Clinical trial NCT02658890
Conditions: Advanced Cancer Melanoma Non-Small Cell Lung Cancer
Sponsor: Bristol-Myers Squibb
Start date: 2016-04-14; Completion date: 2021-10-26
Enrollment: 627 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to determine safety and effectiveness of experimental medication BMS-986205 when combined with Nivolumab and in combination with both Nivolumab and Ipilimumab in patients with cancers that are advanced or have spread. Pharmacokinetics and pharmacodynamics of BMS-986205 when combined with Nivolumab and in combination with Nivolumab and Ipilimumab in this patient population will also be assessed.

Detailed description:

Arms: arm 1: BMS 986205 + Nivolumab specified dose at specified intervals. arm 2: BMS 986205 + Nivolumab specified dose at specified intervals. arm 3: BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals
Interventions: intervention 1: BMS-986205 intervention 2: Nivolumab intervention 3: Ipilimumab
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 1/2a Study of BMS-986205 Administered in Combination with Nivolumab (anti-PD-1 
Monoclonal Antibody) and in Combination with Both Nivolumab and Ipilimumab (anti-CTLA-4 
Monoclonal Antibody) in Advanced Malignant Tumors 
 
PROTOCOL: CA017-003 
 
 
NCT Number: NCT02658890 
 
Document Date (Date in which document was last revised): June 29, 2018 
 


Page:
1
Protocol Number:
CA017003
IND Number:
128331
EUDRACT Number
2015-004914-79
Date:
24-Nov-2015
Revised Date:
29-Jun-2018
CLINICAL Protocol CA017003
A Phase 1/2a Study of BMS-986205 Administered in Combination with Nivolumab (anti-PD-1 
Monoclonal Antibody) and in Combination with Both Nivolumab and Ipilimumab (anti-CTLA-4 
Monoclonal Antibody) in Advanced Malignant Tumors
Revised Protocol Number: 05
Incorporates Amendment 14 and Administrative Letter 03, 04, 06, 07, and 08
Medical Monitor
Study Director
24-hr Emergency Telephone Number
USA:
International: 
Bristol-Myers Squibb Research and Development
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
Route 206 & Province Line Road
Lawrenceville, NJ 08543
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
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IDO1 INHIBITOR
Revised Protocol No.: 05
Date: 29-Jun-2018
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promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
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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Revised Protocol No.: 05
Date: 29-Jun-2018
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 05
29-Jun-2018
Incorporates Amendment 14 and Administrative Letters 03 - 08
Amendment 14
29-Jun-2018
This amendment includes:
•
Updated safety, PK, and efficacy information to support dose 
selections for Parts 2 and 3, update the risk/benefit assessment, 
and to establish HLH and DRESS syndrome as adverse events of 
special interest (AEOSI) requiring expedited reporting
•
Updated preclinical safety, metabolism, and drug interaction 
information to support modifications of concomitant medication 
prohibitions and restrictions (especially regarding CYP1A2) as 
well as changes to condom requirements for male subjects in light 
of animal fetal toxicity information
•
Further evaluation of safety and initial efficacy exploration of 
nivolumab and ipilimumab on a Q4W/Q8W schedule in 
combination with BMS-986205 in a mixed tumor type  cohort in 
Part 3.
•
Alternative dose of BMS-986205 and, if needed, dose and 
schedule of nivolumab and ipilimumab in the Part 3 cohorts to 
allow for optimal exploration of tolerability and safety of the 
triplet combination
•
Age requirements on tumor tissue blocks and slides (except in 
subjects who will undergo pre-treatment biopsies) while 
simultaneously reducing the need for fresh tumor biopsies in 
subjects in Part 2
•
Other changes to align this protocol with the current standards of 
the BMS-986205 and nivolumab programs and enhance subject 
safety by: updating exclusion, dose delay, dose reduction, and 
drug discontinuation criteria, and increasing frequency of 
methemoglobin monitoring to at least monthly across all protocol 
parts
•
Information on the serotonin syndrome as a possible class effect 
of IDO1 inhibitors and additional exclusion criteria and dose 
discontinuation criteria to reflect this possiblity
•
Administrative changes, minor clarifications, typographical 
corrections, and updates for consistency were made
Administrative 
Letter 08
09-Nov-2017
BMS-986205 PK 
 plasma sample
 
.
Administrative 
Letter 07
29-Sep-2017
New study personnel and clarification Flowchart / Time and Events 
Schedule.
Administrative 
Letter 06
29-Sep-2017
New study personnel and clarification Flowchart / Time and Events 
Schedule.
Administrative 
Letter 04
25-May-2017
Sample day of sample collection description change
Administrative 
Letter 03
24-May-2017
 
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Revised Protocol No.: 05
Date: 29-Jun-2018
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Document
Date of Issue
Summary of Change
Revised 
Protocol 04
27-Feb-2017
Incorportates Amendment 08 Global
Amendment 08
27-Feb-2017
•
This protocol amendment adds an evaluation of the safety, 
tolerability, and preliminary anti-tumor activity of the 
combination of BMS-986205, nivolumab, and ipilimumab in 
cohorts of melanoma, non-small cell lung cancer (NSCLC), and 
bladder cancer subjects.  Subjects within these tumor-restricted 
cohorts will receive a selected regimen of nivolumab and 
ipilimumab based on previous evaluations of safety, tolerability, 
and anti-tumor activity in those populations, administered 
together with BMS-986205 given orally daily. The safety and 
tolerability of the triplet combinations will first be assessed in 
safety cohorts in each tumor type.  After establishing initial safety 
and tolerability, expansion cohorts will begin enrolling to further 
assess safety and tolerability, as well as the preliminary anti-
tumor activity of each triplet combination. 
•
RCC was added as an expansion cohort in Part 2 based on data 
showing that RCC expresses high levels of IDO1, as well as 
translational data showing that RCC subjects treated with 
nivolumab have increased expression of IDO1. Furthermore, 
RCC was already previously included as a tumor type for 
evaluation in Part 1 of this study.
•
Administrative changes, minor clarifications, typographical 
corrections, and updates for consistency were made.
Revised 
Protocol 03
14-Dec-2016
Incorporates Amendment 06 Global 
Amendment 06
14-Dec-2016
•
This protocol amendment adds multiple dose expansion cohorts 
with the goal of generating data to further the understanding of 
which tumor types and specific patient populations will benefit 
from treatment with the indoleamine 2,3-dioxygenase 1 
inhibitor/nivolumab combination. In order to ensure consistent 
dosing throughout each cohort, nivolumab will be administered 
at a dose of 240 mg every 2 weeks for the dose escalation (Part 
1) and for the dose expansion cohorts (Part 2) that predated 
Amendment 06. Nivolumab will be administered at a dose 
480 mg intravenously every 4 weeks (Q4W) for the dose 
expansion cohorts added with Amendment 06 (melanoma, non-
small cell lung cancer (NSCLC), and additional signal seeking 
tumors) and the clinical pharmacology substudy (Parts 2 and 3). 
This amendment eliminates the Food Effect substudy from the 
global protocol, as this substudy will only open at sites in the 
United States. Lastly, the duration of study treatment has been 
changed from 24 weeks to approximately 1 year, with up to 12 
cycles. The QTc substudy is modified to utilize Holter monitoring 
in order to allow for multiple QTc sample collection. Biomarker 
analysis was removed. Inclusion criteria have been updated to 
include non-treatment naïve NSCLC subjects and subjects with 
sarcomas and clarification that pre-treatment biopsies are 
required for all subjects including the QTc substudy; required 
period for contraception for men and women of childbearing 
potential has been changed; and some methods of contraception 
are no longer considered highly effective due to potential 
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Document
Date of Issue
Summary of Change
interaction with BMS-986205. Biopsy time window for Cycle 1 
Day 15 (C1D15) in the expansion cohorts has been changed. 
Supine resting time for electrocardiograms (ECGs) has been 
changed, and Dose and Schedule rationale for nivolumab has 
been updated. Guidelines for permanent discontinuation of study 
drugs have been updated. Administrative changes, minor 
clarifications, typographical corrections, and updates for 
consistency were made.
Revised 
Protocol 02a
19-Sep-2016
Incorporates Amendment 04 U.S. sites only
Revised
Protocol 02
13-Jul-2016
Incorporates Amendment 02
Amendment 02
13-Jul-2016
•
This amendment corrects typographical errors, updates language 
for consistency between the synopsis and protocol body, and 
incorporates a sub-study to perform an early assessment of the 
effect of BMS-986205 on the QTc interval
Revised 
Protocol 01
05-Apr-2016
Incorporates Amendment 01
Amendment 01
05-Apr-2016
•
This amendment makes changes to the wording describing the 
DLT period and makes specific changes to the DLT criteria in 
response to 
 received during initial IND review.
•
Correct typographical errors were updated for consistency. 
•
Administrative 
Letter 01
26-Jan-2016
•
Provide clarification and correct typographical errors to Time and 
Events tables 5.1-1 through 5.1-8 for consistency.
•
Correct typographical errors to lab assessment section 5.3.2.
Original 
Protocol
24-Nov-2015
Not Applicable
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SYNOPSIS
Protocol Title: A Phase 1/2a Study of BMS-986205 Administered in Combination with Nivolumab (anti-PD-1 
Monoclonal Antibody) and in Combination with both Nivolumab and Ipilimumab (anti-CTLA-4 Monoclonal 
Antibody) in Advanced Malignant Tumors
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Each subject will be administered a daily oral dose of BMS-986205 in combination with nivolumab (Parts 
1 and 2) or in combination with both nivolumab and ipilimumab (Part 3), both administered as an intravenous (IV) 
infusion per the cohort assignment and the duration of treatment as indicated below.
Study Phase: Phase1/2a
Research Hypothesis: It is anticipated that BMS-986205, administered in combination with nivolumab and in 
combination with both nivolumab and ipilimumab, will demonstrate adequate safety and tolerability, as well as a 
favorable benefit/risk profile, to support further clinical testing. No prospective hypotheses are being formally 
evaluated.
Objectives: 
Primary Objectives:
Part 1: Dose Escalation:
To determine the safety, tolerability, dose limiting toxicities (DLTs), and maximum tolerated dose (MTD)/maximum 
administered dose (MAD)/alternate dose(s) of BMS-986205 administered as monotherapy and in combination with 
nivolumab in subjects with advanced malignant tumors.
Part 2: Dose Expansion:
To investigate the anti-tumor activity of BMS-986205 administered in combination with nivolumab in distinct cohorts 
of subjects with advanced malignant tumors.
To evaluate the safety and tolerability of BMS-986205 in combination with nivolumab in subjects with advanced 
malignant tumors.
Part 3: BMS-986205, Nivolumab and Ipilimumab Combination
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and preliminary anti-tumor activity of BMS-
986205 administered in combination with both nivolumab and ipilimumab in subjects with select advanced malignant 
tumors.
Secondary Objectives:
•
To characterize the pharmacokinetics (PK) of BMS-986205 administered alone, in combination with nivolumab, 
and in combination with both nivolumab and ipilimumab.
•
To investigate the anti-tumor activity of BMS-986205 administered in combination with nivolumab in dose 
escalation and clinical pharmacology substudies.
•
To characterize the pharmacodynamic activity of BMS-986205 administered alone, in combination with 
nivolumab, and in combination with both nivolumab and ipilimumab.
•
To characterize the immunogenicity of nivolumab when administered in combination with BMS-986205 and in 
combination with both BMS-986205 and ipilimumab.
•
To characterize the immunogenicity of ipilimumab when administered in combination with nivolumab and BMS-
986205
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Study Design:
This is a Phase 1/2a, open-label study of BMS-986205 administered as a monotherapy and in combination with 
nivolumab (Parts 1 and 2), and in combination with nivolumab and ipilimumab (Part 3) in subjects with advanced 
malignant tumors.
The study will be conducted in 3 parts. A clinical pharmacology QTc substudy will also be performed. 
Parts 1 and 2: Dose escalation (Part 1) will start with a lead-in Cycle 0 whereby BMS-986205 is administered as 
monotherapy for 2 weeks duration in each dose escalation cohort. Decision to proceed to combination treatment with 
nivolumab (Cycle 1) for each cohort in dose escalation will be determined after tolerability of the monotherapy lead-
in is established in the 2-week Cycle 0 at each dose, as described in Section 3.1.5 in the protocol body. When the 
decision is made to proceed to Cycle 1, BMS-986205 will be administered concomitantly with nivolumab. The starting 
dose of BMS-986205 is 25 mg orally daily. Nivolumab will be administered at a dose of 240 mg every 2 weeks (Q2W) 
for the dose escalation (Part 1) and for the dose expansion (Part 2) cohorts that predated Amendment 06 (cervical, 
diffuse large B cell lymphoma [DLBCL], squamous cell carcinoma of the head and neck [SCCHN], bladder, and 
pancreatic cancer). Nivolumab will be administered at a dose 480 mg intravenously every 4 weeks (Q4W) for the dose 
expansion cohorts added with Amendment 06 (melanoma, NSCLC, and additional signal seeking tumors) and the 
clinical pharmacology substudy).
Dose expansion (Part 2) will include 8 disease-restricted expansion cohorts (cervical cancer, DLBCL, SCCHN, 
bladder cancer, NSCLC, melanoma, renal cell carcinoma, and pancreatic cancer). Various subpopulations of 
melanoma and NSCLC will be included in separate cohorts to further understand the role of indoleamine 2,3-
dioxygenase 1 (IDO1) inhibition in these specific populations. The BRAF mutated, post-BRAF regimen melanoma 
subjects will be randomized to receive either nivolumab or BMS-986205 in combination with nivolumab in order to 
order to generate a robust, prospective dataset with nivolumab monotherapy to serve as a basis for understanding the 
potential added benefit of combination therapy. An additional cohort will be dedicated to tumor types from the 
escalation inclusion criteria that do not currently have a dedicated expansion cohort or plans for evaluation in other 
studies.  
In addition, a clinical pharmacology substudy will be conducted to characterize the effect of BMS-986205 on QTc 
intervals. 
The starting dose of BMS-986205 is 25 mg orally daily. Nivolumab will be administered at a dose of 240 mg Q2W 
for the dose escalation (Part 1) and for the dose expansion (Part 2) cohorts that predated Amendment 06. Nivolumab 
will be administered at a dose 480 mg intravenously Q4W for the dose expansion cohorts added with and after
Amendment 06 (melanoma, NSCLC, and additional signal-seeking tumors; renal cell carcinoma) and the clinical 
pharmacology substudy.
A schematic of Parts 1 and 2 and the pharmacologic substudy is provided in Figure 1.
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Figure 1:
Study Design Schematic for Parts 1 and 2 and Clinical Pharmacology Substudy
*Note: As of Amendment 06, dose escalation beyond 400 mg BMS-986205 may not occur provided that additional 
pharmacodynamic effect is unlikely.
**Note: The BRAF mutated, post-BRAFi regimen melanoma subjects will be randomized to receive either nivolumab 
or BMS-986205 + nivolumab.
Abbreviations: CNS = central nervous system; CTLA-4 = cytotoxic T lymphocyte-associated antigen 4; 
DLBCL = diffuse large B-cell lymphoma; I-O = immuno-oncology; MAD = maximum administered dose; MTD = 
maximum tolerated dose; Nivo = nivolumab; NSCLC = non-small cell lung cancer; PD-L = programmed cell death; 
PD-L1 = programmed death receptor-ligand 1; PD-(L)1 = either PD-1 or PD-L1; SCCHN = squamous cell 
carcinoma of the head and neck.
Please refer to Table 3.1.6-1 in the protocol body for a detailed description of the Part 2 dose expansion cohorts.
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Part 3: Part 3 will include the initial safety evaluation and cohorts of the combination of BMS-986205, nivolumab, 
and ipilimumab in melanoma, NSCLC, and bladder cancer. Subjects with each tumor type will receive BMS 986205 
in combination with a different regimen of nivolumab and ipilimumab based on safety and efficacy data observed in 
previous trials of nivolumab and ipilimumab in that tumor type (see Section 1.1 of the protocol). 
For the safety cohorts, the initial dose level of BMS-986205 for each cohort will be based on the available of safety, 
PK, and PD data for BMS-986205 in combination with nivolumab and any available data from the combination with 
nivolumab and ipilimumab. The starting dose will not exceed 100 mg in any cohort. 
The regimens will consist of:
Melanoma (Ipi 1Q8): BMS 986205 in combination with nivolumab 480 mg Q4W and ipilimumab 1 mg/kg Q8W, all 
given continuously.
NSCLC (Ipi 1Q6): BMS-986205 in combination with nivolumab 360 mg Q3W and ipilimumab 1 mg/kg Q6W, all 
given continuously.  
Bladder (Ipi 3Q3): BMS-986205 given continuously, first in combination with nivolumab 80 mg and ipilimumab 3 
mg/kg both given Q3W for 4 doses, followed by nivolumab 480 mg Q4W continuously 
Evaluation of each regimen will begin with an assessment of safety and tolerability of the triplet combination therapy 
in a limited number of subjects, including a sentinel subject, in a safety evaluation cohort. The melanoma and NSCLC 
safety cohorts will begin safety enrollment simultaneously since the dose of ipilimumab is similar between the cohorts. 
Furthermore, for nivolumab dosing, the 480 mg Q4W and 360 mg Q3W are expected to achieve similar average 
exposure. The safety evaluation for the bladder regimen will begin enrolling subjects once either the melanoma or 
NSCLC regimen has been found to be safe and tolerable, as the bladder regimen uses a higher dose (3 mg/kg Q3W) 
of ipilimumab relative to the melanoma and NSCLC cohorts (1 mg/kg Q6W and Q8W of ipilimumab) during the DLT 
evaluation period.
Once the initial safety and tolerability have been established independently for each regimen with a given tumor type, 
subjects will begin enrolling in expansion cohorts for that tumor type Additionally, subjects may be enrolled into a 
mixed tumor type cohort using the Ipi 1Q8 regimen (nivolumab 480 mg Q4W and ipilimumab 1 mg/kg Q8W) for 
further evaluation of safety and tolerability, as well as preliminary evaluation of anti-tumor efficacy once the safety 
of Ipi 1Q8 is established in the melanoma cohort. 
The study design schematic for Part 3 is presented in Figure 2.
Figure 2
Study Design Schematic for Part 3
Abbreviations: NSCLC--Non-small cell lung cancer
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Study Periods: 
Subjects will complete up to 4 periods of the study: Screening, Treatment, Clinical/Safety Follow-up, and 
Survival/Long-term follow-up, as described below:
Screening (up to 28 days): Subjects will sign consent and be evaluated for study eligibility.
Treatment Phase:
Parts 1 and 2:
Each treatment cycle consists of up to twelve 4-week treatment cycles. For subjects receiving nivolumab on the Q2W 
regimen, each treatment cycle is composed of a daily oral dose of BMS-986205 and 2 doses of nivolumab administered 
intravenously Q2W on Days 1 and 15. For subjects receiving nivolumab on the Q4W regimen, each cycle is composed 
of a daily oral dose of BMS-986205 and 1 dose of nivolumab on Day 1. In addition, Part 1 (dose escalation) and the 
QTc substudy will start with Cycle 0, a lead-in period of 2 weeks duration, during which monotherapy with BMS-
986205 is administered. 
Following every 2 treatment cycles (8 weeks), the decision to treat a subject with additional cycles of study drug will 
be based on radiological tumor assessments (initial evaluation performed at baseline, end of Cycle 2, and every 8 
weeks). Assessment 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) Version 1.1 criteria for solid tumors or International Working Group [IWG] 
criteria for Hodgkin’s and non-Hodgkin’s lymphoma.
Part 3:
For subjects receiving the melanoma/Ipi 1Q8 regimen containing nivolumab 480 mg Q4W and ipilimumab 1 mg/kg 
Q8W, 1 cycle will consist of 2 doses of nivolumab and 1 dose of ipilimumab (ie, 8 weeks). 
For subjects receiving the NSCLC/Ipi 1Q6 regimen containing nivolumab 360 mg Q3W and ipilimumab 1 mg/kg 
Q6W, 1 cycle will consist of 2 doses of nivolumab and 1 dose of ipilimumab (ie, 6 weeks). 
For subjects receiving the bladder/Ipi 3Q3 regimen, during nivolumab and ipilimumab combination dosing, the first 
2 cycles will each consist of 2 doses of nivolumab and ipilimumab (each cycle is 6 weeks); after the first 2 cycles, 
each subsequent cycle will be comprised of 1 dose of nivolumab (ie, 4 weeks). 
For subjects receiving the mixed tumor type regimen containing nivolumab 480 mg Q4W and ipilimumab 1 mg/kg 
Q8W, 1 cycle will consist of 2 doses of nivolumab and 1 dose of ipilimumab (ie, 8 weeks)
Timing of imaging assessments will be based on the regimen the subject is receiving:
Melanoma/Ipi 1Q8: The first imaging assessment will occur at Week 12 (± 1 week); subsequent imaging will be every 
8 weeks (± 1 week) thereafter throughout the treatment period.
NSCLC/Ipi 1Q6: The first imaging assessment will occur at Week 6 (± 1 week), and then every 6 weeks (± 1 week) 
throughout the treatment period.
Bladder/Ipi 3Q3: The first imaging assessment will occur at Week 6 (± 1 week), and then every 6 weeks (± 1 week) 
during the treatment period up to 24 weeks, after which they will occur every 12 weeks (± 1 week) thereafter 
throughout the treatment period.
Mixed tumor type/Ipi 1Q8 cohort: The first imaging assessment will occur at Week 8 (± 1 week); subsequent imaging 
will be every 8 weeks (± 1 week) thereafter throughout the treatment period.
The decision to treat a subject with additional cycles of study drug will be based on the most recent radiological tumor 
assessment preceding that dose. Assessments of PR and CR must be confirmed at least 4 weeks after the initial 
assessment. Tumor progression or response endpoints will be assessed using RECIST v1.1 criteria
Treatment beyond progression in all study Parts may be allowed in select subjects with initial RECIST v1.1 or IWG-
defined progressive disease (PD) if 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 do not 
meet treatment discontinuation criteria as specified in Section 3.5 in the protocol body).
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Treatment with Additional Cycles beyond 48 weeks: Subjects completing approximately 48 weeks of study therapy 
in all study Parts with ongoing disease control (CR, PR or stable disease [SD]) may be eligible for an additional 48 
weeks of study therapy at the originally assigned dose regimen in all study Parts beyond the initial 48 weeks, on a 
case-by case basis, after careful evaluation and discussion with the BMS Medical Monitor to determine whether the 
benefit/risk ratio supports administration of further study therapy. Subjects whose last assessment of the initial 48-
week period shows PD will also be eligible to continue to additional cycles (up to a maximum of 2 years from first 
dose) if they are still deriving clinical benefit, as per the guidance of treatment beyond progression (Section 3.5.1 in 
the protocol body). For subjects in the bladder triplet combination regimen, ipilimumab will not be re-administered 
during additional treatment; only BMS-986205 and nivolumab (480 mg Q4W) will continue. Upon completion of 48 
weeks of study therapy (or up to a maximum of 96 weeks if applicable), all subjects will enter the Clinical/Safety 
Follow-up period.
Clinical/Safety Follow-up period: Upon completion of 48 weeks of study therapy (or up to a maximum of 96 weeks 
if applicable), all subjects will enter the Clinical/Safety Follow-up period once the decision is made to discontinue the 
subject from treatment (eg, at end of treatment [EOT]). 
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 the Week 1 Clinical/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) and does not need to be repeated, and will be considered the start of the Week 1 
Clinical/Safety Follow-up visit.
Subjects who discontinue the treatment phase will enter the Clinical/Safety Follow-up period. Subjects must be 
followed for at least 100 days (representing approximately 5 half-lives for nivolumab) after the last dose of study drug. 
Follow-up visits should occur at Days 30, 60, and 100 (±10 days) after the last dose of study drug or should coincide 
with the date of discontinuation (±10 days) if date of discontinuation is greater than 30 days after the last dose of study 
drug to monitor for AEs. All subjects will be required to complete 3 Clinical/Safety Follow-up visits regardless of 
whether they start new anti-cancer therapy, except those subjects who withdraw consent for study participation.
Survival/Long-term/Response Follow-up: After completion of the Clinical/Safety Follow-up period, all subjects 
will then enter the Survival/Long-term Follow-up period. During this period, clinic visits or telephone contact every 
3 months will be performed to assess survival status. The duration of the Survival/Long-term Follow-up period will 
be approximately 2 years following the first dose of study drug, and a minimum of 12 months following the last dose 
of study drug.
After completion of the Safety Follow-up period, subjects who discontinue study with ongoing SD, PR, or CR at the 
EOT visit will enter the Response Follow-up period. This period will occur simultaneously with the Survival Follow-
up period for these subjects. These subjects will continue to have tumor radiological and clinical tumor assessments 
every 3 months (every 12 weeks) during the Response Follow-up period or until disease progression or withdrawal of 
study. Radiological tumor assessments for subjects who have ongoing clinical benefit may continue to be collected 
after subject complete the survival phase of the study.
Subjects in the Survival/Long-term Follow-up period who have progression of disease will be allowed to receive 
tumor-directed therapy as required.
Data from imaging assessments for subjects who have ongoing clinical benefit may continue to be collected after 
subjects complete the survival phase of the study.
Re-treatment during Survival/Long-term Follow-up with the originally assigned study therapy regimen (eg, same 
dose and dose schedule) or modified dose regimen may be permitted within 12 months of last dose of study therapy 
for subjects who enter Safety/Survival/Long-term Follow-up with ongoing disease control (CR, PR, or SD) for reasons 
other than drug-related toxicity after discussion and agreement with the BMS Medical Monitor that the benefit/risk 
assessment favors re-treatment, and the subject continues to meet eligibility criteria for treatment with study therapy 
as outlined in Section 3.5.1 of the protocol. Subjects meeting criteria for re-treatment will be treated for a maximum 
of 2 years from the first dose of nivolumab, at the same dose and schedule administered during their initial treatment, 
unless that dose and scheduled was subsequently found to exceed the MTD, in which case the subject will be treated 
at the next lower, or alternate dose and schedule (Table 1 in Synopsis). Subjects entering this phase will follow the 
Time and Events schedule as outlined in Section 5 of the protocol. 
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Figure 3:
Treatment and Follow-Up Schematic for CA017003
Note: For Part 3 bladder cohort, Additional Treatment will not include ipilimumab
Abbreviations: CR = complete response; EOT= end of treatment; MM = Medical Monitor; PR= partial response; 
PD = progressive disease; SD = stable disease.
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Figure 4:
Study Schematic of Clinical Pharmacology QTc Substudy
*: Baseline ECGs should be collected prior to the start of Cycle 0 (Day -1 preferred, up to 5 days prior to Cycle 0 is 
allowed).
Abbreviations: ECG = electrocardiogram; Q4W = every 4 weeks; QD = once daily.
Part 1: Dose Escalation: 
The Part 1 dose escalation phase of the study will evaluate the MTD/MAD/alternate dose of BMS-986205 in 
combination with nivolumab based on DLTs using a Bayesian Logistic Regression Method (BLRM) model (for BMS-
986205 monotherapy lead-in) and BLRM-copula model (for BMS-986205 in combination with nivolumab). The 
Bayesian models will be used for recommendation of the next dose to be investigated. BLRM (combined with copula) 
framework with an escalation with overdose control principle will be employed to ensure that safety is not 
compromised during dose escalation.
The initial dose level of BMS-986205 will be 25 mg administered orally daily. Once initial lead-in monotherapy 
(Cycle 0) is deemed tolerable, combination with 240 mg flat dose nivolumab at the same dose level with the same 
subject (Cycle 1) will be initiated. 
Dose levels to be considered for the next combination cohort (with monotherapy lead-in) will be based on 
recommended monotherapy dose from BLRM and recommended combination dose from BLRM-copula. The lower 
dose from these 2 recommendations will be considered. Potential dose levels for dose escalation are provided in Table 
1 in the synopsis. The maximum allowable increase in dose will be 100%. Final dose selection for the next cohort/dose 
level will be made in conjunction with all data available from PK, and pharmacodynamic assessments, and will be 
made after discussion and agreement between investigators and BMS Medical Monitor. Accordingly, intermediate or 
lower doses, or less frequent dosing of BMS-986205 may be tested if none of the planned doses/schedules are found 
to be tolerated as lead-in phase or in combination with nivolumab.
Approximately 30 subjects will be treated in the dose escalation phase. Depending on the dose recommendation, more 
than 3 subjects can be treated at each dose level. Increments of approximately 3 subjects will be added to each dose 
level depending on model recommendation and clinical judgment. Once the safety of any dose level has been 
established, up to 12 additional subjects may be added to better characterize the PK and pharmacodynamic profile.
Cohort-tolerability assessment and subsequent dose recommendation will occur when 2 DLT-evaluable subjects 
within a subject cohort have completed the 6-week DLT observation period (see Section 4.5.1 of the protocol for 
criteria for DLTs). DLTs occurring within the 2 weeks of the lead-in period (DLT observation period for monotherapy) 
will be used to fit BLRM model for monotherapy. DLTs occurring within the 4 weeks of combination period (DLT 
observation period for combination) will be used to fit BLRM-copula model. The lower recommended dose from both 
models will be considered for next dose escalation. Subjects who received ≥75% of BMS-986205 doses and 2 doses 
of nivolumab, and have been followed at least 5 days after second nivolumab dose in the 6-week DLT observation 
period will be considered as DLT-evaluable subjects. Continuous re-assessment of dose recommendation by BLRM 
will be carried out at each dose level after each cohort of subjects with consideration of all available DLT information.
The MTD/MAD/alternate dose of BMS-986205 in combination with nivolumab selected cohort will be based on 
evaluating the recommendation from BLRM-copula and a synthesis of all available data, including clinical and 
laboratory safety assessments, PK, pharmacodynamic, and efficacy data, from all treated subjects at each dose level 
up to the MTD/MAD.
No intra-subject dose escalation is allowed, although dose modifications may be permitted (see Section 4.5.3).
Sentinel Subject: During dose escalation, a staggered dosing (sentinel subject) approach will be used for the first 
subject in the first dose level of both lead-in and combination. The first subject in both lead-in and combination will 
QTc Substudy
Screening
Time-matched 
Baseline ECG
(Day -1)*
BMS-986205 QD 
(Light meal) + 
Nivolumab Q4W 
Combination
BMS-986205 QD 
Monotherapy
(Cycle 0) with serial 
ECG evaluations on 
Day 14
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receive Cycle 0 Day 1 dose of study drugs, and be observed for 5 days before additional subjects, ie, subject 2 onward 
in that cohort receive study drug. The first subjects to be dosed in subsequent cohorts will not be required to observe 
the 5-day interval between treatment start dates.
Table 1:
Dose Escalation Schedule
Dose Level
BMS-986205
Nivolumab
-1
DL-1
240 mg IV Q2W
1
25 mg
240 mg IV Q2W
2
50 mg
240 mg IV Q2W
3
100 mg
240 mg IV Q2W
4
200 mg
240 mg IV Q2W
5
400 mg
240 mg IV Q2W
6
600 mg
240 mg IV Q2W
7
800 mg
240 mg IV Q2W
Note: As of Amendment 06, dose escalation beyond 400 mg BMS-986205 may not occur provided that additional 
pharmacodynamic effect is unlikely.
Note: Up to 12 additional subjects may be added per selected dose levels to provide additional safety, tolerability and 
PK data. This information will be incorporated into final recommendation for MTD/MAD/alternate dose of BMS-
986205.
Abbreviations: DL-1 = dose level-1; IV = intravenous; MAD = maximum administered dose; MTD = maximum 
tolerated dose; PK = pharmacokinetic; Q2W = every 2 weeks.
Part 2: Dose Expansion: 
The purpose of dose expansion is to gather additional safety, tolerability, preliminary efficacy, PK, and 
pharmacodynamic information regarding BMS-986205 in combination with nivolumab.
Continuous evaluation of toxicity events in the cohort expansions will be performed throughout enrollment in the 
expansion cohorts. If, at any time, the aggregate rate of treatment-related toxicities meeting DLT criteria exceeds 33% 
across all subjects treated in cohort expansions, the findings will be discussed and further enrollment may be 
interrupted. At that time, depending on the nature and grade of the toxicity and after assessing the risk/benefit ratio, a 
new dose(s) of BMS-986205 for all cohorts may be initiated at a previously tested lower dose level or at a dose level 
intermediate to previously tested lower dose levels. Additionally, at the discretion of the Sponsor, and in agreement 
with the investigators, the 480 mg Q4W nivolumab dosing regimen in the designated expansion cohorts and clinical 
pharmacology substudy may revert back to 240 mg Q2W based on emerging PK, pharmacodynamic, and/or 
tolerability data from the cohort expansion portion of the study.
Eight disease-restricted populations will be included in cohort expansion. These include cervical cancer, DLBCL, 
SCCHN, bladder cancer, melanoma, NSCLC, renal cell cancer, and pancreatic cancer. Various subpopulations of 
melanoma and NSCLC will be included in separate cohorts to further understand the role of IDO1 inhibition in these 
specific populations (see Table 3.1.5-1 in the protocol body). The BRAF mutated, post-BRAF regimen melanoma 
subjects will be randomized to receive either nivolumab or BMS-986205 in combination with nivolumab in order to 
generate a robust, prospective dataset with nivolumab monotherapy to serve as a basis for understanding potential 
added benefit of combination therapy. An additional cohort will be dedicated to tumor types from the escalation 
inclusion criteria, which do not currently have a dedicated expansion cohort or plans for evaluation in other studies. 
The eligible tumor types will be triple negative breast cancer, adenocarcinoma of the endometrium, epithelial cancer 
of the ovary, and sarcoma. During dose expansion, the Simon 2-stage (optimal) design will be used as a guide for 
some of the tumor-specific expansion cohorts. Those indications will be classified into 3 categories according to 
different sample size modeling settings: SCCHN and bladder cancer in a group; cervical cancer, DLBCL, melanoma 
with prior anti- programmed death receptor-(ligand) 1 (PD-[L]1) therapy, NSCLC with prior anti-PD-(L)1 therapy, 
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and pancreatic cancer in a different group; and melanoma with prior anti-PD-(L)1 and anti-cytotoxic T lymphocyte-
associated antigen 4 (CTLA-4) therapy in another group will be analyzed using a Simon 2-stage design.
Part 3 BMS-986205, Nivolumab, and Ipilimumab Combination
Part 3 of the study will include an initial safety evaluation cohorts of 3 regimens of nivolumab and ipilimumab in 
combination with BMS-986205 in melanoma, NSCLC, and bladder cancer.  Expansion cohorts for each regimen will 
then be conducted in the tumor type evaluated in the safety cohorts. The Ipi 1Q8W regimen will also be evaluated in 
a mixed cohort of other tumor types evaluated in Part 1. Each tumor type will receive BMS-986205 in combination 
with a specific nivolumab and ipilimumab regimen (see Section 3.1.1.2). 
For the safety cohorts, the initial dose level of BMS-986205 for each cohort will be based on the available of safety, 
PK, and PD data for BMS-986205 in combination with nivolumab and any available from the combination with 
nivolumab and ipilimumab.  The starting dose will not exceed 100 mg in any safety cohort. Lower dose levels of 
BMS-986205 (if required) to be evaluated in each safety cohort will be based on Table 3.1.5-1. Intermediate or lower 
doses, or less frequent dosing of BMS-986205 may be tested if none of the planned doses/schedules are found to be 
tolerated. In addition, alternative lower doses and more intermittent schedules of nivolumab and/or ipilimumab may 
be evaluated if the specified regimen used in each tumor type safety cohort is not found to be tolerable with any of the 
doses of BMS-986205 outlined in Table 3.1.5-1. Safety will be evaluated independently for each tumor type/regimen 
combination and treatment regimen based on DLTs using a BLRM-copula model.
All safety cohorts will begin with an assessment of safety and tolerability of the triplet combination regimen in a 
limited number of subjects. As described in Section 3.1.1.2, the NSCLC/Ipi 1Q6 and melanoma/Ipi 1Q8 regimen 
cohorts will begin enrollment first, followed by the bladder/Ipi 3Q3 regimen cohort once safety and tolerability have 
been established in either NSCLC/ Ipi 1Q6 or melanoma/Ipi 1Q8. Initially, approximately 3 subjects will be treated 
at the selected dose combination of BMS-986205 with nivolumab and ipilimumab. The first subject in each safety 
cohort will be a sentinel subject who will be observed for 5 days after administration of the first combination dose to 
ensure safety and tolerability before other subjects can receive treatment within that cohort.
Due to the potential for early discontinuation, an additional subject(s) may be enrolled to ensure approximately 
3 DLT-evaluable subjects. Initial safety assessment to allow enrollment in the bladder/ Ipi 3Q3 safety cohort will 
occur when at least 2 evaluable subjects in either the NSCLC/ Ipi 1Q6 or melanoma/ Ipi 1Q8 safety cohorts have 
completed a 6-week DLT evaluation period (see Section 4.5.1 for criteria for DLTs). In the melanoma and NSCLC 
safety evaluation cohorts, if a potential DLT occurring in any third evaluable subject in the specific dose combination 
does not influence the recommendation by BLRM (-Copula) to open enrollment in the bladder safety cohort, then the 
bladder safety cohort may proceed with enrollment without waiting for the third subject to complete the corresponding 
DLT observation period.
DLT-evaluable subjects will be defined as subjects who in the 6-week DLT evaluation period received ≥75% of 
BMS-986205 doses and the following nivolumab and ipilimumab doses for each regimen:
•
Melanoma/ Ipi 1Q8: 2 doses of nivolumab and 1 dose of ipilimumab, and followed for at least 5 days after the 
second dose of nivolumab
•
NSCLC/ Ipi 1Q6: 2 doses of nivolumab and 1 dose of ipilimumab, and followed for at least 5 days after the 
second dose of nivolumab
•
Bladder/ Ipi 3Q3: 2 doses of nivolumab and 2 doses of ipilimumab, and followed for at least 5 days after the 
second dose of each drug
After the initial subjects in each treatment regimen are evaluated, additional increments of approximately 3 to 6 
subjects will be treated in the same safety cohort as per the BLRM-copula model recommendation that the dose 
combination is safe. At least 6 DLT-evaluable subjects will be treated and assessed for a particular BMS-986205 dose 
in that tumor type/regimen cohort before enrollment in the expansion cohorts for that regimen will begin enrollment. 
Up to 12 DLT-evaluable subjects in total may be treated in each safety evaluation cohort at the BMS-986205 dose 
chosen for expansion regimens for further evaluation of safety and pharmacodynamic/PK parameters as required. 
BLRM (-copula) will be used to monitor the safety of each triplet dose combination on an ongoing basis.
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Once the initial safety and tolerability have been established independently for each regimen based on the safety 
cohorts, enrollment will then begin in expansion cohorts for further evaluation of safety and tolerability, as well as 
preliminary evaluation of anti-tumor efficacy. In the expansion cohorts, BMS-986205 will be administered at a dose 
determined to be tolerable in combination with each nivolumab and ipilimumab regimen. Each BMS-986205 and 
nivolumab/ipilimumab combination regimen will be evaluated in tumor-specific cohorts based on the tumor type 
evaluated in the safety cohorts.  The Ipi 1Q8 regimen will also be evaluated in a mixed tumor-type cohort which may 
incorporate tumor types evaluated in Part 2 Dose Escalation. 
The 3 tumor types for tumor-restricted cohorts will be melanoma, NSCLC, and bladder. As all subjects in these 
disease-specific cohorts will be receiving agents (nivolumab and ipilimumab) with known anti-tumor activity in those 
tumor types, a single-stage design will be utilized for each of these tumor types. Approximately 40 subjects will be 
treated in each of the following expansion cohorts: melanoma PD-L1 positive, melanoma PD-L1 negative, NSCLC 
PD-L1 positive, NSCLC PD-L1 negative, and bladder; this is to allow for the exploration of early efficacy signals of 
BMS-986205 in combination with both nivolumab and ipilimumab in relevant subpopulations. In each NSCLC 
expansion cohort, approximately 10 subjects will be IO-treatment naive, 25 will be treatment-naive, and 5 IO-therapy 
experienced. In the melanoma cohorts, approximately 35 will be treatment naïve in the advanced setting and 5 will be 
IO-therapy experienced in each cohort. In the bladder expansion cohort in Part 3, at least 30 subjects will be I-O 
therapy naive. 
A mixed tumor type expansion cohort will also be evaluated, using the same regimen as in the melanoma safety cohort, 
Ipi 1Q8W. The purpose of this cohort is to obtain preliminary safety, tolerability, and efficacy data in tumor types 
besides melanoma using the nivolumab 480 mg Q4W/Ipilimumab 1 mg/kg Q8W backbone in combination with BMS-
986205 at the dose selected for melanoma expansion cohort. Up to forty subjects may be treated in this cohort. Tumor 
types included in this cohort may be any previously evaluated in Part 2. All subjects in this cohort will be IO-treatment 
naive. Selection of tumor types and number of subjects per tumor type will be at the discretion of the Sponsor and 
based on emerging data from Part 2 of this study as well as other external data (e.g. from studies of nivolumab and 
ipilimumab in a particular tumor type). For each tumor type enrolled into this cohort, approximately 6 subjects will 
be initially evaluated for safety and tolerability for 6 weeks each for toxicities meeting the definition of DLT exceeding 
the threshold defined below prior to enrollment of any other subjects with that tumor type.
Continuous evaluation of toxicity events in the expansion cohorts will be performed throughout enrollment in the 
expansion cohorts. If, at any time, the aggregate rate of treatment-related toxicities meeting DLT criteria within an 
individual tumor type/treatment regimen exceeds 33% across all subjects treated in the safety evaluation and dose 
expansion cohorts, the findings will be discussed and further enrollment may be interrupted. At that time, depending 
on the nature and grade of the toxicities and after assessing the risk/benefit ratio, a new dose(s) of BMS-986205 for 
subjects within that cohort may be initiated at a previously tested lower dose level evaluated in Part 1or at a dose level 
intermediate to previously tested lower dose levels in Part 1.
Duration of Study: The total duration of time for any individual subject is expected to be approximately 2.5 years. 
The total duration of the study is expected to be 5 years from the onset of the first visit of the first subject to the 
required Survival/Long-term Follow-up of the last subject enrolled.
Study Population: Male and/or female subjects who are at least 18 years old and satisfy eligibility by medical history, 
physical examination (PE), 12-lead electrocardiogram (ECG), and clinical laboratory evaluations will be included to 
participate in the study.
Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be using an acceptable method 
of contraception. WOCBP must have a negative pregnancy test within 24 hours prior to dosing with study drug.
Study Drug: Includes both investigational [medicinal] products and non-investigational [medicinal] products as listed 
in Table 2.
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Table 2:
Study Drugs for CA017003
Medications
Potency
IP/Non-IMP
BMS-986205-04 Capsule
5 mg
IP
BMS-986205-04 Capsule
50 mg
IP
BMS-986205-04 Tablet
25 mg
IP
BMS-986205-04 Tablet
50 mg
IP
BMS-986205-04 Tablet
100 mg
IP
Nivolumab Injection
10 mg/mL
(100 mg/vial)
IP
Ipilimumab Injection
5 mg/ml
(200 mg/vial)
IP
Abbreviations: IMP = investigational medicinal product; IP = investigational product.
Study Assessments:
•
Safety Outcome Measures: Safety assessments will be based on medical review of AE reports and the results of 
vital sign measurements, ECGs, PEs, and clinical laboratory tests. AEs will be coded using the most current 
version of Medical Dictionary for Regulatory Activities (MedDRA) and the incidence of observed AEs will be 
tabulated and reviewed for potential significance and clinical importance. AEs will be assessed continuously 
during the study and for 100 days after the last dose of nivolumab. Both AEs and laboratory tests will be graded 
using the NCI CTCAE v4.03.
•
Pharmacokinetic Measures: Serial plasma and urinary samples for BMS-986205 
 will be 
collected from all subjects at specified time points during BMS-986205 monotherapy. PK parameters to be 
assessed following multiple- and single-dose administration are listed in Section 5.5 of the protocol body. Plasma 
samples of BMS-986205 will be collected during combination treatment. Plasma concentration data will be 
tabulated using summary statistics. 
 
