects (in other words, FPR is 5%). If 11 responses are observed (eg, 41% 
observed response rate), the lower limit of the 80% CI for the ORR is 28% (higher than historical 
ORR of 25%). The CI is calculated using Clopper-Pearson method.
For an expansion cohort of 37 subjects with cervical cancer and the assumed true response rate of 
40%, there is an 87% chance of observing at least 12 responses (in other words, the FNR is 13%). 
If the true response rate is only 20% rather than 40%, then there is a 5% chance that there will be 
at least 12 responses in 37 subjects (in other words, FPR is 5%). If 12 responses are observed 
(eg, 32% observed response rate), the lower limit of the 80% CI for the ORR is 22% (higher than 
historical ORR of 20%). The CI is calculated using Clopper-Pearson method.
Table 8.1.2-1:
Dose Expansion - Characteristics of the Simon 2-Stage Design176
Expansion Cohort
Historic 
ORR
(%)
Target 
ORR
(%)
Stage 1/ 
Total N
Stage 1 
Responses 
Futility 
Boundary
FPR/1-FNR
(%)
Probability 
of Early 
Stopping
(%)
CRC, Ovarian Cancer
10
30
12/35
1
10/90
66
Bladder Cancer
25
50
10/27
2
10/90
53
Cervical Cancer
20
40
17/37
3
10/90
55
NSCLC, RCC
40
60
28/41
11
10/90
55
Abbreviations: CRC = colorectal cancer; FNR = false-negative rate; FPR = false-positive rate; NSCLC = non-small 
cell lung cancer; RCC = renal cell carcinoma.
The number of subjects receiving treatment for efficacy evaluation is approximate, and additional 
subjects may be treated in order to have sufficient response-evaluable subjects per expansion 
cohort.
8.1.3
Schedule and Dose Exploration and Safety Exploration
The purpose of Parts 4, 5, 6A, 7A, and 8 is to assess safety, tolerability, preliminary efficacy, PK, 
and PD information of BMS-986178 in combination with nivolumab administered with a less 
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frequent dosing schedule (q4w Part 4 and q12w Part 8 for BMS-986178) or BMS986178 in 
combination with higher dose of ipilimumab (Part 5) or BMS-986178 in combination with 
nivolumab and ipilimumab (Parts 6A and 7A). A minimum of 6 evaluable subjects will be treated 
in these parts at the MTD/RP2D chosen from Part 2A or Part 3A. Up to 12 subjects may be treated 
for further evaluation of safety, PK, or PD parameters. 
Part 9
The purpose of Part 9 is primarily to evaluate safety and tolerability and secondarily to assess PD 
and investigate preliminary anti-tumor activityof BMS-986178 in combination with nivolumab 
and DPV-001 or DPV-001 in combination with nivolumab monotherapy. Part 9 includes a cohort 
for the combination of BMS-986178, nivolumab, DPV-001 vaccine, single dose 
cyclophosphamide (cohort 1) and a cohort for the combination of nivolumab, DPV-001 vaccine, 
and single dose cyclophosphamide (cohort 2). Subjects are to be randomized in a 2:1 ratio. A total
of 12 subjects will be treated in cohort 1 and 6 evaluable subjects will be treated in cohort 2. 
Approximately 20% additional subjects may be enrolled in each cohort to ensure the number of 
evaluable subjects is achieved.
Assuming a 27% acceptable DLT rate, which corresponds to a Beta(1,2.7) distribution, Table 
8.1.3-1 shows the risk associated with selecting a dose level as safe given the number of DLTs 
observed at that dose level based on the posterior probability associated with an observed DLT.
Table 8.1.3-1:
Posterior Probability of DLT in Part 9 Assuming Observed DLTs
Number of Subjects 
DLT Evaluable in a 
Cohort
Number of Subjects 
with Observed DLT
Probability DLT Rate 
>33%
Probability DLT Rate 
>40%
6
1
16%
8%
2
41%
25%
12
2
9%
3%
3
23%
10%
18
3
5%
1%
4
14%
4%
24
4
3%
1%
6
17%
5%
Abbreviations: DLT=dose-limiting toxicities.
For all Parts that assess PD, administration of BMS-986178 in combination with nivolumab, 
nivolumab and ipilimumab, or nivolumab and DPV-001 in 6 to 12 subjects per dose and schedule 
level provides some precision of PD biomarker effect estimation. If more precise estimation is 
needed based on data observed, Part 9 may be further expanded to 24 subjects for Cohort 1 and 12 
subjects for Cohort 2. To assess the PD effects, pre-treatment and on-treatment whole blood and 
serum samples and tumor biopsies will be required. It is of interest to ensure the precision of the 
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estimate of the ratio of on-treatment biomarker assessments to pre-treatment (baseline) levels. 
Assuming that a biomarker is measured as a continuous variable, a given number of subjects will 
provide the confidence that the estimate of the ratio of on-treatment to baseline values will be 
within 20% of the true value, as shown in Table 8.1.3-2.
Table 8.1.3-2:
Probability that Estimated Ratio of On-treatment to Pre-treatment 
(Baseline) Value is Within 20% of True Value
Intra-subject Standard 
Deviation (Log-scale)
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Probability
N = 6
92%
76%
62%
52%
44%
38%
34%
N = 12
99%
90%
78%
68%
59%
52%
46%
N = 24
100%
98%
92%
84%
76%
68%
62%
For example, for a biomarker (eg, activated and memory CD4 and CD8 T-cells) with an 
intrasubject standard deviation of 0.5, if the true ratio of post-baseline to baseline geometric means 
is 1.2 (increase from baseline is 20%), there is 68% probability that the estimated ratio would be 
within 0.96 and 1.44 (or a percent change between -4% and 44%) with 12 subjects per treatment 
arm and the probability is 84% with 24 subjects per arm. If the true increase from baseline is 60%, 
for a biomarker with the same variability, then there is 68% probability that the estimated percent 
change would be between 28% and 92% with 12 subjects per treatment arm and between 37% and 
83% with 24 subjects per treatment arm.
Part 8
Up to approximately 20 evaluable subjects per dose cohort will be treated in Part 8. This sample 
size provides a 90% CI for the true proportion of subjects showing a change in receptor occupancy 
with width of 37% and 26% respectively when the observed proportion of subjects showing a 
change in receptor occupancy is 70% and 90%, as shown in Table 8.1.3-3. The maximum width 
of all 90% CIs is 40% and the maximum margin of error is 21% with a sample size of 20 per 
cohort.
Table 8.1.3-3:
90% Confidence Interval for the True Proportion of Subjects 
Showing a Biomarker Change
n
# subjects showing the trend
90% CI
20
14
(49%, 86%)
18
(72%, 98%)
8.2
Populations for Analyses
•
All Enrolled Subjects: All subjects who signed an ICF and are registered into the IRT.
•
All Treated Subjects: All subjects who received at least 1 dose of study medication.
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•
The PK data set includes all available concentration-time data from subjects who received any 
BMS-986178, nivolumab, or ipilimumab.
•
The immunogenicity data set consists of all available immunogenicity data from subjects who 
received BMS-986178, nivolumab, or ipilimumab.
•
The biomarker data set includes all available biomarker data from subjects who received any 
study drug(s). 
•
Response-evaluable subjects: All treated subjects with measurable disease and any of the 
following: 1) at least 1 post-baseline tumor measurement, 2) clinical progression, or 3) death.
Analyses of safety, extent of exposure, biomarkers, PK, preliminary efficacy, immunogenicity, 
and PD will be based on all treated subjects.
8.3
Endpoints
8.3.1
Primary Endpoint(s)
The assessment of safety will be based on the incidence of AEs, SAEs, AEs leading to 
discontinuation, and deaths. In addition, clinical laboratory test abnormalities will be examined.
AEs and laboratory values will be graded according to NCI CTCAE v4.03.
8.3.2
Secondary Endpoint(s)
8.3.2.1
Efficacy
The anti-tumor activity of BMS-986178 alone, in combination with nivolumab and/or ipilimumab, 
or in combination with nivolumab and DPV-001 and nivolumab in combination with DPV-001
will be measured by ORR based on RECIST v1.1. The above will be determined based on tumor 
measurements occurring at baseline, every 8 weeks (寲1 week) for Parts 1-7 and 9 or every 12 
weeks (±1 week) for Part 8 during the treatment period.
•
Best overall response (BOR) is assessed by investigator and/or BICR per RECIST 1.1 criteria.
•
ORR is defined as the proportion of all treated subjects whose BOR is either CR or PR.
8.3.2.2
Pharmacokinetics
Selected BMS-986178 parameters, such as Cmax, Tmax, AUC(0-t), and AUC(TAU), will be 
assessed in 2 cycles depending on the schedule for monotherapy or in combination with nivolumab 
and/or ipilimumab. Parameters such as Ctau, CLT, Css-avg, accumulation index (AI), and 
effective elimination half-life (T-HALFeff) will be assessed in the second cycle when intensive 
PK are collected. A separate listing, summary, and plot will be generated for Ctrough. 
8.3.2.3
Immunogenicity
The secondary objective of immunogenicity will be assessed by the frequency of positive ADA to 
BMS-986178 or nivolumab or ipilimumab.
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8.3.2.4
Pharmacodynamics
The secondary objective of pharmacodynamics will be assessed by the proportion of subjects 
showing a change in pharmacodynamic biomarkers such as soluble OX40 and peripheral OX40 
receptor occupancy along with tumor pharmacodynamic of BMS-986178 in combination with 
nivolumab or nivolumab monotherapy (Part 8). and sustained T cell expansion with DPV-001 in 
combination with nivolumab or nivolumab monotherapy (Part 9)
 
 
 
 
 
8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
Frequency distributions of gender and race will be tabulated. Summary statistics for age, body 
weight, and height will be tabulated.
8.4.2
Efficacy Analyses
The efficacy analyses will be performed on all treated subjects. Efficacy analyses based on 
response-evaluable subjects may be performed for interim analyses when the minimum follow-up 
period is less than sufficient to warrant adequate interpretation of results. Listing of tumor 
measurements will be provided by subject and study day in each arm and dose level. Individual 
subject’s BOR will be listed based on RECIST 1.1.
To describe the anti-tumor activity of BMS-986178 alone, in combination with nivolumab and/or 
ipilimumab, or in combination with nivolumab and DPV-001 and nivolumab in combination with 
DPV-001, ORR will be calculated. ORR and corresponding two-sided exact 95% CI by the 
Clopper-Pearson method will be provided by treatment and/or dose level and tumor type. 
8.4.3
Safety Analyses
All recorded AEs will be listed and tabulated by system organ class, preferred term, and treatment. 
Vital signs and clinical laboratory test results will be listed and summarized by treatment. Any 
significant physical examination findings and clinical laboratory results will be listed. ECG 
readings will be evaluated by the investigator, and abnormalities, if present, will be listed
8.4.4
Pharmacokinetic Analyses
All individual PK parameters will be listed for each analyte, including any exclusions and reasons 
for exclusion from summaries. Summary statistics will be tabulated for each BMS-986178 PK 
parameter by treatment. Geometric means and coefficients of variation will be presented for Cmax, 
AUC(0-t), AUC(TAU), Ctau, CLT, Css-avg, and AI. Medians and ranges will be presented for 
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Tmax. Medians and ranges will be presented for Tmax. Means and standard deviations will be 
presented for all other PK parameters (eg, T-HALFeff). 
BMS-986178 dose dependency will be assessed in dose escalation monotherapy. To describe the 
dependency on dose of BMS-986178, scatter plots of Cmax, AUC(0-t), and AUC(TAU) versus 
dose may be provided at the cycles when these PK parameters are assessed, as specified in 
Section 5.5. Exploratory assessments of dose proportionality based on a power model with CI 
around the power coefficient may be performed. Nivolumab and ipilimumab EOI and trough 
(Ctrough) concentrations and BMS-986178 trough concentration will be tabulated by treatment 
and study day using summary statistics. These data may also be pooled with other datasets for 
population PK analysis, which will be presented in a separate report.
8.4.5
Biomarker Analyses
In Part 9, summary statistics for the proportion of subjects showing a change in pharmacodynamics 
biomarkers will be tabulated by treatment cohort.
 
 
 
 
 
 
8.4.7
Outcomes Research Analyses
Not applicable.
8.4.8
Other Analyses 
A listing of all available immunogenicity data will be provided by treatment, dose, and 
immunogenicity status. The frequency of subjects with positive ADA assessment of BMS-986178, 
nivolumab, or ipilimumab will be summarized.
8.5
Interim Analyses
Administrative interim analysis for internal decision making or external publication purpose may 
be performed. No formal inferences requiring any adjustment to statistical significance level will 
be performed. 
9
STUDY MANAGEMENT
9.1
Compliance
9.1.1
Compliance with the Protocol and Protocol Revisions
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, BMS. The investigator should not implement any 
deviation or change to the protocol without prior review and documented approval/favorable 
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opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change will be 
submitted to:
•
IRB/IEC for review and approval/favorable opinion
•
BMS
•
Regulatory Authority(ies), if required by local regulations
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the subject: 
(1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a schedule 
of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. 
In addition, the study may be evaluated by BMS 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 BMS. 
9.1.2.1
Source Documentation
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
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Such systems may include, but are not limited to, electronic medical/health records, AE 
tracking/reporting, protocol required assessments, and/or drug accountability records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original. 
9.1.3
Investigational Site Training
BMS will provide quality investigational staff training prior to study initiation. Training topics 
will include but are not limited to: GCP, AE reporting, study details and procedure, electronic 
CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator 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, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study and BMS will notify the investigator 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, IRB). Notice of such 
transfer will be given in writing to BMS. 
9.2.2
Study Drug Records 
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include investigational product. 
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 subject, including unique subject 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
•
Retained samples for bioavailability/bioequivalence, if applicable 
•
Dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form.
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BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
9.2.3
Case Report Forms
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents, or the discrepancies must be 
explained. Additional clinical information may be collected and analyzed in an effort to enhance 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS EDC tool, electronic CRFs will be prepared for all data collection fields 
except for fields specific to SAEs and pregnancy, which will be reported on the or electronic SAE 
form and Pregnancy Surveillance form, respectively. If an electronic SAE form is not available, a 
paper SAE form can be used. Spaces may be left blank only in those circumstances permitted by 
study-specific CRF completion guidelines provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. For electronic CRFs, review and approval/signature is completed 
electronically through the BMS EDC tool. The investigator must retain a copy of the CRFs 
including records of the changes and corrections.
Each individual electronically signing electronic CRFs must meet BMS training requirements and 
must only access the BMS EDC tool using the unique user account provided by BMS. User 
accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report.
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria:
•
Subject recruitment (eg, among the top quartile of enrollers)
•
Involvement in trial design
•
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications or 
abstracts arising from this study require approval by BMS prior to publication or presentation and 
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must adhere to BMS’s publication requirements as set forth in the approved clinical trial agreement 
(CTA). All draft publications, including abstracts or detailed summaries of any proposed 
presentations, must be submitted to BMS at the earliest practicable time for review, but at any 
event not less than 30 days before submission or presentation unless otherwise set forth in the 
CTA. BMS shall have the right to delete any confidential or proprietary information contained in 
any proposed presentation or abstract and may delay publication for up to 60 days for purposes of 
filing a patent application. 
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10
GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
Complete Abstinence is defined as complete avoidance of 
heterosexual intercourse and is an acceptable form of 
contraception for all study drugs. This also means that
abstinence is the preferred and usual lifestyle of the patient. 
This does not mean periodic abstinence (e.g., calendar, 
ovulation, symptothermal, profession of abstinence for entry 
into a clinical trial, post-ovulation methods) and withdrawal, 
which are not acceptable methods of contraception. Women
must continue to have pregnancy tests. Acceptable alternate 
methods of highly or less effective contraception’s must be 
discussed in the event that the subject chooses to forego 
complete abstinence.
Additional Research
Those scientific activities which cannot be reasonably 
anticipated at the time of trial design, for which samples from 
study subjects may be collected and/or retained. Examples of 
additional research include, but are not limited to, new assay 
development and validation, companion diagnostic 
development, new hypotheses in the interaction of drug and 
the human body, and exploration of emerging science in the 
understanding of disease.
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11
LIST OF ABBREVIATIONS
Term
Definition
5-FU
5-fluorouracil
ADA
anti-drug antibody
ADCC
antibody-dependent cellular cytotoxicity
ADCP
antibody-dependent cellular phagocytosis
AE
adverse event
AFP
alpha fetal protein
AI
accumulation index
ALK
anaplastic lymphoma kinase 
ALP
alkaline phosphatase
ALT
alanine aminotransferase
APC
antigen-presenting cell
ASCO
American Society of Clinical Oncology
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-t)
Area under the plasma concentration-time curve from time zero to time 
of last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in 1 dosing interval
BC
bladder cancer 
BCR
B-cell receptor
BICR
Blinded Independent Central Review
BLA
Biologics License Application
BLRM
Bayesian Logistic Regression Method
BMS
Bristol-Myers Squibb
BOR
best overall response
BSC
best supportive care
BUN
blood urea nitrogen
C12
concentration at 12 hours
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Term
Definition
C
Cycle
CAP
College of American Pathologists
Cavgss
steady-state time-averaged concentration
CBC
complete blood count
CEA
carcinoembryonic antigen
CFR
Code of Federal Regulations 
cHL
classical Hodgkin lymphoma
CI
confidence interval
CL
clearance
CLss
steady-state clearance
CLT
total body clearance
Cmax
maximum observed concentration
Cmaxss
steady-state peak concentration
CMI
cell-mediated immunity
Cminss
steady-state trough concentration
CNS
central nervous system
CR
complete response
CRC
colorectal cancer
CrCL
creatinine clearance
CRF
case report form, paper or electronic
CRP
C-reactive protein
Css-avg
average concentration over a dosing interval (AUC[TAU]/tau)
CT
computed tomography
CTA
clinical trial agreement
Ctau
the observed concentration at the end of a dosing interval
CTCAE
Common Terminology Criteria for Adverse Events
CTLA-4
cytotoxic T-lymphocyte associated antigen-4
Ctrough
Trough observed plasma concentration
CV%
Percent coefficient of variation
D
day
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Term
Definition
DRiPs
defective ribosomal products
CV
coefficient of variation
DEHP
diethylhexyl phthalate 
DLT
dose-limiting toxicity
EC50
half maximal effective concentration
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EGFR
epidermal growth factor receptor
EMA
European Medicines Agency
EOI
end of infusion
EOT
end of treatment
ER
estrogen receptor
EWOC
escalation with overdose control
Fc
fragment crystallizable
FDA
Food and Drug Administration
FDG
fluorodeoxyglucose
FFPE
formalin-fixed, paraffin-embedded
FIH
first-in-human
FISH
fluorescence in situ hybridization
FNR
false-negative rate
FPR
false-positive rate
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
Geo Mean
geometric mean
GGT
gamma-glutamyl transferase
gMDSC
granulocytic myeloid-derived suppressor cell
GITR
glucocorticoid-induced TNFR-related gene
HCC
hepatocellular carcinoma
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Term
Definition
hCG
human chorionic gonadotrophin
HER2
human epidermal growth factor receptor 2
hERG
human Ether-à-go-go-Related Gene (hERG)
HIV
human immunodeficiency virus
HPV
human papillomavirus
HR
hazard ratio
HRT
hormone replacement therapy
IASLC
International Association for the Study of Lung Cancer 
IB
Investigator Brochure
ICD
International Classification of Diseases
ICF
informed consent form
ICH
International Conference on Harmonisation
ID
intradermal
IEC
Independent Ethics Committee
IFN-γ
interferon-γ
IgG1
immunoglobulin G1
IgG2
immunoglobulin G2
IHC
immunohistochemistry
IMDC
International Metastatic RCC Database Consortium 
IMP
investigational medicinal products
IL
interleukin
IN
intranodal
IO
immuno-oncology
IP
intraperitoneal
IRB
Institutional Review Board
IRR
infusion-related reaction
IRT
Interactive Response Technology
IUD
intrauterine device
IV
intravenous
KPS
Karnofsky Performance Scale
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Term
Definition
LDH
lactic acid dehydrogenase
LFT
liver function test
mAb
monoclonal antibody
MABEL
minimal anticipated biologic effect level
mCRC
metastatic colorectal cancer
MC38
murine colon carcinoma cell line 38
MDSC
myeloid-derived suppressor cell
MHC
major histocompatibility
mOS
median overall survival
mPFS
median progression free survival
mRCC
metastatic renal cell carcinoma 
MRI
magnetic resonance imaging
MSI
microsatellite instability
MSI-H
microsatellite instability-high
MSKCC
Memorial Sloan-Kettering Cancer Center
MST
Medical Surveillance Team
MTD
maximum tolerated dose
N
number of subjects or observations
NCA
non-compartmental analysis
NCI
National Cancer Institute
NK
natural killer
NKT
natural killer T
NSCLC
non-small cell lung cancer
OC
ovarian cancer
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PBT
platinum-based therapy
PCR
polymerase chain reaction
PD
pharmacodynamics
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Term
Definition
PD-1
programmed cell death-1
PD-L1
programmed cell death ligand-1
pDILI
potential drug-induced liver injury
PET
positron emission tomography
PFS
progression free survival
PFSR
progression free survival rate
PgR
progesterone receptor
PK
pharmacokinetics
PR
partial response
PSA
prostate-specific antigen
q2w
every 2 weeks
q3w
every 3 weeks
q4w
every 4 weeks
q6w
every 6 weeks
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria In Solid Tumors
RNA
ribonucleic acid
RO
receptor occupancy
RP2D
recommended Phase 2 dose (s)
RT-PCR
reverse transcriptase polymerase chain reaction
RT-qPCR
real-time quantitative polymerase chain reaction
SAE
serious adverse event
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SCCHN
squamous cell carcinoma of the head and neck
SD
stable disease
SLiPs
short-lived proteins
SNP
single-nucleotide polymorphism
SOC
standard of care
T
time
T3
triiodothyronine 
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Term
Definition
T4
thyroxine
TCGA
The Cancer Genome Atlas
TCR
T-cell receptor
TF
tumor free
TGI
tumor growth inhibition
TIL
tumor-infiltrating lymphocyte
T-HALF
half life
T-HALFeff
effective elimination half-life that explains the degree of accumulation 
observed for a specific exposure measure (exposure measure includes 
AUC[TAU], Cmax and Ctau)
Tmax
time of maximum observed concentration
TNBC
triple negative breast cancer
TNF-α
tumor necrosis factor-α
TNFRsf
tumor necrosis factor receptor super family
Treg
regulatory T-cell
TSH
thyroid-stimulating hormone
ULN
upper limit of normal
US
United States
Vc
volume of central
VEGF
vascular endothelial growth factor
VS
vital signs
Vss
volume of distribution at steady state
Vz
volume of distribution of terminal phase (if IV and if multi-exponential 
decline)
WOCBP
women of childbearing potential
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APPENDIX 3
RECIST 1.1
1
ASSESSMENT OF OVERALL TUMOR BURDEN AND MEASURABLE 
DISEASE
To assess objective response or future progression, it is necessary to estimate the overall tumor
burden at baseline and use this as a comparator for subsequent measurements. Measurable disease 
is defined by the presence of at least 1 measurable tumor lesion. When computed tomographic 
(CT) scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion 
should be twice the slice thickness.
Central assessments may be planned for this study. Copies of all scans should be kept at the site 
as part of the subject study file.  At the Sponsor’s discretion, scans may be collected centrally for 
further analysis. 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows:
1.1
Measurable Lesions
Measurable lesions must be accurately measured in at least 1 dimension (longest diameter in the 
plane of the measurement to be recorded) with a minimum size of:
•
10 mm by CT/magnetic resonance imaging (MRI) scan (CT/MRI scan slice thickness no 
greater than 5 mm)
•
10-mm caliper measurement by clinical examination (lesions that cannot be accurately 
measured with calipers should be recorded as non-measurable)
•
20 mm by chest X-ray
•
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥15 mm in the short axis when assessed by CT scan (CT scan slice thickness is 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis 
will be measured and followed.
1.2
Non-Measurable Lesions
•
All other lesions, including small lesions (longest diameter < 10 mm or pathological lymph 
nodes with ≥10 to < 15 mm short axis), as well as truly non-measurable lesions
•
Lesions considered truly non-measurable include the following: leptomeningeal disease, 
ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement 
of the skin or lung, and abdominal masses/abdominal organomegaly identified by physical 
examination that are not measurable by reproducible imaging techniques
1.3
Special Considerations Regarding Lesion Measurability
1.3.1
Bone Lesions
•
Bone scan, positron emission tomography (PET) scan or plain films are not considered 
adequate imaging techniques to measure bone lesions. However, these techniques can be used 
to confirm the presence or disappearance of bone lesions. 
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•
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components that 
can be evaluated by cross sectional imaging techniques such as CT or MRI, can be considered 
as measurable lesions if the soft tissue component meets the definition of measurability 
described above.
•
Blastic bone lesions are non-measurable.
1.3.2
Cystic Lesions
•
Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts.
•
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions 
if they meet the definition of measurability described above. However, if non-cystic lesions 
are present in the same subject, these are preferred for selection as target lesions.
1.3.3
Lesions with Prior Local Treatment
Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional 
therapy, are usually not considered measurable unless there has been demonstrated progression in 
the lesion.
1.4
Specifications by Methods of Measurements
1.4.1
Measurement of Lesions
All measurements should be recorded in metric notation (mm). All baseline evaluations should be 
performed as close as possible to the treatment start and never more than 30 days before the 
beginning of the treatment.
1.4.2
Method of Assessment
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation should 
always be done rather than clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical examination.
1.4.2.1
CT/MRI Scan
CT/MRI is the best currently available and reproducible method to measure lesions selected for 
response assessment. Measurability of lesions on CT/MRI scan is based on the assumption that 
CT/MRI slice thickness is 5 mm or less. When CT scans have slice thickness greater than 5 mm, 
the minimum size for a measurable lesion should be twice the slice thickness.
1.4.2.2
Chest X-ray
Chest CT is preferred over chest X-ray, particularly when progression is an important endpoint, 
since CT is more sensitive than X-ray, particularly in identifying new lesions. However, lesions 
on chest X-ray may be considered measurable if they are clearly defined and surrounded by aerated 
lung.
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1.4.2.3
Clinical Lesions
Clinical lesions will only be considered measurable when they are superficial and ≥10 mm 
diameter as assessed using calipers. For the case of skin lesions, documentation by color 
photography including a ruler to estimate the size of the lesion is suggested. As previously noted, 
when lesions can be evaluated by both clinical examination and imaging, imaging evaluation 
should be undertaken since it is more objective and may also be reviewed at the end of the study.
1.4.2.4
Ultrasound
Ultrasound is not useful in assessment of lesion size and should not be used as a method of 
measurement. If new lesions are identified by ultrasound in the course of the study, confirmation 
by CT or MRI is advised. 
1.4.2.5
Endoscopy, Laparoscopy
The utilization of these techniques for objective tumor evaluation is not advised.
2
BASELINE DOCUMENTATION OF ‘TARGET’ AND ‘NON-TARGET’ 
LESIONS
2.1
Target Lesions
When more than 1 measurable lesion is present at baseline all lesions up to a maximum of 
5 lesions total (and a maximum of 2 lesions per organ) representative of all involved organs 
should be identified as target lesions and will be recorded and measured at baseline.
Target lesions should be selected on the basis of their size (lesions with the longest diameter), 
should be representative of all involved organs, and should lend themselves to reproducible
repeated measurements.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then as noted below, only the short axis is added into the sum. The baseline 
sum diameters will be used as reference to further characterize any objective tumor regression in 
the measurable dimension of the disease.
2.1.1
Lymph Nodes
Lymph nodes merit special mention since they are normal anatomical structures that may be 
visible by imaging even if not involved by tumor. Pathological nodes that are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. 
Nodes that have a short axis < 10 mm are considered non-pathological and should not be recorded 
or followed.
2.2
Non-Target Lesions
All other lesions (or sites of disease) including pathological lymph nodes should be identified as 
non-target lesions and should also be recorded at baseline. Measurements are not required and 
these lesions should be followed as ‘present’, ‘absent’, or in rare cases ‘unequivocal 
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progression’. In addition, it is possible to record multiple non-target lesions involving the same 
organ as a single item on the case record form (eg, ‘multiple enlarged pelvic lymph nodes’ or 
‘multiple liver metastases’).
3
TUMOR RESPONSE EVALUATION
3.1
Evaluation of Target Lesions
Complete Response (CR):  Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to < 10 mm.
Partial Response (PR):  At least a 30% decrease in the sum of diameters of target lesions, taking 
as reference the baseline sum diameters.
Progressive Disease (PD):  At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest 
on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm. (Note: The appearance of 1 or more new lesions is also considered 
progression.)
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study.
3.1.1
Special Notes on the Assessment of Target Lesions
3.1.1.1
Lymph Nodes
Lymph nodes merit special mention since they are normal anatomical structures that may be visible 
by imaging even if not involved by tumor. Pathological nodes that are defined as measurable and 
may be identified as target lesions must meet the criterion of a short axis of ≥15 mm by CT scan. 
Only the short axis of these nodes will contribute to the baseline sum. Nodes that have a short axis 
< 10 mm are considered non-pathological and should not be recorded or followed.
3.1.1.2
Target Lesions That Become ‘Too Small to Measure’
All lesions (nodal and non-nodal) recorded at baseline should have their actual measurements 
recorded at each subsequent evaluation, even when very small (eg, 2 mm). If the radiologist is able 
to provide an actual measurement, that should be recorded, even if it is below 5 mm.
However, when such a lesion becomes difficult to assign an exact measure to then:
•
If it is the opinion of the radiologist that the lesion has likely disappeared, the measurement 
should be recorded as 0 mm.
•
If the lesion is believed to be present and is faintly seen but too small to measure, a default 
value of 5 mm should be assigned (note: in case of a lymph node believed to be present and 
faintly seen but too small to measure, a default value of 5 mm should be assigned in this 
circumstance as well). This default value is derived from the 5-mm CT slice thickness 
(but should not be changed with varying CT slice thickness).
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3.1.1.3
Target Lesions That Split or Coalesce on Treatment
•
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should 
be added together to calculate the target lesion sum.
•
As lesions coalesce, a plane between them may be maintained that would aid in obtaining 
maximal diameter measurements of each individual lesion. If the lesions have truly coalesced 
such that they are no longer separable, the vector of the longest diameter in this instance should 
be the maximal longest diameter for the ‘coalesced lesion’.
3.2
Evaluation of Non-Target Lesions
While some non-target lesions may actually be measurable, they need not be measured and instead 
should be assessed only qualitatively at the timepoints specified in the protocol. 
Complete Response (CR):  Disappearance of all non-target lesions. All lymph nodes must be non-
pathological in size (< 10 mm short axis).
Non-CR/Non-PD:  Persistence of 1 or more non-target lesion(s) above the normal limits.
Progressive Disease (PD):  Unequivocal progression of existing non-target lesions. (Note: The 
appearance of 1 or more new lesions is also considered progression.)
3.2.1
Special Notes on Assessment of Non-Target Lesions
The concept of progression of non-target disease requires additional explanation as follows:
3.2.1.1
When the Subject Also Has Measurable Disease
•
To achieve ‘unequivocal progression’ on the basis of the non-target disease, there must be an 
overall level of substantial worsening in non-target disease such that, even in the presence of 
SD or PR in target disease, the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy. 
•
A modest ‘increase’ in the size of 1 or more non-target lesions is usually not sufficient to 
quality for unequivocal progression status. 
3.2.1.2
When the Subject Has Only Non-Measurable Disease
•
To achieve ‘unequivocal progression’ on the basis of the non-target disease, there must be an 
overall level of substantial worsening such that the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy. 
•
A modest ‘increase’ in the size of 1 or more non-target lesions is usually not sufficient to 
qualify for unequivocal progression status. 
•
Because worsening in non-target disease cannot be easily quantified (by definition: if all 
lesions are non-measurable), a useful test that can be applied when assessing subjects for 
unequivocal progression is to consider if the increase in overall disease burden based on the 
change in non-measurable disease is comparable in magnitude to the increase that would be 
required to declare PD for measurable disease: that is, an increase in tumor burden representing 
an additional 73% increase in ‘volume’ (which is equivalent to a 20% increase diameter in a 
measurable lesion). Examples include an increase in a pleural effusion from ‘trace’ to ‘large’
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or an increase in lymphangitic disease from localized to widespread or may be described in 
protocols as ‘sufficient to require a change in therapy’. 
•
If ‘unequivocal progression’ is seen, the subject should be considered to have had overall PD 
at that point.
3.2.1.3
Tumor Markers
Tumor markers alone cannot be used to assess objective tumor responses. If markers are initially 
above the upper normal limit, however, they must normalize in order for a subject to be considered 
as having attained a complete response.
3.3
New Lesions
The appearance of new malignant lesions denotes disease progression. The finding of a new lesion 
should be unequivocal: that is, not attributable to differences in scanning technique, change in 
imaging modality or findings thought to represent something other than tumor (eg, some ‘new’ 
bone lesions may be simply healing or flare of preexisting lesions). This is particularly important 
when the subject’s baseline lesions show partial or complete response. For example, necrosis of a 
liver lesion may be reported on a CT scan report as a ‘new’ cystic lesion, which it is not.
A lesion identified on a follow-up study in an anatomical location that was not scanned at baseline 
is considered a new lesion and will indicate disease progression. An example of this is the subject 
who has visceral disease at baseline and while on study has a CT or MRI brain scan ordered that
reveals metastases. The subject’s brain metastases are considered to be evidence of PD even if 
he/she did not have brain imaging at baseline.
If a new lesion is equivocal, for example because of its small size, continued therapy and follow-up 
evaluation will clarify if it represents truly new disease. If repeat scans confirm there is definitely 
a new lesion, then progression should be declared using the date of the initial scan.
3.3.1
FDG-PET Evaluation
While [18F] fluorodeoxyglucose (FDG)-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of the qualitative assessment of FDG-PET scanning 
to complement CT scanning in assessment of progression (particularly possible ‘new’ disease). 
New lesions on the basis of FDG-PET imaging can be identified according to the following 
algorithm: 
•
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based 
on a new lesion. 
•
No FDG-PET at baseline and a positive FDG-PET at follow-up: 
−
If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by 
CT, this is PD. 
−
If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial positive FDG-PET 
scan).
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−
If the positive FDG-PET at follow-up corresponds to a preexisting site of disease on CT 
that is not progressing on the basis of the anatomic images, this is not PD.
4
RESPONSE CRITERIA
4.1
Timepoint Response
A response assessment should occur at each timepoint specified in the protocol. 
For subjects who have measurable disease at baseline Table 4.1-1 provides a summary of the 
overall response status calculation at each timepoint.
Table 4.1-1:
Timepoint Response: Subjects with Target (+/– Non-Target) Disease
Target Lesions
Non-Target Lesions
New Lesions
Overall Response
CR
CR
No
CR
CR
Non-CR/non-PD
No
PR
CR
Not evaluated
No
PR
PR
Non-PD or not all evaluated
No
PR
SD
Non-PD or not all evaluated
No
SD
Not all evaluated
Non-PD
No
NE
PD
Any
Yes or No
PD
Any 
PD
Yes or No
PD
Any
Any 
Yes
PD
Abbreviations: CR = complete response; NE =not evaluable; PD = progressive disease; PR = partial response; 
SD = stable disease.
Missing Assessments and Not Evaluable Designation
When no imaging/measurement is done at all at a particular timepoint, the subject is not evaluable 
(NE) at that timepoint. If only a subset of lesion measurements are made at an assessment, the case 
is also considered NE at that timepoint, unless a convincing argument can be made that the 
contribution of the individual missing lesion(s) would not have changed the assigned timepoint 
response.
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4.1.1
Confirmation Scans
•
Verification of Response: Confirmation of PR and CR is required after at least 4 weeks 
following initial assessment to ensure responses identified are not the result of measurement 
error.