 
•
Efficacy Measure: Disease assessment with computed tomography and/or magnetic resonance imaging, as 
appropriate, will be performed at baseline, end of Cycle 2 and every 8 weeks until end of treatment or until 
subjects withdraw from the study in Part 2, and using the schedules detailed above for Part 3 until end of treatment 
or until subjects withdraw from the study..  In all Parts, disease assessment will continue every 12 weeks for the 
first year after the EOT visit, and then every 6 months thereafter, up to 2 years following the EOT visit. until 
disease progression, at the completion of follow-up, or until subjects withdraw from the study. For subjects with 
Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL), positron emission tomography will be 
performed at baseline and in order to confirm a CR. Disease assessments at other time points may be performed 
as clinically indicated. In all study parts, scans will be collected centrally and may be reviewed by a blinded 
independent central review (BICR) at a later date, or at any time during the study per Sponsor request. Changes 
in tumor measurements and tumor responses will be assessed by the investigator using RECIST or IWG criteria. 
Investigators will also report the number and size of new lesions that appear while on study. The tumor assessment 
time points will be reported on the case report form based on investigators’ assessment using RECIST or IWG 
criteria. Please refer to Appendix 3 for specifics of RECIST v1.1 and Appendix 4 for specifics of the IWG criteria 
to be utilized in this study.
•
For subjects with marrow involvement at screening, a bone marrow biopsy and aspirate will be required to confirm 
a CR  
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•
Biomarker Measures: Blood and tumor samples will be collected at the times indicated in Section 5.6 of the 
protocol for the measurement of biomarkers relevant to dose selection
 
. Further details of blood and tumor collection and processing will be provided to the site in the 
procedure manual.
•
Immunogenicity Measures: Serum samples to evaluate the development of anti-drug antibody (ADA) response 
to nivolumab and ipilimumab (where applicable) in combination with BMS-986205 will be collected at specified 
time points.
Statistical Considerations:
Sample Size Determination:
Part 1 Dose Escalation: 
As a Phase 1 dose-escalation trial, the sample size at each dose in these arms depends on observed toxicity and 
posterior inference. For BMS-986205 in combination with nivolumab (with BMS-986205 lead-in), approximately 
30 subjects are expected to be treated during the dose escalation phase. Initially, approximately 3 subjects will be 
treated at the starting dose levels of BMS-986205 in combination with nivolumab. Due to the potential for early 
discontinuation, additional subject(s) may be enrolled to ensure approximately 3 evaluable subjects at each dose level. 
Additional increments of approximately 3 evaluable subjects will be treated in recommended dose levels per 
BLRM(-Copula) model during the dose escalation phase. At least 6 DLT-evaluable subjects will be treated in the 
selected dose cohort(s) chosen for expansion. Due to the BMS-986205 lead-in period, more than 3 subjects per cohort 
may be treated per BMS-986205 dose level considering potential DLTs that may happen within the lead-in period.
Part 2 Dose Expansion: 
Eight disease-restricted populations and 1 cohort for various tumors will be included in cohort expansion. These are 
cervical cancer, DLBCL, SCCHN, bladder cancer, NSCLC, melanoma, renal cell carcinoma and pancreatic cancer. 
An additional cohort will be dedicated to tumor types from the escalation inclusion criteria, which do not currently 
have a dedicated expansion cohort or plans for evaluation in other studies. The eligible tumor types will be triple 
negative breast cancer, adenocarcinoma of the endometrium, epithelial cancer of the ovary, and sarcoma. 
A Simon 2-stage (optimal) design will be used as a guide for many of the tumor-specific cohorts (see below for 
exceptions). The 2-stage design with a reasonable false positive rate (FPR) and false negative rate (FNR), based on 
assumptions of true (target) and historic objective response rate (ORR) for each indication, will provide guidance for 
the total sample size for each cohort. The sample sizes are provided in Table 3 although not used for hypothesis testing. 
Enrollment will be continued during initial efficacy evaluation (ie, with the indicated number of subjects at Stage 1) 
to ensure that additional subjects are enrolled to account for unexpected trial impact, such as response non-evaluable 
subjects due to early drop out, design parameter change (eg, historical rate update), and so on.
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Table 3:
Dose Expansion: Example of the Simon 2-stage Design Characteristics
Expansion 
Cohort
Historic 
ORR
(%)
Target 
ORR
(%)
Stage 1/
Total N
Stage 1 
Responses 
Futility 
Boundary
Alpha/
Power
(%)
Probability 
of Early 
Stopping
(%)
Cervical, 
Melanoma: Prior 
anti-PD-(L)1, 
Pancreatic, 
NSCLC: Prior 
anti-PD-(L)1, and 
DLBCL
10
30
12/35
1
10/90
66
Bladder and 
SCCHN
25
50
10/27
2
10/90
53
Melanoma: Prior 
anti-PD-(L)1 and 
anti CTLA-4
5
20
12/37
0
10/90
54
*Note: For the melanoma, prior anti-PD-(L)1 and prior anti-PD-(L)-1/anti-CTLA-4 cohorts, the analysis will be 
focused on approximately 35 subjects who are BRAF wild-type (WT).
Abbreviations: CTLA-4 = cytotoxic T lymphocyte-associated antigen 4; DLBCL = diffuse large B cell lymphoma; 
I-O = immuno-oncology; 
NSCLC = non-small 
cell 
lung 
cancer; 
PD-1 = programmed 
cell 
death; 
PD-L1 = programmed death receptor-ligand 1; PD-(L)1 = either PD-1 or PD-L1; ORR = objective response rate; 
SCCHN = squamous cell cancer of the head and neck.
For an expansion cohort of approximately 35 subjects in the cervical, melanoma: prior anti-PD-(L)1, pancreatic, 
NSCLC: prior anti-PD-(L)1, and DLBCL cohorts, and an 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% confidence interval (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 approximately 27 subjects in the bladder and SCCHN tumors and assumed true response 
rate is 50%, there is a 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, 40% 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 approximately 37 subjects with melanoma with prior anti-PD-(L)1 and anti-CTLA-4 
therapy, and an assumed true response rate of 20%, there is a 85% chance of observing at least 5 responses (in other 
words, the FNR is 15%). If the true response rate is only 5% rather than 20%, then there is a 14% chance that there 
will be at least 5 responses in 37 subjects (in other words, FPR is 14%). Also, if 5 responses are observed (eg, 14% 
observed response rate), the lower bound of the 80% CI for the ORR is 7% (higher than historical ORR of 5%). The 
CI is calculated using the Clopper-Pearson method. 
The Simon 2-stage design will not be used for the mixed cohort of additional signal seeking tumor types. 
Approximately 35 to 40 subjects will be enrolled to allow for the exploration of early efficacy signals seen during the 
dose escalation portion of the trial as well as potential signals arising from ongoing trials of other IDO1 inhibitors in 
combination with anti-PD-(L)1. A 2-stage design will also not be utilized for the I-O naive Melanoma, NSCLC, and 
renal cell carcinoma cohorts, as nivolumab is already an established standard of care. Approximately 40 subjects will 
be enrolled in each of these cohorts to allow for the exploration of early efficacy signals of BMS-986205 in 
combination with nivolumab. 
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Approximately 16 Melanoma IO-naive BRAF mutant subjects post-BRAF regimen therapy will be randomized into 
two cohorts and will either be treated with nivolumab or nivolumab in combination with BMS 986205, though will 
not be used for formal statistical comparison.
If there is preliminary evidence of the treatment effect that may represent substantial improvement over available 
therapies, the protocol may be amended to include sufficient additional subjects who will be treated to demonstrate a 
substantial and clinically meaningful effect in ORR that is supported by duration of the effect. The total sample size 
at this stage will be determined based on the ability to produce a CI which would exclude an ORR of the historic 
response and to provide sufficient information for a reliable understanding of the safety profile.
Part 3 Combination with Nivolumab and Ipilimumab
The combination of BMS-986205 with nivolumab and ipilimumab in Part 3 will be evaluated in 2 parts, the safety 
evaluation phase and the cohort expansion phase of the combination in melanoma, NSCLC, and bladder cancer as 
well as a mixed tumor type cohort.
All safety cohorts will begin with an assessment of safety and tolerability of the triplet combination regimen in a 
limited number of subjects, including a sentinel subject. As described in Section 3.1.1.2, the NSCLC and melanoma 
regimen cohorts will begin enrollment first, followed by the bladder regimen cohort once safety and tolerability has 
been established in either NSCLC or melanoma. Initially, approximately 3 subjects will be treated at the selected dose 
combination of BMS-986205 with nivolumab and ipilimumab. Due to the potential for early discontinuation, an 
additional subject(s) may be enrolled to ensure approximately 3 DLT evaluable subjects. Initial safety assessment to 
allow enrollment in the bladder safety cohort will occur when at least 2 evaluable subjects in either the NSCLC or 
melanoma safety cohorts have completed a 6-week DLT evaluation period (see Section 4.5.1 for criteria for DLTs). 
In the melanoma and NSCLC safety evaluation cohorts, if the potential DLT occurring in any third evaluable subject 
regarding the specific dose combination does not influence the recommendation by BLRM (-Copula) to open 
enrollment in the bladder safety cohort, then the bladder safety cohort may proceed with enrollment without waiting 
for the third subject to complete the corresponding DLT observation period. After the initial subjects in each treatment 
regimen are evaluated, additional increments of approximately 3 to 6 subjects will be treated in the same safety cohort 
as per BLRM-copula model recommendation that the dose combination is safe. At least 6 DLT-evaluable subjects 
will be treated and assessed in the selected dosing regimen safety cohort before starting enrollment in the expansion 
cohort for that tumor type/regimen. Up to 12 DLT-evaluable subjects in total may be treated in the safety evaluation 
cohort for each tumor type at the dose selected for expansion cohorts for evaluation of safety and 
pharmacodynamic/PK parameters as required. BLRM (-copula) will be used to monitor the safety of the triplet dose 
combination on an ongoing basis. If, at any time, the aggregate rate of treatment related toxicities meeting DLT criteria 
within an individual treatment tumor type/regimen exceeds 33% across all subjects treated in the safety evaluation 
and dose expansion cohorts, the findings will be discussed and further enrollment may be interrupted. At that time, 
depending on the nature and grade of the toxicities and after assessing the risk/benefit ratio, a new dose(s) of BMS 
986205 for subjects within that dosing regimen may be initiated at a previously tested lower dose level or at a dose 
level intermediate to previously tested lower dose levels.
Once the initial safety and tolerability has been established independently for each regimen based on safety cohort 
evaluations, enrollment will begin of subjects into expansion cohorts for further evaluation of safety and tolerability, 
as well as preliminary evaluation of anti-tumor efficacy. In the expansion phase, each BMS-986205 and 
nivolumab/ipilimumab combination regimen will be evaluated in tumor-specific cohorts based on the tumor type 
evaluated in the safety cohorts (melanoma, NSCLC, and bladder cancer). The Ipi 1Q8 regimen will also be evaluated 
in a mixed tumor-type cohorts, which may incorporate tumor types evaluated in Part 2 Dose Expansion. This 40 
subject cohort is used to obtain preliminary safety, PK, and PD data for the triplet combination in other tumor types.
As all subjects in the melanoma, NSCLC, and bladder disease-specific cohorts will be receiving agents (nivolumab 
and ipilimumab) with known efficacy, a single-stage design will be utilized for each of these tumor types. 
Approximately 40 subjects will be enrolled in each of the following cohorts: melanoma PD-L1 positive, melanoma 
PD-L1 negative, NSCLC PD-L1 positive, NSCLC PD-L1 negative bladder, and mixed tumor type to allow for the 
exploration of early efficacy signals of BMS-986205 in combination with both nivolumab and ipilimumab in relevant 
subpopulations In each NSCLC expansion cohort, approximately 10 subjects will be IO-treatment naive, 25 will be 
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treatment-naive, and 5 IO-therapy experienced. In the melanoma cohorts, approximately 35 will be treatment naïve in 
the advanced setting and 5 will be IO-therapy experienced in each cohort. In the bladder expansion cohort in Part 3, 
at least 30 subjects will be I O therapy naive.
The anti-tumor activity of the expansion cohorts will be continuously monitored in all subjects who are evaluable for 
response using the measurements described in Section 8.3.1. In the NSCLC cohort, 16 of 25 responses for the 
treatment naïve subjects would result in 80% CIs for an ORR that is strictly higher than the historical rate of 45.3%.
1 In the melanoma cohort, 22 of 35 responses for the treatment naïve subjects would result in 80% CIs for ORRs that 
are strictly higher than the historical rates of 580.0%).2 In the bladder cohort, 16 of 30 responses would result in 80% 
CI for ORR that is strictly higher than the historical rate of 38.5%.3 The CIs are calculated using the Clopper-Pearson 
method.
Endpoints:
Primary Endpoints:
The primary objective of this study is to establish the safety, tolerability, and the MTD/MAD/alternate dose of 
BMS-986205 as monotherapy, and in combination with nivolumab and with nivolumab and ipilimumab. 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 the NCI CTCAE v4.03.
The co-primary objective, anti-tumor activity of BMS-986205 in combination with nivolumab in Part 2 (dose 
expansion) and BMS-986205 in combination with both nivolumab and ipilimumab in Part 3, will be measured by 
ORR, DoR, and PFSR based on RECIST v1.1 for solid tumors or IWG for blood tumor. For Parts 1 and 2, disease 
assessment with CT and/or MRI as appropriate will be performed at baseline, end of Cycle 2, and every 8 weeks. For 
Part 3, in the melanoma cohorts, the first tumor assessment will occur at Week 12; subsequent imaging will be every 
8 weeks thereafter during the treatment period; for NSCLC, imaging assessments will occur every 6 weeks during the 
treatment period; for bladder, imaging assessments will occur every 6 weeks during the treatment period up to 24 
weeks, and then occur every 12 weeks thereafter during the treatment period. For all study parts, assessments continue 
every 12 weeks for the first year after the EOT visit, and then every 6 months thereafter, up to 2 years following the 
EOT visit until disease progression per RECIST v1.1 or IWG, or until confirmed disease progression for subjects 
treated beyond progression (defined as an additional 10% or greater increase in tumor burden volume from time of 
initial progression including all target lesions and new measurable lesions), at the completion of follow-up, or until 
subjects withdraw from the study.
1)
Best overall response (BOR) is defined as the best response designation over the study as a whole, recorded 
between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR 
determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 
weeks after the criteria for response are first met. For those subjects who have surgical resection, only presurgical 
tumor assessments will be considered in the determination of BOR.
2)
ORR is defined as the proportion of all treated subjects whose BOR is either a CR or PR.
3)
DoR, 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.
4)
PFSR at 24 weeks, 1 year, and 2 years: The proportion of treated subjects remaining progression free and 
surviving at 24 weeks, 1 year, and 2 years if sufficient data are available. The proportion will be calculated by the 
Kaplan-Meier estimate, which takes into account censored data.
Secondary endpoints:
Pharmacokinetics: Selected BMS-986205 parameters, such as Cmax, Tmax, AUC(TAU), Ctrough, CLT/F, CLR/F, 
Vss/F, AI, %UR24, 
 
 from concentration-time data during BMS-986205 monotherapy and concentrations at end of infusion and 
Ctrough during combination treatment.
 
Pharmacodynamics: Change from baseline for serum and tumor kynurenine and related metabolites and/or percent 
change from baseline from baseline).
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Efficacy: The best overall response, ORR, DoR, and PFSRs at pre-specified time points based on RECIST v1.1 and 
IWG will be the secondary efficacy endpoints for dose escalation and the clinical pharmacology substudies.
The third secondary objective of immunogenicity will be assessed by the frequency of positive anti-drug antibody 
(ADA) to nivolumab or ipilimumab.
Analyses:
Safety analysis: All recorded AEs will be listed and tabulated by system organ class, preferred term, treatment arm, 
and dose level and coded according to the most current version of MedDRA. Vital signs and clinical laboratory test 
results will be listed. Any significant PE findings and results of clinical laboratory test will be listed.
ECG analysis: Summary statistics will be presented for each ECG parameters (heart rate, QTcF, PR and QRS) and 
the corresponding changes from baseline by dose and time points. Scatter plots of change from baseline values in each 
ECG parameters versus the nearest corresponding plasma drug concentrations will be presented.
 
 
The frequency distribution of subjects’ maximum recorded postdose 
QTcF, PR, QRS and ΔQTcF will be tabulated by treatment and summarized
Efficacy analysis: Listing of tumor measurements will be provided by subject and study day in each arm and dose 
level. Individual subject’s best overall response will be listed based on RECIST v1.1 for solid tumor and IWG for 
blood tumor.
To describe the anti-tumor activity of BMS-986205 in combination with nivolumab and in combination with both 
nivolumab and ipilimumab, ORR will be calculated. ORR and corresponding 2-sided exact 95% CI by the Clopper 
and Pearson method will be provided by treatment, and/or dose level and tumor type (if appropriate). Median DoR 
and corresponding 2 sided 95% CI may be reported by treatment, and/or dose level and tumor type (if appropriate). 
DoR will be analyzed using the Kaplan-Meier method.
PFSR at 24 weeks, 1 year, and 2 years will be estimated by the Kaplan-Meier methodology, by treatment, tumor type 
and dose level. The corresponding 90% CI will be derived based on the Greenwood formula.
Pharmacokinetic analysis: PK parameters for BMS-986205 
 will be calculated using 
noncompartmental analyses.
All individual PK parameters will be listed for each analytic including any exclusions and reasons for exclusion from 
summaries. Summary statistics will be tabulated for each PK parameters by treatment. Geometric means and 
coefficients of variation will be presented for Cmax, AUC(TAU), Ctrough, CLT/F, and CLR/F, after multiple dose 
PK. Medians and ranges will be presented for Tmax. Means and standard deviations will be presented for all other PK 
parameters. 
BMS-986205 dose dependency will be assessed during dose escalation lead-in. To describe the dependency on dose 
of BMS-986205, scatter plots of Cmax, and AUC(TAU) versus dose may be provided for each day measured. 
 