4.2
Best Overall Response: All Timepoints
The best overall response is determined once all the data for the subject are known. It is the best 
response recorded from the start of the study treatment until the date of objectively documented 
progression based on RECIST v1.1, taking into account any requirement for confirmation, or the 
date of subsequent anti-cancer therapy, whichever occurs first in the study. The subject’s best 
overall response assignment will depend on the findings of both target and non-target disease and 
will also take into consideration the appearance of new lesions. 
Best response is defined as the best response across all timepoints with subsequent confirmation. 
Complete or partial responses may be claimed only if the criteria for each are met at a subsequent 
timepoint as specified in the protocol (generally 4 weeks later).
In this circumstance, the best overall response can be interpreted as specified in Table 4.2-1. When 
SD is believed to be best response, it must meet the protocol specified minimum time from 
baseline. Measurements must have met the SD criteria at least once after study entry at a minimum 
interval (in general, not less than 6 to 8 weeks) that is defined in the study protocol.
Table 4.2-1:
Best Overall Response When Confirmation of CR and PR Is 
Required
Overall Response
Overall Response
Best Overall Response
First Timepoint
Subsequent Timepoint
CR
CR
CR
CR
PR
SD, PD, or PRa
CR
SD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
PD
SD provided minimum criteria for SD duration met, otherwise, 
PD
CR
NE
SD provided minimum criteria for SD duration met, otherwise NE
PR
CR
PR
PR
PR
PR
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Table 4.2-1:
Best Overall Response When Confirmation of CR and PR Is 
Required
Overall Response
Overall Response
Best Overall Response
First Timepoint
Subsequent Timepoint
PR
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
Abbreviations: CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response;
SD = stable disease.
a If a CR is truly met at first timepoint, then any disease seen at a subsequent timepoint, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since the disease must have reappeared after CR). 
The best response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may 
be claimed when subsequent scans suggest small lesions were likely still present and in fact the subject had PR, not 
CR at the first timepoint. Under these circumstances, the original CR should be changed to PR and the best response 
is PR.
4.3
Duration of Response
4.3.1
Duration of Overall Response
The duration of overall response is measured from the time measurement criteria are first met for 
CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is 
objectively documented (taking as reference for progressive disease the smallest measurements 
recorded on study).
The duration of overall complete response is measured from the time measurement criteria are first 
met for CR until the first date that recurrent disease is objectively documented.
4.3.2
Duration of Stable Disease
Stable disease is measured from the start of the treatment (in randomized trials, from date of 
randomization) until the criteria for progression are met, taking as reference the smallest sum on 
study (if the baseline sum is the smallest, this is the reference for calculation of PD).
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APPENDIX 4
ECOG PERFORMANCE STATUS
ECOG Performance Statusa
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light housework, office work
2
Ambulatory and capable of all self-care but unable to carry out any work activities
Up and about more than 50% of waking hours
3
Capable of only limited self-care
Confined to bed or chair more than 50% of waking hours
4
Completely disabled
Cannot carry on any self-care
Totally confined to bed or chair
5
Dead
 
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SAP_001.pdf: 
Official Title of Study: 
A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination with Nivolumab and/or 
Ipilimumab in Subjects with Advanced Solid Tumors 
 
 
NCT Number: NCT02737475 
Document Date (Date in which document was last revised): September 3, 2021 


STATISTICAL ANALYSIS PLAN
FOR CLINICAL STUDY REPORT
A PHASE 1/2A STUDY OF BMS-986178 ADMINISTERED ALONE OR IN
COMBINATION WITH NIVOLUMAB AND/OR IPILIMUMAB IN SUBJECTS WITH 
ADVANCED SOLID TUMORS
PROTOCOL(S) CA012004
VERSION # 2.0
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3
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN FOR CLINICAL STUDY REPORT...................................1
REVISION HISTORY................................................................................................................2
TABLE OF CONTENTS 
.............................................. 
..............................................................3
2 
STUDY DESCRIPTION..........................................................................................6
2.1 
Study Design 
............................................................................................................6
2.1.1 
Dose Escalation (Part 1A, 2A and 3A)......................................................................9
2.1.1.1 
Part 1A: Monotherapy Dose Escalation..................................................................10
2.1.1.2 
Part 2A: Combination With Nivolumab Dose Escalation 
........................................10
2.1.1.3 
Part 3A: Combination With Ipilimumab Dose Escalation.......................................10
2.1.2 
Schedule and Dose Exploration (Parts 4,  5 and 8).................................................11
2.1.2.1 
Part 4: Combination With Nivolumab on a 4-week Schedule...................................11
2.1.2.2 
Part 5: Combination With Ipilimumab at 3 mg/kg...................................................11
2.1.2.3 
Part 8: Dose Regimen Exploration of Combination With Nivolumab in 
Bladder Cancer......................................................................................................11
2.1.3 
Safety Cohorts (Parts 6A and 7A) 
...........................................................................12
2.1.3.1 
Part 6A:Combination With Nivolumab and Ipilimumab in RCC..............................12
2.1.3.2 
Part 7A: Combination With Nivolumab and Ipilimumab in NSCLC........................12
2.1.4 
Dose Expansion Parts (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B and 7B)..........................12
2.1.4.1 
Part 2B: Combination With Nivolumab Dose Expansion in Colorectal 
Cancer....................................................................................................................12
2.1.4.2 
Part 2C: Combination With Nivolumab Dose Expansion in Bladder Cancer...........12
2.1.4.3 
Part 2D: Combination With Nivolumab Dose Expansion in Cancer of the 
Cervix.....................................................................................................................13
2.1.4.4 
Part 2E: Combination With Nivolumab Dose Expansion in Other Tumors for 
Signal Finding 
........................................................................................................13
2.1.4.5 
Part 3B: Combination With Ipilimumab Dose Expansion in Ovarian Cancer..........13
2.1.4.6 
Part 3C: Combination With Ipilimumab Dose Expansion in Other Tumors for 
Signal Finding 
........................................................................................................13
2.1.4.7 
Part 6B: Combination With Nivolumab and Ipilimumab in Renal Cell 
Carcinoma..............................................................................................................14
2.1.4.8 
Part 7B: Combination With Nivolumab and Ipilimumab in Non-small Cell 
Lung Cancer...........................................................................................................14
2.2 
Treatment Assignment............................................................................................14
2.3 
Blinding and Unblinding.........................................................................................15
2.4 
Protocol Amendments.............................................................................................15
3 
OBJECTIVES .................................................... ....................................................17
3.1 
Primary...................................................................................................................17
3.2 
Secondary...............................................................................................................17
4 
ENDPOINTS..........................................................................................................18
4.1 
Primary Endpoints..................................................................................................18
4.2 
Secondary Endpoints..............................................................................................18
4.2.1 
Efficacy ..................................................................................................................18
4.2.2 
Pharmacokinetics...................................................................................................19
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6
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
2
STUDY DESCRIPTION
2.1 
Study Design
This is a Phase 1/2a, open-label study of BMS-986178 in subjects with advanced solid tumors that 
integrates  initial  BMS-986178  monotherapy  with  subsequent  nivolumab  and/or  ipilimumab
combination therapy. Study sections (dose escalation and dose expansion) will proceed in a phased 
approach that is based upon study-emergent safety, PK, and PD data. The first section of the study 
will begin with BMS-986178 monotherapy dose escalation cohorts. The clinical data from the first 
3  monotherapy  dose  cohorts  will  serve  as  a  foundation  for  initiating  dose  escalation of  BMS 
986178  in  combination  with  nivolumab.  The  clinical  data  from  the  first  3  monotherapy dose 
cohorts in addition to the clinical data from the first cohort of BMS-986178 in combination with 
nivolumab  will  then  serve  as  a  foundation  for  initiating  dose  escalation  of  BMS-986178  in
combination with ipilimumab. The clinical data for BMS-986178 in combination with nivolumab 
and  BMS-986178  in  combination  with  ipilimumab  will  serve  as  the  foundation  for  initiating 
combination  
therapy  of  BMS-986178  with  nivolumab  and  ipilimumab  in  Parts  6  and  7.  After 
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7
establishment of a tolerable and pharmacologically active MTD/RP2D of BMS-986178 in the dose 
escalation schedule and dose exploration sections, and dose expansion in specific tumor cohorts 
will be initiated.
The study design schematic is presented in Figure 2.1-1andFigure 2.1-2.
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8
Figure 2.1-1: 
Study Design Schematic (Parts 1 to 7)
Dose  levels  are  specific  for  each  part.  Dose  expansion  will  begin  only  after  MTD/RP2D 
determination in the corresponding dose escalation phases of the study.
Abbreviations: MTD = maximum tolerated dose; RP2D = recommended phase 2 dose.
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and 3A doses intermediate to previously tested doses, or doses lower than the starting dose may 
be explored to further characterize the dose response for safety, immunogenecity, PK, or PD as 
appropriate based on clinical data collected.
Approximately 30 subjects will be enrolled in each dose escalation part. The number of subjects
in each dose escalation cohort may  vary depending on the BLRM (-Copula) recommendations.
Initially, approximately 3 subjects will  be treated at the starting dose  
levels of BMS-986178 or
BMS-986178 in combination with nivolumab or ipilimumab. Additional cohorts of approximately 
3 evaluable subjects will be treated at recommended dose levels per BLRM (-Copula) during the 
dose escalation phase. At least 6 DLT-evaluable subjects will be treated at the MTD.
2.1.1.1 
Part 1A: Monotherapy Dose Escalation
Part 1A is BMS-986178 monotherapy dose escalation. The initial dose of BMS-986178 for Part 
1A will be 20 mg with expected subsequent doses of 40, 80, 160, and 320 mg. Dosing of BMS-
986178 will begin on Day 1 of each cycle and will be administered q2w for up to 12 cycles.
2.1.1.2 
Part 2A: Combination With Nivolumab Dose Escalation
Part 2A is the combination arm of BMS-986178 with nivolumab that will be initiated only after at 
least  3  dose  
levels  in  
the  monotherapy  dose  escalation  have  been  found  
to  be  
tolerated  or  an
MTD/RP2D has been determined in the monotherapy dose escalation (Part 1A). The starting dose 
of BMS-986178 in Part 2A will be at least 1 dose level below a dose that was demonstrated to be
tolerated in Part 1A to ensure further safety of the combination. At no time will the dose for BMS-
986178 in Part 2A exceed the highest tolerated dose in Part 1A. Nivolumab will be administered 
at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be 
administered q2w starting on Day 1 of each cycle for up to 12 cycles.
2.1.1.3 
Part 3A: Combination With Ipilimumab Dose Escalation
Part 3A is the combination arm of BMS-986178 with ipilimumab that will be initiated only after 
at least 3 dose levels  
in the  monotherapy dose escalation  have been  
found to be tolerated or an 
MTD/RP2D has been determined in the monotherapy dose escalation (Part 1A) and at least 1 dose 
cohort  has  been  
found  
to  be tolerated  
in  
the  BMS-986178  with  nivolumab  dose  escalation  part
(Part 2A). The starting dose of BMS-986178 in Part 3A will be at least 1 dose level below a dose 
that was demonstrated to be tolerated in Part 1A. At no time will the dose for BMS-986178 in Part 
3A exceed the highest tolerated dose in Part 1A to further ensure safety of the combination doses 
in treated subjects. Ipilimumab will be administered at a dose of 1 mg/kg. Each treatment cycle 
will be 3 weeks in length. BMS-986178 will be administered q3w starting on Cycle 1 Day 1, up 
to and including 8 cycles, and ipilimumab will be administered q3w starting on Day 1 for 4 cycles. 
Only BMS-986178 will be administered in the last 4 cycles.
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2.1.2 
Schedule and Dose Exploration (Parts 4,  5 and 8)
2.1.2.1 
Part 4: Combination With Nivolumab on a 4-week Schedule 
Part 4 is the combination arm of BMS-986178 with nivolumab (480 mg) to be administered q4w. 
The dose of BMS-986178 will be a dose previously evaluated in Part 2A that has been found to 
have a manageable safety profile. If the starting dose of BMS-986178 is not tolerated or to further 
characterize the dose response for safety, PK, or PD as appropriate based on clinical data collected, 
a dose(s) lower or higher than the previously administered dose in this part may be explored. To 
further ensure safety of the combination, at no time will the dose for BMS-986178 in Part 4 exceed 
the highest tolerated dose  
in Part 2A, in which q2w dosing  
is explored. Approximately 6 to 12 
subjects will be treated in this schedule and dose exploration cohort.
2.1.2.2 
Part 5: Combination With Ipilimumab at 3 mg/kg
Part 5 is the combination arm of BMS-986178 with ipilimumab 3 mg/kg q3w for 4 doses, followed 
by  monotherapy with BMS-986178 (maintenance therapy). The dose of BMS-986178 will  be  a 
dose previously evaluated in Part 3A that has been found to have a manageable safety profile. If 
the starting dose of BMS-986178 is not tolerated or to further characterize the dose response for 
safety, PK, or PD as appropriate based on clinical data collected, a dose(s) lower or higher than 
the  previously  administered  dose  
in  
this  part  may  be  explored. To  
further  ensure  safety  of  
the 
combination, at no time will the dose for BMS-986178 in Part 5 exceed the highest tolerated dose 
in Part 3A. Approximately 6 to 12 subjects will  be treated in this schedule and dose exploration 
cohort.
2.1.2.3 
Part 8: Dose Regimen Exploration of Combination With Nivolumab in 
Bladder Cancer
Part 8 is a dose regimen exploration of BMS-986178 in combination with nivolumab or nivolumab
monotherapy. Nivolumab will be administered at a flat dose of 480 mg to be administered every 4
weeks.
Approximately 20 evaluable subjects per cohort will be treated in Part 8.
Part 8 Cohort 1-3:BMS-986178 will be administered as a flat dose of either 20 mg, 40 mg, or 80
mg q12w in combination with nivolumab flat dose (480 mg; q4w). Each treatment cycle will be
12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24
months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the
medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab
and BMS-986178.
Part 8 Cohort 4:Nivolumab monotherapy will be administered as a flat dose of 480 mg (q4w).
Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months
of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. A tetanus vaccine (Tdap
preferred, Td or equivalent after discussion with the medical monitor) will  be administered first
on Cycle 1 Day 1 prior to administration of nivolumab monotherapy.
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2.1.3 
Safety Cohorts (Parts 6A and 7A)
2.1.3.1 
Part 6A:Combination With Nivolumab and Ipilimumab in RCC
Part 6A is the safety cohort for the combination of BMS-986178 with ipilimumab and nivolumab 
in subjects with RCC. BMS-986178 will be administered at a flat dose of 40 mg in combination 
with nivolumab (240 mg) and ipilimumab (1 mg/kg) q3w during Cycles 1 to 4, followed by 
maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 
mg) will be administered q4w. Study drugs will be administered accordingly starting on Day 1 of 
each cycle. If the starting dose of BMS-986178 is not tolerated or to further characterize the dose 
response for safety, PK, or PD as appropriate based on clinical data collected, a dose(s) lower 
than the previously administered dose in this part may be explored. Approximately 6 to 12 
subjects will be treated in this safety cohort. 
2.1.3.2 
Part 7A: Combination With Nivolumab and Ipilimumab in NSCLC 
Part 7A is the safety cohort for the combination of BMS-986178 with ipilimumab and nivolumab 
in  subjects  with  NSCLC.  BMS-986178  will  be  administered  at  a  
flat  dose  of  40  mg  
(q2w)  
in 
combination  with  nivolumab  (240  mg;  q2w)  and  
ipilimumab  (1  mg/kg;  q6w)  for  four  6-week 
cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If the starting 
dose of BMS-986178 is not tolerated or to further characterize the dose response for safety, PK, 
or  PD  as  appropriate  based  on  clinical  data  collected,  a  dose(s)  lower  than  the  previously 
administered dose in this part may be explored. Approximately 6 to 12 subjects will be treated in 
this safety cohort.
2.1.4 
Dose Expansion Parts (Parts 2B, 2C, 2D, 2E, 3B, 3C, 6B and 7B)
Treatment  in  the  dose  expansion  cohorts  will  be  initiated  when  the  MTD/RP2D(s)  has  been
determined based on the evaluation of totality of available clinical safety (DLTs, AEs occurring
after the DLT period), immunogenecity, PK, PD, and modeling data from the dose escalation parts 
(1A,  2A, and  3A) or  schedule  and  dose  exploration  parts  (4  and  5).  Mandatory  pre- and  on-
treatment biopsies of tumor will be obtained for all study subjects.
2.1.4.1 
Part 2B: Combination With Nivolumab Dose Expansion in Colorectal
Cancer
Part 2B is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with CRC at the MTD/RP2D(s) determined in Parts 2A or 4. Nivolumab will be administered at a 
flat dose of 240or 480 mg. Each treatment cycle will be either 2(240 mg) or 4 (480 mg) weeks in 
length and study drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for 
up  
to  12 or  6 cycles,  
respectively.  Approximately 35  subjects  will  be  
treated  
in  
this  expansion
cohort.
2.1.4.2 
Part 2C: Combination With Nivolumab Dose Expansion in Bladder
Cancer
Part 2C is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with BC at the MTD/RP2D(s) determined in Parts 2A or 4. Nivolumab will be administered at a 
flat dose of 240 or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in 
length and study drugs will be administered every 2 or 4 weeks starting on Day 1 of each cycle for 
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up  
to  12 or  6 cycles,  
respectively.  Approximately  27  subjects  will  be  
treated  
in  
this  expansion 
cohort.
2.1.4.3 
Part 2D: Combination With Nivolumab Dose Expansion in Cancer of the
Cervix
Part 2D is the combination therapy (BMS-986178 with nivolumab) dose expansion part in subjects 
with  cervical  cancer  at  the  MTD/RP2D(s)  determined  in  Parts 2A or  4.  Nivolumab  will  be
administered at a flat dose of 240 or 480 mg. Each treatment cycle will be ether 2 (240 mg) or 4 
(480 mg) weeks in length and study drugs will be administered every 2 or 4 weeks starting on Day 
1 of each cycle for up to 12or 6 cycles, respectively. Approximately 37 subjects will be treated in 
this expansion cohort.
2.1.4.4 
Part 2E: Combination With Nivolumab Dose Expansion in Other Tumors
for Signal Finding
Part  2E  
is  
the  combination  
therapy  
(BMS-986178  with nivolumab)  dose  expansion  part  at  
the
MTD/RP2D(s) determined in Part 2Aor 4. Nivolumab will be administered at a flat dose of 240
or 480 mg. Each treatment cycle will be either 2 (240 mg) or 4 (480 mg) weeks in length and study 
drugs will  be administered every 2 or 4 weeks starting on Day 1 of each cycle for up to 12 or 6
cycles, respectively. Approximately 40 subjects will be treated in this expansion cohort.
Tumor types for this cohort will  be selected by Sponsor from those permitted in dose escalation
which do not have a dedicated expansion cohort or plans for evaluation in other studies and those
tumors  selected  will  be  communicated  
to  
the  investigators.  This  cohort  will  allow  for  further
exploration of early signs of clinical activity observed in tumors during the dose escalation phase
of the trial as well as potential signals arising from ongoing trials of other anti OX40 agonists in
combination with anti-PD(L)-1. Subjects enrolled in this cohort must be refractory to or intolerant 
of established therapy known to provide clinical benefit for their condition, i.e.,subjects must not 
be candidates for regimens known to provide clinical benefit.
2.1.4.5 
Part 3B: Combination With Ipilimumab Dose Expansion in Ovarian
Cancer
Part  3B  is  the  combination  therapy  (BMS-986178  with  ipilimumab)  dose  expansion  part  in 
subjects  with  OC  at  the  MTD/RP2D(s)  determined  in  Part  3A or  5. Ipilimumab  will  be 
administered at 1 or 3 mg/kg. Each treatment cycle will be 3 weeks in length. Ipilimumab will be 
administered  in  the  initial  4  cycles  in  combination  with  BMS-986178.  Then  the  subject  will 
continue  on  BMS-986178  monotherapy  
for  up to  an  additional  4  cycles  
for  a total  of  up  
to  24 
weeks (8 cycles) of treatment. Approximately 35 subjects with OC will be treated in this expansion 
cohort.
2.1.4.6 
Part 3C: Combination With Ipilimumab Dose Expansion in Other 
Tumors for Signal Finding
Part  3C  is  the  combination  therapy  (BMS-986178  with  ipilimumab)  dose  expansion  part  in
subjects with other tumors from dose escalation for signal finding at the MTD/RP2D(s) determined 
in Part 3A or 5. Ipilimumab will be administered at 1 or 3 mg/kg. Each treatment cycle will be 3 
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• Date of Birth
Based  on  
the  
rate  of  subject  enrollment,  
the  Sponsor  will  
implement  an  
IRT  
to  assign  subject
numbers,  study  part  and  dose  level  as  well  as  manage  drug  supply.  IRT  instructions  will  be
provided to the sites in a separate instruction manual.
Treatment group/dose level will be provided to the site study team through the IRT after the subject 
has been deemed eligible and is assigned for the study. Site personnel/investigator will receive a 
receipt confirming the treatment assignment. A copy of this documentation should remain in the 
subject’s chart. Because of the nature of the study design, limited early access to the assignment 
information will be granted to the study team.
Once it is determined that the subject meets the eligibility criteria, the investigative site will register 
the subject through IRT prior to the first study drug administration.
In  the  dose  escalation  phases,  if  a  subject  discontinues  treatment  with  either  BMS-986178,
nivolumab, or ipilimumab during the DLT period for reasons other than a DLT, the subject may
be replaced with a new subject, if  necessary,  
for safety assessments. Replacement subjects will
receive the same treatment but will be assigned a new subject number.
Subjects will be assigned to a part or a cohort within a part by IRT. Details about how the subjects 
will be assigned to a specific part/cohort will be provided in IRT training documentation.
Additional subjects may be added to expansion cohorts if adequate paired pre-treatment and on-
treatment  biopsy specimens  are  not obtained from  previously  assigned  subjects.  The  additional 
subjects will receive the same treatment as the subjects being replaced, but new subject numbers 
will be assigned.
Subjects may be permitted to rescreen for the study following agreement between the investigator 
and the Sponsor/medical monitor
2.3 
Blinding and Unblinding
This is an open label study.
2.4 
Protocol Amendments
Table 2.4-1: 
List of Protocol Amendment
Amendment 
number
Date 
Summaries
1
26-Apr-2016
• The timing of the initiation of combination therapy dose
escalation cohorts was revised, a sentinel subject was added 
to all dose cohorts, Parts 1B and 2B were removed and the
subsequent study parts were renamed (Part 1C to Part 1B, 
Part 2C to Part 2B, and Part 2D to Part 2C), DLT period 
across the study (28 days) was made uniform, the post-
infusion observation period was extended to 4 hours, 
contraceptive requirements were updated, lipase and amylase 
≤ 1.5×ULN were removed as criteria for adequate organ 
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Table 2.4-1: 
List of Protocol Amendment
Amendment 
number
Date 
Summaries
• Update of inclusion and exclusion criteria to include the new 
parts and clarify the maximum number of prior treatments 
allowed
• Update of study drug dosing and method of assigning 
subjects
• Update of dose delay language and addition of criteria for 
resuming treatment in subjects with an infusion reaction
• Update/addition of tables for treatment procedures, 
pharmacokinetic and anti-drug antibody sampling schedule, 
and pharmacodynamic/ biomarker sampling schedule
• Update of sample size information to include the new parts
• Update of Appendix 1 to include statistical methods for the 
new parts
• Typographical errors were corrected, and edits were made 
for consistency and clarity.
5
11-Dec-2017
• Addition of Part 8
• Update of Appendix 1
• Update schedule of assessments
• Update of address
• Typographical errors were corrected, and edits were made for 
consistency and clarity
3 
OBJECTIVES
3.1 
Primary
• To  determine  
the  safety,  
tolerability,  DLTs,  and  MTD/RP2D  of  BMS-986178  administered 
alone or in combination with  nivolumab and/or ipilimumab  
in subjects with advanced solid 
tumors
3.2 
Secondary
• To investigate the preliminary anti-tumor  activity of BMS-986178 administered alone or in 
combination with nivolumab and/or ipilimumab in subjects with advanced solid tumors
• To characterize the PK of BMS-986178 administered alone or in combination with nivolumab 
and/or ipilimumab
• To  characterize  
the  
immunogenicity  of  BMS-986178  administered  alone  or  
in  combination 
with  nivolumab  and/or  ipilimumab,  and  the  immunogenicity  of  nivolumab  or  ipilimumab 
administered with BMS-986178
• To  assess  the  proportion  of  subjects  showing  a  change  in  peripheral  pharmacodynamic 
biomarkers such as soluble OX40 and peripheral OX40 receptor occupancy along with tumor 
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• ORR: the total number of subjects whose BOR is either a complete response (CR) or partial 
response (PR) divided by the total number of subjects in the population of interest.
• Duration of response, computed for subjects with a BOR of CR or PR, is defined as the time 
between  
the  date  of  first  
response  and  
the  subsequent  date  of  disease  progression  or  death
(death after re-treatment will not be considered), whichever occurs first. The detailed censoring 
scheme is defined in Table 4.2.1-1
• PFSR at 24 weeks is defined as the proportion of treated subjects remaining progression free
and surviving at 24 weeks since the first dosing date. The proportion will be calculated by the 
Kaplan-Meier estimate, which takes into account censored data.
• Progression Free Survival (PFS) is specified as the time between the date of first dose and the 
first date of documented progression, (as per RECIST 1.1 criteria), or death due to any cause, 
whichever occurs first. The detailed censoring scheme is defined in Table 4.2.1-1.
aDeath and study tumor assessments after subsequent therapy or re-treatment are not considered
4.2.2 
Pharmacokinetics
The PK of BMS-986178 may be characterized using the following endpoints:
• Cmax: Maximum observed serum concentration
• Tmax: Time of maximum observed serum concentration
• Ctau: Observed serum concentration at the end of a dosing interval when intensive samples are 
collected
• AUC(0-t): Area under the serum concentration-time curve from time 0 to time t
Table 4.2.1-1: 
Censoring Scheme Used for Analysis of PFS on Initial Treatment
Situation 
Date of Progression or Censoring 
Outcome 
No baseline tumor assessmentsa
First Dosing date
Censored 
No on study tumor assessments and 
no deatha
First Dosing date
Censored
Documented progressiona
Date of the first documented 
progression per RECIST 1.1
Progressed 
No progression and no deatha
Date of last evaluable tumor 
assessment prior to re-treatment or 
subsequent therapy if exist
Censored 
New anticancer therapy, tumor-
directed radiotherapy, tumor-
directed surgery on target lesions or 
re-treatment therapy received 
without progression reported prior or 
on the same day
Date of last evaluable tumor 
assessment prior to initiation of the 
subsequent therapy or re-treatment
Censored 
Death without progressiona
Date of death 
Progressed 
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• AUC(TAU): Area under the serum concentration-time curve in 1 dosing interval
• CLT: Total body clearance
• Ctrough:  Trough observed  plasma  concentration  (this  includes  predose  concentrations  and 
Ctau concentrations).
• Css-avg: Average concentration over a dosing interval (AUC(TAU)/tau)
• AI: Accumulation Index. Ratio of an exposure measure at steady state (eg, following Cycle 3 
Day  1  dose) to that  after the  
first  dose (exposure  measure  
includes  AUC(TAU),  Cmax  and 
Ctau)
• T-HALFeff: Effective elimination half-life that explains the degree of accumulation observed 
for a specific exposure measure (exposure measure includes AUC(TAU), Cmax)
4.2.3 
Immunogenicity
The secondary objective of immunogenicity will be assessed by the frequency of positive ADA to 
BMS-986178 or nivolumab or ipilimumab.
At the sample  
level,  
individual samples will  be characterized  
into following category as shown 
below.
Table 4.2.3-1: 
Sample ADA Status
Sample ADA Status
Definition
Baseline ADA-positive sample
ADA is detected in the last sample before initiation of treatment
Baseline ADA-negative sample
ADA is not detected in the last sample before initiation of treatment
ADA-positive sample
after initiation of treatment, 1) an ADA detected (positive 
seroconversion) sample in a participant for whom ADA is not 
detected at baseline, or (2) an ADA detected sample with ADA titer 
to be at least 4-fold or greater (≥) than baseline positive titer
ADA-negative sample
After initiation of treatment, ADA not positive sample relative to 
baseline
Next, using the sample ADA status, participant ADA status is defined as follows:
Table 4.2.3-2: 
Participant ADA Status
ADA Status
Definition
Baseline ADA-positive subject
A participant with baseline ADA-positive sample
ADA-positive subject
A participant with at least one ADA positive-sample relative to 
baseline at any time after initiation of treatment
• Persistent Positive (PP)
ADA-positive sample at 2 or more consecutive timepoints, 
where the first and last ADA-positive samples are at least 16b
weeks apart
• Not PP-Last Sample Positive
Not persistent positive with ADA-positive sample at the last 
sampling timepoint 
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between simulation setting and the conduct of the actual trial: 1) dose skipping is allowed in the 
simulation setting whereas in the actual clinical trial, dose skipping is not permitted, 2) the clinical 
team can override BLRM (-Copula) dose recommendation based on the totality of data (clinical 
safety data along with available PK, immunogenecity and PD data). Based on these factors, there 
may be more subjects in the dose escalation phase than the number estimated in the simulation. 
For planning purposes, it is assumed that approximately 30 subjects may be treated in each dose 
escalation part.
5.2 
Dose Expansion
The  purpose of  dose  expansion  
is  
to  gather  additional  safety,  
tolerability,  preliminary  efficacy,
immunogenecity, PK, and PD information regarding BMS-986178 alone or in combination with 
nivolumab and/or ipilimumab.
In general, the estimated sample size for Parts 2B, 2C, 2D, 3B, 6B, and 7B in expansion phase is 
guided  by Simon 2-stage design, which  
is based on target response rates (target ORR), and the 
ability  
to  
identify  a  signal  for  such  clinical  response  
that  
is  above  
the  SOC  (historical  ORR). 
Enrollment  of  subjects  at  
the  end  of  Stage  1  will  continue  while  
the  initial  efficacy  evaluation  is 
ongoing. Decisions regarding continuing or not continuing enrollment of a specific arm will be based 
on a combination of model guidance, clinical judgment on the totality of data (clinical safety, PK, PD, 
and efficacy), and communication between the Sponsor and investigators. Parts 2E and 3C include 
tumors from dose escalation for signal seeking. Due to the heterogeneity of response rates of the 
mixed tumors, approximately 40 subjects is assigned for each part(Part 2E and Part 3C). It is not 
the intent of the study to use Simon 2-stage design for formal hypothesis testing.
The Simon 2-stage design will be used as a guide for the disease-restricted expansion cohorts in 
Parts 2B, 2C, 2D, 3B, 6B and 7B.The total sample size for each expansion cohort will be calculated 
to  provide  a  reasonable  false-positive  rate  (FPR)  and  false-negative  rate (FNR)  based  on 
assumptions of true (target) and historic ORR for each indication. The sample size and operating 
characteristics of the Simon 2-stage design are provided in Table 5.2-1,although this is not used 
for  hypothesis  testing.  Approximately  12  subjects  for  CRC  and  OCs. 10  subjects  for  BC. 17 
subjects for Cervical Cancer, and 28 subjects for RCC and NSCLCwill be treated in Stage 1 for 
an initial evaluation  of  efficacy.  This  will  inform  potential  early  decisions  and  guide 
planning/operations or  early  termination  after  taking  into  consideration  additional  data,  (eg, 
duration of response and/or SD and safety). If the true response rate is 10% for CRC and OC, the 
study has a 66% probability of early termination of the cohort. If the true response rate is 25% for 
BC, the study has a 53% probability of early termination of the cohort. If the true response rate is 
20% for cervical cancer, the study has a 55% probability of early termination of the cohort. If the 
true  response  rate  is  40%  for RCC  and  NSCLC,  the  study  has  a  55%  probability  of  early 
termination of the cohorts.
For an expansion cohort of 35 subjects in CRC and OC and the assumed true response rate of 30%, 
there is a 94% chance of observing at least 7 responses (in other words, the FNR is 6%). If the true 
response rate is only 10% rather than 30%, then there is a 6% chance that there will be at least 7 
responses in 35 subjects (in other words, FPR is 6%). Also, if 7 responses are observed (eg, 20% 
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observed response rate), the lower bound of the 80% confidence interval (CI) for the ORR is 11% 
(higher than historical ORR of 10%). The CI is calculated using Clopper-Pearson method.
Table 5.2-1: 
Dose Expansion - Characteristics of the Simon 2-Stage Design
Expansion Cohort
Historic
ORR
(%)
Target
ORR
(%)
Stage 1/
Total N
Stage 1
Responses
Futility
Boundary
FPR/1-FNR
(%)
Probability
Of Early
Stopping
(%)
CRC, Ovarian Cancer 
10 
30 
12/35
1
10/90
66
Bladder Cancer
25 
50 
10/27
2
10/90
53
Cervical Cancer
20 
40 
17/37
3
10/90
55
NSCLC, RCC
40 
60 
28/41
11
10/90
55
Abbreviations: CRC = colorectal cancer; FNR = false-negative rate; FPR = false-positive rate; ORR = objective
response rate.
For an expansion cohort of 27 subjects with BC and the assumed true response rate of 50%, there
is an 88% chance of observing at least 11 responses (in other words, the FNR is 12%). If the true
response rate is only 25% rather than 50%, then there is a 5% chance that there will be at least 11
responses  in  27  subjects  (in  other  words,  FPR  
is  5%).  If  11  responses  are  observed  (eg,  41%
observed response rate), the lower limit of the 80% CI for the ORR is 28% (higher than historical
ORR of 25%). The CI is calculated using Clopper-Pearson method.
For an expansion cohort of 37 subjects with cervical cancer and the assumed true response rate of 
40%, there is an 87% chance of observing at least 12 responses (in other words, the FNR is 13%). 
If the true response rate is only 20% rather than 40%, then there is a 5% chance that there will be 
at least 12 responses in 37 subjects (in other words, FPR is 5%). If 12 responses are observed (eg, 
32%  observed  
response  
rate),  
the  
lower  
limit  of  
the  80%  CI  
for the  ORR  
is  22% (higher than 
historical ORR of 20%). The CI is calculated using Clopper-Pearson method.
The number of subjects receiving treatment for efficacy evaluation is approximate and additional 
subjects may  be  treated  in  order  
to  have  sufficient  response-evaluable  subjects  per  expansion 
cohort.
5.3 
Schedule and Dose Exploration and Safety Exploration
The purpose of Parts 4, 5, 6A, 7A, and 8 is to assess safety, tolerability, preliminary efficacy, PK,
and  PD  
information  of  BMS-986178  
in  combination  with  nivolumab administered  with  a  
less
frequent  dosing  schedule  (q4w  Part  4 and  q12w  Part  8  for  BMS-986178)  or  BMS-986178  
in 
combination  with  higher  dose  of ipilimumab  (Part  5)  or  BMS-986178  in  combination  with 
nivolumab and ipilimumab (Parts 6A and 7A). 
In Parts 4, 5, 6A, and 7A, a minimum of 6 subjects will be treated at the MTD/RP2D chosen from 
Part 2A or Part 3A. Up to 12 subjects may be treated for further evaluation of safety, PK, or PD 
parameters. Administration of BMS-986178 in combination with nivolumab and/or ipilimumab in
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6  
to 12  subjects  per  dose  and schedule  
level  provides  90%  probability  of  observing  at  
least 1 
occurrence  of  a  specific  AE that  would  occur  with  a  32% or  17% incidence  
in  
the  population,
respectively.  Furthermore,  6  to  12  subjects  provide  some  precision  of PD  biomarker  effect
estimation.  To  assess  the  PD  effects,  pre-treatment  and  on-treatment  whole  blood  and  serum
samples and tumor biopsies will be required. It is of interest to ensure the precision of the estimate 
of the ratio of on-treatment biomarker assessments to pre-treatment (baseline) levels. Assuming 
that a biomarker is measured as a continuous variable, a given number of subjects will provide the 
confidence that the estimate of the ratio of on-treatment to baseline values will be within 20% of 
the true value, as shown in Table 5.3-1.