 
 Nivolumab and ipilimumab EOI and trough (Ctrough) concentrations and BMS-986205 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. Urinary recovery data of 
BMS-986205 will be listed. Cumulative amount and cumulative percent recovered per interval will be summarized. 
Plots of individual cumulative percent of dose recovered in urine versus end of interval time will be provided. Mean 
plots of cumulative percent of dose recovered in urine versus end of interval time will also be provided.
Immunogenicity analysis: A listing of all available immunogenicity data will be provided by treatment, dose, and 
immunogenicity status. The frequency of subjects with a baseline and/or at least 1 positive ADA assessment of 
nivolumab and/or ipilimumab will be summarized.
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Biomarker analysis: Summary statistics for biomarkers and their corresponding changes (or percent changes) from 
baseline will be tabulated by planned study day and dose in each arm. The time course of biomarker measures will be 
investigated graphically. If there is indication of meaningful pattern over time, further analysis (eg, by linear mixed 
model) may be performed to characterize the relationship. Methods such as, but not limited to, logistic regression may 
be used to better characterize possible associations between biomarker measures from peripheral blood or tuRmor 
biopsy and clinical outcomes.
References:
1
Hellmann MD, Ciuleanu T-E, Pluzanski A, et al. Nivolumab Plus Ipilimumab in Lung Cancer with a High 
tumor Mutational Burden. N Engl J Med. 2018; 378:2093-2104.
2
Opdivo (nivolumab) US Prescribing Information. Bristol-Myers Squibb Company; Revised 2018.
3
Sharma P, Callahan MK, Calvo E, et al. Efficacy and Safety of Nivolumab Plus Ipilimumab in Metastatic 
Urothelial Carcinoma: First Results from the Phase I/II CheckMate 032 Study. Journal of ImmunoTherapy of 
Cancer. 2016; 4(Suppl 2):O3. 
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Study Rationale ................................................................................................. 
1.1.1 Background and Rationale for Inhibition of IDO .................................... 
1.1.2 Rationale for BMS-986205 Monotherapy Lead-in Cycle ........................ 
1.1.3 Rationale for Combination of BMS-986205 with Nivolumab .................. 
1.1.4 Rationale for Combination of BMS-986205 with Both Nivolumab and 
Ipilimumab .................................................................................................. 
1.1.5 Rationale for Tumor Selection ................................................................. 
1.1.5.1 BMS-986205 and Nivolumab Combination .................................... 
1.1.5.2 BMS-986205, Nivolumab, and Ipilimumab Combinations ............. 
1.1.6 Rationale for Dose and Schedule ............................................................. 
1.1.6.1 Dose and Schedule for BMS-986205 .............................................. 
1.1.6.2 Dose and Schedule for Nivolumab in Combination with BMS-
986205...................................................................................................
1.1.6.3 Doses and Schedules for Nivolumab and Ipilimumab in 
Combination with BMS-986205 ............................................................ 
1.1.7 Rationale for Nivolumab and Ipilimumab 30-minute Infusion ................ 
1.1.8 Rationale for the Use of Tablet Formulation ........................................... 
1.1.9 Rationale for Clinical Pharmacology Substudy ...................................... 
1.1.9.1 QTc Substudy .................................................................................. 
1.1.10 Rationale for Use of Blood and Tumor Tissue in Biomarker Studies .... 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objectives .................................................................................. 
1.3.2 Secondary Objectives ............................................................................... 
1.4 Product Development Background ................................................................... 
1.4.1 Pharmacology .......................................................................................... 
1.4.2 Toxicity ..................................................................................................... 
1.4.3 Preclinical Metabolism and Pharmacokinetics ....................................... 
1.4.4 Clinical Pharmacology and Safety .......................................................... 
1.4.4.1 Pharmacokinetics of BMS-986205 ................................................. 
1.4.4.2 Pharmacokinetics of Nivolumab ..................................................... 
1.4.4.3 Pharmacokinetics of Ipilimumab .................................................... 
1.4.4.4 Clinical Safety ................................................................................. 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
1.5.1 Risk/Benefit for BMS-986205 .................................................................. 
1.5.2 Risk/Benefit for Combination with Nivolumab ........................................ 
1.5.3 Risk/Benefit for Combination with Both Nivolumab and Ipilimumab ..... 
1.5.4 Summary .................................................................................................. 
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2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3 INVESTIGATIONAL PLAN .................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.1.1 Screening and Treatment ......................................................................... 
3.1.1.1 Parts 1 and 2 (BMS-986205 Monotherapy and Combination with 
Nivolumab) ............................................................................................ 
3.1.1.2 Part 3 (Combination with Both Nivolumab and Ipilimumab) ........ 
3.1.2 Treatment with Additional Cycles Beyond 48 Weeks .............................. 
3.1.3 Follow-up ................................................................................................. 
3.1.3.1 Clinical/Safety Follow-up ............................................................... 
3.1.3.2 Survival/Long-term/Response Follow-up ....................................... 
3.1.4 Re-treatment during Safety/Survival/Long-term Follow-up .................... 
3.1.5 Part 1: Dose Escalation ........................................................................... 
3.1.6 Part 2: Dose Expansion ........................................................................... 
3.1.7 Part 3: BMS-986205, Nivolumab, and Ipilimumab Combination ........... 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Other Restrictions and Precautions ......................................................... 
3.4.3 Permitted Therapy ................................................................................... 
3.4.3.1 Palliative Local Therapy................................................................. 
3.5 Discontinuation of Subjects Following any Treatment with Study Drug ......... 
3.5.1 Treatment Beyond Progression ................................................................ 
3.5.2 Discontinuation Due to Further Progression (Confirmed Progression) . 
3.5.3 Assessment Schedule for Subjects with Postprogression Treatment ....... 
3.6 Post Study Drug Follow-up .............................................................................. 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG AND STUDY DRUG ADMINISTRATION .................................. 
4.1 Investigational Product ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Dose-limiting Toxicities ........................................................................... 
4.5.2 Management Algorithms for Immuno-oncology Agents .......................... 
4.5.3 Guidelines for Dose Modification ............................................................ 
4.5.4 Dose Delays due to Toxicity .................................................................... 
4.5.5 Criteria to Resume Treatment .................................................................. 
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4.5.6 Guidelines for Permanent Discontinuation ............................................. 
4.5.7 Detection and Management of Methemoglobinemia ............................... 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.7.1 Treatment of Drug-related Infusion Reactions ........................................ 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
4.10 Retained Samples for Bioavailability/Bioequivalence ................................... 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Laboratory Test Assessments ................................................................... 
5.3.2.1 Microsatellite Instability Testing .................................................... 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.2 Secondary Efficacy Assessments .............................................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Pharmacokinetic Assessment following BMS-986205 Monotherapy ...... 
5.5.2 Pharmacokinetic Assessment following Combination Therapy of BMS-
986205 and Nivolumab ............................................................................... 
5.5.3 Pharmacokinetic Assessment following Combination Therapy of BMS-
986205, Nivolumab, and Ipilimumab.......................................................... 
5.5.4 Pharmacokinetics: Collection and Processing ........................................ 
5.5.4.1 BMS-986205 Monotherapy and in Combination with Nivolumab 
(Parts 1 and 2) ...................................................................................... 
5.5.4.2 BMS-986205 in Combination with Both Nivolumab and Ipilimumab 
(Part 3) .................................................................................................. 
5.5.4.3 Pharmacologic Substudy ................................................................ 
5.5.5 Pharmacokinetic Sample Analyses .......................................................... 
5.5.6 Labeling and Shipping of Biological Samples ......................................... 
5.6 Biomarker Assessments .................................................................................... 
5.7 
 Assessments ................................................................ 
5.7.1 Peripheral Blood Markers ....................................................................... 
5.7.1.2 Serum 
 for Kynurenine and Related 
Metabolites ............................................................................................ 
5.7.2 Tissue Markers from Fresh Tumor Biopsies ............................................ 
5.7.2.1 Tumor Kynurenine and Related Metabolites .................................. 
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5.7.3 Tissue Markers from Archived Tumor Samples ....................................... 
5.8 Outcomes Research Assessments ..................................................................... 
6 ADVERSE EVENTS ................................................................................................. 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Adverse Events of Special Interest ................................................................... 
6.4 Laboratory Test Result Abnormalities .............................................................. 
6.5 Pregnancy .......................................................................................................... 
6.6 Overdose ........................................................................................................... 
6.7 Potential Drug-induced Liver Injury ................................................................. 
6.8 Other Safety Considerations ............................................................................. 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.1.1 Dose Escalation (Part 1) ......................................................................... 
8.1.2 Dose Expansion (Part 2) .......................................................................... 
8.1.3 Combination with Both Nivolumab and Ipilimumab (Part 3) ................. 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s) ................................................................................ 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.3.2.1 Pharmacokinetics ............................................................................ 
8.3.2.2 Pharmacodynamics ......................................................................... 
8.3.2.3 Efficacy ........................................................................................... 
8.3.2.4 Immunogenicity ............................................................................... 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.7 Outcomes Research Analyses .................................................................. 
8.4.8 Other Analyses ......................................................................................... 
8.4.9 Immunogenicity Analyses ......................................................................... 
8.4.10 ECG Analyses ........................................................................................ 
8.5 Interim Analyses ............................................................................................... 
9 STUDY MANAGEMENT ........................................................................................ 
9.1 Compliance ....................................................................................................... 
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9.1.1 Compliance with the Protocol and Protocol Revisions ........................... 
9.1.2 Monitoring ............................................................................................... 
9.1.2.1 Source Documentation .................................................................... 
9.1.3 Investigational Site Training.................................................................... 
9.2 Records ............................................................................................................. 
9.2.1 Records Retention .................................................................................... 
9.2.2 Study Drug Records ................................................................................. 
9.2.3 Case Report Forms .................................................................................. 
9.3 Clinical Study Report and Publications ............................................................ 
10 GLOSSARY OF TERMS ........................................................................................ 
11 LIST OF ABBREVIATIONS .................................................................................. 
12 REFERENCES ........................................................................................................ 
APPENDIX 1 STATISTICAL METHODOLOGY ..................................................... 
APPENDIX 2 ECOG PERFORMANCE STATUS ..................................................... 
APPENDIX 3 RECIST 1.1 ........................................................................................... 
APPENDIX 4 INTERNATIONAL WORKSHOP GROUP RESPONSE CRITERIA 
FOR NHL (2014) .................................................................................................... 
APPENDIX 5 MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS ................................................................................................................. 
APPENDIX 6 REVISED INTERNATIONAL PROGNOSTIC INDEX (IPI) SCALE
................................................................................................................................. 
APPENDIX 7 CYP3A4, CYP1A2 AND CYP2B6 GUIDANCE ................................ 
APPENDIX 8 MEDICATIONS ASSOCIATED WITH QT PROLOGATION .......... 
APPENDIX 9 P-GP AND BCRP GUIDANCE ........................................................... 
APPENDIX 10 AGENTS KNOWN TO CAUSE METHEMOGLOBINEMIA .......... 
APPENDIX 11 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
APPENDIX 12 DIAGNOSTIC CRITERIA FOR HLH AND DRESS SYNDROME  
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INTRODUCTION AND STUDY RATIONALE
This is a dose escalation and cohort expansion study of BMS-986205, an inhibitor of the 
indoleamine 
2,3-dioxygenase 
1
(IDO1) 
enzyme, 
in 
combination 
with 
nivolumab 
(anti-programmed cell death-1 [PD-1]) and in combination with both nivolumab and ipilimumab 
(anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) in humans with advanced 
malignant tumors. This study will be conducted in 3 parts. Part 1 (Dose Escalation) will evaluate 
the safety profile, tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating oral 
doses of BMS-986205 in combination with a flat dose of nivolumab in order to identify the 
maximum tolerated dose (MTD)/recommended Phase 2 dose(s) of BMS-986205 in combination 
with nivolumab to be used in Part 2. Part 2 (Dose Expansion) will assess the preliminary efficacy 
of BMS-986205 in combination with nivolumab in specific malignant disease populations and 
will also serve to generate further data to support dose optimization of the combination. Part 3 
will evaluate the safety profile, tolerability, and preliminary efficacy of BMS-986205 in 
combination with both nivolumab and ipilimumab in specific malignant disease populations. The 
study also includes a clinical pharmacology substudy designed to evaluate the potential effect of 
BMS-986205 on the QTc interval.
1.1
Study Rationale
1.1.1
Background and Rationale for Inhibition of IDO
Immunomodulation-based therapies for cancer have become established in recent years and are 
now one of the most successful and important strategies for treating subjects with hematological 
malignancies and solid tumors.1 It is now clear that an anti-cancer antigen-specific immune 
response is the result of a complex dynamic interplay between antigen-presenting cells (APCs), 
T lymphocyte cells, and the target cancer cells.2 The most extensively studied targets of 
immunotherapy in cancer are the negative regulatory receptors, CTLA-4 and PD-1.3 Inhibition of 
these negative regulatory receptors, referred to as immune checkpoint blockade, results in the 
enhanced activation of T-cell responses and potent anti-tumor activity in preclinical models. 
Trials with CTLA-4 blockade provided the first clinical evidence of improvement in overall 
survival with immune modulatory anti-cancer therapy in subjects with metastatic melanoma.4,5
Following that, Topalian et al showed that anti-PD-1 antibody produced objective responses in 
subjects with non-small cell lung cancer (NSCLC), melanoma, and renal cell cancer (RCC).6
Following on the success of CTLA-4 and anti-PD-1 pathway-targeted agents, the field of tumor 
immunotherapy is rapidly expanding. In addition to blocking co-inhibitory pathways, targeting 
the immunosuppressive properties of the cancer cells themselves is considered a promising 
approach especially in combination with antibody-based immunotherapy. It is possible that 
combination therapies could potentially lead to greater depth of response and overall survival as 
has been noted with the combination of anti-PD-1 and anti-CTLA-4 in advanced melanoma 
subjects.7,8 Subjects with metastatic or refractory tumors have a very poor prognosis, and despite 
advances in multimodal therapy, increases in overall survival in this subject population have 
been limited. 
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IDO1 catalyzes the degradation of tryptophan to N-formyl-kynurenine, which is the first and 
rate-limiting step leading to the production of kynurenine and downstream metabolites. The 
activity of IDO1 causes immune tolerance by inhibiting T-cell function through local depletion 
of the essential amino acid tryptophan and through generation of inhibitory kynurenine pathway 
metabolites.9 In healthy humans, IDO1 is expressed in the placenta, the mucosa of the female 
genital tract, the lungs, and the lymphoid organs.10 IDO1 expression in the placenta is believed 
to play a role in maternal tolerance to allogeneic fetuses11; however, its functional roles in the 
lungs and female genital tract are not as clear, but it may be involved in combating infections or 
play a role in immune tolerance in those tissues. In the immune system, IDO1 is expressed in 
dendritic cells and macrophages. It is strongly induced by pro-inflammatory mediators such as 
interferon-gamma (IFNγ) and endotoxins during the late phase of inflammatory reactions, in 
which its immunosuppressive role contributes to the physiologic feedback control of the immune 
response.12
IDO1 is highly expressed in several types of human malignancies. High levels or frequencies of 
IDO1 expression are detected in endometrial, cervical, head and neck, non-small cell lung, 
kidney, colorectal, bladder/urothelial, and ovarian carcinomas as well as in renal cell carcinoma, 
melanoma and diffuse large B-cell lymphoma (DLBCL).10,13 IDO1 expression in tumors is 
believed to induce immune tolerance as evident by a decrease in tumor infiltration of immune 
cells and an increase in the proportion of regulatory T cells (Treg) in the tumor infiltrating 
lymphocytic populations. Increased IDO1 is also correlated with diverse tumor progression 
parameters and shorter patient-survival time in many cancer indications.14 In melanoma, IDO1
has been shown to be significantly up-regulated together with the programmed death receptor-
ligand 1 (PD-L1).15 The enzyme is also reported to be a critical resistance mechanism in anti-
tumor T-cell immunotherapy targeting CTLA-4.16 Furthermore, tumor IDO1 transcript is 
increased in subjects with advanced melanoma and metastatic RCC after treatment with the 
anti-PD-1 antibody nivolumab.17,18 These findings suggest that IDO1 is an important regulator 
of the immunosuppressive mechanisms responsible for tumor escape from host immune 
surveillance. 
Inhibition 
of 
IDO1
using 
pharmaceutical 
agents 
may 
alleviate 
the 
immunosuppressive properties of the tumor microenvironment and achieve more durable 
responses and greater subject survival benefits, particularly when used in combination with other 
cancer immunotherapy agents, such as nivolumab and ipilimumab.
1.1.2
Rationale for BMS-986205 Monotherapy Lead-in Cycle
The totality of the preclinical data with BMS-986205 as well as published clinical data from 
another IDO1 inhibitor (epacadostat, Incyte corporation) showing no objective responses in 
approximately 50 subjects with advanced malignancies treated in a monotherapy trial19, strongly 
suggest that BMS-986205 will not provide benefit to subjects as a monotherapy. It is, however, 
expected to broaden and deepen the responses that have been seen with other immune-
modulating anti-cancer agents. Thus, this first-in-human Phase 1/2a study has been designed in 
such a way as to balance the need for sufficient assessment of the short-term clinical profile of 
BMS-986205 monotherapy prior to allowing the same subjects to receive treatment in 
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combination with nivolumab (an anti-PD-1 antibody). In Part 1 of this study, subjects will 
receive 1 monotherapy lead-in cycle with daily oral administration of BMS-986205 for 2 weeks 
duration in order to characterize the safety, PK, and pharmacodynamic profile of BMS-986205 
monotherapy. Based on the predicted human half-life of BMS-986205 of 23 hours, this 2-week 
interval is expected to cover the anticipated time frame for the occurrence of clinically 
significant early-onset adverse events (AEs) related to BMS-986205 monotherapy.
1.1.3
Rationale for Combination of BMS-986205 with Nivolumab
PD-1 is a transmembrane protein primarily expressed on activated T cells, B cells, myeloid cells, 
and APCs.20 Binding of PD-1 to PD-L1 and PD-L2 has been shown to down-regulate T-cell 
activation in both murine and human systems.21,22,23,24 PD-1/PD-L1 interactions may also 
indirectly modulate the response to tumor antigens through T-cell/APC interactions. Therefore, 
PD-1 engagement may represent one means by which tumors evade immunosurveillance and 
clearance.25 Blockade of the PD-1 pathway by nivolumab has been studied in a variety of 
preclinical in vitro assays, and anti-tumor activity using a murine analog of nivolumab has been 
shown in a number of immunocompetent mouse cancer models.26 Nivolumab has been approved 
as treatment for melanoma, NSCLC (both non-squamous and squamous histologies), head and 
neck cancer, RCC, bladder cancer, and Hodgkin’s lymphoma (HL) in the United States (US),
and is being evaluated extensively across a wide range of other solid tumors and hematological 
malignancies.
PD-1-blockade enhances T-cell migration to tumors by elevating IFNγ inducible chemokines. 
IDO1 expression is also known to be strongly regulated by IFNγ. In fact, in clinical trials of 
subjects with advanced melanoma and metastatic RCC treated with nivolumab, IDO1 gene 
expression was increased in subjects on treatment17,18. These post-treatment increases in the 
expression of IDO1 are indicative of potential adaptive mechanisms of resistance to counteract 
the increased anti-tumor immune cell activity potentiated by PD-1/PD-L1 blockade. These data 
support the hypothesis that combination treatment could result in enhanced anti-tumor activity by 
providing a second mechanism of alleviating tumor mediated immunosuppression.
1.1.4
Rationale for Combination of BMS-986205 with Both Nivolumab and 
Ipilimumab
Immunosuppression within tumors is the result of a complex interaction of multiple signaling 
pathways. Signaling may be accomplished through cell surface-bound proteins such as PD-1 and 
CTLA-4, as well as through soluble mediators such as kynurenine (produced via IDO1) and 
others. Therefore, there are multiple points at which immune-directed therapies could act to 
relieve tumor-induced immune suppression.
Support for the synergistic effects of combining individual immuno-oncology agents with 
non-overlapping mechanisms of action has been provided by both preclinical and clinical 
studies. The most well-studied combination to date has been PD-1 and CTLA-4 receptor 
blockade in improving anti-tumor activity. Preclinically, in vitro combinations of nivolumab and
ipilimumab increase IFNγ production 2- to 7-fold over either agent alone in a mixed lymphocyte 
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reaction. Increased anti-tumor activity of the combination was also observed in 3 of 5 syngeneic 
murine cancer models. In a murine MEL vaccine model, blockade with either CTLA-4 or PD-1 
antibodies increased the proportion of CTLA-4 and PD-1-expressing CD4/CD8 tumor infiltrating 
T effector cells, and dual blockade increased tumor infiltration of T effector cells and decreased 
intratumoral Tregs, as compared to either agent alone.
Clinical evidence supporting the combination of immune-modulating therapies has been 
observed across multiple tumor types in the combination of nivolumab and ipilimumab, as well 
as other agents targeting PD-1, PD-L1, and CTLA-4. See Section 1.1.5.2 for a discussion of the 
synergistic clinical effects of combining these agents in specific tumor types. In addition,
expression of IDO1 has been found to correlate with that of PD-L1 in tissue from patients with 
melanoma. Clinically, treatment with anti-PD1 is associated with increases in IDO1 transcript 
levels in melanoma and RCC17,18. Preclinically, there is also evidence that treatment with anti-
CTLA-4 therapy leads to an increase in IDO1 transcripts16.These findings suggest that a 
combination of therapies targeting PD-1, CTLA-4, and IDO1 may be synergistic and provide 
additional benefit over therapies targeting only one or two of these immune-regulatory pathways.
This in turn may lead to improved clinical outcomes by increasing the number of patients who 
response to nivolumab and ipilimumab therapies, while also potentially increasing the depth and 
duration of responses to those therapies.  
1.1.5
Rationale for Tumor Selection
IDO1 is overexpressed in several types of human malignancies and is often correlated with poor 
prognosis. Examination of The Cancer Genome Atlas (TCGA) database reveals that IDO1
exhibits a broad range of gene expression across these various tumor types. In order to address 
the question of which tumor types will be most likely to respond to IDO1 inhibition, tumors with 
varying levels of IDO1 expression were selected for further study during cohort expansion in 
Part 2, including cervical cancer and DLBCL at the high end and pancreatic cancer at the lower 
end. Published data describing IDO1 protein expression by immunohistochemistry (IHC) across 
multiple tumor types were used to confirm presence of IDO1 in the tumor indications suggested 
by the TCGA analysis. Human tumor samples from priority indications were obtained and 
analyzed for kynurenine levels to confirm that elevated IDO1 expression levels also correlate 
with elevated IDO1 activity. 
1.1.5.1
BMS-986205 and Nivolumab Combination
Given the hypothesis that IDO1 inhibition will increase both the depth and breadth of anti-PD-1 
therapy, tumor selection for Parts 1 and 2 was further prioritized based on tumors in which PD-1 
blockade has shown activity (ie, melanoma, NSCLC, renal cell carcinoma [RCC], and squamous 
cell carcinoma of the head and neck [SCCHN]), as well as tumors that to date have shown 
insensitivity to anti-PD-1 treatment (ie, pancreatic cancer). 
As of Nov-2016, there are external data from another IDO1 inhibitor/anti-PD-1 combination 
(epacadostat/pembrolizumab), showing clinical proof of concept in treatment-naïve advanced 
melanoma subjects. There was an objective response rate (ORR) of 58% in 19 evaluable 
advanced melanoma patients, as compared to an ORR of 34% reported for pembrolizumab 
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monotherapy as per the European Union (EU) Summary of Product Characteristics27 and the 
Food and Drug Administration (FDA) prescribing information.28
In order to gain understanding of which specific subset(s) of patients with melanoma will benefit 
from IDO1 inhibition in combination with nivolumab, distinct cohorts of melanoma subjects will 
be studied during dose expansion in Part 2:
•
Immuno-oncology (I-O) naïve, PD-L1 positive and negative: Nivolumab is approved for the 
treatment of first-line advanced melanoma across PD-L1 status. These cohorts (40 subjects 
each) are added in order to assess potential synergistic activity of adding IDO1 inhibition to a 
known standard of care. 
•
I-O naïve, BRAF mutated, post-BRAF-targeted therapy: Nivolumab is also approved for the 
treatment of first-line advanced melanoma across BRAF mutation status. Many of the BRAF 
mutated subjects who were treated in nivolumab trials had received prior BRAF-targeted 
therapy and still demonstrated clinical benefit with nivolumab. In addition, there is evidence 
of an increase in tumor infiltrating lymphocytes and an upregulation of PD-L1 following 
BRAF inhibition,29 which suggests that the combination of an anti-PD-1 agent with an IDO1 
inhibitor may be particularly beneficial in this subset of patients. However, there are not 
sufficient prospective data on the efficacy of nivolumab monotherapy (40 subjects per arm)
in this population. Thus, these subjects will be randomized to receive either BMS-986205 in 
combination with nivolumab or nivolumab monotherapy in order to generate a robust, 
prospective dataset with nivolumab monotherapy to serve as a basis for understanding the 
potential added benefit of combination therapy. 
•
Prior anti-PD-(L)1 and prior anti-PD-(L)1 + anti-CTLA-4 combination regimen therapy: 
Recurrent or progressive melanoma following treatment with anti-PD-(L)1 monotherapy or 
the anti-PD-(L)1 + anti-CTLA-4 combination represents areas of high unmet medical need. 
These cohorts (approximately 35 subjects each) are added in order to assess whether IDO1 
inhibition can act as a mechanism to restore anti-tumor activity in these subjects (refer to 
Section 1.1.1 for supporting data).
NSCLC will also be evaluated in distinct settings:
•
I-O naïve, PD-L1 positive and negative: Nivolumab is an approved therapy for the treatment 
of advanced NSCLC across PD-L1 status. These cohorts (40 subjects) are added in order to 
assess potential synergistic activity of adding IDO1 inhibition to a known standard of care.
•
I-O experienced: Recurrent
or progressive NSCLC following anti-PD-(L)1 therapy 
represents an area of high unmet medical need. This cohort (35 subjects) is added in order to 
assess if IDO1 inhibition can act as a mechanism to restore anti-tumor activity in these 
patients.
Decisions regarding tumor selection were made so that novel combination therapies could 
potentially bring benefit to subjects with high unmet medical need, as is the case with these 
subjects with advanced malignancy. Additionally, consideration was given to the inclusion of 
other tumor types from the dose escalation portion of the trial that do not currently have plans for 
evaluation in other studies, which will be based on emerging clinical data.
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1.1.5.2
BMS-986205, Nivolumab, and Ipilimumab Combinations 
The tumors selected for the evaluation of triplet combination in Part 3 are NSCLC, melanoma, 
and bladder cancer. Selection was based on evidence of high levels of IDO1 expression (see 
Section 1.1.1); the potential to evaluate BMS-986205 with varying doses and schedules of 
nivolumab and ipilimumab in tumor types with established safety and tolerability profiles for 
those regimens (see Section 1.1.6.2); and evidence of increasing clinical benefit with 
combination immuno-therapy over monotherapy with either agent, described below.
Melanoma
Ipilimumab and nivolumab were both initially evaluated and approved as single agents in 
metastatic melanoma before being approved in combination.
Ipilimumab was initially approved as monotherapy based on the Phase 3 MDX010-020 study. In 
this study, compared to melanoma peptide vaccine (gp100), ipilimumab improved OS (10 versus 
6 months) and ORR (6 and 11% for ipilimumab-containing arms versus 2% in the gp100 arm).30
Subsequent to this, nivolumab was approved for the treatment of metastatic melanoma based on 
the CA209037 and CA209066 studies. In CA209037, compared to investigator’s choice of 
chemotherapy, nivolumab administered at 3 mg/kg every 2 weeks improved both objective 
response (32% versus 11%) and CR rates (3% versus 0%).31
The synergistic combination of the 2 agents was evaluated in the CA209067 and CA209069 
studies. In both studies, the combination of nivolumab with ipilimumab improved outcomes
compared to ipilimumab. In CA20906732, the combination demonstrated a response rate of 58%, 
numerically higher than either single agent (44% for nivolumab, 19% for ipilimumab). In 
CA209069, the same combination doses achieved a response rate of 61%, significantly greater 
than that of ipilimumab alone (11%).33 PD-L1 status appeared to affect response rates in 
CA209067, as subjects treated with nivolumab and ipilimumab with PD-L1 positive tumors had 
a response rate of 72.1% versus 54.8% in PD-L1 negative tumors.  Based on those initial results, 
the combination of nivolumab and ipilimumab was approved as therapy in the first-line treatment 
of metastatic melanoma and became the first combination immuno-oncology regimen approved 
in any tumor type.
NSCLC
Nivolumab has been approved as monotherapy in patients with squamous NSCLC with 
progression on or after platinum-based chemotherapy. The approval was based on the results of 
CA209017, a randomized trial of nivolumab versus docetaxel. The median overall survival (OS) 
for patients in the nivolumab arm was 9.2 months versus 6 months for those in the docetaxel arm 
(HR = 0.59). Improvement in survival was observed for nivolumab.34 A second Phase 3 study, 
CA209057, lead to the approval in non-squamous histologies with a 27% reduction in risk of 
death (HR = 0.73; P = 0.0015). Nivolumab also significantly improved ORR versus docetaxel (P
= 0.0246), with ORR as high as 36% in subjects with PD-L1 expressing tumors. OS
approximately doubled with nivolumab versus docetaxel.35
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Ipilimumab has been shown to have activity in lung cancer. A Phase 2 study (CA184041) in 
subjects with NSCLC or small cell lung cancer (SCLC) investigated the addition of ipilimumab
to carboplatin and paclitaxel using 2 different schedules (concurrent and phased). The phased
schedule demonstrated a significant improvement of immune-related progression-free survival as
well as progression-free survival by modified WHO criteria compared to chemotherapy alone, in
both NSCLC and SCLC.32
Based on data in melanoma, which led to the approval of ipilimumab and nivolumab 
combination therapy, as well as the activity observed with nivolumab and ipilimumab
individually in NSCLC, the nivolumab plus ipilimumab combination has been also evaluated as 
first-line therapy in patients with advanced NSCLC. In the CA209012 trial, various schedules of 
nivolumab and ipilimumab were evaluated in treatment-naïve subjects with stage IV or 
metastatic NSCLC. Promising clinical activity was observed, with response rates for the 
combinations of nivolumab plus ipilimumab (38% to 47%) at least similar if not improved 
relative to those observed with platinum-based chemotherapy. Response rates appeared greater in 
subjects when PD-L1 status was taken into account, with ORR reaching 90% in those subjects 
with PD-L1 expression greater than 50%.36
These data provided proof of concept of combinatorial activity of immunotherapy agents in 
NSCLC and led to the initiation of CA209227, a randomized, open-label Phase 3 trial evaluating 
nivolumab monotherapy or nivolumab plus ipilimumab versus platinum doublet chemotherapy in 
subjects with stage IV or recurrent NSCLC.
Bladder Cancer 
High levels of programmed death 1 (PD-1) ligand 1 (PD-L1) expression have been noted in 
bladder/urothelial carcinoma (UC), suggesting tumor-associated immune tolerance and escape 
from immune surveillance. PD-L1 expression has been reported in approximately 20% (5% 
cutoff) and 30% (1% cutoff) of tumor tissue sample.37,38,39 PD-1 and PD-L1 immune checkpoint 
inhibitors appear to show benefit in patients with disease progression on platinum-based 
therapy.37 In an open-label, multicenter Phase 1/2 expansion cohort in patients with metastatic 
UC, nivolumab elicited a response rate of 24.4% with acceptable safety, regardless of tumor PD-
L1 expression, in patients who had received 1 or more prior lines of chemotherapy 
(CA209032).38 In a larger study in unresectable or metastatic UC, CA209275, nivolumab had 
clinically meaningful efficacy and a manageable safety profile.39 At 7 months of median follow-
up, 24.4% of patients remain on therapy. Confirmed overall response rate (ORR) was 19.6% 
(95% CI: 15.0, 24.9). Nivolumab was granted accelerated approval in 2017 as monotherapy in 
bladder cancer based on these results.
Ipilimumab has been explored precystectomy in a pilot trial of patients with clinically localized 
bladder cancer. In this trial, 12 patients were treated with 2 doses of ipilimumab (n = 6 treated 
with 3 mg/kg and n = 6 treated with 10 mg/kg).40 Most drug-related adverse events (AEs) were 
Grade 1 or 2, all patients demonstrated an increase in CD4+ ICOShi T cells in tumor tissue and 
systemic circulation, and 8/12 patients had down-staging of their disease on final pathology 
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review. The efficacy and safety of first-line gemcitabine, cisplatin plus ipilimumab for metastatic 
UC is being investigated in a Phase 2 trial (NCT01524991).
The CA209032 study has evaluated the combination of nivolumab and ipilimumab in bladder 
cancer after first-line chemotherapy. Preliminary results from that study revealed overall 
response rates of 36% to 38.5% for a nivolumab and ipilimumab combinations in this patient 
population.41 To evaluate this further, a Phase 3 trial of nivolumab and ipilimumab in recurrent 
or platinum refractory bladder cancer has been initiated. The potential for increasing clinical 
activity with the combination of immunotherapy agents in bladder cancer supports the evaluation 
of the combination of BMS-986205, nivolumab, and ipilimumab.
1.1.6
Rationale for Dose and Schedule
1.1.6.1
Dose and Schedule for BMS-986205
Selection of FIH Starting Dose
The selection of BMS-986205 starting dose and schedule is based on the pivotal 1-month 
toxicology studies in rats and dogs and the extrapolation of in vivo data from preclinical efficacy 
models in mice.
In the pivotal 1-month oral repeat-dose toxicity study in rats, the dose of 20 mg/kg once daily 
(QD) was established as the MTD and the dose that produces severe toxicity to 10% (STD10) of 
rats. A dose of 5 mg/kg/day was considered to be the no-observed adverse effect level (NOAEL) 
in the 1-month rat study. In the 1-month dog study, a dose of 30 mg/kg/day was the highest 
nonseverely toxic dose (HNSTD) and also the NOAEL. Using body surface area conversion, a 
human equivalent dose (HED) of 3.2 mg/kg was determined based on the rat STD10, one-tenth 
of which will suggest a starting dose of 0.32 mg/kg in humans. Similarly, based on the dog 
HNSTD and scaled by body surface area, a HED of 16.2 mg/kg can be calculated, one-sixth of 
which would suggest a starting dose of 2.7 mg/kg. The rat was considered the most appropriate 
species to determine the maximum recommended starting dose because, although the toxicity 
profiles were generally similar in both rats and dogs, the rat was the most sensitive species with a 
lower projected starting dose. The maximum starting dose of 0.32 mg/kg (25 mg based on a 
median body weight of 80 kg) was therefore selected for this study. Based on the observed 
exposure in rats and predicted human PK, the starting dose of 25 mg would project an exposure 
(area under the concentration-time curve from time zero to 24 hours postdose [AUC(0-24h)])
margin of 65 relative to the MTD/STD10 and 15 relative to the NOAEL. At the 
HNSTD/NOAEL in dogs, the exposure margin was 33 relative to the projected AUC at the 
starting dose of 25 mg in humans.
In preclinical models in mice (M109), administration of BMS-986205 QD resulted in significant 
reduction in kynurenine levels in both serum and in tumor tissues in a dose-dependent manner. 
Given the projected human half-life of ~23 hours, a QD dosing schedule was selected for this 
initial study.
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In preclinical studies in dogs, approximately 2- to 3-fold higher exposures were observed when 
dosing with food compared to under fasting condition (see Section 1.4.3). BMS-986205 will be 
administered after a light meal (see Section 4.2) in order to optimize the systemic exposure. 
Selection of Dose for Dose Expansion (Part 2), Combination with Nivolumab and 
Ipilimumab (Part 3)
Based on the preliminary clinical safety, pharmacokinetic, and pharmacodynamic data observed 
to date, cohort expansion in Part 2 was opened using both 100 and 200 mg doses in combination 
with nivolumab.  This initial selection of two doses for cohort expansion in Part 2 allowed for the 
continued accrual of data at both doses to support a final dose decision. After review of safety, 
PK, and PD data, 100 mg was selected as the dose to be used for remaining subject enrollment in 
Part 2. See Section 1.4.4.4, for the description of clinical safety and tolerability of 100 and 
200 mg and Section 1.4.4.1 for a discussion of the preliminary pharmacokinetic profile.
For Part 3 of this study, the maximum initial dose of BMS-986205 evaluated will be 100 mg 
daily. The selection of 100 mg was based on the aggregate safety and PK data in combination 
with nivolumab across doses of BMS-986205 found to be safe and tolerable, as well as to 
provide an additional safety margin since the safety profile of BMS-986205 at 200 mg is 
acceptable in combination with nivolumab.  Lower doses may be evaluated based on emerging 
safety, PK, and PD data.
1.1.6.2
Dose and Schedule for Nivolumab in Combination with BMS-986205
Nivolumab 240 mg every 2 weeks (Q2W) has been approved for use as monotherapy in patients 
with melanoma, RCC, and NSCLC, and will be administered in combination with BMS-986205
for the dose escalation portion of the study (Part 1), as well as for the dose expansion cohorts that 
were included in the protocol prior to Amendment 06. Nivolumab 480 mg every 4 weeks (Q4W)
will be administered in combination with BMS-986205 for the dose expansion cohorts that are 
added with Amendment 06 (Part 2) [melanoma, NSCLC, and additional signal-seeking tumors]
and the clinical pharmacology substudy (Part 3). This change in dosing interval as of 
Amendment 06 will provide a more convenient regimen for the patients. The expansion cohorts 
that predated Amendment 06 will continue with the nivolumab 240 mg Q2W dosing regimen in 
order to ensure consistent dosing within each cohort.
The safety and efficacy of the 480 mg Q4W flat dose of nivolumab are expected to be similar to 
the approved nivolumab dose of 240 mg flat doses or 3 mg/kg Q2W. The nivolumab dose of 
480 mg Q4W was selected based on clinical data and modeling and simulation approaches using 
population PK (PPK) and exposure-response analyses of data from studies in multiple tumor 
types (melanoma, NSCLC, and RCC) where body weight normalized dosing (mg/kg) has been 
used. The PPK analyses have shown that exposure to nivolumab increased dose proportionally 
over the dose range of 0.1 to 10 mg/kg administered Q2W, and no clinically meaningful 
differences in PK across ethnicities and tumor types were observed. Nivolumab clearance and 
volume of distribution were found to increase as the body weight increases, but less than 
proportionally with increasing weight, indicating that milligram per kilogram dosing represents 
an over-adjustment for the effect of body weight on nivolumab PK. Using the PPK model, the 
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overall distributions of nivolumab average steady-state exposures are comparable after treatment 
with either nivolumab 3 mg/kg Q2W or nivolumab 480 mg Q4W, although the flat dose regimen 
of 480 mg Q4W is predicted to result in approximately 40% higher steady-state peak 
concentration (Cmaxss) and approximately 20% lower steady-state trough concentrations
compared to the reference regimen of 3 mg/kg Q2W. Across the various tumor types in the 
clinical program, nivolumab has been shown to be safe and well tolerated up to a dose level of 
10 mg/kg, and the relationship between nivolumab exposure produced by 3 mg/kg and efficacy 
and safety has been found to be relatively flat. Although nivolumab Cmaxss is predicted to be 
higher following 480 mg Q4W, these exposures are predicted to be lower than or within the 
exposure ranges observed at doses up to 10 mg/kg Q2W used in the nivolumab clinical program 
and are not considered to put subjects at increased risk. The exposures predicted following 
administration of nivolumab 480 mg Q4W are on the flat part of the exposure-response curves 
for previously investigated tumors (melanoma and NSCLC) and are not predicted to affect 
efficacy. Based on these data, nivolumab 480 mg Q4W is expected to have similar efficacy and 
safety profiles to nivolumab 3 mg/kg Q2W.
Of note, as an immunoglobulin G4 (IgG4) monoclonal antibody, nivolumab does not interact 
directly with cytochrome P450 (CYP) enzyme systems. Systemic cytokine modulation data 
indicated that there were no meaningful changes in cytokines known to have indirect effects on 
CYP enzymes across all dose levels of nivolumab (0.3, 2, and 10 mg/kg) during the course of 
treatment. Therefore, it is unlikely that nivolumab administered at either 240 mg Q2W or 480 mg 
Q4W will affect the systemic exposures of BMS-986205.
At the discretion of the Sponsor, and in agreement with the investigators, the 480 mg Q4W 
nivolumab dosing regimen in the designated expansion cohorts and clinical pharmacology 
substudy may revert back to 240 mg Q2W based on emerging PK, pharmacodynamic, and/or 
tolerability data from the cohort expansion portion of the trial.
1.1.6.3
Doses and Schedules for Nivolumab and Ipilimumab in Combination 
with BMS-986205
The safety profile of nivolumab and ipilimumab is well characterized from a large safety 
database at different dose and schedules as monotherapy or in combination in different tumor 
indications. Consistent with the mechanism of action of nivolumab and ipilimumab, the most 
frequently reported drug-related AEs observed in clinical trials are those associated with 
activation of the immune system. The most common types of immune-mediated AEs include 
endocrinopathies, diarrhea/colitis, hepatitis, pneumonitis, nephritis, and rash. In combination 
regimens, the frequency and intensity of these events vary and appear to depend on the specific 
dose and schedule used as well as the patient population/tumor type being treated. As described 
below, while the overall pattern of AEs observed with the combination of nivolumab and 
ipilimumab remains relatively consistent across doses and schedules evaluated, the incidence and
severity of immune-mediated AEs varies across tumor types. Therefore, evaluation of safety and 
tolerability of specific dose/schedule combinations of nivolumab and ipilimumab with BMS-
986205 in Part 3 will be evaluated in tumor types in which that nivolumab/ipilimumab regimen
has evidence of both tolerability and efficacy (see Section 1.1.5.2).
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Melanoma
The regimen selected for evaluation of triplet therapy in melanoma is BMS-986205 in 
combination with nivolumab 480 mg Q4W and ipilimumab 1 mg/kg Q8W.
The currently approved combination of nivolumab and ipilimumab in metastatic melanoma is 
nivolumab 1 mg/kg with ipilimumab 3 mg/kg Q3W (N1I3) for 4 doses, followed by nivolumab 
3 mg/kg Q2W ongoing. Two large randomized trials (CA209069 and CA209067) utilized this 
same dose regimen N1I3. In CA209067, Grade 3 and 4 adverse events were: nivolumab alone 
43.5%, ipilimumab alone 55.6%, and nivolumab plus ipilimumab (N1I3) 68.7%. Discontinuation 
as a result of treatment was also highest in the combination group, 36.4%, as compared to 7.7% 
with nivolumab alone group and 14.8% of those in the ipilimumab alone group.33 While the 
safety of N1I3 ratio was considered acceptable and majority of the AEs were managed with 
recommended treatment algorithms, there is rationale that lowering the dose of ipilimumab from 
3 mg/kg to 1 mg/kg could potentially reduce the incidence of high grade AEs. This led to the 
initiation of the CA209511 study, which is comparing N1I3 to a nivolumab 3 mg/kg and 
ipilimumab 1 mg/kg Q3W (N3I1) regimen. In addition, a separate cohort consisting ipilimumab 
1 mg/kg Q8W together with nivolumab 6 mg/kg (alternating with 480-mg flat dose) Q4W, all 
continuing until unacceptable toxicity is being evaluated.
The rationale for a regimen with Q8W ipilimumab dosing is to potentially optimize safety and 
efficacy while also extending the dosing intervals for the convenience of patients and health care 
providers. From a safety perspective, this extended schedule of ipilimumab is predicted to lead to 
reduced incidence of high grade adverse events compared to regimens utilizing more frequent 
and/or higher doses of ipilimumab, while simultaneously allowing for an increase in the dose of 
nivolumab used in combination with ipilimumab.
Regarding PK, nivolumab dosing at 480 mg Q4W is expected to result in similar time averaged 
concentrations at steady state (Cavgss) as nivolumab 3 mg/kg Q2W. In addition, nivolumab 
exposures following 480 mg are predicted to be below the those observed at doses up to 10 
mg/kg Q2W (used in the Phase 1 nivolumab clinical program) that have been shown to be safe 
and well tolerated26.
Efficacy may also be improved through the addition of BMS-986205 to the use nivolumab 
480 mg plus ipilimumab 1 mg/kg regimen.  Combination regimens in which ipilimumab is 
continued beyond 4 doses until progression or intolerability have not been assessed in patients 
with advanced melanoma. Furthermore, it is possible that patients receiving lower and less 
frequent ipilimumab doses will stay on the combination longer by reducing high grade AEs and 
thereby increasing the number of combination doses administered. This may result in improved 
efficacy.
Lastly, the proposed regimen may provide convenience to patients and health care providers, due 
to the increased interval between doses ( i.e. every 4 weeks instead of every 3 weeks). 
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NSCLC
The regimen selected for evaluation of triplet therapy in NSCLC is BMS-986205 in combination 
with nivolumab 360 mg Q3W and ipilimumab 1 mg/kg Q6W.
Previous evaluations of nivolumab and ipilimumab combinations in NSCLC were based on the 
success of combination therapy in melanoma as well as the evidence of monotherapy activity of 
nivolumab in NSCLC. Data from these cohorts demonstrate nivolumab 3 mg/kg Q2W given with 
ipilimumab at 1 mg/kg Q6W is tolerable. Of particular note, the rate of discontinuation for this 
combination due to drug-related AEs  was 11% compared to 10% in the nivolumab monotherapy 
arm; fatigue was the most commonly reported AE related to study therapy in the combination 
arm (23.1%).36 This combination regimen is being evaluated currently in the CA209227 study in 
first-line treatment of NSCLC.
A flat dose of nivolumab has been selected for the current study. From a PK perspective, using 
the PPK model, the overall distributions of nivolumab average steady-state exposures (Cavgss)
are predicted to be comparable after treatment with either nivolumab 3 mg/kg Q2W or 360 mg 
Q3W. Although nivolumab Cmaxss is predicted to be higher (23%) following 360 mg Q3W, 
these exposures are predicted to be within the exposure ranges observed at doses up to 10 mg/kg 
Q2W used in the nivolumab clinical program, and are not considered to put subjects at increased 
risk. The exposures predicted following administration of nivolumab 360 mg Q3W are on the 
flat part of the exposure-response curves for previously investigated tumors, melanoma and 
NSCLC, and are not predicted to affect efficacy. Based on these data, nivolumab 360 mg Q3W is 
expected to have similar efficacy and safety profiles to nivolumab 3 mg/kg Q2W. Therefore the 
combination dosing schedule selected for this study (nivolumab 360 mg Q3W plus ipilimumab 
1 mg/kg Q6W) provides a combination regimen where the immune-mediated AEs were mostly 
low grade and manageable with prompt use of corticosteroids.
Bladder Cancer
The regimen selected for evaluation of triplet therapy in bladder cancer is BMS-986205 in 
combination with nivolumab 80 mg Q3W and ipilimumab 3 mg/kg Q3W for four doses, 
followed by nivolumab 480 mg Q4W.
Nivolumab and ipilimumab combinations have been evaluated in advanced bladder cancer in the 
CA209032 trial. Subjects were treated with either nivolumab 1 mg/kg and ipilimumab 3 mg/kg 
(N1I3) or nivolumab 3 mg/kg and ipilimumab 1 mg/kg (N3I1), both given Q3W for 4 cycles and 
then followed by nivolumab monotherapy. In contrast to the experience with nivolumab and 
ipilimumab combinations evaluated in other tumor types such as melanoma and NSCLC, 
treatment with higher doses of ipilimumab in bladder cancer were not associated with increased 
toxicity. Preliminary analysis of 24 subjects in the N1I3 (median follow-up: 7.8 months) and 104 
subjects in N3I1 (median follow-up: 16.7 months) showed that discontinuations due to study 
drug toxicity were approximately equal between the groups (8% for N1I3, 14% for N3I1) as 
were the rates of Grade 3 or 4 toxicity (30.8% for N1I3 and 31.7% for N3I1).41 As higher doses 
of ipilimumab may provide additional clinical activity, and taking into consideration the equal 
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safety to date between the N1I3 and N3I1 arms in CA209032, the N1I3 regimen was selected for 
evaluation in combination with BMS-986205 in the current trial.
1.1.7
Rationale for Nivolumab and Ipilimumab 30-minute Infusion
Long infusion times place a burden on subjects and treatment centers. Establishing that 
nivolumab can be safely administered using shorter infusion times of 30 minutes duration in 
subjects will diminish the burden provided no change in safety profile. Both nivolumab and 
ipilimumab have been administered safely at doses ranging up to 10 mg/kg over these treatment 
durations. Overall, infusion reactions including high-grade hypersensitivity reactions have been 
uncommon across multiple clinical studies, and all have been managed by following the safety 
algorithms. Infusion duration of 30 minutes for 3 mg/kg nivolumab (30% of the dose provided at 
10 mg/kg) is not expected to present any safety concerns compared with the prior experience at 
10 mg/kg nivolumab dose infused over the 60-minute duration. Similarly, shortened infusion 
duration of 30 minutes for ipilimumab is not expected to present additional safety concerns.42
1.1.8
Rationale for the Use of Tablet Formulation
A capsule formulation was used in the dose escalation (Part 1) and in patients participating the 
dose expansion (Part 2) of the study prior to Amendment 8. A tablet formulation has been 
developed to help reduce the pill burden and with its smaller size, provide ease of administration. 
The tablet formulation became available for use for subjects in Part 2 (after implementation of 
Amendment 7), Part 3 and in the QTc clinical pharmacology substudy.
Biopharmaceutics studies (in vitro biorelevant dissolution and non-clinical pharmacokinetic 
studies) were conducted to investigate the in vitro and in vivo performance of the two dosage 
forms.
Biorelevant dissolution of the two dosage forms were compared in a non-sink, 2-stage USP-II 
apparatus (fed state gastric fluid, pH 5 → fed-state simulated intestinal fluid (FeSSIF), pH 5, 
transitioned at 20 min).  At a representative human dose of 100 mg, the dissolution profiles 
showed that both dosage forms disintegrate and dissolve rapidly, reaching a solubility indicative 
of complete drug release and dissolution in the intestinal fluid.  To confirm the finding, a 
pharmacokinetic study was conducted in the dog model using 4 male dogs, pentagastrin-treated, 
as a cross-over between the tablet and capsule dosage form (50 mg) in the fed-state. The 50 mg 
dog dose is equivalent to roughly 150 mg human effective dose based on body surface area dose 
adjustment.  The mean PK profiles for the two dosage forms were similar. The tablet was 80% 
bioavailable relative to the capsule formulation. The Cmax was 85% of the capsule, while the 
Tmax was the same43.The mean values for Cmax and AUC were not statistically different 
(p>0.05, Student’s t-test).  The comparative PK parameters are listed in Table 1.1.8-1. 
Table 1.1.8-1:
Comparative Pharmacokinetic Parameters
PK Parameters
Capsule (50 mg)
Tablet (25 mg x 2)
Cmax (ng/mL)
332.12 ± 98.04
282.67 ± 99.88
Tmax (h)
2
2
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Table 1.1.8-1:
Comparative Pharmacokinetic Parameters
PK Parameters
Capsule (50 mg)
Tablet (25 mg x 2)
AUC (ng·h/mL)
1252.91 ± 392.91
1000.48 ± 416.89
AUC variability (%CV)
31.34
41.67
Cmax and AUC are mean values ± standard deviation (n=4 dogs), Tmax is the median value
Preliminary results from the dose escalation cohorts indicated potentially significant biomarker 
(peripheral kynurenine inhibition) over a wide dose/exposure range (See Section 1.4.4.1). Given 
the significant overlap in the in vitro and in vivo performance of the dose forms, the tablet is 
expected to perform similarly compared to the capsule while improving subject convenience and 
compliance.
1.1.9
Rationale for Clinical Pharmacology Substudy
1.1.9.1
QTc Substudy
In this substudy, the effect of BMS-986205 on the QTc interval will be evaluated. Preclinical 
evaluations did not identify a signal indicating that BMS-986205 may increase the QTc interval 
or have an adverse effect on cardiac conduction (Section 1.4.2). Despite the low risk, such 
evaluation is required during the development of a therapeutic agent and the design of this study 
(treating subjects across a wide range of doses, the inclusion of a 2-week BMS-986205 
monotherapy leading-in period) is well suited for the evaluation of QTc risk, in particular, the 
characterization of the impact of BMS-986205 exposure on QTc changes. Serial 
electrocardiograms (ECGs; reviewed by a core laboratory) will be collected with matching PK 
samples during the BMS-986205 monotherapy at steady state in subjects participating in the 
substudy. To minimize the potential effects of intrinsic factors such as food ingestion and 
circadian patterns on QTc intervals, time-matched baseline ECGs will be collected prior to the 
start of BMS-986205 treatment.
As nivolumab is known not to affect the QTc interval, only routine ECG monitoring will be 
collected during combination treatment in both dose escalation and dose expansion phase of the 
study.
1.1.10
Rationale for Use of Blood and Tumor Tissue in Biomarker Studies
Biomarkers are increasingly playing a key role in the development of cancer therapeutics. By 
tracking treatment-induced changes in molecular markers measured in tissue and body fluids, the 
activity of experimental agents may be assessed and the details of their mechanisms of action 
may be elucidated. Such pharmacodynamic measures may be instrumental also for identifying 
appropriate doses and treatment schedules and may provide supporting information for future 
regimens.
This study includes fresh pre- and on-treatment biopsies as well as collection of archival tissue.  
Fresh biopsies will allow for assessment of key biomarker correlates which require 
contemporaneous tissue and specific processing (eg tumor kynurenine). Age limits on archival 
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tissues from subjects not providing fresh biopsies are required to allow for accurate interpretation 
of key biomarkers (eg PDL1) which may become compromised with age of sample.
The evaluation of pre- and on-treatment biopsies in this study is particularly critical for 
understanding biological consequences and clinical effects of combining therapies targeting 
multiple mechanisms simultaneously.  The collection of both pre-treatment tumor biopsies and 
archival tumor tissue will provide important insight into questions related to mechanism of 
action and response to therapy. 
 