Table 5.3-1: 
Probability that Estimated Ratio of On-treatment to Pre-treatment 
(Baseline) Value is Within 20% of True Value
Intra-subject Standard 
Deviation (Log-scale)
0.2 
0.3 
0.4 
0.5 
0.6 
0.7 
0.8
Probability 
N=6 
92% 
76% 
62% 
52% 
44% 
38% 
34%
N=12 
99% 
90% 
78% 
68% 
59% 
52% 
46%
For  example,  
for  a  biomarker  
(eg,  activated  and  memory  CD4  and CD8  T-cells)  with  an  
intra-
subject standard deviation of 0.5, if the true ratio of post-baseline to baseline geometric means is 
1.2 (increase from  baseline  
is 20%), there  
is  68%  probability  
that the  estimated  
ratio  would  be 
within 0.96 and 1.44 (or a percent change between -4% and 44%) with 12 subjects per treatment 
arm. If the true increase from baseline is 60%, for a biomarker with the same variability, then there 
is  68%  probability  
that the  estimated  percent  change  would  be  between  28%  and  92%  with  12 
subjects  per  
treatment  arm.Up  
to  approximately  20  evaluable  subjects  per  dose cohort  will  be 
treated in Part 8. This sample size provides a 90% CI for the true proportion of subjects showing 
a  change  in  receptor  occupancy  with  width  of  37%  and  26%  respectively  when  
the  observed 
proportion of subjects showing a change in receptor occupancy is 70% and 90%, as shown in Table 
5.3-2. The maximum width of all 90% CIs is 40% and the maximum margin of error is 21% with 
a sample size of 20 per cohort.
Table 5.3-2: 
90% Confidence Interval for the True Proportion of Subjects 
Showing a Biomarker Change
n
# subjects showing the trend
90% CI
20
14
(49%, 86%)
18
(72%, 98%)
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6 
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES STUDY PERIODS
6.1 
Study Periods
For the purpose of analysis, baseline period (Section 6.1.1) and post baseline period (Section 6.1.2)
will be considered.
6.1.1 
Baseline Period
Baseline evaluations or events will be defined as evaluations or events that occur before the date 
and time of the first dose of study medication.
The following definitions will apply:
• Pre-treatment AEs will be defined as AEs with an onset date and time prior to but not including 
the day and time of the first dose of study treatment (or with an onset date prior to the day of 
the first dose of study treatment if time is not collected or is missing).
• Baseline evaluations (laboratory tests, pulse oximetry, vital signs, and ECG) will be defined as 
evaluations  with  a  date and  
time on  or  prior  
to  
the  day  and  
time of the first dose of study
treatment (or with an onset date on or prior to the day of the first dose of study treatment if 
time is not collected or is missing).
If there are multiple valid assessments, the assessment that is closest to day (and time if collected) 
of  the  first  dose  of  study  treatment  will  be  used  as  the  baseline  in  the  analyses.  If multiple 
assessments are collected at the same date (and time if collected), the assessment with the latest 
database entry date (and time if collected) will considered as baseline.
Tumor assessments will be slotted in the baseline period if assessments are before or on start of 
the treatment date. Baseline tumor assessment is the last assessment in the baseline period.
6.1.2 
Post Baseline Period
Post baseline period is further characterized into Treatment, and Re-treatment Periods.
Treatment Period
Treatment Period starts with the first dose date-time of initial study treatment.
On-treatment AEs will be defined as AEs with an onset date-time on or after the datetime
of the first dose of study treatment (or with an onset date on or after the day of the first
dose of  study  
treatment  
if  
time  
is  not  collected or  
is  missing).  For  subjects  who  are off
initial treatment, AEs will be counted as on-treatment if the event occurred within 100 days
of  
the  
last  dose of  
initial  study  medication  and  prior to the  
first  dose of  
re-treatment (if 
exist). No “subtracting rule” will  be applied when an AE occurs both pre-treatment and 
post-treatment with the same preferred term and grade. For subjects who are still on initial 
study treatment, all  available  AEs  will  be counted as on-treatment after the datetime (or 
date if time is not collected or missing) of the first dose.
On-treatment evaluations (laboratory tests, pulse oximetry and vital signs) will be defined
as evaluations taken after the day (and time, if collected and not missing) of the first dose 
of study treatment. For subjects who are off initial treatment, evaluations will be counted 
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as  on-treatment  if  evaluation  is  
taken within 100  days  of  
the  last dose  of  initial  study 
medication and on or prior to the first dose of the re-treatment (if exist). For subjects who 
are  still  on  initial study  treatment, all  available  evaluations  will  be  considered  as  on-
treatment after the datetime of the first dose.
Principal analysis of safety endpoints will be based on the treatment period. AEs and other 
evaluations  reported  during  the  re-treatment  period  will  be  listed  and  summarized
separately.
Tumor assessments will be slotted in the post-baseline period if assessments are after start 
of the treatment date and prior to the first dose of re-treatment (if exist).
Optional Re-treatment Period 
Optional Re-treatment Period starts with the first dose date-time of re-treatment
On-re-treatment AEs, will be defined as AEs with an onset date-time on or after the date-
time of the the first dose of re-treatment (or with an onset date on or after the day of the 
first  dose  re-treatment  
if  
time  is  not  collected  or  
is  missing).  For  subjects  who  are  off 
treatment  in  the  re-treatment  period,  AEs  will  be  counted  as  on  re-treatment  if  event 
occurred within 100 days of the last dose of re-treatment. For subjects who are still on re-
treatment  of  study  medication, all  available  AEs  with  onset  date-time  on  or  after  the 
datetime (or date if time is not collected or missing) of the first dose of re-treatment will 
be counted as on-re-treatment. 
On-re-treatment  evaluations  (laboratory  tests,  pulse  oximetry  and  vital  signs)  will  be 
defined as evaluations taken after the day (and time, if collected and not missing) of the 
first dose of re-treatment. For subjects who are off treatment  
in the re-treatment period, 
evaluations will be counted as on-re-treatment if evaluation is taken within 100 days of the 
last dose of re-treatment. For subjects who are still on re-treatment, all available evaluations 
taken after the day of the first dose of re-treatment will be considered as on-re-treatment.
Tumor assessments will be slotted in the post-baseline period if assessments are after the 
day (and time, if collected and not missing) of the first dose of re-treatment.
Baseline tumor assessment for re-treatment period is the last assessment prior to or on the date of 
the first dose of re-treatment.
6.2 
Treatment Regimens
The BMS-986178  monotherapy and combination arm of BMS-986178 with nivolumab 240  mg 
will be given on Day 1 of each cycle and will be administered every 2 weeks for up to 12 cycles
in Part 2 and Part 4. 
The combination arm of BMS-986178 with nivolumab 480  mg will  be given on Day 1 of each 
cycle. Nivolumab  will be administered every 4 weeks. BMS-986178 will be administered every 
4 weeks in Part 4 and every 12 weeks for Part 8. 
For combination arm of BMS-986178 with ipilimumab, BMS-986178 will be administered every 
3  weeks  starting  on  Cycle  1  Day  1,  up  to  and  including  8  cycles,  and  ipilimumab  will  be 
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administered every 3 weeks starting on Day 1 for 4 cycles. Only BMS-986178 will be administered 
in the last 4 cycles in Part 3 and Part 5.
In Part 6, For combination arm of BMS-986178 with nivolumab and ipilimumab for RCC, BMS-
986178 will be administred at a flat dose of 40 mg every 3 weeks during Cycles 1 to 4 starting on 
Cycle 1 Day 1, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 
mg) will  be admistered every 4 weeks. Nivolumab 240 mg will  be administered every 3 weeks 
during Cycles 1 to 4 starting on Cycle 1 Day 1, followed by maintenance therapy (Cycle 5 and 
beyond) in which Nivolumab 480 mg will be admistered every 4 weeks. Ipilimumab 1 mg/kg will 
be administered every 3 weeks starting on Cycle 1 Day 1 for 4 cycles.
In  Part  7,  For  combination  arm  of  BMS-986178  with  nivolumab  and  
ipilimumab  for  NSCLC, 
BMS-986178 will be administred at a flat dose of 40 mg every 2 weeks starting on Cycle 1 Day 1. 
Nivolumab 240 mg will be administered every 2 weeks starting on Cycle 1 Day 1. Ipilimumab 1 
mg/kg will be administered every 6 weeks starting on Cycle 1 Day 1 for 4, 6-week cycles.
Planned treatment are listed below. Some of the treatment arm may not have any subjects. Dose 
level for BMS-986178 in expasion cohort will be decided later based on esclation results.
Treatment Arm
Treatment Description
Esc BMS20
Escalation Part 1 BMS 20 mg Q2W
Esc BMS40
Escalation Part 1 BMS 40 mg Q2W
Esc BMS80
Escalation Part 1 BMS 80 mg Q2W
Esc BMS160
Escalation Part 1 BMS 160 mg Q2W
Esc BMS320
Escalation Part 1 BMS 320 mg Q2W
Esc BMS20+NIVO240 Q2W
Escalation Part 2 BMS 20 mg + Nivo 240 mg Q2W
Esc BMS40+NIVO240 Q2W
Escalation Part 2 BMS 40 mg + Nivo 240 mg Q2W
Esc BMS80+NIVO240 Q2W
Escalation Part 2 BMS 80 mg + Nivo 240 mg Q2W
Esc BMS160+NIVO240 Q2W
Escalation Part 2 BMS 160 mg + Nivo 240 mg Q2W
Esc BMS320+NIVO240 Q2W
Escalation Part 2 BMS 320 mg + Nivo 240 mg Q2W
Esc BMS20+IPI1
Escalation Part 3 BMS 20 mg + Ipi 1 mg/kg Q3W
Esc BMS40+IPI1
Escalation Part 3 BMS 40 mg + Ipi 1 mg/kg Q3W
Esc BMS80+IPI1
Escalation Part 3 BMS 80 mg + Ipi 1 mg/kg Q3W
Esc BMS160+IPI1
Escalation Part 3 BMS 160 mg + Ipi 1 mg/kg Q3W
Esc BMS320+IPI1
Escalation Part 3 BMS 320 mg + Ipi 1 mg/kg Q3W
Exp 2B
Expansion Part 2B (CRC)
Exp 2C
Expansion Part 2C BMS 80 mg + Nivo 240 mg Q2W (BDC)
Exp 2D
Expansion Part 2D (CVC)
Exp 2E
Expansion Part 2E (OT)
Exp 3B
Expansion Part 3B (OC)
Exp 3C
Expansion Part 3C (OT)
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Treatment Arm
Treatment Description
SDE Part 4
Schedule and Dose Exploration Part 4 BMS 80 mg + Nivo 480 mg
Q4W
SDE Part 5
Schedule and Dose Exploration Part 5 BMS 80 mg + Ipi 3 mg/kg
Q3W
SC Part 6A
Safety Cohort Part 6A BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg 
Q3W / BMS 40 mg + Nivo 480 mg Q4W (for RCC)
Exp Part 6B
Expansion Part 6B BMS 40 mg + Nivo 240 mg + Ipi 1 mg/kg  Q3W / 
BMS 40 mg + Nivo 480 mg Q4W(for RCC)
SC Part 7A
Safety Cohort Part 7A BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 
mg/kg Q6W (NSCLC)
Exp Part 7B
Expansion Part 7B BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 
mg/kg Q6W (NSCLC)
SDE Part 8 Cohort 1
Schedule and Dose Exploration Part 8 Cohort 1 BMS 20 mg Q12W + 
Nivo 480 mg Q4W
SDE Part 8 Cohort 2
Schedule and Dose Exploration Part 8 Cohort 2 BMS 40 mg Q12W + 
Nivo 480 mg Q4W
SDE Part 8 Cohort 3
Schedule and Dose Exploration Part 8 Cohort 3 BMS 80 mg Q12W + 
Nivo 480 mg Q4W
SDE Part 8 Cohort 4
Schedule and Dose Exploration Part 8 Cohort 4 Nivo 480 mg Q4W
The treatment group “as treated” will be the same as the arm as assigned by IRT. However, if a 
subject received the incorrect drug for the entire periodof treatment, the subject’s treatment group 
will be defined as the incorrect drug the subject actually received.
6.3 
Populations for Analyses
• All enrolled subjects: All subjects who signed an informed consent form and were registered 
into the IRT.
• All treated subjects: All subjects who received any dose of study therapy. This is the primary 
population for drug exposure, efficacy and safety analysis.
• PK  subjects:  All  subjects  with  available  serum  
time-concentration  data  
from  subjects  who 
received any BMS-986178 or Nivolumab or Ipilimumab.
• Immunogenicity subjects: All subjects with available data from subjects who received any 
BMS-986178 or Nivolumab or Ipilimumab and have  baseline and at least one post baseline 
immunogenicity measurement.
• Biomarker  Evaluable  Subjects:  All Treated  Subjects  with  at  least  one  evaluable 
measurement for a specific marker will be included in the dataset for that marker. Evaluable 
may differ depending on the analysis.
• Response Evaluable Subjects: All treated subjects with measurable disease at baseline and 
one of the following: 1) at least one postbaseline tumor measurement, 2) clinical progression 
or 3) death. This population may be used for interim efficacy analysis due to insufficient follow 
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7 
STATISTICAL ANALYSES
All analyses will be performed in SAS using version 9.2 or higher.
7.1 
General Methods
Continuous variables will be summarized by treatment group using the mean, standard deviation, 
median,  minimum,  and  maximum  values.  Some  continuous  variables may  also  be  summarized 
using the geometric mean and coefficient of variation. Categorical variables will be summarized 
by frequencies and percentages. Percentages will be rounded and may not always add up to 100. 
Percentages less than 0.1 will be indicated as “< 0.1”.
7.2 
Study Conduct
7.2.1 
Study Information
Listing:
• Batch  number.  Sort  by  batch  number  and  subject.  
It  
is  noted that  a  subject  may  appear 
multiple times under different batch numbers. 
7.2.2 
Accrual
The following will be presented on the All Enrolled Subjects. 
Summary:
• Number  (%)  of  subjects  accrued  by country and  investigational  site:  Include  country,  site 
number, Principal Investigator’s name, number of subjects enrolled, and number of subjects 
treated
Listing: 
• Subjects accrued by country and investigational site 
7.2.3 
Relevant Protocol Deviations
A relevant protocol deviation is a deviation from the protocol which is programmed in the database 
and  which  could  potentially  affect  
the  
interpretability  of  
the  study  results.  Non-programmable 
relevant eligibility and on-treatment protocol deviations, as well as significant (both programmable 
and  non-programmable)  will  be  reported  through  ClinSIGHT  listings.  The  following 
programmable  deviations  from  inclusion  and  exclusion  criteria  will  be  considered  as  relevant 
protocol deviations and a listing will be provided. 
At Entrance: 
• Subject without measurable disease at baseline
• Subjects with baseline ECOG performance status > 1
−Subjects  with  
inadequate  organ  function defined  as  one  of  
the  following:Neutrophils  < 
1500/μL
−Platelets < 80 × 10
3/μL
−Hemoglobin < 8 g/dL
−ALT or AST > 3 × upper limit of normal (ULN)
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−Total bilirubin > 1.5 × ULN (subjects with Gilbert’s Syndrome will be excluded only if the 
information is available in the database)
−Albumin < 2 g/dL
−Serum creatinine > 1.5 × ULN with creatinine clearance (CrCl) < 40 mL/min
On-Treatment: 
• Subjects receiving doses or frequencies that is different than what they was assigned.
7.3 
Study Population
7.3.1 
Subject Disposition
Summary: 
• Pre-treatment period: The number (%) of subjects of the following will be summarized on the 
All Enrolled Subjects.
−Subjects enrolled 
−Subjects treated
−Subjects enrolled but not treated with the reasons 
• End of treatment period: The number (%) of subjects of the following will be summarized by 
treatment and part, based on the All Treated Subjects.
−Subject completing the treatment (including additonal cycles when applicable)
−Subject  still  on  treatment (subjects  who  continued  to  additional  cycles  and  still  being 
treated are considered as on-treatment)
−Subject discontinued treatment
−Reasons  for  discontinuation  (including  the  reason  for  discontinuation  from  additional 
cycles when subjects continued to them after completing 24 weeks for parts 1-7 and 24 
months for Part 8)
−Subjects continuing in the study
−Subjects not continuing in the study
−Reason for not continuing in the study
−Subject received re-treatment 
Listing: 
• Pre-treatment period: Screen failure Subjects with reason
• End of treatment period: Treated subjects with off discontinuation reason for initial treatment 
( by treatment), Treated subjects with off discontinuation reason for re-treatment. 
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7.3.2 
Demographics and Other Baseline Characteristics
The following subject demographics and baseline characteristics will be summarized by treatment 
arm and overall for each part where applicable using descriptive statistics or frequency statistics. 
The definition of baseline defined in Section 6.1.1 will be applied here. 
• Age (in years); age category (<65, >=65) 
• Gender 
• Race 
• Ethnicity 
• Height 
• Weight 
• ECOG status 
• Prior therapy (surgery, radiotherapy, systemic therapy setting, number of regimen) 
• Mutation status (B-RAF, ALK/EGFR/K-RAS/ROS1 etc.) 
• Disease characteristics
−Colorectal Cancer
♦Stage at initial diagnosis and at study entry
♦Cell type
−Bladder Cancer
♦Tumor type
♦Stage at initial diagnosis and at study entry
♦Cell type
♦Minor Histological Variants
♦Subtype of disease
−Cancer of the Cervix
♦Stage at initial diagnosis and at study entry
♦Cell type
−Ovarian Cancer
♦Stage at initial diagnosis and at study entry
♦Cell type
♦Histologic
−Other Tumors
♦Stage at initial diagnosis and at study entry
♦Cell type
Listing: 
• All relevant data, generally variables listed above 
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• General medical history 
7.4 
Extent of Exposure
The extent of exposure will be characterized according to the number of subjects exposed, the duration 
of exposure, and the dose to which they were exposed. Analyses in this section will be performed on 
the population of All Treated Subjects “as treated” as described in Section 6.2.