 
Identification and validation of critical markers in archival tissue will potentially enable 
diagnostic test development for future selection of patients most likely to respond to therapy
based on archival tissue alone and obviate the need for fresh biopsies in larger groups of patients.  
Blood and tumor tissue samples will be collected in this study at baseline and on treatment to 
identify molecular markers associated with clinical activity and mechanism of action of 
BMS-986205 in the lead-in phase or in combination with nivolumab ± ipilimumab. This 
information will be used to identify appropriate doses and treatment schedules of BMS-986205 
in combination with nivolumab and in combination with both nivolumab and ipilimumab. 
Additionally, examination of biomarkers in samples obtained prior to treatment may provide 
information that allows identification of subjects with specific characteristics that will respond 
best to these agents. Information gained from tumor samples will not be used to make individual 
subject treatment decisions, but may inform pursuit of a validated marker to inform optimized 
treatment decisions in future protocol amendments or separate studies. 
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1.2
Research Hypothesis 
It is anticipated that BMS-986205, administered in combination with nivolumab and in 
combination with both nivolumab and ipilimumab, will demonstrate adequate safety and 
tolerability, as well as a favorable benefit/risk profile, to support further clinical testing. No 
prospective hypotheses are being formally evaluated.
1.3
Objectives(s)
1.3.1
Primary Objectives
Part 1: Dose Escalation
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and MTD/maximum
administered dose (MAD)/alternate dose(s) of BMS-986205 administered as monotherapy and in 
combination with nivolumab in subjects with advanced malignant tumors.
Part 2: Dose Expansion
To investigate the anti-tumor activity of BMS-986205 administered in combination with 
nivolumab in distinct cohorts of subjects with advanced malignant tumors.
To evaluate the safety and tolerability of BMS-986205 in combination with nivolumab in 
subjects with advanced malignant tumors.
Part 3: BMS-986205, Nivolumab and Ipilimumab Combination
To determine the safety, tolerability, dose-limiting toxicities (DLTs), and preliminary anti-tumor 
activity of BMS-986205 administered in combination with both nivolumab and ipilimumab in 
subjects with select advanced malignant tumors.
1.3.2
Secondary Objectives
1) To characterize the PK of BMS-986205 administered alone, in combination with nivolumab,
and in combination with both nivolumab and ipilimumab.
2) To investigate the anti-tumor activity of BMS-986205 administered in combination with 
nivolumab in dose escalation and clinical pharmacology substudies.
3) To characterize the pharmacodynamic activity of BMS-986205 administered alone, in 
combination with nivolumab, and in combination with both nivolumab and ipilimumab.
4) To characterize the immunogenicity of nivolumab when administered in combination with 
BMS-986205 and in combination with both BMS-986205 and ipilimumab.
5) To characterize the immunogenicity of ipilimumab when administered in combination with 
nivolumab and BMS-986205
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1.4
Product Development Background
1.4.1
Pharmacology
BMS-986205
BMS-986205 is a small molecule inhibitor of IDO1 with half maximal inhibitory concentration
(IC50) biochemical potency of 13.3 ± 1.8 nM and inhibitory constant (Ki) value of 21 ± 3 nM. 
Cellular potency as measured by the IC50 inhibition of kynurenine production was determined to 
be 1.11 ± 0.93 nM in human embryonic kidney 293 (HEK293) cells transiently expressing IDO1
and 1.71 ± 0.07 nM in HeLa cells stimulated with IFNγ. In addition, BMS-986205 inhibited 
kynurenine production in human whole blood (hWB) stimulated with IFNγ and LPS with an 
IC50 value of 33 ± 4.2nM. In an allogeneic mixed lymphocyte reaction (MLR) using IDO1
expressing dendritic cells, BMS-986205 restored T-cell proliferation with a half maximal 
effective concentration (EC50) value of 1.2 ± 0.4 nM.
BMS-986205 also exhibited significant pharmacodynamic effects in reducing tumor and serum 
kynurenine levels in at least 2 different murine syngeneic tumor models. The maximal reduction 
in tumor kynurenine levels was observed between 6 and 7 hours after dosing and the effects were 
sustained for 24 hours.
More detailed information can be found in the current version of the BMS-986205 Investigator 
Brochure (IB).
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Nivolumab
Nivolumab is a fully human, IgG4 (kappa) isotype monoclonal antibody that binds to PD-1 with 
nanomolar affinity (dissociation constant [Kd], 3.06 nM) and a high degree of specificity. 
Nivolumab blocks binding of PD-1 to its ligands PD-L1 and PD-L2. Nonclinical in vitro testing 
of nivolumab demonstrated that binding to PD-1 results in enhanced T-cell proliferation and 
release of IFNJ in vitro in MLR and cytomegalovirus assays. Additional details are provided in 
the current version of the nivolumab IB.
Ipilimumab
Ipilimumab is a fully human IgG1 (kappa) monoclonal antibody that has specificity and a high 
affinity for human CTLA-4. The calculated dissociation constant value from an average of 
several studies was 5.25 nM. Binding of ipilimumab to purified, recombinant human CTLA-4 
antigen was also demonstrated by enzyme-linked immunosorbent assay with half-maximal 
binding at 15 ng/mL, whereas saturation was observed at approximately 0.1 Pg/mL. No cross-
reactivity was observed against human CD28. Ipilimumab completely blocked binding of B7.1 
and B7.2 to human CTLA-4 at concentrations higher than 6 and 1 Pg/mL, respectively.
Additional details are provided in the current version of the ipilimumab IB.
1.4.2
Toxicity
The safety profile of BMS-986205 was evaluated in single- and repeat-dose oral toxicity studies 
up to 3 months in duration (rats and dogs) and in genetic toxicity, phototoxicity, and safety 
pharmacology assessments. Rats and dogs were used as the main species for toxicologic 
evaluation and unless otherwise stated, all animal studies were dosed daily by the oral route. 
Dogs were considered an appropriate nonrodent species for nonclinical evaluation because of 
greater oral bioavailability (39%) compared to monkeys (10%) and consequently higher systemic 
exposure to BMS-986205. The rat data was used to calculate the maximum recommended 
starting dose because the rat was more sensitive to BMS-986205 toxicity on a mg/m2 basis, 
although the toxicity profiles in the rat and dog were generally similar. Animal-to-human 
exposure multiples were calculated relative to either the preliminary mean Cmax or AUC in 
humans at the clinical dose of 100 mg (Cmax 0.476 ȣg/mL, AUC [0-24h] 4.85 ȣg•h/mL).
BMS-986205 is not phototoxic or genotoxic in vitro, and demonstrated no significant in vitro 
interactions with a broad spectrum of pharmacologic receptors, transporters, ion channels, 
nuclear hormones, or enzymes at t 30 M except for moderate inhibition at the Į7 nicotinic 
cholinergic receptor (IC50 of 0.7 P0 to 0.9 M). In patch-clamp ion channel assays, 
BMS-986205 produced low to moderate inhibitory effects on the cardiac human 
ether-à-go-go-related gene (hERG) rapid delayed rectifier (IKr) potassium channel current 
(75% inhibition at 3 M and IC50 1.1 M), on the cardiac SCN5A sodium channel 
(d 13% inhibition at 10 M), and on the L-type calcium channel (83% inhibition at 10 M). In 
addition, similar testing of BMT-238450, a pharmacologically inactive metabolite of 
BMS-986205, demonstrated no significant off target receptor, ion channel, or transporter 
interactions (including cardiac ion channels) at t 10 M. The in vitro concentrations tested 
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above (≥0.7 μM) are substantially higher (≥580×) than the preliminary free Cmax (1.2 nM or 
0.5 ng/mL) at the current Phase 3 dose of 100 mg. Additionally, there were no clinically 
significant effects on cardiovascular, respiratory, or central nervous system (CNS) endpoints 
evaluated in the 1- and 3-month pivotal repeat-dose toxicity studies in rats and dogs. In 
particular, no BMS-986205-related hemodynamic or electrocardiogram (ECG) changes were 
observed in dogs at doses up to 100 mg/kg with associated Cmax values up to 3.6 μg/mL 
(8.8 μM; safety multiple of 8× relative to preliminary Cmax of 0.476 μg/mL at the clinical dose 
of 100 mg).
The results from the pivotal 1-month toxicity studies in rats and dogs were generally similar to 
those from the pivotal 3-month studies and are detailed in Section 4.3 of the Investigator 
Brochure. However, as higher doses were administered in the 1-month studies, there were some 
adverse findings highlighted below that were not observed in the 3-month studies. In the 1-
month rat study, doses were 5, 20, and 80 mg/kg/day. BMS-986205 was not tolerated at 
80 mg/kg/day with signs of overt toxicity that included decreased activity, coolness to touch, 
hunched posture, piloerection, partially closed eyelids, recumbency, abnormal gait, 
aggressiveness, chromorhinorrhea, dehydration, body weight loss, and/or reduced food 
consumption resulting in death or early euthanasia; at ≥20 mg/kg/day, adverse findings included
minimal hepatocellular necrosis with correlative increases in serum alanine aminotransferase 
(ALT: ∼2× control) and minimal bile duct hyperplasia/fibroplasia in the liver. The severely toxic 
dose in 10% of animals (STD10) in rats was 20 mg/kg/day (mean combined-sex AUC 
≤11.1 μg•h/mL) and the no-observed adverse effect level (NOAEL) was 5 mg/kg/day 
(AUC: 2.5 μg•h/mL). Relative to the preliminary human AUC values at the 100 mg clinical 
dose, the corresponding AUC exposure multiples are 2.3× and 0.5× at the STD10 and NOAEL, 
respectively. In the 1-month dog study, doses were 10, 30, and 100 mg/kg/day. At 
100 mg/kg/day, BMS-986205 was not tolerated (body weight loss), and there were adverse 
findings in the liver (hepatocellular necrosis, centrilobular rarefaction, and bile stasis) with 
associated increases in serum transaminases (up to 18×) and total bilirubin (TBIL) (up to 4.3×). 
The dose of 30 mg/kg/day (mean combined-sex AUC: 5.6 μg•h/mL) was considered the highest 
non-severely toxic dose (HNSTD) and also the NOAEL for this study. At the current Phase 3 
dose of 100 mg the dose multiple is 24× and, relative to preliminary human AUC values, the 
corresponding AUC exposure multiple is 1× at the HNSTD/NOAEL.
In the 3-month Good Laboratory Practice (GLP) oral toxicity study in rats doses were 0 (vehicle 
control), 1, 3, or 10 mg/kg/day (0, 6, 18, and 60 mg/m2), respectively. BMS-986205 was well 
tolerated at doses ≤10 mg/kg/day (mean AUC ≤9.66 μg•h/mL). At ≥1 mg/kg/day, 
BMS-986205-related findings included dose-dependent increases in minimal to marked tubular 
regeneration in the kidney of male rats that lacked increased cellular stratification and nuclear or 
cellular pleomorphism seen with atypical hyperplasia. This finding was considered adverse at 
≥3 mg/kg/day due to the extensive change that was accompanied by circumferential basement 
thickening and/or mononuclear infiltrates in the adjacent interstitium. At ≥3 mg/kg/day, there 
were additional generally dose-related changes that reflected oxidative injury to erythrocytes by 
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the BMS-986205 metabolite, p-chloroaniline,44,45 with subsequent accelerated red blood cell 
(RBC) turnover and active hematopoiesis. These included minimal to mild increases in 
methemoglobin (metHb) concentrations (1.41× to 8.81× control); minimal decreases in RBC 
count (0.88× to 0.93×), hemoglobin (0.90× to 0.95×), and hematocrit in females (0.91× to 
0.96×); minimal to moderate increased hematopoiesis and pigment accumulation in the spleen 
that correlated with increases in absolute and/or relative (to body and/or to brain) spleen weights 
(13% to 32%); minimal to moderate increases in reticulocyte counts in females (1.16× to 2.00×); 
transient and minimal increase in red blood cell distribution width (RDW) in females (1.05× to 
1.06×); and increased incidence of females showing minimal degree of acanthocytes and/or 
echinocytes; and at 10 mg/kg/day, minimal increases in mean corpuscular volume (MCV) (1.05×
to 1.06×); in mean corpuscular hemoglobin concentration (MCHC) (1.04× to 1.07×); increases in 
absolute and/or relative (to body and/or to brain) spleen weights that correlated microscopically 
with minimal to moderate pigment accumulation and increased hematopoiesis in the spleen; and 
presence of RBCs with crystallized hemoglobin-like structures in 1 female. In females at 
10 mg/kg/day, the magnitude of increases in metHb and changes in RBC parameters (including 
morphology) together were considered adverse as these changes are expected to collectively 
result in decreased total functional oxygen-carrying capacity, paralleling the occurrence of 
clinical symptoms in humans (cyanosis, headache, and dizziness) with low-grade 
methemoglobinemia (∼8%) and concurrent anemia. Although a recovery period was not included 
in this study, there was evidence of a regenerative process in the kidney that was likely a 
response to previous BMS-986205-related renal tubular injury in male rats and would be 
expected to recover once the insult was removed. In addition, the changes associated with 
p-chloroaniline formation would be expected to recover once the insult was removed. The 
NOAEL was considered to be 1 mg/kg/day (mean sex-combined AUC ≤0.666 μg•h/mL) and the 
STD10 was considered to be 10 mg/kg/day (mean sex combined AUC ≥9.66 μg•h/mL). 
Relative to the preliminary human AUC values at the 100 mg clinical dose, the corresponding 
AUC exposure multiples are 2× and 0.14× at the STD10 and NOAEL, respectively. Dose 
multiples are 8× and 0.8× at the STD10 and NOAEL, respectively.
In the 3-month GLP oral toxicity study in dogs doses were 0 (vehicle control) 10, 30, or 
60 mg/kg/day (0, 60, 180, and 360 mg/m2), respectively. BMS-986205 was well tolerated at 
doses ≤60 mg/kg/day (mean AUC ≤18.6 μg•h/mL). At all doses, there was a spectrum of 
generally dose-related changes that reflected oxidative injury to erythrocytes by the 
p-chloroaniline metabolite,44,45
with subsequent accelerated RBC turnover and active 
hematopoiesis. These changes included the following: 1) minimal to mild, reversible increases in 
metHb concentration at ≥10 mg/kg/day (1.63× to 6.3× pretest); 2) minimal decreases in red cell 
mass at ≥30 mg/kg/day in females only (0.94× to 0.86×) and 60 mg/kg/day in both sexes (0.97×
to 0.82×); 3) poikylocytosis (abnormal RBC shape) with crystallized hemoglobin-like structures 
in 3 animals at 60 mg/kg/day; 4) changes consistent with an erythroid regenerative response 
including minimal to moderate increases in reticulocyte counts (1.73× to 2.76×), minimal 
increases in platelet counts (1.30× to 1.76×) at ≥30 mg/kg/day, and minimal decreases in MCHC 
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(0.94× to 0.98×) at 60 mg/kg/day; 5) in the liver, minimal to mild increased hematopoiesis and
increased incidence and/or severity of minimal to mild pigment (likely hemosiderin) 
accumulation in Kupffer cells, consistent with hemolysis (extravascular), and minimal bile stasis 
at ≥30 mg/kg/day; 6) in the kidney, increased incidence and/or severity of minimal to moderate 
pigment accumulation in kidney tubules (likely hemosiderin [a breakdown pigment of 
hemoglobin]); and 7) minimal to mild increased hematopoiesis in the bone marrow and spleen at 
all doses. The magnitude of increases in metHb and decreases in red cell mass together were 
considered adverse at 60 mg/kg/day as these changes are expected to collectively result in 
decreased total functional oxygen-carrying capacity, paralleling the occurrence of clinical 
symptoms in humans (cyanosis, headache, and dizziness) with low-grade methemoglobinemia 
(∼8%) and concurrent anemia. All other findings were considered nonadverse, adaptive, or 
regenerative changes. Although a recovery period was not included in this study, the changes 
associated with p-chloroaniline formation would be expected to recover once the insult was 
removed. The NOAEL was considered to be 30 mg/kg/day (mean sex-combined AUC 
≤8.47 μg•h/mL), and the HNSTD was considered to be 60 mg/kg/day (mean sex-combined 
AUC ≤18.6 μg•h/mL). Relative to preliminary human AUC values at the current Phase 3 
clinical dose of 100 mg QD, the corresponding AUC multiples are 2× and 4× at the NOAEL and 
HNSTD, respectively. Dose multiples are 24× and 48× at the NOAEL and HNSTD, respectively.
BMS-986205 was associated with fetal loss and fetal malformations in an embryofetal 
development study in rats. In this study, oral doses of 20 and 50 mg/kg/day (only doses tested) 
were administered over the relevant period of organogenesis in rats and were associated with 
exposure multiples of 5× and 14×, respectively, compared to the exposures at the current Phase 3 
clinical dose of 100 mg. There was a dose-dependent increase in the incidence of fetal loss and 
fetal malformations. Thus, exposure to BMS-986205 poses a potential risk to human pregnancy. 
BMS-986205 should not be administered to pregnant women.
Overall, the nonclinical toxicology profile of BMS-986205 has been well characterized, 
supporting clinical use in oncology subjects.
1.4.3
Preclinical Metabolism and Pharmacokinetics
The PK and metabolism of BMS-986205 were characterized in a series of in vitro studies in 
animal species and human models and in vivo studies that were conducted in mice, rats, dogs, 
and monkeys.46,47 After IV administration, the apparent  elimination half-life (T-HALF) of 
BMS-986205 ranged from 1.8 hours to 6.6 hours and total plasma clearance (CLTp) was 
equivalent to ≤48% of the respective reported liver blood flows in animals48, suggesting that the 
compound has low to moderate systemic clearance. The volume of distribution at steady-state 
(Vss) indicated that BMS-986205 is distributed extravascularly, with low brain distribution 
observed in rats following IV dosing. BMS-986205 (10 μM, 4.1 μg/mL)was > 99.9% bound to 
serum proteins in humans and in the animal species studied.
After oral administration of BMS-986205, the time of maximum observed concentration (Tmax) 
ranged from 0.5 hours to 1.7 hours and absolute oral bioavailability (F) of BMS-986205 given as 
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a solution or suspension formulation was 29% to 55%, 64%, 39%, and 10% in mice, rats, dogs, 
and monkeys, respectively. Preliminary data showed that following a single 5 mg/kg and 25 
mg/kg oral dose of BMS-986205 in pentagastrin-treated dogs, BMS-986205 AUC(0-24h) 
increased by approximately 2.2× and 3.0×, respectively, under fed conditions compared to 
fasting conditions, indicating that there was a food effect, but the observed food effect was not 
dose related. Following a single oral dose of BMS-986205 (5 mg/kg oral dose) to famotidine 
pretreated dogs under fasted condition, there was no reduction in AUC(0-24h) or maximum 
plasma concentration (Cmax) and the values were within PK experimental variability, compared 
to pentagastrin pretreated dogs.
The biotransformation of BMS-986205 was characterized by the production of numerous 
metabolites; biotransformation reactions included mono- and di-oxidation to form various 
oxidative metabolites including BMT-269044 (hydroxylation) and BMT-303671 (N-oxide), 
oxidation followed by glutathione (GSH) conjugation, and amide hydrolysis to an acid 
metabolite, M9 (BMT-238450) and p-chloroaniline. In vitro incubations of [14C]BMS-986205 in
rat, dog, monkey, and human hepatocytes  demonstrated  that  p-chloroaniline was further 
metabolized to form an aniline sulfate (M1, BMT-242377) and 4-chloroacetanilide (M3, BMS-
215753). The rank order of the extent of hydrolysis was rat (21%) > dog (13%) > human (4%) ~
monkey (4%). In addition, GSH adducts of oxidative metabolites were detected in hepatocyte 
incubations from rat, dog, and monkey, but were not observed in humans. No unique human 
metabolite was observed in hepatocytes. The primary in vivo biotransformation pathways in 
intact rats and dogs, and in bile duct-cannulated (BDC) rats administered [14C]BMS-986205 
were mono- and di-oxidation and hydrolysis of BMS-986205 to form BMT-238450 and p-
chloroaniline. Subsequent metabolism of p-chloroaniline formed BMT-242377 and BMS-
215753. Unchanged parent drug was a prominent circulating component in intact rat and dog. 
Other circulating drug-related materials included aniline-derived metabolites (BMT-242377 and 
BMS-215753), acid metabolite M9 (BMT-238450), and oxidative metabolites (BMT-269044 
and BMT-303671). Preliminary reaction phenotyping studies in human liver microsomes 
demonstrated that cytochrome P450 (CYP) 3A4 was the major enzyme responsible for the 
oxidative metabolism of BMS-986205.
Preliminary data suggest that BMT-303671 blocked kynurenine production in hWB, with an 
IC50 value comparable to BMS-986205. BMT-269044 was also active in inhibiting kynurenine 
production in hWB, but was ~ 5-fold less potent than BMS-986205, while BMT-238450 was 
pharmacologically inactive under the same conditions.
A few selected metabolites including BMT-269044, BMT-303671, BMT-238450, and those 
derived from p-chloroaniline are being monitored in the ongoing, first-in-human (FIH), 
Phase1/2a Study CA017-003. Preliminary results suggest that plasma concentrations of BMT-
269044 and BMT-303671 were approximately 30% to 40% of BMS-986205 levels. In the 3-
month rat oral toxicity study, the AUC(0-24h) exposures of BMT-303671, BMT-269044, and 
BMT-238450 measured at the STD10 dose of 10 mg/kg/day were 11.2 μg•h/mL, -8.26 μg•h /mL 
and 18.4 μg•h /mL, respectively. At these exposures, the multiples over the AUC(0-24h) for 
BMT-303671 (2.10 μg•h /mL), BMT-269044 (1.88 μg•h /mL), and BMT-238450 (0.498 μg•h 
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/mL) at the 100 mg clinical dose are 5×, 4×, and 37×, respectively. In the 3-month dog oral 
toxicity study, the AUC(0-24h) exposures of BMT-303671, BMT-269044, and BMT-238450 
measured at the HNSTD of 60 mg/kg/day were 0.728 μg•h /mL, 0.483 μg•h /mL, and 17.4 μg•h 
/mL, respectively, with associated exposure multiples at the 100 mg clinical dose of 0.35×, 
0.26×, and 35×, respectively.
In human liver microsomes, BMS-986205 inhibited CYP1A2, CYP2B6, CYP2C8, CYP2C9, and 
CYP2C19 with IC50 values ranging from 1.0 μM to 26.5 μM. BMS-986205 also inhibited 
CYP3A4 with IC50s of 13.3 μM and 7.5 μM using midazolam and testosterone as the probe 
substrates, respectively. Additionally, BMS-986205 appeared to be a time-dependent inhibitor of 
CYP3A4, which had a 5× shift in IC50 values. However, the inhibitor concentration 
corresponding to the half-maximal rate of inactivation (KI) was determined to be greater than 20 
μM, indicating that time-dependent inhibition of CYP3A4 by BMS-986205 is not anticipated. 
BMS-986205 
also 
inhibited 
recombinant 
human 
uridine 
diphosphate 
glucuronosyltransferase(UGT) 1A1 (IC50 = 3.5 μM). BMT-269044 and BMT-303671 exhibited 
inhibition of CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4. BMT-238450 was not a 
CYP or UGT1A1 inhibitor. BMS-986205 inhibited digoxin and cladribine transport, as well as 
organic anion transporting polypeptide (OATP)1B1, OATP1B3, bile salt export pump (BSEP), 
organic cation transporter (OCT)1, and multidrug and toxin extrusion protein 1 (MATE1) (IC50 
= 2.1 μM to 19.0 μM). In human hepatocytes, BMS-986205 did not cause any meaningful 
increase in CYP1A2, CYP2B6, and CYP3A4 enzyme activity, but did show some increase in 
corresponding CYP2B6 and CYP3A4 mRNA levels, indicating a potential for drug-drug 
interaction (DDI) with substrates of CYP2B6 and CYP3A4 through CYP induction.
Based on the preliminary human Cmax concentration (1.2 μM [0.5 μg/mL) at the current Phase 3 
clinical dose (100 mg), using a 1% free fraction, the potential for BMS-986205 and its 
metabolites to cause DDIs by inhibition of CYP enzymes or UGT1A1 is low. However, drugs 
that inhibit or induce CYP3A4 may alter the plasma concentrations of BMS-986205. The 
potential to inhibit the human drug transporters OATP1B1, OATP1B3, BSEP, MATE1, and 
OCT1 is low, but BMS-986205 has been shown to inhibit P-glycoprotein (P-gp)/breast cancer 
resistance protein (BCRP), suggesting that BMS-986205 could affect the absorption and 
distribution of compounds that are P-gp/BCRP substrates. Additional details can be found in the 
IB for BMS-986205.
1.4.4
Clinical Pharmacology and Safety
1.4.4.1
Pharmacokinetics of BMS-986205
Preliminary PK for BMS-986205 are evaluated based on results from the dose escalation cohorts. 
Following BMS 986205 administration with a light meal, the exposures of BMS-986205 appear 
to increase in a dose proportional manner when the dose was increased from 50 mg to 400 mg. 
The time to reach peak plasma concentrations (Tmax) varied in a wide range with median about 
3 hours to 5 hours. Following 100 mg QD doses, the geometric mean (CV%) accumulation ratio 
based on AUC(0 24h) between Day 1 and Day 14 was estimated to be 2 (79%), which 
corresponded to an estimated effective half-life of 37 hours, supportive of QD dosing of BMS-
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986205. The geometric mean BMS-986205 concentration at the end of the dosing interval on 
Day 14 exceeded the in vitro hWB IC50 value (7.4 ng/mL) for all dose levels and exceeded the 
in vitro hWB IC90 (92 ng/mL) at dose levels of 100 mg and above. Main circulating metabolites 
(> 10% metabolite to parent AUC ratio based on AUC[0-24h] on Day 14) following the 100 mg 
QD doses were 12% for BMT-238450, 34% for BMS-269044, and 39% for BMS 303671. 
Preliminary results indicated BMT-303671 blocked kynurenine production in hWB with similar 
IC50 as BMS-986205 whereas BMS-269044 was~5-fold less potent and BMT-238450 was 
pharmacologically inactive (Section 1.4.3). Thus, it is possible that BMT-303671 contributes to 
the overall pharmacological activity. Additionally, preliminary data from an ADME study (Study 
CA017-052A) in healthy subjects suggest that unlike non-clinical toxicology species (rats and 
dogs), the hydrolysis pathway, which forms the p chloroaniline metabolite, represents a minor 
pathway in humans, accounting for ~7% of the total clearance.
Effect of food on the PK of BMS-986205 was evaluated in healthy subjects in 
Study CA017-053. Preliminary PK data indicate that following a single 100 mg dose, 
BMS-986205 geometric mean Cmax and AUC(0-168h) are 114% (90% CI 75.4% to 161.1%) 
and 52.8% (37.2% to 70.3%) higher, respectively, when dosed after a high fat meal compared to 
under fasting condition. BMS-986205 Cmax and AUC(0-168h) are 96.5% (71.7% to 124.8%) 
and 42.6% (28.0% to 58.8%) higher respectively, when dosed after a light meal compared to 
under fasting condition. Tmax ranged from 2 hours to 4 hours when dosing fasted and from 
2 hours to 5 hours when dosed after a meal. PK variabilities are generally smaller when dosed 
after a meal. The terminal half-life averaged from 52 hours to 62 hours across the treatment 
groups.
1.4.4.2
Pharmacokinetics of Nivolumab
Single-dose PK of nivolumab was evaluated in 39 subjects with multiple tumor types in 
CA209001 in the dose range of 0.3 to 10 mg/kg. The median Tmax across dose levels ranged 
from 1.6 to 3.1 hours with individual values ranging from 0.9 to 7 hours. The PK of nivolumab 
was linear in the range of 0.3 to 10 mg/kg with dose-proportional increase in Cmax and 
AUC(INF). Geometric mean clearance after a single IV dose ranged from 0.13 to 0.19 mL/h/kg, 
while mean volume of distribution of terminal phase (Vz) varied between 83 to 113 mL/kg 
across doses. The mean terminal T-HALF of nivolumab was 17 to 25 days, consistent with half-
life of endogenous IgG4, indicating that the elimination mechanism of nivolumab may be similar 
to IgG4. Both elimination and distribution of nivolumab appeared to be independent of dose 
within the dose range studied.
The multiple dose PK of nivolumab given Q2W in subjects with multiple tumor types was 
determined from the CA209003 study as well as PPK analyses using data from 909 subjects 
across nivolumab studies. Multiple-dose PK of nivolumab following Q2W dosing was linear 
with dose-proportional increase in Cmax and AUC(TAU) in the studied range of 0.1 to 
10 mg/kg. The geometric mean of terminal T-HALF was 26.7 days and the typical clearance was 
8.7 mL/h, which are consistent with those of full human immunoglobulin antibodies.
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Nivolumab 480 mg Q4W is currently under active clinical evaluation across multiple tumor 
types. Using a PPK model, nivolumab 480 mg Q4W is predicted to provide average steady-state 
concentrations (Cavgss) similar to nivolumab 3 mg/kg Q2W. Nivolumab 480 mg Q4W is 
predicted to provide greater (approximately 40%) Cmaxss and lower (approximately 20%) 
trough steady-state concentrations (Cminss). Nivolumab has been shown to be safe and well 
tolerated up to doses of 10 mg/kg Q2W and has not demonstrated a clear dose response or 
exposure-response safety relationship. Based on these safety findings, the predicted Cmaxss at 
480 mg Q4W is not considered to put subjects at increased risk for AEs. The approved dose of 
3 mg/kg Q2W has shown survival benefit across multiple tumor types compared to respective 
standards of care. Nivolumab exposure was not a predictor of survival in exposure-response 
efficacy analyses conducted for multiple tumor types. The Cminss values following nivolumab 
480 mg Q4W are predicted to be in the range of those on the flat part of the exposure-response 
efficacy curves and are not expected to impact efficacy. 
As of Nov-2016, approximately 50 subjects in the nivolumab clinical development programs 
have received at least 1 dose of nivolumab 480 mg Q4W, either as the starting therapy or as 
maintenance treatment following nivolumab 240 mg Q2W. Bristol-Myers Squibb (BMS) has a 
clinical safety program that monitors symptoms potentially related to infusion-related reactions 
reported on the day of infusion and the following day. For the approximately 50 subjects treated 
with 30-minute infusions of nivolumab 480 mg, there have been no reports of any symptoms that 
may potentially be linked to infusion reactions on the day of infusion or the following day. There 
have been no new safety signals identified during routine clinical and pharmacovigilance 
monitoring of these studies. Clinical evaluation of this dose regimen is ongoing; as such, 
summaries of safety information, PK, and immunogenicity are not currently available.
Additional details are provided in the current version of the nivolumab IB.
1.4.4.3
Pharmacokinetics of Ipilimumab
The PK of ipilimumab has been extensively studied in subjects with melanoma at the 3- and 
10-mg/kg doses administered as a 1.5-hour IV infusion. The PK of ipilimumab was characterized 
by population PK (PPK) analysis and determined to be linear and time invariant in the dose 
range of 0.3 to 10 mg/kg. The mean CL (± standard deviation) value after IV administration of 
10 mg/kg was 18.3 ± 5.88 mL/h, and the mean Vss (± standard deviation) value was 5.75 ± 1.69 
L. The PPK of ipilimumab was studied in 785 subjects (3,200 serum concentrations) with 
advanced MEL in 4 Phase 2 studies (CA184004, CA184007, CA184008, and CA184022),36 1 
Phase 3 study (CA184024), and 1 Phase 1 study (CA184078). The PPK analysis demonstrated 
that the PK of ipilimumab is linear, the exposures are dose proportional across the tested dose 
range of 0.3 to 10 mg/kg, and the model parameters are time invariant, similar to that determined 
by
non-compartmental analyses. Volume of central compartment (Vc) and peripheral 
compartment were found to be 4.35 and 3.28 L, respectively, suggesting that ipilimumab first 
distributes into plasma volume and, subsequently, into extracellular fluid space. CL of 
ipilimumab and Vc were found to increase with increase in body weight. However, there was no 
significant increase in exposure with increase in body weight when dosed on a milligram per 
kilogram basis, supporting dosing of ipilimumab based on a weight-normalized regimen. The PK 
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of ipilimumab is not affected by age, gender, race, and immunogenicity (anti-drug antibody 
[ADA] status); concomitant use of chemotherapy; prior therapy; body weight; performance 
status; or tumor type. Other covariates had effects that were either not statistically significant or 
were of minimal clinical relevance.
1.4.4.4
Clinical Safety 
The information provided below is a general summary of safety.  Please refer to the BMS-
986205 Investigator Brochure for full safety information. 
Safety of BMS-986205 as Monotherapy and in Combination with Nivolumab 
The overall safety experience with BMS-986205 is based on treatment of 477 subjects as of a 15-
Nov-2017 database lock, the majority of whom have been treated with BMS-986205 and 
nivolumab in this study.
As monotherapy and in combination with nivolumab, BMS-986205 overall has been well 
tolerated in both subjects with malignancies and healthy volunteers in other studies, with
treatment-related adverse events (TRAEs) that were generally low grade and manageable. The 
safety profile of combination therapy with nivolumab and BMS-986205 has been largely 
comparable to that of nivolumab given as monotherapy. The most commonly reported TRAEs 
(in > 10% of subjects) during combination therapy with nivolumab were fatigue (14.1%) and 
nausea (11.1%). Grade 3 TRAEs have been reported in approximately 11% of subjects receiving 
the combination and treatment-related SAEs in approximately 7%. There has been 1 treatment-
related death due to myocarditis prior to the clinical data cutoff date (15-Nov-2017), which 
occurred during combination with nivolumab. In addition, there was one treatment-related death 
due to Stevens-Johnson syndrome and one treatment-related death due to hepatic failure which 
occurred after the clinical data cutoff date. 
With regard to p-chloroaniline, there have been no clinically significant metHb events at the 
100 mg dose level, and the highest reported metHb value was 16% in a subject receiving 200 mg 
of BMS-986205; no other subjects had reported metHb levels over 10%, none have required 
specific treatment for methemoglobinemia, and there have been no treatment discontinuations 
due to methemoglobinemia. Anemia and hemolytic anemia have also occurred infrequently 
(2.5% and 0.3% of subjects receiving combination therapy with nivolumab, respectively) and 
responded to dose holding, reductions, and other standard clinical measures.
Based on the available safety data,100 and 200 mg dose levels were opened in cohort expansion 
to allow for further evaluation of safety, PK, and PD data in order to ultimately allow for a final 
selection of dose for cohort expansion.
Safety of BMS-986205 in Combination with both Nivolumab and Ipilimumab
Preliminary safety information for the combination of BMS-986205, nivolumab, and ipilimumab 
is available as of 3-May-2018 for the 13 subjects treated in Part 3 to date. This data is 
preliminary and subject to change.
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In melanoma, 8 subjects have been treated: 4 at 100 mg BMS-986205 and 4 at 50 mg.  In the 
100 mg group, 2 DLTs (G3 autoimmune hepatitis in both) were reported out of 4 DLT evaluable 
subjects.  While further enrollment was permitted at this dose per BLRM, given the observed 
DLTs in melanoma subjects as well as those in NSCLC (see below), the dose was reduced to 
50 mg.  With 50 mg, there have been no DLTs reported in 3 DLT-evaluable subjects.  
Enrollment at 50 mg is ongoing.
In NSCLC, 3 subjects were treated at 100 mg. Two discontinued due to disease progression and 
were not evaluable for DLTs. The third subject experienced a DLT of Grade 3 transaminase 
elevations. In consideration of the DLTs observed in melanoma at 100 mg described above, 
further enrollment at 100 mg in NSCLC was held and subjects were then treated with 50 mg.  In 
the 50 mg cohort, both DLT-evaluable subjects experienced DLTs (Gr 3 transaminase elevations 
in both).  Per the BLRM analysis, further enrollment at 50 mg was held and enrollment at 25 mg 
opened.
As described above, among all subjects in Part 3, hepatic events have been the most commonly 
observed toxicities. These events have resolved with interruption or discontinuation of study 
drugs and administration of immunosuppressive treatments. No deaths have been reported in 
either cohort.
1.5
Overall Risk/Benefit Assessment
1.5.1
Risk/Benefit for BMS-986205 
As of 15-Nov-2017, 90 subjects have been treated with BMS-986205 monotherapy in this and 
other studies.  TRAEs have been infrequent and generally mild.  As BMS-986205 is not 
anticipated to have monotherapy antitumor activity, it is being developed as a combination agent,