Extent of Exposure will be assessed separately for original treatment and re-treatment.
7.4.1 
Study Therapy 
Summary: 
• Number (%) of treated subjects exposed for specified periods of time such as less than 1 week, 
1 week to 1 month, 1 month to 6 months by treatment group (initial treatment and re-treatment). 
• Descriptive statistics will be provided by study drug and treatment period (initial treatment and 
re-treatment) for the following. For part 6, the following information will be summarized by 
treatment period, treatment cycle (first 4 cycle vs. cycle 5 and above) and study drug.
−Number of doses 
−Duration of therapy (weeks)
−Cumulative dose, dose intensity, relative dose intensity  may  also be presented if deemed 
appropriate.
Table 7.4.1-1, Table 7.4.1-2and Table 7.4.1-3summarizes the key parameters used to calculate 
dosing data for each treatment group.
Table 7.4.1-1: 
Study Duration of Therapy Parameter Definitions for BMS-986178
Treatment
Duration of Therapy (day)
BMS-986178 Q2W in Parts 1,2 and 7
Last dose date - Start dose date +14
BMS-986178 Q3W in Parts 3 and 5
Last dose date - Start dose date +21
BMS-986178 Q4W in Parts 2 and  4
Last dose date - Start dose date +28
BMS-986178 in Part 6
Last dose date prior to cycle 5 dosing - Start dose date +21 for  Cycle 1 to 
Cycle 4
Last dose date - first cycle 5 dose date +28 for  Cycle 5 or above
BMS-986178 Q12W in Part 8
Last dose date - Start dose date +84
Table 7.4.1-2: 
Study Duration of Therapy Parameter Definitions for Nivolumab
Treatment
Duration of Therapy (day)
Nivolumab Q2W in Parts 2 and 7
Last dose date - Start dose date +14
Nivolumab Q4W in Parts 2, 4 and 8
Last dose date - Start dose date +28
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Table 7.4.1-2: 
Study Duration of Therapy Parameter Definitions for Nivolumab
Treatment
Duration of Therapy (day)
Nivolumab in Part 6
Last dose date prior to cycle 5 dosing - Start dose date +21 for Cycle 1 to 
Cycle 4
Last dose date - first cycle 5 Start dose date +28 for Cycle 5 or above
Table 7.4.1-3: 
Study Duration of Therapy Parameter Definitions for Ipilimumab
Treatment
Duration of Therapy (day)
Ipilimumab Q3W in Parts 3, 5 and 6
Last dose date - Start dose date +21
Ipilimumab Q6W in Part 7
Last dose date - Start dose date +42
Listing: 
• Drug administration of study medication 
• Number  of  doses,  duration  of  therapy,  cumulative  dose,  dose  intensity,  and  relative  dose 
intensity 
7.4.2 
Modification of Study Therapy
Summary: 
The following will be provided by study drug and treatment period (initial treatment and re-treatment). 
• Number (%) of subjects with dose delay along with the reason
• Number (%) of subjects with treatment discontinuation along with the reason
• Infusion interruptions 
−Number (%) of subjects with at least one infusion interruption along with the reason* 
−Number of infusion interruptions per subject 
−Number (%) of subjects with at least one IV infusion rate reduction along with the reason* 
*More than one reason or one interruption per patient may be counted in these statistics 
Listing:
All relevant information on dose modification listed above
 
 
 
 
 
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7.5
Efficacy
The primary efficacy analyses will be performed on All Treated Subjects for the final analysis. For 
interim analyses when the minimum follow-up period is less than sufficient to warrant adequate 
interpretation of the result, efficacy analyses may be performed on Response-evaluable Subjects. 
All  analysis  
listed  below  will be  performed  for  
initial  
treatment.  Some  of  
the  analysis  may  be 
performed for re-treatment if deemed appropriate. 
Summary analysis will be performed for expansion cohorts only (include subjects treated at the 
same dose level in dose escalation with same tumor type if appropriate). In the case of superior 
response observed  
in escalation phase, summary  analysis  may also be performed  
for escalation 
dose levels as appropriate. All analyses will be presented by part , treatment group and/or tumor 
type (if appropriate), unless otherwise specified. Listings will be provided for all dose levels. 
Time  to  event  distribution  (e.g.  progression  free  survival,  overall  survival,  and  duration  of 
response) will  be  estimated  using  Kaplan-Meier  
(K-M)  method.  When  appropriate, the  median 
along  with  95%  confidence  interval  (CI)  will  be provided  using  Brookmeyer  and  Crowley 
methodology.  Rates  at  
fixed  
timepoints  
(eg,  PFSR  at  6  months)  will  be  derived  
from  
the  K-M 
estimate  and  corresponding  CI  will  be  derived  based  from  Greenwood’s  formula.  Confidence 
intervals  for  binomial proportions  will  be  derived  using  
the  Clopper-Pearson  method.  Time  
to 
event rates will not be reported if the number of subjects at risk at that time is too small (eg, <5).
Summary: 
The following will be summarized 
• The ORR with corresponding 2-sided 95% CI based on the Clopper-Pearson method, along 
with each category of BOR. .
• The DOR with median (95% CI) by K-M method along with the range (min, max). The number 
of subjects still in response at the time of database lock will be indicated. 
• The PFS and   with median (95% CI) by K-M method along with the range (min, max). 
• The PFSR at specified timepoints by K-M method. 
•
 
Figure: 
• Percent change from baseline in target lesion tumor burden over time (spider plot) 
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• Maximum reduction in target lesions tumor burden (waterfall plot) 
• Kaplan-Meier plot of DOR for responders only 
• Swimmer plot of DOR, and time on therapy for responders only 
• Kaplan-Meier plot of PFS 
• Kaplan-Meier plot of OS 
Listing: 
The following will be listed by tumor type and treatment group. 
• Tumor lesion measurements 
• Tumor evaluation at each  visit,  
including  non-target lesions and  new  
lesions, tumor change 
from smallest sum of diameters in target lesions, and corresponding change (or percent change) 
from baseline 
• Subject level efficacy for All Treated Subjects: BOR, OS, PFS, best response in target lesions,
death indicator, duration of response for responders 
• Survival - survival status, first dose date, last dose date, last known alive date, death date, time 
to death
7.6 
Safety
Analysis  of  safety  will  be  based  on  All  Treated  Subjects  and  presented  by  
treatment arm  and 
overall. Deaths and SAEs will be listed using All Enrolled Subjects. 
Adverse  events  will  be  coded  according  
to  
the  most  recent  version  of  Medical  Dictionary  for 
Regulatory Activities (MedDRA) at the time of database lock and the severity will be graded using 
the NCI CTCAE version 4.03. Drug-related AEs are those events with relationship to study drug 
“Related” as recorded on the Case Report Form (CRF). If the relationship to study drug is missing, 
the AE will be considered as drug-related. 
Listing  of  adverse  events  will  include  all  enrolled  subjects  as  SAEs  and  deaths  are  collected 
pretreatment. Summaries of adverse events will include all on-treatment adverse events as defined 
in section  6.1.2.  Adverse  events  occurred  after  original  treatment  or  re-treatment  will  be 
summarized and listed separately. 
When reporting adverse events by CTC grade, summary tables will be provided based on the event 
with  worst  CTC  grade  
(independent  of  
relationship  
to  study  medication).  Subjects  will  only  be 
counted (1) once at the preferred term (PT) level, (2) once at the system organ class (SOC) level, 
and (3) once in the ‘Total subject’ row at their worst CTC grade, regardless of SOC or PT. 
The analysis of laboratory results will be based on All Treated Subjects. Laboratory results will be 
categorized according to NCI CTCAE (version 4.03) grade. Baseline is defined as the last non-
missing  measurement  prior  
to  
the  first  dosing  date  and  
time.  Summaries  of  laboratory  results 
include baseline and on-treatment results as defined in section 6.1.2. 
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After trial completion, the final posteriors for parameters of BLRM (-Copula) model that describe 
the DLT profile of BMS-986178 alone or in combination with nivolumab will be summarized.
7.6.1 
All Adverse Events
Summary:
AEs  and  drug-related  AEs  will  be  
tabulated  by  descending  frequency  of  SOC  and  descending 
frequency of PT within each SOC, unless specified otherwise. 
• Overall summary of any AEs by worst CTC grade (grade 1, 2, 3, 4, 3-4, 5, unknown, total) 
presented by SOC/PT 
• Overall  summary  of  drug-related  AEs  by  worst  CTC  grade  (grade  1,  2,  3,  4,  3-4,  5, 
unknown, total) presented by SOC/PT 
DLT rate will be summarized by treatment group.
Listing: 
• All recorded Adverse Events will be listed.
• All recorded DLTs will be listed.
7.6.2 
Deaths
Summary: 
• All deaths will be summarized for cause of deaths by treatment group. 
Listing: 
• All recorded deaths for All Enrolled Subjects will be listed 
7.6.3 
Serious Adverse Events
Summary: 
The following will be summarized by treatment arm and study part. 
• Overall  summary  of  SAEs  by  worst  CTC  grade  
(grade  1,  2,  3,  4, 3-4, 5)  presented  by 
SOC/PT 
• Overall  summary  of  drug-related  SAEs  by  worst  CTC  grade  (grade 1,  2,  3,  4, 3-4,  5) 
presented by SOC/PT. 
Listing: 
• By-subject SAE listing will be provided for the All Enrolled Subjects. 
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7.6.4 
Adverse Events Leading to Discontinuation of Study Therapy
Adverse  events  
leading  
to  study drug  discontinuation  are  AEs  with  action  
taken  as  “Drug  was 
discontinued”. 
Summary: 
• Overall summary of AEs leading to discontinuation by worst CTC grade (grade 1, 2, 3, 4, 3-
4, 5, total) presented by SOC/PT 
• Overall summary of drug-related AEs leading to discontinuation by worst CTC grade (grade 
1, 2, 3, 4, 3-4, 5, total) presented by SOC/PT 
Listing: 
• By-subject AEs leading to discontinuation listing will be provided 
7.6.5 
Adverse Events Leading to Dose Delay
Adverse events leading to study drug dose delay are AEs with action taken as “Dose was delayed”. 
Summary: 
• Overall summary of AEs leading to dose delay by worst CTC grade (grade 1, 2, 3, 4, 3-4, 5, 
total) presented by SOC/PT 
• Overall summary of drug-related AEs leading to dose delay by worst CTC grade (grade 1, 2, 
3, 4, 3-4, 5, total) presented by SOC/PT 
Listing: 
• By-subject AEs leading to dose delay listing will be provided 
7.6.6 
Events of Special Interest
The  events  of  special  interest  (EOSI)  consist  of  a  list  of  preferred  terms  grouped  by  specific 
categories (endocrinopathies, infusion reactions, gastrointestinal, hepatobiliary, pulmonary, renal, 
skin). These categories are defined by the Sponsor and the list that is most current at the time of 
analysis will be used. Changes may be made to this list with each new version of MedDRA and 
the final list used for the CSR will be included in an Appendix of the CSR. At the time this SAP 
is  
finalized,  Select  AEs  and  
IMAEs  
identified  
in  
the  Nivolumab program  will  be  used  
for  
this 
study.
Summary: 
The following will be summarized by treatment arm and overall. 
• Overall summary of any EOSI by worst CTC grade presented by Category/PT (grade 1, 2, 
3, 4, 3-4, 5, total). 
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• Overall summary of drug-related EOSI by worst CTC grade presented by Category/ PT 
(grade 1, 2, 3, 4, 3-4, 5, total). 
• Overall  summary  of  any  serious  EOSI  by  worst  CTC  grade  presented  by  Category/PT 
(grade 1, 2, 3, 4, 3-4, 5, total). 
• Overall  summary  of  any  drug  related  serious  EOSI  by  worst  CTC  grade  presented  by 
Category/PT (grade 1, 2, 3, 4, 3-4, 5, total). 
• Overall summary of any EOSI leading to discontinuation by worst CTC grade presented 
by Category/PT (grade 1, 2, 3, 4, 3-4, 5, total). 
• Overall  summary  of  drug-related  EOSI  
leading  
to  discontinuation  by  worst  CTC  grade 
presented by Category/PT (any grade, grade 3-4, grade 5). 
Listing: 
• EOSI definition 
• Listings for the EOSI will be provided.
7.6.7 
Multiple Events
Analyses that take into account the multiple occurrences of a given AE will be conducted. In order 
to prepare these analyses, the CRF data will be processed according to standard BMS algorithms
in order to collapse AE records into unique records based on the PT. This data will be presented 
as the rate per 100 person-years of exposure. These analyses will take into account all on-treatment 
events (allowing more than 1 event per subject) and the total duration of exposure. The person-
year exposure will be computed as the sum over the subjects’ exposure expressed in years where 
the duration of exposure is defined as:
• Date of last dose of study treatment - date of first dose of study treatment + 101 days, for 
subject who are off study treatment and were followed for at least 100 days after last dose 
of study medication.
• Last known date alive - date of first dose of study medication +1, for subjects who are still 
on-treatment or who are off study treatment and were followed less than 100 days after last 
dose of study medication.
When specified, the 95% CI of the rate per 100 person-years of exposure will  be derived using 
normal approximation and variance estimation proposed in Cook and Lawless.
Summary: 
The following summary tables will be provided: 
• Total number and rate (exposure adjusted) of occurrences for all AEs.
• For EOSI:
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− Frequency of unique AEs, meaning the number of subjects experiencing an AE once or 
multiple times by treatment arm and dose 
Listing: 
• Unique instances of all AEs, ie, after duplicates have been eliminated and overlapping and 
contiguous occurrences of the same event (ie, same PT) have been collapsed. 
7.6.8 
Clinical Laboratory Evaluations
Clinical laboratory data will be analyzed using International System of Units (SI). Analyses may 
be  repeated  using  US  conventional units.  In  addition,  further  analyses  on  specific  laboratory 
parameters will be performed by treatment group and is described in Sections 7.6.8.1and 7.6.8.2.
Summary: 
The number (%) of subjects with the following will be summarized by treatment group and study 
part, if appropriate, using the worst CTC grade on-treatment per subject. 
• Post-baseline grade 
• Shift-table of worst on-study CTC grade compared to baseline CTC grade 
Listing: 
• A by-subject listing of these laboratory parameters will be provided. 
• Laboratory abnormality criteria 
• Laboratory results outside of normal range 
7.6.8.1 
Abnormal Hepatic Function Test
Summary: 
The number of subjects with the following laboratory abnormalities from on-treatment evaluations 
will be summarized by treatment group. 
• ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN 
• Total bilirubin > 2 x ULN 
• Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN 
• Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN 
Figure: 
The following scatter plots will be produced for the following hepatic laboratory parameters. On-
treatment  peak total  bilirubin  and  on-treatment  peak  AST/ALT  may  or  may  not  happen  on  
the 
same day of liver testing. 
• Total bilirubin peak vs. AST peak 
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• Total bilirubin peak vs. ALT peak 
Listing: 
• A by-subject listing of these specific abnormalities will be provided. 
7.6.8.2 
Abnormal Thyroid Function Test 
Summary: 
The number of subjects with the following laboratory abnormalities from on-treatment evaluations 
will be summarized by treatment group. 
• TSH value > ULN and
−with baseline TSH value ≤ ULN 
−at least one T3/T4 test value < LLN 
• TSH < LLN and
−with baseline TSH value ≥ LLN 
−at least one T3/T4 test value > ULN 
Listing: 
• A by-subject listing of these specific abnormalities will be provided. 
7.6.9 
Electrocardiograms
Summary: 
Summary  statistics  of  baseline and  change  from  baseline will  be  presented  for  heart  rate, PR 
interval, QRS width, QT interval, QTcF and change in QTcF (ΔQTcF) by treatment group. 
In addition, the frequency distribution of subjects’ maximum recorded post-dose PR interval, QRS 
width, QTcF and change in QTcF (ΔQTcF) will be tabulated by treatment and summarized for the 
following ranges: 
• For PR:
−PR ≤ 200 msec 
−PR > 200 msec 
• For QRS:
−QRS ≤ 120 msec 
−QRS > 120 msec 
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• For QTcF:
−QTcF ≤ 450 msec 
−450 msec < QTcF ≤ 480 msec 
−480 msec < QTcF ≤ 500 msec 
−QTcF > 500 msec 
• For ΔQTcF:
−ΔQTcF ≤ 30 msec 
−30 msec < ΔQTcF ≤ 60 msec 
−ΔQTcF > 60 msec 
Listing:
• A by-subject listing of all ECG measures 
• A listing of only abnormal ECG interpretations 
7.6.10 
Vital Signs and Physical Findings
Summary: 
The following parameters and their corresponding change from baseline will be summarized by 
timepoint and treatment group. 
• Vital Signs 
Listing: 
• Vital Signs 
• Abnormal physical examination findings 
• Diagnostic procedures 
• Medical treatment procedures 
7.6.11 
Exploratory Safety Analysis: DLT
All  available  DLT  information  (DLTs  within  DLT  observation  period  and  outside  DLT 
observation period) may be considered to assess posterior dose-toxicity profile.
Summary: 
• After completion of dose escalation, the final posteriors for parameters of BLRM and
BLRM-Copula models that describe the DLT profile of BMS-986178 alone and in
combination with nivolumab and/or ipilimumab may be summarized.
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• Plots of fitted dose-DLT curve may be presented for BMS-986178 alone and in
combination with nivolumab and/or ipilimumab.
7.7
Immunogenicity
Analysis dataset and data listing will include all available ADA samples.
Summary:
Number (%) of subjects will be reported for the following parameters based on Immunogenicity 
(ADA)  Population by treatment  for BMS-986178,  nivolumab  and  ipilimumab: Impact  of  re-
treatment might be explored.
• Baseline ADA-positive
• ADA-positive
o Persistent Positive (PP)
o Not PP-Last Sample Positive
o Other positive
• ADA-negative
Listings:
• A listing all ADA assessments will be provided. 
Associations between immunogenicity measures and PK and/or selected AEs may be explored.
7.8
Pharmacokinetics
Summary:
• Summary statistics will be provided for PK parameters for BMS-986178 by treatment across 
all Parts:
Geometric  means  and  coefficients  of  variation  
(CV[%])  will  be  presented  
for  Cmax,  AUC, 
Ctau,  AI,  CLT,  Ctrough, and  Css-avg.  Medians  and  ranges  will  be presented for  
time  of 
maximum  observed  serum  concentration  (Tmax). Means  and  standard deviations  will  be 
presented for all other PK parameters (e.g. T-HALFeff).
• Geometric means and coefficients of variation (CV[%]) for Ctrough for BMS-986178, Nivo 
and Ipi will be summarized by treatment and time point.
• Nivolumab and  
ipilimumab end of  
infusion and trough (Ctrough) concentrations and BMS-
986178  
trough  concentration  will  be  
tabulated  by  
treatment  and  study  day  using  summary 
statistics. These data may also be pooled with other datasets for population PK analysis, which 
will be presented in a separate report.
Listing:
• All individual PK parameters will be listed for PK Subjects by treatment
• Ctrough will be listed by treatment, treatment cycle, and study day.
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Figure: 
• The following scatter plots will be produced for the following PK parameters for BMS-986178 
by treatment across all Parts:
o Cmax
o Ctrough
o AUC(0-t)
o AUC(TAU)
7.8.1 
Dose Proportionality 
Summary statistics as well as plots will be provided for dose proportionality analyses focusing on 
initial treatment and additional treatments. Re-treatment phase might be explored if data permits. 
Plot  of  individual  BMS-986178 serum  PK  parameter  (Cmax,  AUC(TAU))  values  with  fitted 
regression line versus dose will also be presented on a log-log scale by treatment and cycle/day.
To assess the dose proportionality, the power model described by Gough et al4
PK Parameter = A*Doseβ
will be estimated by the simple linear regression of the natural log of the PK Parameter (Cmax, 
AUC(TAU)) on the natural log of Dose: 
E[log(PK Parameter)| Dose] = α + β*log(Dose).
A slope (β) equal to 1 would indicate perfect dose proportionality. For each PK parameters (Cmax, 
AUC (TAU)), the point estimates and 90% CI of the slopes will be provided. 
AUC(0-T) will not be used for dose proportionality as it is largely redundant with AUC(TAU).
7.9 
Biomarker Analysis
Due to the exploratory nature of this study, analyses listed below may or may not be performed 
depending on  data  availability  
(some  exploratory  measurements  
in  
the  study  may  be  subject to 
change as technologies and assay methods evolve). Additional types of analyses may be conducted 
on a post-hoc basis pending review of data. Not all  exploratory analyses will be included in the 
Clinical Study Report (CSR) unless they represent meaningful findings or are relevant to subject 
management. The biomarker subject population will be used to present results.
7.9.1 
Primary Biomarker Analysis
Not applicable.
7.9.2 
Secondary Biomarker Analysis
Not applicable.
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8 
CONVENTIONS
The following conventions may be used for imputing partial dates for analyses requiring dates:
For missing and partial adverse event onset dates, imputation will be performed using the Adverse 
Event Domain Requirements Specification1. Missing and partial Non-Study Medication Domain 
dates  will  be  imputed  using  the  derivation algorithm  described  in 4.3.3  of  BMS  Non-Study 
Medication Domain Requirements Specification2.
For death dates, the following conventions will be used for imputing partial dates:
• If only the day of the month is missing, the 1st of the month will be used to replace 
the missing day. The imputed date will be compared to the last known date alive and
the maximum will be considered as the death date.
• If the month or the year is missing, the death date will be imputed as the last known 
date alive
• If the date is completely missing but the reason for death is present the death date will 
be imputed as the last known date alive
For date of progression, the following conventions will be used for imputing partial dates:
• If only the day of the month is missing, the 1st of the month will be used to replace 
the missing day
*.
• If the day and month are missing or a date is completely missing, it will be considered 
as missing.
*In cases where the date of death is present and complete, the imputed progression date will be 
compared to the date of death. The minimum of the imputed progression date and date of death 
will be considered as the date of progression.
For other partial/missing dates, the following conventions may be used:
• If only the day of the month is missing, the 15th of the month will be used to replace 
the missing day.
• If both the day and the month are missing, “July 1” will be used to replace the missing 
information.
• If a date is completely missing, it will be considered as missing.
The  following  conversion  factors  will  be  used  
to  convert  days  
to  months  or  years:  1  month  = 
30.4375 days and 1 year = 365.25 days.
Duration  
(e.g. time  from  first  diagnosis  
to  
first  dosing  date, duration  of  
response,  and  
time  
to 
response) will be calculated as follows:
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Duration = (Last date - first date + 1)
All statistical analyses will be carried out using SAS (Statistical Analysis System software, SAS 
Institute, North Carolina, USA) unless otherwise noted.
8.1 
Pharmacokinetic Summaries
In-text Tables
For in-text PK tables, %CV will be reported as integers. For other statistics except for SDs, values 
of 100 or higher will be presented as integers, values of 10 to < 100 will be displayed to 1 decimal 
place, and  values of 1 to < 10 will  be  displayed to  2 decimal places. Values  
less than 1 will  be 
displayed  to  3  decimal  places.  Ratios  will  also  be  displayed  to  3 decimal  places. Standard 
deviations will be reported to the same precision as the mean.
Handling of Non-quantifiable Concentrations
For the summaries of plasma concentration-time data, concentrations that are less than the lower 
limit of quantification (LLOQ) should be displayed as “< LLOQ” in the listings and be treated as 
missing  in  summary  tables  and  plots.  For  
the  purpose  of  calculating  PK  parameters,  predose 
concentrations  that  are  less  than  LLOQ  and  concentrations  prior  to  the  first  quantifiable 
concentration that are less than LLOQ will be set to zero, and all other concentrations less than 
LLOQ will be set to missing.
All available plasma concentration-time data and derived PK parameter values will be included in 
the PK data set and listed accordingly.
Treatment of Outliers
Individual plasma concentrations, if deemed to be anomalous, may be excluded from the analysis 
following a review of available documentation (e.g., bioanalytical report, clinical data). Any such 
exclusion  will  be  clearly  listed  in  the  clinical  study  report (CSR) along  with  justification  for 
exclusion.
Entire plasma concentration-time profiles for a participant may be excluded following review of 
available documentation (e.g., bioanalytical report, clinical data). However, results of analysis with 
and without the excluded profiles may be presented in the CSR. Any such exclusion will be clearly 
listed in the clinical study report (CSR) along with justification for exclusion.
Pharmacokinetic Exclusions3
Pharmacokinetic analysis,  reporting,  and  exclusion  criteria  should  following  the  BMS  PK 
Harmonization  document  Version  2.0.  Specific  guidelines for  exclusionary  criteria  
for  half-life 
and how other PK parameters are affected for exclusion are included in Section 9.2 of the BMS 
PK Harmonization document.
Exclusion  of  1 or  more  parameters  or  
the  entire  dataset  may  be  considered  due  
to  
incomplete 
profiles such as AUC(INF) or when T-HALF cannot be reliably calculated, or there is no sample 
around the suspected Cmax. In addition, participants may be excluded from the analysis if they 
missed doses, had diarrhea, or vomited at or before a time equal to twice the  median Tmax  
for 
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A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination with Nivolumab 
and/or Ipilimumab in Subjects with Advanced Solid Tumors
PROTOCOL(S) CA012004
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7.5.3 
Serious Adverse Events...........................................................................................21
7.5.4 
Adverse Events Leading to Discontinuation of Study Therapy.................................21
7.5.5 
Clinical Laboratory Evaluations.............................................................................22
7.6
Immunogenicity......................................................................................................22
7.7
Pharmacokinetics...................................................................................................22
7.8 
Biomarker Analysis 
................................................................................................23
8 
CONVENTIONS....................................................................................................24
8.1 
Pharmacokinetic Summaries...................................................................................25
9 
CONTENT OF REPORTS ............................................ .........................................26
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LIST OF TABLES
Table 2.4-1: 
List of Protocol Amendment...................................................................11
Table 4.2.3-1: 
Sample ADA Status................................................................................15
Table 4.2.3-2: 
Participant ADA Status...........................................................................15
Table 5.1-1: 
Probability that Estimated Ratio of On-treatment to Pre-treatment 
(Baseline) Value is Within 20% of True Value.......................................17
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LIST OF FIGURES
Figure 2.1-1: 
Study Design Schematic (Part 9)..............................................................8
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2 
STUDY DESCRIPTION
2.1 
Study Design
This is a Phase 1/2a, open-label study of BMS-986178 in subjects with advanced solid tumors that 
integrates  initial  BMS-986178  monotherapy  with  subsequent  nivolumab  and/or  ipilimumab 
combination therapy. 
Parts 1-8 have been completed, and the scope of this SAP is limited to Part 9 expansion. In Part 9, 
subjects  will  be  
randomized  
to cohort  1  or  cohort  2. The  study  design  schematic for  Part  9 is 
presented in Figure 2.1-1.
Figure 2.1-1: 
Study Design Schematic (Part 9)
Part 9 Cohort 1
Cohort 1 is a combination of BMS-986178, nivolumab, DPV-001 (UbiLT3 and UbiLT6) vaccine, 
and  single  dose  cyclophosphamide.  Single-dose  cyclophosphamide 300  mg/m2 is  to  be 
administered IV over a 30 to 60 minute infusion, 3 days prior to C1D1. On C1D1 the subjects will 
receive both UbiLT3 and UbiLT6 intranodal (IN) injection by ultrasound guidance. DPV-001 on 
C1D1  will  consist  of  both  UbiLT3  and  UbiLT6  vaccine  (total  of  1.0  mL  suspension,  0.5  mL 
suspension UbiLT3 into 1 lymph node and 0.5 mL of UbiLT6 into another lymph node). After the 
DPV-001 is administered on C1D1, the subject will be administered BMS-986178, as a flat dose 
of  40  mg  
(q4w)  over  a  30-minute  
infusion.  The order of  dose  administration  
is  DPV-001  
then 
BMS-986178 for C1D1. 
On day C1D8, the subject will be administered both UbiLT3 and UbiLT6, at the same dose listed 
on C1D1, but it will be administered intradermally (ID). 
On C1D15, the subject with be administered UbiLT3 ID which will then commence alternating 
between  UbiLT3  and  UbiLT6  on  subsequent  doses,  then  the  subject  will  be  administered 
nivolumab at 240 mg infusion over 30 minutes. BMS-986178 will only be given on day 1 of cycles 
1-6, 9, and 12.
DPV-001  vaccine  will  be  given  as  a  
total  of  1  mg  
(in  1.0  mL)  
flat  dose  at  each  adminstration
starting  on  C1D15.  Vaccine  may  be  given as  multiple  injections  due  
to  volume,  according  
to 
institutional policy.
Part 9:
Cohort 1:
BMS-986178 40 mg/Nivo 480 mg q4w/DPV-001 1 mg
Combination Therapy: DPV-001 + BMS
-986178 + Nivolumab or DPV-
001 + Nivolumab Monotherapy Dose Regimen Exploration
Cohort 2:
Nivo 480 mg q4w/DPV-001 1 mg
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Subsequent  doses  of  DPV-001  are  delivered  
ID  q2w  
(1.0  mL  suspension  
ID  
rotating  between 
UbiLT3 and UbiLT6 on alternate vaccinations, starting with UbiLT3) which starts at C1D15 for a
total  of  4  doses.  From  C3D1  
to  C6D1,  subjects  will  
receive  
this  vaccine  q4w,  
(still  alternating 
between the UbiLT3 and UbiLT6). After cycle 6, the vaccine will be given 2 more times, at C9D1 
and C12D1 (still alternating between the UbiLT3 and UbiLT6).
From C2D1 through C6D1, nivolumab will be administered as a 480 mg flat dose q4w. It will be 
administered as an infusion over a 30-minute period, after DPV-001 is given. BMS-986178 will 
be administered following a 30-minute observation period after the nivolumab dosing. Nivolumab 
will continue to be administered as a 480 mg flat dose q4w. At C7D1, C8D1, C10D1, C11D1 and 
C13D1 to C26D1, nivolumab will be given as a monotherapy dose. 
Approximately 12 subjects will be treated in this cohort. All cycles will be 4 weeks in length. 
Part 9 Cohort 2
Cohort 2 is a combination of nivolumab, DPV-001 (UbiLT3 and UbiLT6) vaccine, and single dose 
cyclophosphamide. Single-dose cyclophosphamide 300 mg/m2is to be administered IV over a 30 
to 60 minute infusion, 3 days prior to C1D1. On C1D1 the subjects will receive DPV-001 IN by 
ultrasound guidance. DPV-001 on C1D1 will consist of both UbiLT3 and UbiLT6 vaccine (total 
of 1.0 mL suspension, 0.5 mL suspension UbiLT3 into one lymph node and 0.5 mL of UbiLT6 
into another lymph node). 
On day C1D8, the subject will be administered both UbiLT3 and UbiLT6, at the same dose level 
above, but it will be administered ID. 
On C1D15, the subject will  be  administered  UbiLT3 ID which will then commence alternating 
between  UbiLT3  and  UbiLT6  on  subsequent  doses.  Then  the  subject  will  be  administered 
nivolumab at 240 mg infusion over 30 minutes on C1D15.
DPV-001  vaccine  will  be  given  as  a  
total  of  1  mg  
(in  1.0  mL)  
flat  dose  at  each  adminstration
starting  on  C1D16.  Vaccine  may  be  given  as  multiple  injections due  
to  volume,  according  
to 
institutional policy.
Subsequent  doses  of  DPV-001  are  delivered  
ID  q2w  
(1.0  mL  suspension  
ID  
rotating  between 
UbiLT3 and UbiLT6 on alternate vaccinations, starting with UbiLT3), which starts at C1D15 for 
a total of 4 doses. From C3D1 to C6D1, subjects will receive this vaccine q4w, still alternating 
between the UbiLT3 and UbiLT6). After cycle 6, the vaccine will be given 2 more times, at C9D1 
and C12D1. 
Beginning at C2D1 through C26D1, nivolumab will be administered as a 480 mg flat dose q4w on 
Day 1 of each cycle, as an infusion over a 30-minute period. When nivolumab and DPV-001 are 
given together, DPV-001 will be given first. 
Approximately 6 subjects will be treated in this cohort. All cycles will be 4 weeks in length. 
One sentinel subject will be dosed initially in each cohort in Part 9, prior to dosing of subsequent 
subjects.  The  sentinel  subject  will  be  observed  for  5  days  before  
the  next  subject  
is  dosed.  If 
cytokine  
release  syndrome  or  unexpected  
toxicity  occurs  
in  
the first  
treated  subject  during  
the 
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2.4 
Protocol Amendments
Table 2.4-1: 
List of Protocol Amendment
Amendment 
number
Date 
Summaries
1
26-Apr-2016
• The timing of the initiation of combination therapy dose 
escalation cohorts was revised, a sentinel subject was added 
to all dose cohorts, Parts 1B and 2B were removed and the 
subsequent study parts were renamed (Part 1C to Part 1B, 
Part 2C to Part 2B, and Part 2D to Part 2C), DLT period 
across the study (28 days) was made uniform, the post-
infusion observation period was extended to 4 hours, 
contraceptive requirements were updated, lipase and amylase 
≤ 1.5×ULN were removed as criteria for adequate organ 
function, DLT criteria were revised, a timepoint was added 
for safety monitoring, the rationale for use of blood and 
tumor tissue in biomarker studies was clarified, prior therapy 
requirements for dose expansion cohorts were updated, and 
BLRM language was clarified
• Typographical errors were corrected, and clarifications were 
made for consistency.
2
08-Jun-2016
• Change the definition for “Related AE’s” and “Not Related 
AE’s”.
• Update prior therapy inclusion criteria for dose escalation 
subjects
• Remove timeframe from hematologic DLT grade 3 febrile 
neutropenia.
• Change to have CBC with differential processed through 
LLDS.
• Add new model document language for Additional Research 
Collection and Imaging scans.
• Typographical errors were corrected, and clarifications were 
made for consistency.
3
23-Nov-2016 • Removal of Part 1B
• Addition of Part 2D, 2E, 3C and Part 2A cohort dose -1
• Change to have imaging as central read
• Add text to allow for intermediate and lower doses in 
escalation
• Included text to add potentially more than 1 dose at RP2D
• Updated versions numbers for current IB’s.
• Updating to the new PMD for WOCBP Section
• Require fresh tumor biopsy from all subjects
• Additional sample to be collected in combination cohorts for 
RO
• Update to not require archived tumor biopsies
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4.2.3 
Immunogenicity
The secondary objective of immunogenicity will be assessed by the frequency of positive ADA to 
BMS-986178 or nivolumab. Ipilimumab is not applicable for Part 9.
At the sample  
level,  
individual samples will  be characterized  
into following category as shown 
below.
Table 4.2.3-1: 
Sample ADA Status
Sample ADA Status
Definition
Baseline ADA-positive sample
ADA is detected in the last sample before initiation of treatment
Baseline ADA-negative sample
ADA is not detected in the last sample before initiation of treatment
ADA-positive sample
after initiation of treatment, 1) an ADA detected (positive 
seroconversion) sample in a participant for whom ADA is not 
detected at baseline, or (2) an ADA detected sample with ADA titer 
to be at least 4-fold or greater (≥) than baseline positive titer
ADA-negative sample
After initiation of treatment, ADA not positive sample relative to 
baseline
Next, using the sample ADA status, participant ADA status is defined as follows:
Table 4.2.3-2: 
Participant ADA Status
ADA Status
Definition
Baseline ADA-positive subject
A participant with baseline ADA-positive sample
ADA-positive subject
A participant with at least one ADA positive-sample relative to 
baseline at any time after initiation of treatment
• Persistent Positive (PP)
ADA-positive sample at 2 or more consecutive timepoints, 
where the first and last ADA-positive samples are at least 16a
weeks apart
• Not PP-Last Sample Positive
Not persistent positive with ADA-positive sample at the last 
sampling timepoint 
• Other Positive
Not persistent positive with ADA-negative sample at the last 
sampling timepoint
ADA-negative subject
A participant with no ADA-positive sample after the initiation 
of treatment
a16 week threshold was chosen based on the long half-life of immunoglobulin.