primarily with other immune-modulatory agents.  Monotherapy treatment periods in this protocol 
are used primarily to provide preliminary safety and PK information..
Metabolism of BMS-986205 produces a p-chloroaniline (PCA) metabolite, which is associated 
with the formation of methemoglobin as well as with hemolytic anemia, as was observed in 
animal studies using BMS-986205. As of 15-Nov-2017, the peak metHb reported was 16% in a 
subject receiving BMS-986205 at 200 mg this study, below the commonly accepted threshold for 
the development of clinically significant symptoms (20%).49. This level was not associated with 
clinical sequelae, and the subject continued therapy at 100 mg of BMS-986205 with resolution of 
the methemoglobinemia. No other subjects had a metHb value of > 10% reported. No subject on 
study has required specific treatment for methemoglobinemia or had BMS-986205 discontinued 
due to methemoglobinemia. Drug-related Grade 3 anemia was reported in approximately 1% of 
subjects and hemolytic anemia in 0.3% during combination therapy with nivolumab.
Based on the findings from animal studies, entry criteria and monitoring parameters were 
developed in an attempt to reduce the risk of methemoglobinemia and hemolytic anemia. 
Subjects with cytochrome b5 reductase and glucose-6-phosphate dehydrogenase (G6PD) 
deficiencies are excluded due to the increased risk of methemoglobinemia and hemolysis, 
respectively. Guidance for detection and management of methemoglobinemia as well as 
guidelines for dose interruptions, reductions, and discontinuation are provided in Section 4.5.7
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for the management of treatment-related hematological adverse events. In addition, complete 
physical examinations (PEs) will be conducted on Day 1 of each cycle, with symptom-directed 
PEs weekly during monotherapy and Q2W during combination. With regard to animal findings 
of hepatocyte damage, subjects with viral hepatitis or other liver disease, such as nonalcoholic 
fatty liver disease (NAFLD), will be excluded to minimize the potential for hepatotoxicity; 
frequent monitoring of liver function tests and guidance for dose modification and treatment 
interruptions have also been implemented. Similarly, subjects with inadequate renal function will 
be excluded to minimize the potential for nephrotoxicity due to renal findings in animals. While 
there was an in vitro hERG inhibition (IC50 at ~1.2 uM), high (> 99%) serum protein binding, 
projected human free Cmax of 0.018 uM at the highest dose planned, and lack of in vivo ECG 
findings in dogs suggest low cardiovascular risk to human subjects. Nevertheless, subjects with 
QTc prolongation at baseline will be excluded, medications known to cause prolonged QT will 
be restricted, and ECGs will be monitored during the study. 
Continuous safety assessments will be utilized by the investigators and Sponsor to determine 
whether dose modification, additional safety measures, or termination of the study is required at 
any time. In addition, AEs and SAEs will be reviewed on an ongoing basis by the Sponsor’s 
Medical Monitor and Global Pharmacovigilance and Epidemiology representatives to monitor 
for any safety signals or trends. 
The International Agency for Research on Cancer classifies p-chloroaniline as Group 2B, or 
possibly carcinogenic to humans (1993),50 but the human relevance of this classification is 
questionable since it does not take into account dose/exposure multiples, mechanism, and species 
differences. The secondary mechanism of carcinogenicity (following hematologic toxicity) in 
rats is not considered a significant issue for patients. This conclusion is further supported by the 
dose multiple of 52× when considering the NOEL for rat tumors and the daily exposure of 
patients to p-chloroaniline at the 100 mg clinical dose. Using ICH M7 principles, the less-than-
lifetime exposures are calculated for p-chloroaniline, then the associated, theoretical cancer risks 
are the following: For 1 year of p-chloroaniline exposure associated with the 100 mg BMS-
986205 dose, the risk is < 1 in 100,000; for 2 years of exposure, the risk is 1.83 in 100,000, both 
of which approximate the acceptable risk of 1 in 100,000 (per ICH M7) for drugs of any 
therapeutic class that may provide clinical benefit.
Since BMS-986205 is an experimental agent, it is possible that unforeseen, unknown, or 
unanticipated reactions may occur. However, the safety profile has been manageable thus far at 
doses of up to 200 mg. 
1.5.2
Risk/Benefit for Combination with Nivolumab
As of 15-Nov-2017, 397 subjects have received BMS-986205 in combination with nivolumab 
(n=303 BMS-986205 100 mg + nivolumab 240 mg Q2W; n = 92 BMS-986205 100 mg + 480 
mg Q4W) in this study. The MTD of BMS-986205 in combination with nivolumab was 
established at 200 mg based on the safety and tolerability profile and incidence of dose-limiting 
toxicities. Full information regarding the clinical safety information available as of the 15-Nov-
2017 cut off can be found in the most recent version of the BMS-986205 Investigator Brochure
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Nivolumab has demonstrated a manageable safety profile. The overall safety experience, when 
used either as a monotherapy or in combination with another therapeutic, is based on experience 
in approximately 12,300 subjects treated to date. There is no pattern in the incidence, severity, or 
causality of AEs to nivolumab dose level. The most common AEs include fatigue, rash, pruritus, 
diarrhea, and nausea. Side effects of nivolumab therapy may include those associated with 
immune-mediated activation, such as pneumonitis, thyroiditis, and hepatitis. Most of these 
events resolved with immune-modulating medication. To mitigate risk from serious immune-
mediated AEs, subject management algorithms for nivolumab-related AEs from prior collective 
nivolumab experience have been included. 
There is potential for overlapping toxicity between the preclinical toxicology findings of 
BMS-986205 involving the liver and nivolumab-related hepatotoxicity. However, the incidence 
of nivolumab-related hepatitis is quite low (~ 1%) and thus the liver-related exclusion criteria 
and the monitoring of liver function specified in the protocol will help to minimize the risk of 
hepatotoxicity.  The immuno-oncology AE management algorithms also provide guidance for 
management of hepatic events.  
The overall safety profile of BMS-986205 and nivolumab observed to date in Study CA017-003 
has shown that the safety of the combination is largely consistent with that of nivolumab 
monotherapy and that the combination is well tolerated. The most common TRAEs (occurring in 
> 5% of subjects) occurring during treatment with this combination were fatigue (14.1%),nausea 
(11.1%), decreased appetite (9.1%), AST increased (7.6%), and ALT increased (7.1%). Grade 3 
TRAEs have been reported in approximately 11% and Grade 4 TRAEs in 1.5% of subjects 
receiving the combination (n=397 in CA017-003), with treatment-related SAEs in approximately 
7% and TRAEs leading to discontinuation in approximately 4%. Three treatment-related deaths 
have been reported: myocarditis, Stevens-Johnson syndrome, and hepatic failure; the latter two 
occurred after the data cut-off date (15-Nov-2017).
Nivolumab has demonstrated clinical activity in subjects with advanced NSCLC, RCC, 
melanoma, head and neck cancer, and lymphomas, as well as in subjects with other tumors. As 
outlined in Section 1.1.3, there is a mechanistic rationale that combination of an IDO1 inhibitor 
with checkpoint blockade will bring enhanced benefit to patients. Preliminary evidence of 
clinical activity for BMS-986205 plus nivolumab has been observed in the current study in both 
cervical and bladder cancers.51
1.5.3
Risk/Benefit for Combination with Both Nivolumab and Ipilimumab
Nivolumab and ipilimumab combinations have a well-defined toxicity profile based on a safety 
database of patients treated with the combination across multiple tumor types. Multiple dosing 
regimens have been evaluated. While the pattern and immune-mediated nature of toxicities 
remains relatively consistent, the severity and incidence of the toxicities does appear to differ by 
tumor type in each regimen evaluated. Therefore, within this protocol, the selection of each 
tumor type to be evaluated in safety lead-in Part 3 has been linked to a particular nivolumab and 
ipilimumab combination regimen known to have acceptable tolerability within that tumor type. 
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This should help to minimize the impact that the addition of BMS-986205 will have on the safety 
and tolerability of the nivolumab and ipilimumab regimens being evaluated.  
As described in Section 1.5.2, preliminary data from the combination of BMS-986205 with 
nivolumab have not revealed any unforeseen toxicities to date. BMS-986205 has not been 
previously evaluated in combination with ipilimumab. Preliminary safety data are available from 
11 subjects treated in Part 3 of this study. In those subjects, treatment-related hepatic events have 
been the most commonly observed TRAEs/DLTs. These events have been manageable with 
treatment interruption or discontinuation as well as administration of immunosuppressive 
therapies. While preliminary, these data also suggest that the dose of BMS-986205 may be 
related to the observed hepatic toxicities in this combination regimen, as 0/3 DLTs have been 
observed in melanoma at 50 mg versus 2/4 at 100 mg.  
Similar to this, the IDO1 inhibitor epacadostat has been previously evaluated with ipilimumab in 
patients with metastatic melanoma. Initial doses of 300 mg BID in combination with ipilimumab 
3 mg/kg Q3W led to unacceptable rates of Grade 3 to 4 ALT elevations, although these were 
reversible with treatment discontinuation and corticosteroid administration.52 When lower doses 
of epacadostat up to 50 mg BID were evaluated with the same ipilimumab regimen, treatment-
related toxicity rates were acceptable. 
To address the potential for hepatotoxicity with triplet combinations of BMS-986205, 
nivolumab, and ipilimumab, initial safety of the triplet combination will be evaluated in NSCLC 
and melanoma cohorts using an ipilimumab dose of 1 mg/kg Q6-8W; only after safety is 
established with the 1 mg/kg dose of ipilimumab will the higher dose of 3 mg/kg ipilimumab
Q3W be evaluated in a bladder cohort (see Section 1.1.6.3). Careful safety monitoring will be 
undertaken with frequent assessment of liver chemistries in addition to other safety laboratories 
and physical exams. During the first 6 weeks of the DLT evaluation period for the safety cohorts, 
liver chemistries will be checked on a more frequent, weekly basis. Rules for dose modification 
and discontinuation have been created to allow for rapid identification of toxicities requiring 
intervention, and investigators will be provided with algorithms for management of immune 
related adverse events that have been developed to address toxicity associated with 
immuno-oncology therapies, including combination regimens.
Nivolumab and ipilimumab combinations have demonstrated clinical activity in melanoma, 
NSCLC, and bladder cancer that exceed the clinical activity of each agent alone. Subjects 
receiving the triplet therapy regimens will therefore be receiving active combinations for their 
individual tumor types, with the addition of BMS-986205, which may lead to increasing benefit. 
Furthermore, the combinations of IDO1 inhibition with nivolumab and ipilimumab separately
have been shown to have clinical activity and are actively being investigated in other trials.  
1.5.4
Summary
Despite innovations in cancer treatment, alternative therapies are needed for subjects with 
advanced cancer. The emerging role of combination immune-modulating therapies in producing 
deep and durable responses in a variety of tumor types, as well as emerging clinical data from 
trials studying the combination of an IDO1 inhibitor with PD-(L)1-targeted therapies, suggest 
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that there may be a potential benefit of IDO1 inhibition with BMS-986205 when used in 
combination with nivolumab. Furthermore, there are preliminary clinical data showing possibly 
clinical activity of the combination of BMS-986205 with nivolumab in cervical and bladder 
cancers.51 This together with the known improvement in clinical activity of nivolumab and 
ipilimumab combinations over monotherapy treatments support the evaluation of combination 
therapies with BMS-986205, nivolumab, and ipilimumab. Overall, the safety profile of 
BMS-986205 has been manageable both as monotherapy and in combination with nivolumab. It 
is expected that the addition of BMS-986205 (in doses already shown to be safe in combination 
with nivolumab) to nivolumab and ipilimumab backbone regimens with known tolerability in 
specific tumor types will be safe. The incidence of immune-related events will continue to be 
monitored across all combinations in the study as more subjects are treated in order to assess the 
impact of IDO1 inhibition on the known toxicity of nivolumab monotherapy and nivolumab and 
ipilimumab combination regimens. The benefit/risk ratio supports continued evaluation of BMS-
986205 as monotherapy, in combination with nivolumab, and in combination with both 
nivolumab and ipilimumab in subjects with advanced cancer.
2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
International Conference on Harmonisation (ICH) and in accordance with the ethical principles 
underlying EU 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 (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. 
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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) (ICFs) which will include all elements required by ICH, GCP and applicable 
regulatory requirements. The sample ICF will adhere to the ethical principles that have their 
origin in the Declaration of Helsinki.
Investigators must:
1) 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 nontechnical and easily understood. 
2) Allow time necessary for subject or subject's legally acceptable representative to inquire 
about the details of the study.
3) 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. 
4) Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF(s) 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.
5) 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.
6) 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. 
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.
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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-986205 administered as a monotherapy, in 
combination with nivolumab (Parts 1 and 2), and in combination with both nivolumab and 
ipilimumab (Part 3) in subjects with advanced malignant tumors. A clinical pharmacology QTc 
substudy will also be conducted.
3.1.1
Screening and Treatment
3.1.1.1
Parts 1 and 2 (BMS-986205 Monotherapy and Combination with 
Nivolumab)
Dose escalation (Part 1) will start with a lead-in Cycle 0 whereby BMS-986205 is administered
as monotherapy of 2 weeks duration in each dose escalation subject. Decision to proceed to 
combination treatment with nivolumab (Cycle 1) for each subject in dose escalation will be 
determined after tolerability of the monotherapy lead-in is established in the 2-week Cycle 0 (see 
Section 3.1.4). The starting dose of BMS-986205 is 25 mg orally daily. Nivolumab will be 
administered at a dose of 240 mg Q2W for the dose escalation (Part 1) and for the dose 
expansion (Part 2) cohorts that predated Amendment 06 (cervical, DLBCL, SCCHN, bladder, 
and pancreatic cancer). Nivolumab will be administered at a dose 480 mg intravenously Q4W for 
the dose expansion cohorts in Part 2 added with Amendment 06 (melanoma, NSCLC, and 
additional signal-seeking tumors) and Amendment 08 (RCC), as well as for the clinical 
pharmacology substudy. In the event the 25 mg dose of BMS-986205 is determined to exceed 
the MTD in monotherapy or in combination with nivolumab, a lower BMS-986205 dose (DL-1) 
may be explored based on available safety, PK, and biomarker information. Please refer to 
Appendix 1. At no point will the dose of BMS-986205 administered in combination with 
nivolumab exceed doses of BMS-986205 that have been demonstrated previously to be safe in 
the monotherapy lead-in Cycle 0 (Section 3.1.4). Subjects with select malignant tumor types will 
be enrolled per the inclusion criteria in Section 3.3.1.
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Each Part 1 dose escalation subject will start with Cycle 0, which is a 2-week BMS-986205 
monotherapy lead-in. If there are no DLTs (see Section 4.5.1), subjects will proceed to receive 
the combination of nivolumab and BMS-986205 (Cycle 1). In addition to the defined DLTs, the 
following AEs will also prohibit a subject from proceeding to combination with nivolumab:
•
Grade 2 or higher immune-related AEs considered related to BMS-986205 (eg, 
immune-mediated pneumonitis, colitis, hepatitis, nephritis, and renal dysfunction) with the 
exception of immune-mediated hypothyroidism and hyperthyroidism
•
Grade 2 AST and ALT elevations that do not resolve to Grade 1 or baseline within 1 week
Dose expansion (Part 2) will be carried out at the combination dose of BMS-986205 selected 
from dose escalation in combination with nivolumab 240 mg Q2W (cohorts 1 to 5) or 480 mg
Q4W (cohorts 6 to 9), and may represent the MTD, MAD, or an alternate dose for the 
combination. 
Study drug consisting of BMS-986205 daily and nivolumab will be administered in 4-week 
cycles, for up to 12 cycles. Subjects in 8 disease-restricted populations and subjects in 1 mixed 
signal-seeking cohort of additional tumors will be enrolled as follows: SCCHN, RCC, bladder 
cancer, cervical cancer, DLBCL, melanoma, NSCLC, and pancreatic cancer. The mixed
signal-seeking cohort will include triple-negative breast cancer, adenocarcinoma of the 
endometrium, epithelial cancer of the ovary, and sarcoma. The doses selected for dose expansion 
will not exceed the MTD or MAD determined in dose escalation. 
Clinical Pharmacology Substudy: 
QTc Substudy
A clinical pharmacology substudy will be conducted in parallel with dose expansion to 
characterize the effect of BMS-986205 on the QTc intervals.
To minimize the influence of intrinsic factors such as food ingestion and circadian patterns on 
the QTc evaluation, time-matched baseline ECGs following a light meal will be collected prior 
to the start of BMS-986205 treatment cycles. During Cycle 0, subjects will receive BMS-986205 
QD monotherapy with a light meal on Days 1 to 14 (see Table 5.1-14). Serial ECG samples in 
addition to the matched PK samples will be collected on Day 14 (Table 5.5.4.3-1). Subjects will 
then receive BMS-986205 in combination with nivolumab on Cycle 1 Day 1 and will follow all 
assessments as per Table 5.1-15. 
The inclusion criteria (Section 3.3.1) used in the dose escalation phase will apply to subjects 
participating in the QTc substudy. At least 3 dose levels (below, at, and above the expected 
clinical dose) will be evaluated in at least 6 subjects per dose level in the substudy. Additional 
doses at supratherapeutic level may be evaluated in the substudy if warranted to allow for 
characterization of concentrations/QTc relationship at exposures that may exceed expected 
therapeutic levels due to extrinsic or intrinsic factors such as drug interactions, food effect, or 
organ dysfunction. The doses to be evaluated in the substudy will be determined based on 
available safety, PK, and biomarker data.
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The study design schematic for Parts 1 and 2, and the Clinical Pharmacology Substudy is 
presented in Figure 3.1.1.1-1.
Figure 3.1.1.1-1:
Parts 1, 2, and Clinical Pharmacology Substudy Study Design 
Schematic
*Note: As of Amendment 06, dose escalation beyond 400 mg BMS-986205 may not occur provided that additional 
pharmacodynamic effect is unlikely.
**Note: The BRAF-mutated, post-BRAFi regimen melanoma subjects will be randomized to receive either 
nivolumab or BMS-986205 + nivolumab.
Abbreviations: CTLA-4 = cytotoxic T lymphocyte-associated antigen 4; DLBCL = diffuse large B-cell lymphoma; 
I-O = immuno-oncology; MAD = maximum administered dose; MTD = maximum tolerated dose; Nivo = 
nivolumab; NSCLC = non-small cell lung cancer; PD1 = programmed cell death-1; PD-L1 = programmed death 
receptor-ligand 1; PD-(L)1 = either PD-1 or PD-L1; SCCHN = squamous cell carcinoma of the head and neck.
Please refer to Table 3.1.6-1 for a detailed description of the Part 2 dose expansion cohorts.
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Subjects will complete up to 4 phases of the study: Screening, Treatment, Clinical/Safety 
Follow-up and Survival/Long-term Follow-up, as described below:
Screening:
The screening phase will last for up to 28 days. The screening phase begins by establishing the 
subject’s initial eligibility and signing of the ICF. Subjects will be enrolled using the Interactive 
Voice Response System (IVRS).
Treatment Phase:
The treatment phase consists of up to twelve 4-week treatment cycles. For subjects receiving 
nivolumab on the Q2W regimen, each treatment cycle is composed of a daily oral dose of 
BMS-986205 and 2 doses of nivolumab administered intravenously Q2W on Days 1 and 15. For 
subjects receiving nivolumab on the Q4W regimen, each cycle is composed of a daily oral dose 
of BMS-986205 and 1 dose of nivolumab on Day 1. In addition, the dose escalation (Part 1) and 
the QTc substudy will start with Cycle 0, a lead-in period of 2 weeks duration, during which 
monotherapy with BMS-986205 is administered. 
Following every 2 treatment cycles (8 weeks), the decision to treat a subject with additional 
cycles of study drug will be based on radiological tumor assessments (initial evaluation 
performed at baseline, end of Cycle 2, and every 8 weeks). 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 for solid tumors and International Working Group (IWG) criteria 
for HL and non-Hodgkin’s lymphoma (NHL; Appendices 3 and 4). 
Treatment beyond progression may be allowed in select subjects with initial RECIST v1.1 or 
IWG-defined progressive disease (PD) if the benefit/risk assessment favors continued 
administration of study drug (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 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 drug 
until the first occurrence of either 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 drug as outlined in 
Section 4.5.3. Individual subjects with confirmed CR will be given the option to discontinue 
study drug on a case-by-case basis after specific consultation and agreement between the 
investigator and BMS Medical Monitor in settings where benefit/risk justifies the discontinuation 
of study drug. 
3.1.1.2
Part 3 (Combination with Both Nivolumab and Ipilimumab)
Part 3 is the safety evaluation and cohort expansion of the combination of BMS-986205, 
nivolumab, and ipilimumab. Initial safety evaluations will be performed in subjects with
melanoma, NSCLC, and bladder cancer. Subjects with each tumor type will receive
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BMS-986205 in combination with a different regimen of nivolumab and ipilimumab based on 
safety and efficacy data observed in previous trials of nivolumab and ipilimumab in that tumor 
type (see Section 1.1).  After this initial safety evaluation, dosing regimens will then be evaluated 
in expansion cohorts, which may include subjects with other types of malignancies.  
Subjects in safety evaluation cohorts will receive BMS-986205 at a dose which was shown to be 
tolerable in combination with nivolumab (from Parts 1 and 2) and nivolumab plus ipilimumab
(from Part 3), as applicable.  The dose of BMS-986205 will not exceed 100 mg daily. 
The regimens will consist of:
•
Melanoma (Ipi 1Q8 regimen): BMS-986205 in combination with nivolumab 480 mg Q4W 
and ipilimumab 1 mg/kg Q8W, all given continuously.
•
NSCLC (Ipi 1Q6 regimen): BMS-986205 in combination with nivolumab 360 mg Q3W and 
ipilimumab 1 mg/kg Q6W, all given continuously.  
•
Bladder (Ipi 3Q3 regimen): BMS-986205 given continuously, first in combination with 
nivolumab 80 mg and ipilimumab 3 mg/kg both given Q3W for 4 doses, followed by 
nivolumab 480 mg Q4W continuously 
Evaluation of each regimen will begin with an assessment of safety and tolerability of the triplet
combination therapy in a limited number of subjects, including a sentinel subject (see Section 
3.1.7), in a safety evaluation cohort. The melanoma and NSCLC safety cohorts will begin safety 
enrollment simultaneously since the dose of ipilimumab is similar between the cohorts. 
Furthermore, for nivolumab dosing, the 480 mg Q4W and 360 mg Q3W are expected to achieve 
similar average exposure. The safety evaluation for the bladder regimen will begin enrolling 
subjects once either the melanoma or NSCLC regimen has been found to be safe and tolerable, 
as the bladder regimen uses a higher dose (3 mg/kg Q3W) of ipilimumab relative to the 
melanoma and NSCLC cohorts (1 mg/kg Q6W and Q8W of ipilimumab) during the DLT 
evaluation period.
Once the initial safety and tolerability have been established independently for each regimen (see 
Section 3.1.7) within a given tumor type, subjects will begin enrolling in expansion cohorts for 
that tumor type. 
Additionally, subjects may be enrolled into a mixed tumor type cohort using the Ipi 1Q8 regimen
for further evaluation of safety and tolerability, as well as preliminary evaluation of anti-tumor 
efficacy once the safety of Ipi 1Q8 is established in the melanoma cohort. 
The study design schematic for Part 3 is presented in Figure 3.1.1.2-1.
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Figure 3.1.1.2-1:
Part 3
Screening:
The screening phase will last for up to 28 days. The screening phase begins by establishing the 
subject’s initial eligibility and signing of the ICF. Subjects will be enrolled using the Interactive 
Voice Response System (IVRS).
Treatment Phase:
For subjects receiving the melanoma/Ipi 1Q8regimen containing nivolumab 480 mg Q4W and 
ipilimumab 1 mg/kg Q8W, 1 cycle will consist of 2 doses of nivolumab and 1 dose of 
ipilimumab (ie, 8 weeks). For subjects receiving the NSCLC/Ipi 1Q6 regimen containing 
nivolumab 360 mg Q3W and ipilimumab 1 mg/kg Q6W, 1 cycle will consist of 2 doses of 
nivolumab and 1 dose of ipilimumab (ie, 6 weeks). For subjects receiving the bladder/Ipi 3Q3
regimen, during the nivolumab and ipilimumab lead-in, the first 2 cycles will each consist of 2 
doses of nivolumab and ipilimumab (each cycle is 6 weeks); after the first 2 cycles, each 
subsequent cycle will be comprised of 1 dose of nivolumab (ie, 4 weeks). 
Timing of imaging assessments will be based on the regimen the subject is receiving:
•
Melanoma/ Ipi 1Q8: The first imaging assessment will occur at Week 12 (± 1 week); 
subsequent imaging will be every 8 weeks (± 1 week) thereafter throughout the treatment 
period.
•
NSCLC/ Ipi 1Q6: The first imaging assessment will occur at Week 6 (± 1 week), and then 
every 6 weeks (± 1 week) throughout the treatment period.
•
Bladder/ Ipi 3Q3: The first imaging assessment will occur at Week 6 (± 1 week), and then 
every 6 weeks (± 1 week) during the treatment period up to 24 weeks, after which they will 
occur every 12 weeks (± 1 week) thereafter throughout the treatment period.
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•
Mixed tumor type/ Ipi 1Q8: The first imaging assessment will occur at Week 8 (± 1 week); 
subsequent imaging will be every 8 weeks (± 1 week) thereafter throughout the treatment 
period.
The decision to treat a subject with additional cycles of study drug will be based on the most 
recent radiological tumor assessment preceding that dose. Assessments of PR and CR must be 
confirmed at least 4 weeks after the initial assessment. Tumor progression or response endpoints 
will be assessed using RECIST v1.1 criteria. 
Treatment beyond progression may be allowed in select subjects with initial RECIST v1.1 or 
IWG-defined progressive disease (PD) if the benefit/risk assessment favors continued 
administration of study drug (eg, subjects are continuing to experience clinical benefit as 
assessed by the investigator, tolerating treatment, and meeting other criteria other criteria 
specified in Section 3.5.1).
Subjects with a response of stable disease (SD), PR, or CR at the most recent imaging 
assessment will continue to receive study treatment. Subjects will generally be allowed to 
continue study drug until the first occurrence of either 1) completion of the maximum duration of 
study therapy (2 years from first dose), 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 drug as outlined in Section 4.5.3. Individual subjects with confirmed CR 
will be given the option to discontinue study drug on a case-by-case basis after specific 
consultation and agreement between the investigator and BMS Medical Monitor in settings 
where benefit/risk justifies discontinuation of study drug. 
3.1.2
Treatment with Additional Cycles Beyond 48 Weeks
In all Parts of this study, all subjects will be treated for 48 weeks of BMS-986205 in combination 
with nivolumab or both nivolumab and ipilimumab unless criteria for study drug discontinuation 
are met earlier (Section 3.4.3). All subjects completing approximately 48 weeks of study therapy
with ongoing disease control (CR, PR, or SD) may be eligible for up to an additional 48 weeks (a 
maximum of 2 years from first dose of study therapy) of treatment at the originally assigned dose 
regimen (except for the bladder triplet regimen) beyond the initial 48 weeks, on a case-by-case 
basis, after careful evaluation and discussion with the BMS Medical Monitor to determine 
whether the benefit/risk ratio supports administration of further study drug. For the bladder 
triplet combination, the additional 48 weeks of study treatment will include nivolumab and 
BMS-986205 but not ipilimumab; nivolumab will be given as 480 mg Q4W starting with the 
first cycle of additional treatment. Subjects whose last assessment of the initial 48-week period 
shows PD will also be eligible to continue to additional cycles if they are still deriving clinical 
benefit, as per the guidance of treatment beyond progression (Section 3.5.1). Upon completion of 
48 weeks of study drug (or up to a maximum of 96 weeks [2 years] if applicable), all subjects 
will enter the Clinical/Safety Follow-up period.
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3.1.3
Follow-up
3.1.3.1
Clinical/Safety Follow-up
Upon completion of 48 weeks of study drug (or up to a maximum of 96 weeks if applicable), all 
subjects will enter the Clinical/Safety Follow-up period once the decision is made to discontinue 
the subject from treatment (eg, at end of treatment [EOT]). 
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 the Week 1 Clinical/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) and does 
not need to be repeated, and will be considered the start of the Week 1 Clinical/Safety Follow-up 
visit.
Subjects who discontinue the treatment phase will enter the Clinical/Safety Follow-up period. 
Subjects must be followed for at least 100 days (representing approximately 5 half-lives for 
nivolumab) after the last dose of study drug. Follow-up visits should occur at Days 30, 60, and 
100 (±10 days) after the last dose of study drug or should coincide with the date of 
discontinuation (±10 days) if date of discontinuation is greater than 30 days after the last dose of 
study drug to monitor for AEs. All subjects will be required to complete 3 Clinical/Safety 
Follow-up visits regardless of whether they start a new anti-cancer therapy, except those subjects 
who withdraw consent for study participation.
3.1.3.2
Survival/Long-term/Response Follow-up
After completion of the Clinical/Safety Follow-up period, all subjects will then enter the 
Survival/Long-term Follow-up period. During this period, clinic visits or telephone contact every 
3 months will be performed to assess survival status. The duration of the Survival/Long-term
Follow-up period will be approximately 2 years following the first dose of study drug, and a 
minimum of 12 months following the last dose of study drug. 
After completion of the Safety Follow-up period, subjects who discontinue study with ongoing 
SD, PR, or CR at the EOT visit will enter the Response Follow-up period. This period will occur 
simultaneously with the Survival Follow-up period for these subjects. These subjects will 
continue to have radiological and clinical tumor assessments every 3 months (12 weeks) during 
the Response Follow-up period or until disease progression or withdrawal of study. Radiological 
tumor assessments for subjects who have ongoing clinical benefit may continue to be collected 
after subjects complete the survival phase of the study.
Subjects in the Survival/Long-term Follow-up period who have progression of disease will be 
allowed to receive tumor-directed therapy as required.
Data from imaging assessments for subjects who have ongoing clinical benefit may continue to 
be collected after subjects complete the survival phase of the study.
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3.1.4
Re-treatment during Safety/Survival/Long-term Follow-up
Re-treatment may be allowed in this study with disease progression during follow-up. Subjects 
completing approximately 48 weeks of study treatment or who discontinue therapy due to a CR, 
who enter Safety/Survival/Long-term Follow-up with ongoing disease control (CR, PR, or SD) 
for reasons other than drug-related toxicity, may be eligible for re-treatment upon subsequent 
confirmed disease progression within 12 months of the last dose of study drug, on a case-by-case 
basis, after careful evaluation and discussion with the BMS Medical Monitor to determine 
whether the benefit/risk ratio supports administration of further study drug. Subjects meeting 
criteria for re-treatment will be treated for a maximum duration of 2 years from first dose of 
nivolumab, with the originally assigned dose regimen (eg, same dose and dose schedule 
administered during the initial treatment period) or modified dose regimen, unless that dose and 
schedule were subsequently found to exceed the MTD, in which case the subject will be treated 
at the next lower or alternate dose and schedule (see Table 4.5.3-1). Subjects entering this phase 
will follow the same Time and Events schedule as outlined in Section 5. Samples for PK will be 
collected less frequently. During re-treatment, pharmacodynamic biomarker samples obtained 
from blood will be collected as outlined in Section 5.7. 
The treatment and follow-up schematic for Parts 1, 2, and 3, and the pharmacology substudy is 
presented in Figure 3.1.4-1. The study design schematic for the clinical pharmacology substudy 
is presented in Figure 3.1.4-2.
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Figure 3.1.4-1:
Treatment and Follow-Up  Schematic for CA017003--All Study Parts 
Note: For Part 3 bladder cohort, Additional Treatment will not include ipilimumab
Abbreviations: CR = complete response; EOT= end of treatment; PD = progressive disease; PI = principal 
investigator; PR= partial response; SD = stable disease.
Figure 3.1.4-2:
Study Schematic of Clinical Pharmacology QTc Substudy
*: Baseline ECGs should be collected prior to the start of Cycle 0 (Day -1 preferred, up to 5 days prior to Cycle 0 is 
allowed).
Abbreviations: ECG = electrocardiogram; Q4W = every 4 weeks; QD = once daily.
Screening
Treatment
Safety Follow-up
Response / Survival 
Follow-up
Additional Treatment
Subjects with CR, PR, SD, or 
Unconfirmed PD
BMS-986205 + Nivolumab 
(+ Ipilimumab [Part 3 only]) 
up to 2 years from first dose
30, 60, and 100d 
follow-up visits 
after EOT
Survival Follow-Up
Up to 2 years from first 
dose of study therapy
Re-Treatment
Progression within 12 months of last 
dose and CR, PR, or SD at end of 
initial/additional treatment
BMS-986205 + Nivolumab
(+ Ipilimumab [Part 3 only]) 
For a maximum treatment duration of 2 
years from first dose of nivolumab. 
Response Follow-Up
Only for subjects with CR, 
PR. or SD at EOT
Up to 2 years from first 
dose of study therapy
Efficacy assessments
Disease 
progression 
(<12months 
after EOT)
Initial Treatment
Up to 48 weeks of combination
BMS-986205 
Monotherapy
BMS-986205 + 
Nivolumab
BMS-986205 + Nivolumab 
BMS-986205 + Nivolumab + 
Ipilimumab 
Part 1
Part 2
Part 3
Disease 
progression
QTc Substudy
Screening
Time-matched 
Baseline ECG
(Day -1)*
BMS-986205 QD 
(Light meal) + 
Nivolumab Q4W 
Combination
BMS-986205 QD 
Monotherapy
(Cycle 0) with serial 
ECG evaluations on 
Day 14
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3.1.5
Part 1: Dose Escalation
The dose escalation phase of the study will evaluate the MTD/MAD/alternate dose of 
BMS-986205 in combination with nivolumab based on DLTs using a BLRM model (for 
BMS-986205 monotherapy lead-in) and BLRM-copula model (for BMS-986205 in combination 
with nivolumab). The Bayesian models will be used for recommendation of the next dose to be 
investigated. A BLRM (combined with copula) framework with an escalation with overdose 
control principle will be employed to ensure that safety is not compromised during dose 
escalation.
The initial dose level of BMS-986205 will be 25 mg administered orally daily. Once initial 
lead-in monotherapy (Cycle 0) is deemed tolerable, combination with a 240-mg flat dose of 
nivolumab at the same dose level with the same subject (Cycle 1) will be initiated. 
Dose levels to be considered for the next combination cohort of the subject (with monotherapy 
lead-in) will be based on recommended monotherapy dose from the BLRM and recommended 
combination dose from the BLRM-copula. The lower dose from these 2 recommendations will 
be considered. Potential dose levels for dose escalation are provided in Table 3.1.5-1. The 
maximum allowable increase in dose will be 100%. Final dose selection for the next cohort/dose 
level will be made in conjunction with all data available from PK and pharmacodynamic 
assessments, and will be made after discussion and agreement between investigators and the 
BMS Medical Monitor. Accordingly, intermediate or lower doses, or less frequent dosing of 
BMS-986205 may be tested if none of the planned doses/schedules are found to be tolerated as 
lead-in phase or in combination with nivolumab.
Approximately 30 subjects will be treated in the dose escalation phase. Depending on the dose 
recommendation, more than 3 subjects can be treated at each dose level. Increments of 
approximately 3 subjects will be added to each dose level depending on model recommendation 
and clinical judgment. Once the safety of any dose level has been established, up to 12 additional 
subjects may be added to better characterize the PK and pharmacodynamic profile.
Cohort-tolerability assessment and subsequent dose recommendation
will occur when 
2 DLT-evaluable subjects within a subject cohort have completed the 6-week DLT observation 
period (see Section 4.5.1 for criteria for DLTs). DLTs occurring within the 2 weeks of the lead-
in period (DLT observation period for monotherapy) will be used to fit the BLRM model for 
monotherapy. DLTs occurring within the 4 weeks of combination period (DLT observation 
period for combination) will be used to fit the BLRM-copula model. The lower recommended 
dose from both models will be considered for next dose escalation. Subjects who received ≥75% 
of BMS-986205 doses and 2 doses of nivolumab, and have been followed at least 5 days after the 
second nivolumab dose, in the 6-week DLT observation period will be considered as 
DLT-evaluable subjects. Continuous re-assessment of dose recommendation by BLRM will be 
carried out at each dose level after each cohort of subjects with consideration of all available 
DLT information.
The MTD/MAD/alternate dose of BMS-986205 in combination with nivolumab selected for the 
cohort will be based on evaluating the recommendation from the BLRM-copula and a synthesis 
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of all available data, including clinical 
and 
laboratory 
safety assessments, PK, 
pharmacodynamic, and efficacy data, from all treated subjects at each dose level up to the 
MTD/MAD.
Up to 12 additional subjects may be added per selected dose levels to provide additional safety, 
tolerability, and PK data. This information will be incorporated into the final recommendation 
for the MAD/MTD/alternate dose of BMS-986205.
No intra-subject dose escalation is allowed, although dose modifications may be permitted (see 
Table 4.5.3-1).
Sentinel Subject: During dose escalation, a staggered dosing (sentinel subject) approach will be 
used for the first subject in the first dose level of both lead-in and combination. The first subject 
in both lead-in and combination will receive Cycle 0 Day 1 dose of study drugs and will be 
observed for 5 days before additional subjects (ie, subject 2 onward) in that cohort receive study 
drug. The first subjects to be dosed in subsequent cohorts will not be required to observe the 5-
day interval between treatment start dates.
Table 3.1.5-1:
Dose Escalation Schedule
Dose Level
BMS-986205
Nivolumab
-1
DL-1
240 mg IV Q2W
1
25 mg
240 mg IV Q2W
2
50 mg
240 mg IV Q2W
3
100 mg
240 mg IV Q2W
4
200 mg
240 mg IV Q2W
5
400 mg
240 mg IV Q2W
6
600 mg
240 mg IV Q2W
7
800 mg
240 mg IV Q2W
Note: As of Amendment 06, dose escalation beyond 400 mg BMS-986205 may not occur provided that additional 
pharmacodynamic effect is unlikely.
Note: Up to 12 additional subjects may be added per selected dose levels to provide additional safety, tolerability,
and PK data. This information will be incorporated into the final recommendation for the MTD/MAD/alternate 
dose of BMS-986205.
Abbreviations: DL-1 = dose level-1; IV = intravenous; MAD = maximum administered dose; MTD = maximum 
tolerated dose; PK = pharmacokinetic; Q2W = every 2 weeks.
3.1.6
Part 2: Dose Expansion
The purpose of dose expansion is to gather additional safety, tolerability, preliminary efficacy, 
PK, and pharmacodynamic information regarding BMS-986205 in combination with nivolumab.
Eight disease-restricted populations will be included in dose expansion. These include cervical 
cancer, DLBCL, SCCHN, bladder cancer, melanoma, NSCLC, RCC, and pancreatic cancer. 
Various subpopulations of melanoma and NSCLC will be included in separate cohorts to further 
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understand the role of IDO1 inhibition in these specific populations as described in Section 1.1.5
and Table 3.1.6-1). An additional cohort will be dedicated to tumor types from the escalation 
inclusion criteria that do not currently have a dedicated expansion cohort or plans for evaluation 
in other studies. The eligible tumor types will be triple negative breast cancer, adenocarcinoma 
of the endometrium, epithelial cancer of the ovary, and sarcoma. Enrollment to this additional 
cohort will not exceed approximately 35 to 40 subjects. It will allow for the exploration of early 
efficacy signals seen during the dose escalation portion of the trial as well as potential signals 
arising from ongoing trials of other IDO1 inhibitors in combination with anti-PD-(L)1. 
During dose expansion, the Simon 2-stage (optimal) design will be used as a guide for some of 
the tumor-specific expansion cohorts , although not used for hypothesis testing. Enrollment will 
continue for these tumor-specific expansion cohorts while evaluation of efficacy at stage 1 is 
ongoing. The 2-stage design with a reasonable false-positive rate (FPR) and false-negative rate 
(FNR) will provide guidance for the total sample size for these cohorts based on assumptions of 
true (target) and historic ORR for these indications. The sample sizes for each expansion cohort 
are provided in Table 3.1.5-1.
Initially, guided by, a minimum of 10 subjects in the SCCHN and bladder tumor cohorts; 
12 subjects in the cervical, pancreatic, DLBCL, melanoma with prior anti-PD-(L)1 therapy, and 
NSCLC with prior anti-PD-(L)1 therapy cohorts; and 12 subjects in the melanoma with prior 
anti-PD-(L)1 and anti-CTLA-4 therapy cohort will be treated in Stage 1 for an initial evaluation 
of efficacy. 
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Table 3.1.6-1:
Part 2 Expansion Cohorts
Cohort
BMS-986205 + Nivolumab
Total Subjects (Approximately)
1
Cervical
35
2
DLBCL
35
3
SCCHN
27
4
Bladder
27
5
Pancreatic
35
6
Melanoma
6a
Melanoma, I-O naïve, PD-L1 
positive
40
6b
Melanoma, I-O naïve, PD-L1 
negative
40
6c*
BRAF-MT Melanoma, I-O naïve, 
post BRAFi 
8
6d*
BRAF-MT Melanoma, I-O naïve, 
post BRAFi (nivolumab therapy)
8
6e
Melanoma, prior anti-PD-(L)1 
35
6f
Melanoma, prior anti-PD-(L)1 and 
anti-CTLA-4 
37
7
NSCLC
7a
NSCLC, I-O naïve, PD-L1 positive
40
7b
NSCLC, I-O naïve, PD-L1 negative
40
7c
NSCLC, prior anti-PD-(L)1
35
8
Additional signal-seeking tumors
35
9
Renal cell carcinoma
40
NOTE: The BRAF-mutated, post-BRAF regimen melanoma subjects will be randomized to receive either 
nivolumab or BMS-986205 + nivolumab.
Abbreviations: BRAFi = BRAF inhibitor; CTLA-4 = cytotoxic T lymphocyte-associated antigen 4; DLBCL = 
diffuse large B-cell lymphoma; I-O = immuno-oncology; NSCLC = non-small cell lung cancer, PD-1 = programmed 
cell death-1; PD-L1 = programmed death receptor-ligand 1; PD-(L)1 = either PD-1 or PD-L1; SCCHN = squamous 
cell carcinoma of the head and neck.
Continuous evaluation of toxicity events in the dose expansions will be performed throughout 
enrollment in the expansion cohorts. If, at any time, the aggregate rate of treatment-related 
toxicities meeting DLT criteria exceeds 33% across all subjects treated in the dose expansions, 
the findings will be discussed and further enrollment may be interrupted. At that time, depending 
on the nature and grade of the toxicities and after assessing the risk/benefit ratio, a new dose(s) 
of BMS-986205 for all cohorts may be initiated at a previously tested lower dose level or at a 
dose level intermediate to previously tested lower dose levels. Additionally, at the discretion of 
the Sponsor, and in agreement with the investigators, the nivolumab 480 mg Q4W dosing 
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regimen in the designated expansion cohorts and clinical pharmacology substudy may revert 
back to 240 mg Q2W based on emerging PK, pharmacodynamic, and/or tolerability data from 
the cohort expansion portion of the study.
3.1.7
Part 3: BMS-986205, Nivolumab, and Ipilimumab Combination
Part 3 of the study will include a initial safety evaluation cohorts of 3 regimens of nivolumab and 
ipilimumab in combination with BMS-986205 in melanoma, NSCLC, and bladder cancer.  
Expansion cohorts for each regimen will then be conducted in the tumor type evaluated in the 
safety cohorts. The Ipi 1Q8W regimen will also be evaluated in a mixed cohort of other tumor 
types evaluated in Part 2. Each tumor type will receive BMS-986205 in combination with a 
specific nivolumab and ipilimumab regimen (see Section 3.1.1.2).
For the safety cohorts, the initial dose level of BMS-986205 for each cohort will be based on the 
available of safety, PK, and PD data for BMS-986205 in combination with nivolumab and any 
available from the combination with nivolumab and ipilimumab.  The starting dose will not 
exceed 100 mg in any safety cohort.  Lower dose levels of BMS-986205 (if required) to be
evaluated in each safety cohort will be based on Table 3.1.5-1. Intermediate or lower doses, or 
less frequent dosing of BMS-986205 may be tested if none of the planned doses/schedules are 
found to be tolerated. In addition, alternative lower doses and more intermittent schedules of 
nivolumab and/or ipilimumab may be evaluated if the specified regimen used in each tumor type
safety cohort is not found to be tolerable with any of the doses of BMS-986205 outlined in Table 
3.1.5-1. Safety will be evaluated independently for each tumor type/regimen combination and 
treatment regimen based on DLTs using a BLRM-copula model.
All safety cohorts will begin with an assessment of safety and tolerability of the triplet 
combination regimen in a limited number of subjects. As described in Section 3.1.1.2, the 
NSCLC/Ipi 1Q6 and melanoma/Ipi 1Q8 regimen cohorts will begin enrollment first, followed by 
the bladder/Ipi 3Q3 regimen cohort once safety and tolerability have been established in either 
NSCLC/ Ipi 1Q6 or melanoma/Ipi 1Q8. Initially, approximately 3 subjects will be treated at the 
selected dose combination of BMS-986205 with nivolumab and ipilimumab. The first subject in 
each safety cohort will be a sentinel subject who will be observed for 5 days after administration 
of the first combination dose to ensure safety and tolerability before other subjects can receive
treatment within that cohort.
Due to the potential for early discontinuation, an additional subject(s) may be enrolled to ensure 
approximately 3 DLT-evaluable subjects. Initial safety assessment to allow enrollment in the 
bladder/ Ipi 3Q3 safety cohort will occur when at least 2 evaluable subjects in either the NSCLC/
Ipi 1Q6 or melanoma/ Ipi 1Q8 safety cohorts have completed a 6-week DLT evaluation period
(see Section 4.5.1 for criteria for DLTs). In the melanoma and NSCLC safety evaluation cohorts, 
if a potential DLT occurring in any third evaluable subject in the specific dose combination does 
not influence the recommendation by BLRM (-Copula) to open enrollment in the bladder safety 
cohort, then the bladder safety cohort may proceed with enrollment without waiting for the third
subject to complete the corresponding DLT observation period.
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DLT-evaluable subjects will be defined as subjects who in the 6-week DLT evaluation period 
received ≥75% of BMS-986205 doses and the following nivolumab and ipilimumab doses for 
each regimen:
•
Melanoma/ Ipi 1Q8: 2 doses of nivolumab and 1 dose of ipilimumab, and followed for at 
least 5 days after the second dose of nivolumab
•
NSCLC/ Ipi 1Q6: 2 doses of nivolumab and 1 dose of ipilimumab, and followed for at least 5 
days after the second dose of nivolumab
•
Bladder/ Ipi 3Q3: 2 doses of nivolumab and 2 doses of ipilimumab, and followed for at least 
5 days after the second dose of each drug
After the initial subjects in each treatment regimen are evaluated, additional increments of 
approximately 3 to 6 subjects will be treated in the same safety cohort as per the BLRM-copula 
model recommendation that the dose combination is safe. At least 6 DLT-evaluable subjects will 
be treated and assessed for a particular BMS-986205 dose in that tumor type/regimen cohort
before enrollment in the expansion cohorts for that regimen will begin. Up to 12 DLT-evaluable 
subjects in total may be treated in each safety evaluation cohort at the BMS-986205 dose chosen 
for expansion regimens for further evaluation of safety and pharmacodynamic/PK parameters as 
required. BLRM (-copula) will be used to monitor the safety of each triplet dose combination on 
an ongoing basis.
Once the initial safety and tolerability have been established independently for each regimen
based on the safety cohorts, enrollment will then begin in expansion cohorts for further 
evaluation of safety and tolerability, as well as preliminary evaluation of anti-tumor efficacy. In 
the expansion cohorts, BMS-986205 will be administered at a dose determined to be tolerable in 
combination with each nivolumab and ipilimumab regimen. Each BMS-986205 and 
nivolumab/ipilimumab combination regimen will be evaluated in tumor-specific cohorts based 
on the tumor type evaluated in the safety cohorts.  The Ipi 1Q8 regimen will also be evaluated in 
a mixed tumor-type cohorts which may incorporate tumor types evaluated in Part 2.
The 3 tumor types for tumor-restricted cohorts will be melanoma, NSCLC, and bladder. As all 
subjects in these disease-specific cohorts will be receiving agents (nivolumab and ipilimumab) 
with known anti-tumor activity in those tumor types, a single-stage design will be utilized for 
each of these tumor types. Approximately 40 subjects will be treated in each of the following
expansion cohorts: melanoma PD-L1 positive, melanoma PD-L1 negative, NSCLC PD-L1 
positive, NSCLC PD-L1 negative, and bladder; this is to allow for the exploration of early 
efficacy signals of BMS-986205 in combination with both nivolumab and ipilimumab in relevant 
subpopulations. In each NSCLC expansion cohort, approximately 10 subjects will be IO-
treatment naive, 25 will be treatment-naive, and 5 IO-therapy experienced. In the melanoma 
cohorts, approximately 35 will be treatment naïve in the advanced setting and 5 will be IO-
therapy experienced in each cohort. In the bladder expansion cohort in Part 3, at least 30 subjects 
will be I-O therapy naive.
A mixed tumor type expansion cohort will also be evaluated, using the same regimen as in the 
melanoma safety cohort, Ipi 1Q8W. The purpose of this cohort is to obtain preliminary safety, 
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tolerability, and efficacy data in tumor types besides melanoma using the nivolumab 480 mg 
Q4W/Ipilimumab 1 mg/kg Q8W backbone in combination with BMS-986205 at the dose 
selected for the melanoma expansion cohort. Up to forty subjects may be treated in this cohort. 
Tumor types included in this cohort may be any previously evaluated in Part 2. All subjects in 
this cohort will be IO-treatment naive. Selection of tumor types and number of subjects per 
tumor type will be at the discretion of the Sponsor and based on emerging data from Part 2 of 
this study as well as other external data (e.g. from studies of nivolumab and ipilimumab in a 
particular tumor type). For each tumor type enrolled into this cohort, approximately 6 subjects 
will be initially evaluated for safety and tolerability for 6 weeks each for toxicities meeting DLT 
criteria exceeding the threshold defined below prior to enrollment of any other subjects with that 
tumor type.
Continuous evaluation of toxicity events in the expansion cohorts will be performed throughout 
enrollment in the expansion cohorts. If, at any time, the aggregate rate of treatment-related 
toxicities meeting DLT criteria within an individual tumor type/treatment regimen exceeds 33% 
across all subjects treated in the safety evaluation and dose expansion cohorts, the findings will 
be discussed and further enrollment may be interrupted. At that time, depending on the nature 
and grade of the toxicities and after assessing the risk/benefit ratio, a new dose(s) of 
BMS-986205 and/or dose and schedule of nivolumab and/or ipilimumab (as described above) for 
subjects within that cohort may be initiated.
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit may be 
eligible to receive BMS-supplied study drug. Study drug may be provided via an extension of the 
study, a rollover study requiring approval by responsible health authority and ethics committee,
or through another mechanism at the discretion of BMS. BMS reserves the right to terminate 
access to BMS-supplied study drug if any of the following occur: a) the marketing application is 
rejected by responsible health authority; b) the study is terminated due to safety concerns; c) the 
subject can obtain medication from a government-sponsored or private health program; or 
d) therapeutic alternatives become available in the local market.
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) The subject must sign the ICF prior to the performance of any study-related procedures 
that are not considered part of standard of care.
b) Consent for tumor biopsy samples
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2) Target Population
a) Subjects must be at least 18 years old and have histologic or cytological confirmation of a 
malignancy that is advanced (metastatic and/or unresectable) with measureable disease 
per RECIST v1.1 or revised IWG criteria for lymphomas (see Appendices 3 and 4).
1) Dose Escalation (Part 1 only): Subjects must have received, and then progressed or been 
intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting, if 
such a therapy exists, EXCEPT for subjects with melanoma, who can be treatment naïve, as
they will be given concomitant nivolumab, which constitutes standard of care.
The following tumor histologies will be permitted except for subjects with primary CNS 
tumors or with CNS metastases as the only site of active disease. 
a) Melanoma: BRAF mutation status must be known.
b) NSCLC (squamous and non-squamous histology): Subjects’ epidermal growth factor 
receptor (EGFR), anaplastic lymphoma kinase (ALK), and KRAS mutational status will 
be recorded if available.
c) Head and neck cancer restricted to squamous cell carcinoma: Human papillomavirus 
(HPV) status must be documented.
i)
Confirmation of tumor human papillomavirus (HPV) status for subjects with 
oropharyngeal SCCHN: Prior testing results are acceptable if known. 
(1) If tumor HPV status is unknown, subjects must consent to allow their submitted 
archived tumor tissue sample in the form of block or unstained slides to be tested 
for confirmation of tumor HPV status.
d) Transitional cell carcinoma of the genitourinary tract
e) RCC
f)
Pancreatic adenocarcinoma
g) Colorectal neoplasm: Microsatellite Instability (MSI) status must be documented.
h) HL
i)
B cell NHL
excluding Burkett’s
lymphoma and precursor B-lymphoblastic 
leukemia/lymphoma
j)
Cervical cancer
k) Triple negative breast cancer
l)
Adenocarcinoma of the endometrium
m) Ovarian epithelial cancer
n) Sarcoma: Limited to the following histologies:
i)
Undifferentiated pleomorphic sarcoma
ii) Liposarcoma: dedifferentiated and myxoid
iii) Angiosarcoma
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iv) Alveolar soft part sarcoma
v) Synovial sarcoma
vi) Ewing’s sarcoma
vii)Osteosarcoma
viii)
Chondrosarcoma
ix) Gastrointestinal stromal tumor
2) Dose Expansion (Part 2 Only):
The following tumor types will be permitted:
a) Cervical Cancer
i)
Persistent, recurrent, or metastatic cervical cancer with documented disease 
progression.
ii) Squamous, adenosquamous,
or adenocarcinoma histology-confirmation of the 
original primary tumor is required.
iii) Must have had 1 prior systemic chemotherapeutic regimen (eg, paclitaxel/cisplatin, 
paclitaxel/cisplatin/bevacizumab) for persistent, recurrent, or metastatic disease. 
Chemotherapy administered concurrently with primary radiation (eg, weekly 
cisplatin), adjuvant chemotherapy given following completion of radiation therapy or 
as concurrent chemotherapy, and radiation therapy (eg, paclitaxel and carboplatin for 
up to 4 cycles) is not counted as a systemic chemotherapy regimen.
iv) Confirmation of tumor human papillomavirus (HPV) status: Prior testing results are 
acceptable if known. 
(1) If tumor HPV status is unknown, subjects must consent to allow their submitted 
fresh or archived tumor tissue sample in the form of block or unstained slides to 
be tested for confirmation of tumor HPV status.
b) Diffuse Large B-cell lymphoma
i)
Subjects must have received and then progressed or become refractory to at least 1 
prior standard systemic therapy such as cytotoxic chemotherapy and anti-CD-20 
targeted immunotherapy. The following are not considered separate lines of 
treatment: addition of a compound to an ongoing regimen, restarting the same 
regimen after a drug holiday, or switching from IV to oral therapy.
ii) Subjects must have received high-dose chemotherapy with autologous stem cell 
transplant (ASCT), if eligible. Ineligibility for ASCT will be determined using local 
institutional criteria. 
iii) Subjects must be more than 100 days post autologous transplant.
iv) Prior allogeneic stem-cell transplantation is excluded.
v) Not a candidate for potentially curative therapy.
c) SCCHN-Oral Cavity, Pharynx, Larynx
i)
Histologically confirmed recurrent or metastatic SCCHN not amenable to local 
therapy with curative intent (surgery or radiation with or without chemotherapy).
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ii) Must have evidence of progression or recurrence after platinum therapy in the 
adjuvant (ie, with radiation after surgery), primary (ie, with radiation), recurrent, or 
metastatic setting.
iii) Radiation therapy must have been completed at least 4 weeks prior to study drug 
administration.
iv) Documentation of p16-positive or p16-negative disease to determine HPV status of 
tumor for SCC of the oropharynx.53
(1) Confirmation of tumor human papillomavirus (HPV) status: Prior testing results 
are acceptable if known. If tumor HPV status is unknown, subjects must consent 
to allow their submitted fresh or archived tumor tissue sample in the form of 
block or unstained slides to be tested for confirmation of tumor HPV status.
d) Bladder Cancer
i)
Evidence of metastatic or surgically unresectable transitional cell carcinoma of the 
urothelium involving the bladder, urethra, ureter, or renal pelvis.
ii) Progression or recurrence after treatment:
•
With at least 1 platinum-containing chemotherapy regimen for metastatic or surgically 
unresectable locally advanced urothelial cancer OR
•
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.
e) Pancreatic Cancer
i)
Documented locally advanced, unresectable, or metastatic pancreatic cancer that has
progressed on, or after, or been intolerant to (or are not candidates for) at least 1 line 
of standard therapy.
f)
Melanoma, I-O Naïve, PD-L1 Positive (Number 6a in Table 3.1.6-1)
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system.
ii) PD-L1 positive subjects, defined as PD-L1 ≥1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
iii) Must not have received prior systemic therapy in the unresectable or metastatic 
setting.
iv) BRAF (V600) mutation status must be known. Both BRAF-mutated and WT subjects 
are permitted in this cohort.
g) Melanoma, I-O Naïve, PD-L1 Negative (Number 6b in Table 3.1.6-1)
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system.
ii) PD-L1 negative subjects, defined as PD-L1 < 1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
iii) iii. Must not have received prior systemic therapy in the unresectable or metastatic 
setting.
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iv) BRAF (V600) mutation status must be known. Both BRAF-mutated and WT subjects 
are permitted in this cohort.
**Note for the melanoma I-O naïve cohorts: If the PD-L1 status from the pre-treatment biopsy is not 
available prior to the start of treatment, subjects will be retrospectively assigned to the correct cohort 
once the result is available.
h) Melanoma: I-O Naïve, BRAF Mutated, Post-BRAF Inhibitor Therapy (Nivolumab 
with and without BMS-986205) [Numbers 6c and 6d in Table 3.1.6-1]
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system. Subjects must 
have documented BRAF (V600) mutation and have had progressive or recurrent 
disease either during or after BRAF-targeted therapy in the unresectable or metastatic 
setting.
ii) PD-L1 status must be documented if available. PD-L1 status will also be re-tested 
using tissue acquired from the mandatory pre-treatment biopsy.
iii) Subjects must not have received prior systemic treatment in the unresectable or 
metastatic setting, except for BRAF- or BRAF/MEK-targeted therapy as stated above.
i)
Melanoma, Prior Anti-PD-(L)1 Therapy (Number 6e in Table 3.1.6-1)
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system.
ii) PD-L1 status must be documented if available. PD-L1 status will also be re-tested 
using tissue acquired from the mandatory pre-treatment biopsy.
iii) Must have had progressive or recurrent disease either during or within 6 months after 
anti-PD-(L)1 monotherapy. Subjects may have received other systemic therapies for 
their disease; however anti-PD-(L)1 targeted therapy must have been the most recent 
therapy administered.
iv) BRAF (V600) mutation status must be known. Both BRAF-mutated and WT subjects 
are permitted in this cohort. 
j)
Melanoma, Prior Anti-PD-(L)1 and Anti-CTLA-4 Therapy (Number 6f in Table 
3.1.6-1)
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system.
ii) PD-L1 status must be documented if available. PD-L1 status will also be re-tested 
using tissue acquired from the mandatory pre-treatment biopsy.
iii) Must have had progressive or recurrent disease either during or within 6 months after 
anti-PD-(L)1 component of the combination therapy. Subjects may have received 
other systemic therapies for their disease; however, anti-PD-(L)1 and anti-CTLA-4 
therapy must have been the most recent therapies administered.
iv) BRAF (V600) mutation status must be known. Both BRAF-mutated and WT subjects 
are permitted in this cohort.
k) NSCLC, I-O Naïve, PD-L1 Positive (Number 7a in Table 3.1.6-1)
i)
Histologically or cytologically confirmed, advanced (ie, unresectable or metastatic) 
NSCLC of either squamous or non-squamous histology. 
ii) Subjects must have received platinum-based chemotherapy.
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iii) EGFR and ALK status must be known. KRAS mutational status should be 
documented if available. 
(1) EGFR and ALK may be unknown for subjects with squamous cell histology. 
iv) Subjects with a sensitizing EGFR mutation or ALK rearrangement must have 
received EGFR-directed or ALK-directed therapy, respectively. 
v) Prior anti-PD-(L)1 or anti-CTLA-4 therapy is not permitted.
vi) PD-L1 positive subjects, defined as PD-L1 ≥1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
l)
NSCLC, I-O Naïve, PD-L1 Negative (Number 7b in Table 3.1.6-1)
i)
Histologically or cytologically confirmed, advanced (ie, unresectable or metastatic) 
NSCLC of either squamous or non-squamous histology.
ii) Subjects must have received platinum-based chemotherapy.
iii) Prior treatment of an I-O agent is not permitted.
iv) EGFR and ALK status must be known. KRAS mutational status should be 
documented if available. 
(1) EGFR and ALK may be unknown for subjects with squamous cell histology. 
v) Subjects with a sensitizing EGFR mutation or ALK rearrangement must have 
received EGFR-directed or ALK-directed therapy, respectively.
vi) PD-L1 negative subjects, defined as PD-L1 < 1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
**Note for the NSCLC I-O naïve cohorts: If the PD-L1 status from the pre-treatment biopsy is 
not available prior to the start of treatment, subjects will be retrospectively assigned to the 
correct cohort once the result is available.
m) NSCLC, Prior Anti-PD-(L)1 Therapy (Number 7c in Table 3.1.6-1)
i)
Histologically or cytologically confirmed, advanced (ie, unresectable or metastatic) 
NSCLC of either squamous or non-squamous histology.
ii) Must have had progressive or recurrent disease either during or within 6 months after 
anti-PD-(L)1 therapy (administered as monotherapy or as part of a combination). No 
intervening systemic therapy is permitted between anti-PD-(L)1 treatment and 
enrollment on this trial.
iii) PD-L1 status must be documented if available. PD-L1 status will also be re-tested 
using tissue acquired from the mandatory pre-treatment biopsy.
iv) Subjects must have received platinum-based chemotherapy in the recurrent or 
metastatic setting.
v) EGFR and ALK status must be known. KRAS mutational status should be 
documented if available. 
(1) EGFR and ALK may be unknown for subjects with squamous cell histology. 
vi) Subjects with a sensitizing EGFR mutation or ALK rearrangement must have 
received EGFR-directed or ALK-directed therapy, respectively.
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n) Mixed Cohort of Signal-seeking Tumors
Subjects must have histologically documented:
i)
Triple negative breast cancer
ii) Adenocarcinoma of the endometrium
iii) Epithelial cancer of the ovary
iv) Sarcoma (as outlined in Target Population, Dose Escalation)
v) Subjects must have completed, or been intolerant to, at least 1 standard chemotherapy 
regimen in the advanced or metastatic setting (eg, platinum-based therapy for ovarian 
cancer), if such therapy exists. Subjects must also have been considered for all other 
potentially efficacious therapies. 
vi) Subjects with ovarian cancer should have a platinum-free interval of < 9 months.
o) Renal cell carcinoma
i)
Advanced or metastatic RCC with a clear cell component.
ii) Must have received at least 1 but not more than 2 prior anti-angiogenic therapy 
regimens (including but not limited to sunitinib, sorafenib, pazopanib, axitinib, 
tivozanib, and bevacizumab) in the advanced or metastatic setting. Prior cytokine 
therapy (eg, IL-2 IFN-α), vaccine therapy, or treatment with cytotoxics is allowed.
iii) Must have received no more than 3 total prior systemic treatment regimens in the 
advanced or metastatic setting and must have evidence of progression on or after the 
last treatment regimen received and within 6 months prior to study enrollment.
3) Part 3: Combination with both Nivolumab and Ipilimumab (Safety and Expansion 
Cohorts)
a) Melanoma, PD-L1 positive
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system.
ii) Subjects must be either I-O therapy naïve, or may have received and then had disease 
progression after 1 prior I-O therapy in the advanced or metastatic setting. For 
subjects who have received prior immuno-oncology therapy, prior treatment with
only 1 agent is permitted; subjects who have received combination I-O therapy are 
excluded. At least 35 subjects in this cohort will be I-O treatment naïve.
iii) PD-L1 positive subjects, defined as PD-L1 ≥1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
(Note: If the PD-L1 status from the pre-treatment biopsy is not available prior to the start 
of treatment, subjects will be retrospectively assigned to the correct cohort once the result 
is available.)
iv) BRAF (V600) mutation status must be known. Both BRAF-mutated and WT subjects 
are permitted in this cohort
b) Melanoma, PD-L1 negative
i)
Histologically confirmed, unresectable Stage III or Stage IV melanoma, as specified 
in the American Joint Committee on Cancer (AJCC) staging system.
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ii) Subjects must be either I-O therapy naïve, or may have received and then had disease 
progression after 1 prior I-O therapy in the advanced or metastatic setting. For 
subjects who have received  prior immuno-oncology therapy, prior treatment with 
only 1 agent is permitted; subjects who have received combination I-O therapy are 
excluded. At least 20 subjects in this cohort will be I-O treatment naïve
iii) PD-L1 negative subjects, defined as PD-L1 <1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
(Note: If the PD-L1 status from the pre-treatment biopsy is not available prior to the start 
of treatment, subjects will be retrospectively assigned to the correct cohort once the result 
is available.)
iv) BRAF (V600) mutation status must be known. Both BRAF-mutated and WT subjects 
are permitted in this cohort
c) NSCLC PD-L1 positive
i)
Histologically or cytologically confirmed, advanced (ie, unresectable or metastatic) 
NSCLC of either squamous or non-squamous histology.
ii) Subjects must be either treatment naïve in the advanced setting or may have received 
and then had disease progression after at least one line of prior therapy.  For subjects 
who received chemotherapy or a TKI as first line therapy, no subsequent therapy is 
permitted. For subjects who received PD-(L)1 targeted therapy as first line treatment,  
this may have been given either as monotherapy or in combination with 
chemotherapy only; no prior I-O combination therapy is permitted. Subjects who 
received PD-(L)1 targeting monotherapy as first-line treatment may also have 
received chemotherapy or TKI therapy after disease progression. At least 25 subjects 
in this cohort will be treatment naïve in the advanced setting and at least 10 subjects 
IO-therapy naive.
iii) EGFR and ALK status must be known. KRAS mutational status should be 
documented if available. 
(1) EGFR and ALK may be unknown for subjects with squamous cell histology. 
(2) Subjects with a sensitizing EGFR mutation or ALK/ROS1 rearrangement must 
have received appropriate therapy directed at the mutation or rearrangement
iv) PD-L1 positive subjects, defined as PD-L1 ≥1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
(Note: If the PD-L1 status from the pre-treatment biopsy is not available prior to the start 
of treatment, subjects will be retrospectively assigned to the correct cohort once the result 
is available.)
d) NSCLC PD-L1 negative
i)
Histologically or cytologically confirmed, advanced (ie, unresectable or metastatic) 
NSCLC of either squamous or non-squamous histology.
ii) Subjects must be either treatment naïve in the advanced setting or may have received 
and then had disease progression after at least one line of prior therapy.  For subjects 
who received chemotherapy or a TKI as first line therapy, no subsequent therapy is 
permitted. For subjects who received PD-(L)1 targeted therapy as first line treatment,  
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this may have been given either as monotherapy or in combination with 
chemotherapy only; no prior I-O combination therapy is permitted. Subjects who 
received PD-(L)1 targeting monotherapy as first-line treatment may also have 
received chemotherapy or TKI therapy after disease progression. At least 25 subjects 
in this cohort will be treatment naïve in the advanced setting and at least 10 subjects 
IO-therapy naive.
iii) EGFR and ALK status must be known. KRAS mutational status should be 
documented if available. 
(1) EGFR and ALK may be unknown for subjects with squamous cell histology. 
(2) Subjects with a sensitizing EGFR mutation or ALK/ROS1 rearrangement must 
have received appropriate therapy directed at the mutation or rearrangement.
iv) PD-L1 negative subjects, defined as PD-L1 < 1%, are eligible for this cohort. PD-L1 