4.2.4 
Pharmacodynamics
The  secondary  objective  of  pharmacodynamics will  be  assessed  by  
the  proportion  of  subjects 
showing a change in pharmacodynamic biomarkers such as soluble OX40 and peripheral OX40 
receptor  occupancy  along  with  
tumor  pharmacodynamic  of  BMS-986178  in  combination  with 
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precise estimation is needed based on data observed, Part 9 may be further expanded to 24 subjects 
for Cohort 1 and 12 subjects for Cohort 2. To assess the PD effects, pre-treatment and on-treatment 
whole blood and serum samples and tumor biopsies will be required. It is of interest to ensure the 
precision  of  the  estimate  of  the  ratio  of  on-treatment  biomarker  assessments  to  pre-treatment 
(baseline) levels. Assuming that a biomarker is measured as a continuous variable, a given number 
of subjects will provide the confidence that the estimate of the ratio of on-treatment to baseline 
values will be within 20% of the true value, as shown in Table 5.1-1.
Table 5.1-1: 
Probability that Estimated Ratio of On-treatment to Pre-treatment 
(Baseline) Value is Within 20% of True Value
Intra-subject Standard 
Deviation (Log-scale)
0.2 
0.3 
0.4 
0.5 
0.6 
0.7 
0.8
Probability 
N = 6 
92% 
76% 
62% 
52% 
44% 
38% 
34%
N = 12 
99% 
90% 
78% 
68% 
59% 
52% 
46%
N = 24 
100% 
98% 
92% 
84% 
76% 
68% 
62%
For  example,  for  a  biomarker  (eg,  activated  and  memory  CD4  and CD8  T-cells)  with  an 
intrasubject standard deviation of 0.5, if the true ratio of post-baseline to baseline geometric means 
is 1.2 (increase from baseline is 20%), there is 68% probability that the estimated ratio would be 
within 0.96 and 1.44 (or a percent change between -4% and 44%) with 12 subjects per treatment 
arm and the probability is 84% with 24 subjects per arm. If the true increase from baseline is 60%, 
for a biomarker with the same variability, then there is 68% probability that the estimated percent 
change would be between 28% and 92% with 12 subjects per treatment arm and between 37% and 
83% with 24 subjects per treatment arm.
6 
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES STUDY PERIODS
6.1 
Study Periods
For the purpose of analysis, baseline period (Section 6.1.1) and post baseline period (Section 6.1.2)
will be considered.
6.1.1 
Baseline Period
Baseline evaluations or events will be defined as evaluations or events that occur before the date 
and time of the first dose of study medication.
The following definitions will apply:
• Pre-treatment AEs will be defined as AEs with an onset date and time prior to but not including 
the day and time of the first dose of study treatment (or with an onset date prior to the day of 
the first dose of study treatment if time is not collected or is missing).
• Baseline evaluations (laboratory tests, pulse oximetry, vital signs, and ECG) will be defined as 
evaluations  with  a  date  and  
time  on  or  prior  
to  
the  day  and  
time  of  
the  
first  dose  of  study 
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treatment (or with an onset date on or prior to the day of the first dose of study treatment if 
time is not collected or is missing).
If there are multiple valid assessments, the assessment that is closest to day (and time if collected) 
of  the  first  dose  of  study  treatment  will  be  used  as  the  baseline  in  the  analyses.  If  multiple 
assessments are collected at the same date (and time if collected), the assessment with the latest 
database entry date (and time if collected) will considered as baseline.
Tumor assessments will be slotted in the baseline period if assessments are before or on start of 
the treatment date. Baseline tumor assessment is the last assessment in the baseline period.
6.1.2 
Post Baseline Period
Treatment Period starts with the first dose date-time of study treatment.
On-treatment AEs will be defined as AEs with an onset date-time on or after the date and 
time of the first dose of study treatment (or with an onset date on or after the day of the 
first dose of study treatment if time is not collected or is missing). For subjects who are off 
treatment, AEs will be counted as on-treatment if the event occurred within 100 days of 
the last dose of study medication. No “subtracting rule” will be applied when an AE occurs 
both pre-treatment and post-treatment with the same preferred term and grade. For subjects 
who are still on study treatment, all available AEs will be counted as on-treatment after the 
datetime (or date if time is not collected or missing) of the first dose.
On-treatment evaluations (laboratory tests, pulse oximetry and vital signs) will be defined 
as evaluations taken after the day (and time, if collected and not missing) of the first dose 
of study treatment. For subjects who are off treatment, evaluations will be counted as on-
treatment if evaluation is taken within 100 days of the last dose of study medication. For 
subjects who are still on study treatment, all available evaluations will be considered as on-
treatment after the datetime of the first dose.
Principal analysis of safety endpoints will be based on the treatment period. 
Tumor assessments will be slotted in the post-baseline period if assessments are after start 
of the treatment date.
6.2 
Treatment Regimens
The treatment group “as treated” will  be the same as the arm as assigned by IRT. However, if a 
subject received the incorrect drug for the entire period of treatment, the subject’s treatment group 
will be defined as the incorrect drug the subject actually received.
6.3 
Populations for Analyses
• All enrolled subjects: All subjects who signed an informed consent form and were registered 
into the IRT.
• All treated subjects: All subjects who received any dose of study therapy. This is the primary 
population for drug exposure, efficacy and safety analysis.
• PK  subjects:  All  subjects  with  available  serum  
time-concentration  data  
from  subjects  who 
received any BMS-986178 or Nivolumab.
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• Immunogenicity subjects: All subjects with available data from subjects who received any 
BMS-986178 or Nivolumab and have baseline and at least one post baseline immunogenicity 
measurement.
• Biomarker  Evaluable  Subjects:  All Treated  Subjects  with  at  least  one  evaluable 
measurement for a specific marker will be included in the dataset for that marker. Evaluable 
may differ depending on the analysis.
• Response Evaluable Subjects: All treated subjects with measurable disease at baseline and 
one of the following: 1) at least one post-baseline tumor measurement, 2) clinical progression 
or 3) death. This population may be used for interim efficacy analysis due to insufficient follow 
up
7 
STATISTICAL ANALYSES
All analyses will be performed in SAS using version 9.2 or higher.
7.1 
General Methods
Continuous variables will be summarized by treatment group using the mean, standard deviation, 
median,  minimum,  and  maximum  values.  Some  continuous  variables may  also  be  summarized 
using the geometric mean and coefficient of variation. Categorical variables will be summarized 
by frequencies and percentages. Percentages will be rounded and may not always add up to 100. 
Percentages less than 0.1 will be indicated as “< 0.1”.
Data will be summarized only if there are more than 5 subjects in Part 9.
7.2 
Study Population
7.2.1 
Subject Disposition
The following subject disposition will be listed
Listing: 
• Pre-treatment period: All enrolled Subjects with reason
• End of treatment period: Treated subjects with reason for discontinuation of treatment. 
7.2.2 
Demographics and Other Baseline Characteristics
The following subject demographics will be listed by treatment arm. 
• Age (in years); 
• Gender 
• Race 
• Ethnicity 
Listing: 
• All relevant data, variables listed above 
7.3 
Extent of Exposure
Listings  will  
include  all  available  exposure  data,  andwill  be  performed  on  
the  population  of  All 
Treated Subjects “as treated” as described in Section 6.2.
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Listing: 
• Drug administration of study medication 
7.4 
Efficacy
The primary efficacy analyses will  be  performed  on  All  Treated Subjects for the final analysis. 
Summary analysis including ORR and BOR summary will  be performed only  
if there are more 
than 5 subjects in Part 9. All analyses will be presented by part, treatment group and/or tumor type 
(if appropriate), unless otherwise specified. Listings of BOR will be provided. 
Summary: 
The following will be summarized only if there are more than 5 subjects in Part 9
• The ORR with corresponding 2-sided 95% CI based on the Clopper-Pearson method, along 
with each category of BOR. .
Listing: 
The following will be listed by tumor type and treatment group. 
• Subject level efficacy for All Treated Subjects: BOR, best response in target lesions, duration 
of response for responders 
7.5 
Safety
Analysis  of  safety  will  be  based  on  All  Treated  Subjects  and  presented  by  
treatment  arm  and 
overall. Deaths and SAEs will be listed using All Enrolled Subjects. Data will be summarized only 
if there are more than 5 subjects in Part 9. Moreover, a single Adverse Event listing is sufficient if 
there are 5 subjects or less in Part 9.
Adverse  events  will  be  coded  according  
to  
the  most  recent  version  of  Medical  Dictionary  for 
Regulatory Activities (MedDRA) at the time of database lock and the severity will be graded using 
the NCI CTCAE version 4.03. Drug-related AEs are those events with relationship to study drug 
“Related” as recorded on the Case Report Form (CRF). If the relationship to study drug is missing, 
the AE will be considered as drug-related. 
Listing  of  adverse  events  will  include  all  enrolled  subjects  as  SAEs  and  deaths  are  collected 
pretreatment. Summaries of adverse events will include all on-treatment adverse events as defined 
in section 6.1.2. 
When reporting adverse events by CTC grade, summary tables will be provided based on the event 
with  worst  CTC  grade  
(independent  of  
relationship  
to  study  medication).  Subjects  will  only  be 
counted (1) once at the preferred term (PT) level, (2) once at the system organ class (SOC) level, 
and (3) once in the ‘Total subject’ row at their worst CTC grade, regardless of SOC or PT. 
The analysis of laboratory results will be based on All Treated Subjects. Laboratory results will be 
categorized according to NCI CTCAE (version 4.03) grade. Baseline is defined as the last non-
missing  measurement  prior  
to  
the  first  dosing  date  and  
time.  Summaries  of  laboratory  results 
include baseline and on-treatment results as defined in section 6.1.2. 
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7.5.1 
All Adverse Events
Summary:(Applicable only if there are more than 5 subjects in Part 9)
AEs  and  drug-related  AEs  will  be  
tabulated  by  descending  frequency  of  SOC  and  descending 
frequency of PT within each SOC, unless specified otherwise. 
• Overall summary of any AEs by worst CTC grade (grade 1, 2, 3, 4, 3-4, 5, unknown, total) 
presented by SOC/PT 
• Overall  summary  of  drug-related  AEs  by  worst  CTC  grade  (grade  1,  2,  3,  4,  3-4,  5, 
unknown, total) presented by SOC/PT 
• DLT rate will be summarized by treatment group.
Listing: 
• All recorded Adverse Events will be listed.
• All recorded DLTs will be listed.
7.5.2 
Deaths
Summary: (Applicable only if there are more than 5 subjects in Part 9)
• All deaths will be summarized for cause of deaths by treatment group. 
Listing: 
• All recorded deaths for All Enrolled Subjects will be listed 
7.5.3 
Serious Adverse Events
Summary: (Applicable only if there are more than 5 subjects in Part 9)
The following will be summarized by treatment arm and study part. 
• Overall  summary  of  SAEs  by  worst  CTC  grade  
(grade  1,  2,  3,  4, 3-4, 5)  presented  by 
SOC/PT 
• Overall  summary  of  drug-related  SAEs  by  worst  CTC  grade  (grade 1,  2,  3,  4,  3-4,  5) 
presented by SOC/PT. 
Listing: 
• By-subject SAE listing may be provided for the All Enrolled Subjects. 
7.5.4 
Adverse Events Leading to Discontinuation of Study Therapy
Adverse  events  
leading  
to  study drug  discontinuation  are  AEs  with  action  
taken  as  “Drug  was 
discontinued”. 
Summary: (Applicable only if there are more than 5 subjects in Part 9)
• Overall summary of AEs leading to discontinuation by worst CTC grade (grade 1, 2, 3, 4, 3-
4, 5, total) presented by SOC/PT 
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• Overall summary of drug-related AEs leading to discontinuation by worst CTC grade (grade 
1, 2, 3, 4, 3-4, 5, total) presented by SOC/PT 
Listing: 
• By-subject AEs leading to discontinuation listing may be provided 
7.5.5 
Clinical Laboratory Evaluations
Clinical laboratory data will be analyzed using International System of Units (SI). 
Summary: (Applicable only if there are more than 5 subjects in Part 9)
The number (%) of subjects with the following will be summarized by treatment group and study 
part, if appropriate, using the worst CTC grade on-treatment per subject. 
• Post-baseline grade 
• Shift-table of worst on-study CTC grade compared to baseline CTC grade 
Listing: 
• A by-subject listing of these Laboratory results outside of normal range will be provided
7.6
Immunogenicity
Analysis dataset and data listing may be performed if datafrom ADA samples are available.
Summary:
Number (%) of subjects may be reported for the following parameters based on Immunogenicity 
(ADA) Population by treatment for BMS-986178, nivolumab and ipilimumab:
• Baseline ADA-positive
• ADA-positive
o Persistent Positive (PP)
o Not PP-Last Sample Positive
o Other positive
• ADA-negative
Listings:
• A listing all ADA assessments may be provided. 
Associations between immunogenicity measures and PK and/or selected AEs may be explored.
7.7
Pharmacokinetics
PK analysis may be performed if data is available.
Summary:
• Summary statistics may be provided for PK parameters for BMS-986178 by treatment across 
all Parts:
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Listing:
• All clinically relevant biomarkers may be listed, by treatment, and subject
8 
CONVENTIONS
The following conventions may be used for imputing partial dates for analyses requiring dates:
For missing and partial adverse event onset dates, imputation will be performed using the Adverse 
Event Domain Requirements Specification1. Missing and partial Non-Study Medication Domain 
dates  will  be  imputed  using  the  derivation  algorithm  described  in 4.3.3  of  BMS  Non-Study 
Medication Domain Requirements Specification2.
For death dates, the following conventions will be used for imputing partial dates:
• If only the day of the month is missing, the 1st of the month will be used to replace 
the missing day. The imputed date will be compared to the last known date alive and 
the maximum will be considered as the death date.
• If the month or the year is missing, the death date will be imputed as the last known 
date alive
• If the date is completely missing but the reason for death is present the death date will 
be imputed as the last known date alive
For date of progression, the following conventions will be used for imputing partial dates:
• If only the day of the month is missing, the 1st of the month will be used to replace 
the missing day
*.
• If the day and month are missing or a date is completely missing, it will be considered 
as missing.
*In cases where the date of death is present and complete, the imputed progression date will be 
compared to the date of death. The minimum of the imputed progression date and date of death 
will be considered as the date of progression.
For other partial/missing dates, the following conventions may be used:
• If only the day of the month is missing, the 15th of the month will be used to replace 
the missing day.
• If both the day and the month are missing, “July 1” will be used to replace the missing 
information.
• If a date is completely missing, it will be considered as missing.
The  following  conversion  factors  will  be  used  
to  convert  days  
to  months  or  years:  1  month  = 
30.4375 days and 1 year = 365.25 days.
Duration  
(e.g. time  from  first  diagnosis to  
first  dosing  date, duration  of  
response,  and  
time  
to 
response) will be calculated as follows:
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Duration = (Last date - first date + 1)
All statistical analyses will be carried out using SAS (Statistical Analysis System software, SAS 
Institute, North Carolina, USA) unless otherwise noted.
8.1 
Pharmacokinetic Summaries
In-text Tables
For in-text PK tables, %CV will be reported as integers. For other statistics except for SDs, values 
of 100 or higher will be presented as integers, values of 10 to < 100 will be displayed to 1 decimal 
place, and  values of 1 to < 10 will  be  displayed to  2  decimal places. Values  
less than 1 will  be 
displayed  to  3  decimal  places.  Ratios  will  also  be  displayed  to  3  decimal  places.  Standard 
deviations will be reported to the same precision as the mean.
Handling of Non-quantifiable Concentrations
For the summaries of plasma concentration-time data, concentrations that are less than the lower 
limit of quantification (LLOQ) should be displayed as “< LLOQ” in the listings and be treated as 
missing  in  summary  tables  and  plots.  For  
the  purpose  of  calculating  PK  parameters,  predose 
concentrations  that  are  less  than  LLOQ  and  concentrations  prior  to  the  first  quantifiable 
concentration that are less than LLOQ will be set to zero, and all other concentrations less than 
LLOQ will be set to missing.
All available plasma concentration-time data and derived PK parameter values will be included in 
the PK data set and listed accordingly.
Treatment of Outliers
Individual plasma concentrations, if deemed to be anomalous, may be excluded from the analysis 
following a review of available documentation (e.g., bioanalytical report, clinical data). Any such 
exclusion  will  be  clearly  listed  in  the  clinical study  report  (CSR)  along  with  justification  for 
exclusion.
Entire plasma concentration-time profiles for a participant may be excluded following review of 
available documentation (e.g., bioanalytical report, clinical data). However, results of analysis with 
and without the excluded profiles may be presented in the CSR. Any such exclusion will be clearly 
listed in the clinical study report (CSR) along with justification for exclusion.
Pharmacokinetic Exclusions3
Pharmacokinetic  analysis,  reporting,  and  exclusion  criteria  should  following  the  BMS  PK 
Harmonization  document  Version  2.0.  Specific  guidelines  
for  exclusionary  criteria  
for  half-life 
and how other PK parameters are affected for exclusion are included in Section 9.2 of the BMS 
PK Harmonization document.
Exclusion  of  1  or  more  parameters  or  
the  entire  dataset  may  be considered  due  
to  
incomplete 
profiles such as AUC(INF) or when T-HALF cannot be reliably calculated, or there is no sample 
around the suspected Cmax. In addition, participants may be excluded from the analysis if they 
missed doses, had diarrhea, or vomited at or before a time equal to twice the  median Tmax  
for 
3.0
Approved 
930118648
3.0
v