status will be determined using tissue acquired from the mandatory pre-treatment 
biopsy. Results of previous PD-L1 status testing must be documented if available.
(Note: If the PD-L1 status from the pre-treatment biopsy is not available prior to the start 
of treatment, subjects will be retrospectively assigned to the correct cohort once the result 
is available.)
e) Bladder cancer
i)
Evidence of metastatic or surgically unresectable transitional cell carcinoma of the 
urothelium involving the bladder, urethra, ureter, or renal pelvis.
ii) Progression or recurrence after treatment with:
−
At least 1 platinum-containing chemotherapy regimen for metastatic or surgically 
unresectable locally advanced urothelial cancer OR
−
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.
iii) Subjects may have received prior I-O therapies, but at least 30 subjects in this cohort 
will be I-O therapy naive.
f)
Mixed Tumor Type Cohort (Ipi 1Q8)
i)
Subjects must have tumor types included in Part 2 and meet inclusion criteria defined 
for each tumor type in Part 2
ii)
All subjects must be I-O therapy naive. 
3) General Inclusion Criteria:
a) Eastern Cooperative Oncology Group performance status of ≤1
b) Ability to swallow pills or capsules.
c) Presence of at least 1 lesion with measurable disease as defined by RECIST v1.1 for solid 
tumors and IWG for lymphomas 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.
d) Subjects with prior exposure to therapy with any agent specifically targeting checkpoint 
pathway inhibition (such as anti-PD-[L]1, anti-PDL-2, anti-LAG-3, and anti-CTLA-4 
antibodies) are permitted after a washout period of any time greater than 4 weeks from 
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the last treatment.**Note that certain expansion cohorts do not allow prior treatment 
with immunotherapy agents, including I-O naïve melanoma and NSCLC. See 
tumor-specific eligibility criteria above. In addition, the 4-week washout period is 
not required for the following Part 2 expansion cohorts: Melanoma, prior 
anti-PD-(L)1 and prior anti-PD-(L)1/anti-CTLA-4 combination and NSCLC, prior 
anti-PD-(L)1 or for subjects in Part 3 Melanoma and NSCLC cohorts with prior IO-
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 PE, 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 drug.
(ii) Eligibility of subjects with prior ≥Grade 3 checkpoint therapy-related immune AEs, 
will be considered on a case-by-case basis after discussion with the Medical Monitor (eg,
asymptomatic isolated Grade 3 lipase elevations without clinical or radiological features 
of pancreatitis will be permitted to enroll).
e) Subjects with prior therapy with any agent specifically targeting T-cell co-stimulation 
pathways such as anti-glucocorticoid-induced TNFR family related gene antibody, anti-
CD137, anti-OX40 antibody are permitted after a washout period of any time greater than 
4 weeks from the last treatment.
f)
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.
g) All subjects must have archival FFPE tumor tissue available. This must be a block or 20 
FFPE unstained slides (fewer slides may be acceptable with the approval of the medical 
monitor, but generally at least 15 will be required). With Amendment 14, archival tissues 
from subjects in Parts 1 and 3 may be of any age, while for all other subjects blocks must 
have been obtained less than 1 year prior to enrollment, and FFPE slides must have been 
cut less than 4 months prior to enrollment; if archival tissue meeting these age 
requirements is not available, subjects must undergo fresh biopsies as detailed below. 
Tumor samples for archival tissue obtained by fine needle aspirate/biopsy or from bone 
lesion are not acceptable. Subjects must consent to the acquisition of this archival tissue.  
In limited circumstances, subjects with newly diagnosed, untreated melanoma and 
NSCLC without archival tissue available may be permitted to enroll after permission is 
obtained from the Medical Monitor or Study Director, but will be required to undergo 
fresh biopsy.
h) All subjects in Parts 1 and 3 (as well as subjects in other parts without archival tissue 
meeting the requirements above) will be required to undergo mandatory pre-treatment 
biopsies. All subjects will be required to undergo an on-treatment biopsy, unless 
considered to pose unacceptable clinical risk, as judged by the investigator and in 
consultation with the medical monitor/study director.
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i)
Pre-treatment tissue must be collected prior to first dose of study drug. Recent fresh 
samples (frozen and FFPE) obtained prior to start of screening that meet biomarker 
requirements (Section 5.7.2) of the study as determined by the Study Director or 
Medical Monitor may be substituted for fresh biopsies, after permission from the 
Study Director or Medical Monitor is obtained. 
ii) The 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 and randomization. Biopsies of 
bone lesions that do not have a soft tissue component or decalcified bone tumor 
samples are also not acceptable.
iii) Where possible, the biopsied lesion should be distinct from target lesions being 
evaluated for radiologic response, and the same lesion should be used for both the 
baseline and on-treatment sampling. 
i)
Blood methemoglobin levels within the ULN
j)
Adequate marrow function for subjects with solid tumor histologies as defined by the 
following:
i. White blood cell (WBC) ≥2000/μL (stable off any growth factor within 4 weeks of 
first study drug administration)
ii. Neutrophils ≥1500/μL (stable off any growth factor within 4 weeks of first study 
drug administration)
iii. Platelets ≥100× 103/μL (transfusion to achieve this level is not permitted within 
2 weeks of first study drug administration)
iv. Hemoglobin ≥8.5 g/dL (transfusion to achieve this level is not permitted within 
2 weeks of first study drug administration)
k) Adequate marrow function for subjects with B-cell NHL and HL malignancies as defined 
by the following:
i. Absolute neutrophil count ≥750/μL (no WBC growth factors for prior 14 days)
ii. Platelets ≥50× 103/μL (no platelet transfusions for prior 14 days)
iii. Hemoglobin > 8.0 g/dL (no RBC transfusions for prior 7 days)
l)
Adequate other organ functions as defined by the following:
i. ALT and AST ≤3× institutional ULN
ii. Total bilirubin ≤1.5× institutional ULN (except subjects with Gilbert’s Syndrome 
who must have normal direct bilirubin)
iii. [This criterion is no longer applicable]
iv. Normal thyroid function, subclinical hypothyroidism (thyroid-stimulating hormone 
[TSH] < 10 mIU/mL), or have controlled hypothyroidism on appropriate thyroid 
supplementation 
v. Serum creatinine ≤1.5× ULN or creatinine clearance (CrCl) ≥40 mL/min 
(measured using the Cockcroft-Gault formula below):
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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
vi. Ability to comply with treatment, PK, and pharmacodynamic sample collection, and 
required study follow-up.
Subject Re-enrollment: This study permits the re-enrollment of a subject who has discontinued 
the study as a pre-treatment failure (eg, subject has not been treated). If re-enrolled, the subject 
must be re-consented.
4) 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 (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of 
human chorionic gonadotropin) 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(s) plus an additional 5 months (approximately 23 weeks) 
post-treatment completion.
e) Males who are sexually active with WOCBP must agree to use a synthetic or latex
condom during sexual activity for the duration of treatment with study treatment plus an 
additional 7 months after the last dose of the study treatment (ie, 90 days [the duration of 
sperm turnover] plus the time required for nivolumab to undergo approximately 5 half-
lives). This criterion applies to azoospermic males as well. In addition, male subjects 
must be willing to refrain from sperm donation during this time.
f)
WOCBP who are continuously not heterosexually active are exempt from contraceptive 
requirements. However, WOCBP must still undergo pregnancy testing as described in 
this section.
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 WOCBP and male subjects who are sexually active with WOCBP on 
the use of highly effective methods of contraception (Appendix 11). Highly effective methods of 
contraception have a failure rate of < 1% when used consistently and correctly. Hormonal 
contraceptives are not highly effective methods of contraception for subjects receiving
BMS-986205 in this study who are WOCBP.
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3.3.2
Exclusion Criteria
1) Target Disease Exceptions
a) Subjects with known or suspected CNS metastases, 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), off of 
steroids for at least 2 weeks, and no new or progressive neurological signs and symptoms. 
Please note: SCCHN subjects with direct extension of tumor through the base of skull 
will not be excluded, as they are considered distinct from hematogenously spread 
parenchymal brain metastasis.
b) Ocular melanoma
c) [This criterion is no longer applicable]
2) Medical History and Concurrent Diseases
a) Subjects with a history or presence of G6PD deficiency, cytochrome b5 reductase 
deficiency, or other diseases that put them at risk of methemoglobinemia.
b) History of congenital or autoimmune hemolytic disorders.
If subject has history of transient acquired hemolytic anemia, discuss with Medical 
Monitor for study eligibility.
c) History or presence of hypersensitivity or idiosyncratic reaction to methylene blue.
d) Subjects with a prior malignancy are excluded (except non-melanoma skin cancers and in 
situ cancers such as the following: bladder, colorectal, cervical/dysplasia, melanoma, or 
breast). 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.
e) Other active malignancy requiring concurrent intervention.
f)
Prior organ allograft or allogeneic bone marrow transplantation.
g) Any anti-cancer therapy (eg, chemotherapy, biologics, vaccines, or hormonal treatment) 
including investigational drugs within 4 weeks prior to the first dose of study drug 
administration, except for non-cytotoxic therapies, for which at least 4 weeks or 5 half-
lives (whichever is shorter) must have elapsed between last dose and first treatment with 
any study drugs; if 5 half-lives is shorter than 4 weeks, agreement with the Medical 
Monitor must be obtained. **Note that this criterion does not apply for anti-PD-(L)1 
therapy in the following Part 2 expansion cohorts: Melanoma, prior anti-PD-(L)1 
and anti-PD-(L)1/anti-CTLA-4 combination and NSCLC, prior anti-PD-(L)1.
h) Prior therapy with an IDO inhibitor.
i)
Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, 
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only 
requiring hormone replacement, euthyroid subjects with a history of Grave’s disease 
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(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.
j)
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.
k) Requirement for daily supplemental oxygen.
l)
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) QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation 
> 480 msec
v) History of other clinically significant heart disease (eg, cardiomyopathy, congestive 
heart failure with New York Heart Association functional classification III-IV, 
pericarditis, significant pericardial effusion, or myocarditis)
vi) Cardiovascular disease-related requirement for daily supplemental oxygen therapy
m) 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
n) History of other preexisting liver disease (eg, NAFLD).
o) Evidence of active infection ≤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).
p) Known history of testing positive for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome (AIDS). Note: Testing for HIV must be performed 
at sites where mandated by local requirements.
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q) Evidence or history of active or latent tuberculosis infection including PPD recently 
converted to positive; chest x-ray with evidence of infectious infiltrate; and recent 
unexplained changes in fever/chill patterns.
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.
s) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must 
have resolved to Grade 1 (National Cancer Institute Common Terminology Criteria for 
Adverse Events [NCI CTCAE] v4.03) or baseline before administration of study drug. 
Subjects with toxicities attributed to prior anti-cancer therapy that are not expected to 
resolve and result in long lasting sequelae, such as neuropathy after platinum-based 
therapy, are permitted to enroll.
t)
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)
u) Concomitant use of strong inhibitors of CYP3A4 or strong inducers of CYP3A4 (see 
Appendix 7).
i)
Per Amendment 14, also includes strong inhibitors/inducers of CYP1A2
v) Use of nononcology vaccines containing live virus for prevention of infectious diseases 
within 12 weeks prior to study drug. The use of inactivated seasonal influenza vaccines 
(eg, Fluzone®) will be permitted on study without restriction.
w) Use of packed red blood cells or platelet transfusion within 2 weeks prior to the first dose 
of study drug as specified in Section 3.3.1, j and k.
x) A known or underlying medical condition that, in the opinion of the investigator or 
Sponsor, could make the administration of study drug hazardous to the subjects or could 
adversely affect the ability of the subject to comply with or tolerate the study.
y) Subjects with confirmed or suspected serotonin syndrome
z) Subjects with active ILD/pneumonitis or with recent history of ILD/ pneumonitis 
requiring steroids (excluding radiation pneumonitis)
aa) Subjects with impairment of gastrointestinal function or gastrointestinal disease, or other 
conditions known to interfere significantly with the absorption of oral medication, per 
investigator judgement
3) Physical and Laboratory Test Findings
a) Positive test for hepatitis B virus surface antigen or hepatitis C ribonucleic acid (RNA).
(Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR 
are eligible.) Additional testing or substitute testing per institutional guidelines to rule out 
infection is permitted. 
i)
[This criterion is no longer applicable]
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ii) [This criterion is no longer applicable]
b) Any of the following on 12-lead ECG prior to study drug administration, confirmed by 
repeat:
i)
QRS ≥120 msec, except right bundle branch block
ii) QTcF ≥480 msec, except right bundle branch block
c) Second or third degree heart block at Screening (QTc substudy only)
4) Allergies and Adverse Drug Reaction
a) History of allergy to nivolumab (all study parts) or ipilimumab (Part 3 only).
b) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) to prior 
anti-cancer immune-modulating therapies
(eg,
checkpoint inhibitors
and
T-cell 
co-stimulatory antibodies).
5) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated.
b) Subjects who are compulsorily detained for treatment of either a 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, who has not undergone 
surgical sterilization (hysterectomy or bilateral oophorectomy), and who is not postmenopausal. 
Menopause is defined as 12 months of amenorrhea in a woman over age 45 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 > 40mIU/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 duration of the washout period is a function of the type of HRT used. The durations of 
the washout periods below are suggested guidelines, and the investigators should use their 
judgment in checking serum FSH levels. 
•
1 week minimum for vaginal hormonal products (eg, rings, creams, gels)
•
4 weeks minimum for transdermal products
•
8 week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mlU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Prohibited and/or restricted medications taken prior to and during study drug administration in 
the study are described below. Medications taken within 2 weeks prior to study drug 
administration must be recorded on the case report form (CRF).
The following medications are prohibited during the study:
•
Prior exposure to BMS-986205 or other IDO inhibitor.
•
Concurrent administration of any anti-cancer therapies (investigational or approved) with the 
exception of subjects in the follow up and survival period of the study. 
•
Concomitant use of strong inhibitors of CYP3A4 and/or CYP1A2 or strong inducers of 
CYP3A4 and/or CYP1A2 (see Appendix 7).
•
Immunosuppressive agents (except as stated in Section 3.4.3), unless they are utilized to treat 
an AE.
•
Use of any medicinal herbal preparations within 2 weeks of the first dose of study drug and 
during study treatment unless prescribed by a treating physician. Please see restrictions on 
the use of marijuana in Section 3.4.2.
•
Palliative radiotherapy is permitted only under certain conditions as described in 
Section 3.3.1.
Any concomitant therapies must be recorded on the CRF.
3.4.2
Other Restrictions and Precautions
Restricted therapies are not prohibited but are not recommended; consult BMS medical monitor 
if the following are clearly medically indicated:
1) Grapefruit and Seville oranges and their juices can inhibit CYP3A4 and should not be 
consumed while on study.
2) Concurrent use of moderate inhibitors or inducers of CYP3A4 and/or CYP1A2 may affect 
the systemic exposure of BMS-986205. See Appendix 7 for a list of CYP3A4 and/or 
CYP1A2 modulators.
3) Concurrent smoking (tobacco, marijuana, etc.) may induce CYP1A2 and decrease the 
systemic exposure of BMS-986205. 
4) Caution is warranted when consuming marijuana by means other than smoking as it may lead 
to increased exposure of BMS-986205 through interaction with metabolic enzymes. 
5) Caution is warranted when administering BMS-986205 to subjects taking drugs that are
highly dependent on CYP3A4 or CYP2B6 for metabolism. See Appendix 7 for a list of 
sensitive CYP3A4 and CYP2B6 substrates.
6) Caution is warranted when administering BMS-986205 to subjects taking drugs that may be 
associated with QT prolongation. Drugs that may prolong QT intervals are prohibited during 
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Cycle 0 of the QTc substudy. See Appendix 8 for a list of common medications associated 
with QT prolongation.
7) Caution is warranted when administering BMS-986205 to subjects taking drugs that are 
subject to extensive intestinal efflux by P-gp/BCRP. See Appendix 9 for a list of common 
P-gp/BCRP substrates.
8) In vitro solubility data indicate that BMS-986205 has decreased solubility with increasing 
pH. Until further data are available, subjects should try to avoid taking proton pump 
inhibitors. H2 antagonists and short-acting antacid agents, such as Maalox® or TUMS®, may 
be taken, but it is recommended that these not be taken 4 hours before or 4 hours after dosing 
of BMS-986205.
9) Caution is warranted when using other agents known to cause methemoglobinemia (see 
Appendix 10). Dapsone, topical anesthetics, and antimalarial drugs are the most likely 
agents, and thus these drugs should only be used after discussion with the Study 
Director/Medical Monitor.
10) Preclinical studies suggest potential effect of food on BMS-986205 absorption (see 
Section 1.4.3). BMS-986205 should be administered following a light meal (see Table 4-2
for a sample light meal). Subjects should avoid heavy meals with high fat content 4 hours 
prior until 4 hours post BMS-986205 dose.
The development of serotonin syndrome has been associated with exposure to another 
investigational agent that inhibits the IDO1 enzyme. No case of serotonin syndrome has been 
observed with administration of BMS-986205. Given the possibility of a class effect, there is a 
theoretical risk that BMS-986205 could cause an increase in serotonin levels in the brain that 
might trigger serotonin syndrome when administered in combination with serotonergic agents or 
tryptophan supplements. Use caution and monitor for symptoms of serotonin syndrome in 
subjects 
receiving concurrent 
serotonergic 
psychiatric 
medications 
and/or 
tryptophan 
supplements.
3.4.3
Permitted Therapy
•
Subjects are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Treatment with a short course of steroids 
(< 5 days) up to 7 days prior to initiating study drug is permitted. A brief course of 
corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of nonautoimmune 
conditions (eg, delayed-type hypersensitivity reaction caused by a contact allergen) is 
permitted.
•
Inhaled or intranasal corticosteroids (with minimal systemic absorption may be continued if 
the subject is on a stable dose) and adrenal replacement steroid doses > 10 mg daily 
prednisone equivalent are permitted in the absence of active autoimmune disease. 
Nonabsorbed intra-articular steroid injections will be permitted.
•
Immunosuppressive agents and the use of systemic corticosteroids are permitted in the 
context of treating AEs. Subjects receiving corticosteroids for treatment of drug-related AEs 
must be at < 10 mg/day prednisone or equivalent prior to re-initiation of study drug. Subjects 
may continue to receive HRT.
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•
Subjects receiving RANK-L inhibitors or bisphosphonates are permitted as clinically 
indicated but should be avoided, if possible, prior to completion of Cycle 1.
3.4.3.1
Palliative Local Therapy
Palliative and supportive care for disease-related symptoms may be offered to all subjects on the 
trial; however, investigators should consult with the BMS Medical Monitor prior to initiating 
palliative radiation in subjects who have not yet completed the DLT evaluation period. Limited 
radiation therapy or surgery to control isolated lesions is permitted for subjects who have 
investigator-assessed clinical benefit following consultation with the BMS Medical Monitor.
Subjects should not receive study drug during radiation as the potential for overlapping toxicities 
with radiotherapy and BMS-986205 or with radiotherapy and the combination of BMS-986205 
and nivolumab is currently not known. Anecdotal data suggest that radiotherapy administered to 
subjects while receiving nivolumab therapy is tolerable. However, because concurrent 
radiotherapy and immunotherapies in cancer have not been formally evaluated, in cases where 
palliative radiotherapy is required for a tumor lesion, then BMS-986205 alone or BMS-986205
in combination with nivolumab (and ipilimumab, where applicable) should be withheld for at 
least 1 week before, during, and 1 week after radiation. Subjects should be closely monitored for 
any potential toxicity during and after receiving radiotherapy, and AEs related to radiotherapy 
should resolve to Grade 1 prior to resuming study drug.
3.5
Discontinuation of Subjects Following any Treatment with Study Drug
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:
•
Subject’s request to stop study treatment and/or participation in the study
•
Any clinical AE, laboratory abnormality or intercurrent illness that in the opinion of the 
investigator indicates that continued participation in the study is not in the best interest of the 
subject
•
Termination of the study by BMS
•
Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness
•
Inability to comply with protocol
•
Discretion of the investigator
•
Pregnancy
•
Completion of study-required procedures. 
•
Documented and confirmed disease progression as defined by RECIST v1.1 or IWG (see 
Appendix 3 and 4) unless subject meets criteria for treatment beyond progression 
(Section 3.5.1)
•
Clinical deterioration while receiving active study drug that in the opinion of the investigator 
indicates that continued participation in the study is not in the best interest of the subject
•
Protocol-defined reasons for discontinuation (see Sections 3.5.1 and 4.5.6).
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In the case of pregnancy, the investigator must immediately, within 24 hours of the event, notify 
the BMS Medical Monitor/designee of this event. In most cases, the study drug will be 
permanently discontinued in an appropriate manner. If the investigator determines a possible 
favorable benefit/risk ratio that warrants continuation of study drug, a discussion between the 
investigator and the BMS Medical Monitor/designee must occur.
All subjects who discontinue investigational product should comply with protocol-specified 
follow-up procedures as outlined in Section 5. 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 either a psychiatric or physical illness).
If 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 Progression
A subset of subjects with solid tumors treated with immunotherapy may derive clinical benefit 
despite initial evidence of PD. Subjects will be permitted to continue on treatment beyond initial 
RECIST v1.1 (see Appendix 3) or IWG-defined PD, as long as they meet the following criteria:
•
Investigator-assessed clinical benefit and not having rapid disease progression;
•
Continue to meet all other study protocol eligibility criteria;
•
Tolerance of study drug;
•
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 nivolumab, 
ipilimumab, or BMS-986205 treatment using an ICF describing any reasonably foreseeable 
risks, 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 documented in the study records. Subjects 
will be re-consented to explain the rationale for this ongoing treatment.
3.5.2
Discontinuation Due to Further Progression (Confirmed Progression)
Subjects should discontinue study drug upon further evidence of further progression, defined as 
an additional 10% or greater increase in tumor burden volume from time of initial progression 
(including all target lesions and new measurable lesions).
The tumor burden volume from time of initial progression should be used as the reference 
baseline for comparison with the postprogression assessment.
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Any new lesion considered nonmeasurable 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 initial investigator-assessed, RECIST v1.1
or IWG-defined 
progression will be considered to have investigator-assessed PD at the time of the initial 
progression event.
3.5.3
Assessment Schedule for Subjects with Postprogression Treatment
Subjects should continue to receive monitoring according to the On-Treatment Assessments in 
Section 5.4. Radiographic assessment by computed tomography (CT; preferred) or magnetic 
resonance imaging (MRI) described in Section 5 is required when subjects continue 
postprogression treatment. For subjects who discontinue postprogression treatment with study 
drug, 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 for collection of outcome and/or 
Survival Follow-up data as required and in line with Section 3.1.3 until death or the conclusion 
of the study.
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 subject to 1 registered mail letter. All 
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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 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 AND STUDY DRUG ADMINISTRATION
All protocol-specified investigational and non-investigational products are considered study 
drug.
Study Drug:
Product description and storage information is described in Table 4-1. Preparation and 
administration instructions will be provided separately via site training materials.
For study drugs not provided by BMS and obtained commercially by the site, storage should be 
in accordance with the package insert, summary of product characteristics, or similar 
documentation.
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Table 4-1:
Study Drugs for CA017003
Product Description Class 
and Dosage Form
Potency
IP/
Non-IMP
Blinded or 
Open Label
Packaging/
Appearance
Storage Conditions
(per label)
BMS-986205-04
5 mg
IP
Open
Capsule
Refer to the label on container and/or 
pharmacy manual
BMS-986205-04
25 mg
IP
Open
Tablet
Refer to the label on container and/or 
pharmacy manual
BMS-986205-04
50 mg
IP
Open
Capsule/Tablet
Refer to the label on container and/or 
pharmacy manual
BMS-986205-04
100 mg
IP
Open
Tablet
Refer to the label on container and/or 
pharmacy manual
Nivolumab
(BMS-936558-01)
Solution for Injection
100 mg
(10 mg/mL)
IP
Open
Vial
Refer to the label on container and/or 
pharmacy manual
Ipilimumab
(BMS-734016)
Solution for Injection
200 mg
(5 mg/mL)
IP
Open
Vial
Refer to the label on container and/or 
pharmacy manual
Abbreviations: IP = investigational product.
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Study drugs not provided by BMS and obtained commercially by the site should be stored in 
accordance with the product label. Compounding instructions will be provided separately to the 
site. 
Study Drug Administration:
BMS-986205
At scheduled PK sample collection as well as on laboratory evaluation days, BMS-986205 will 
be administered to the subject in the clinical facility. At all other times throughout the study, 
BMS-986205 will be administered on an out-subject basis, except when subjects are seen in the 
clinic for administration of nivolumab, assessment of AEs, and laboratory evaluation.
Restrictions related to food and fluid intake are described in Section 3.4.2.
Dose Escalation (Part 1)
BMS-986205 should be administered using the capsule formulation in Part 1.
BMS-986205 should be administered in the morning following a light meal approximately 
24 hours apart. On the morning of Days 1 and 14 when serial PK samples are collected, after 
fasting for at least 10 hours, each subject will receive a single oral dose of BMS-986205 within 
approximately 5 minutes of completing a light meal. At the time of dosing, approximately 240 
mL of water will be administered to the subject along with BMS-986205. The time of BMS-
986205 administration will be called “0” hour. A description of a sample light breakfast meal is 
provided in Table 4-2.
Table 4-2:
Representative Light Breakfast Meal
Food Item 
Calories (kcal)
Fat (g) 
Carbohydrates (g) 
Protein (g)
2 slices of white bread
128 
1.8 
24.0 
4.0 
1 teaspoonful low fat 
margarine
26 
2.9 
trace 
trace 
1 tablespoon jam
56 
trace 
13.8 
trace 
5 oz apple juice
71
0.2 
17.5
0.2 
5 oz skim (nonfat) milk
54 
0.3 
7.5 
5.3 
Total grams (g)
-
5.2 
62.8
9.5
Total calories (kcal)
335
47 
251 
38 
% of total calories
100 
14 
75 
11 
Source: US Department of Agriculture Nutrient Database for Standard Reference, Release 28 (September 2015)54
QTc Substudy
BMS-986205 should be administered using the tablet formulation in QTc Substudy, unless the 
Sponsor specifies that the capsule formulation should be used.
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On ECG baseline day, after fasting for at least 10 hours, subjects should receive a light meal at 
approximately the same time as they would on Cycle 0 Day 14. Within approximately 5 minutes 
of completing the light meal, approximately 240 mL of water will be administered, although no 
BMS-986205 will be given. Time-matched baseline ECG will be collected (taken at the same 
time-points on the baseline day as on Cycle 0 Day 14). During Cycle 0 of the QTc substudy, 
subjects will receive BMS-986205 QD following a light meal on Days 1-14. On Day 14, 
following an overnight fast of at least 10 hours, each subject will receive BMS-986205 within 
approximately 5 minutes of completing a light meal. At the time of dosing, approximately 240 
mL of water will be administered to the subject along with BMS-986205. Serial ECGs and PK 
samples will be collected as indicated in Table 5.5.4.3-1.
Dose Expansion (Part 2) and Dose Escalation/Expansion (Part 3) 
BMS-986205 should be administered using the tablet formulation in Parts 2 and 3, unless the 
Sponsor specifies that the capsule formulation should be used. Patients enrolled prior to 
Amendment 8 should continue to use the capsule formulation unless otherwise specified by the 
Sponsor. 
BMS-986205 should be administered following light meals approximately 24 hours apart.
Nivolumab (Part 2) 
Nivolumab infusions should start approximately 30 minutes following BMS-986205. Nivolumab 
should be infused over 30 minutes. After the first nivolumab infusion, subjects should be 
monitored per local/institutional guidelines. If no such guidelines exist, an observation period of 
2 hours after the end of the nivolumab infusion is suggested.
Further details regarding preparation and administration will be provided separately in 
site/pharmacy training materials.
Nivolumab and Ipilimumab (Part 3)
Nivolumab infusions should start approximately 30 minutes following BMS-986205. For all 
doses used within Part 3, Nivolumab should be infused over 30 minutes. Further details 
regarding preparation and administration will be provided separately in site/pharmacy training 
materials.
The second infusion in the combination cohort will always be ipilimumab, and will start 
approximately 30 minutes after completion of the nivolumab infusion and the infusion line has
been flushed, filters changed and the patient has been observed to ensure no infusion reaction has
occurred. Subjects should receive ipilimumab as a 30-minute IV infusion. Further details 
regarding preparation and administration will be provided separately in site/pharmacy training 
materials.
After the first nivolumab infusion, subjects should be monitored per local/institutional 
guidelines. If no such guidelines exist, an observation period of 2 hours after the end of the 
nivolumab infusion is suggested.
Product description and storage information are described in Table 4-1.
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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 that 
are used or assembled (formulated or packaged) differently than the authorized form, used for an 
unauthorized indication, or 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 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, investigational products are BMS-986205, nivolumab, and ipilimumab.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or 
therapeutic reasons as components of the standard of care for a given diagnosis may be
considered noninvestigational 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 BMS contacted immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained 
and include all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage; administration; and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
Storage facilities for controlled substances must be securely locked and substantially constructed, 
with restricted access to prevent theft or diversion, as applicable by local regulations.
4.4
Method of Assigning Subject Identification
During the Screening visit, the investigative site will call into the enrollment option of the IVRS
designated by BMS for assignment of a 5-digit subject number that will be unique across all 
sites. Enrolled subjects, including those not dosed, will be assigned sequential subject numbers 
starting with 00001 (eg, 00001, 00002, 00003... 00010). The subject identification number (PID) 
will ultimately be composed of the site number and subject number. For example, the first 
subject screened (ie, enrolled) at site number 1, will have a PID of 0001 00001. Once it is 
determined that the subject meets the eligibility criteria following the Screening visit, the 
investigator site will call the IVRS within 3 days prior to the first study drug administration for 
the subject to be assigned treatment groups.
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If the clinical pharmacology substudy and dose escalation cohort are open at the same time,
subjects will be assigned to the dose escalation cohort first. If no escalation cohort is open, 
subjects will be assigned to the clinical pharmacology substudy. If the clinical pharmacology
substudy and dose expansion are open at the same time, subjects with the specific tumor type for 
dose expansion will be assigned to the dose expansion. All other subjects will be assigned to the 
clinical pharmacology substudy.
For the QTc substudy, subjects will be assigned to one of the 3 doses within the substudy. The 
doses or assignments may be adjusted based on future findings. Subjects who did not finish 
Day 14 of the QTc substudy will be replaced.
During dose escalation in Part 1 and safety cohort evaluation in Part 3, subjects who are not 
evaluable for DLT determination may be replaced. Replacement subjects will be assigned to the 
same treatment but will be assigned a new subject number.
4.5
Selection and Timing of Dose for Each Subject
BMS-986205 will be administered orally daily at the doses listed in Section 3.1.5
Each subject will be assigned to a specific dose level as listed in Section 4 in sequential order 
during dose escalation Part 1. Subjects in dose expansion Part 2 will be treated at the MTD, the 
MAD, or at an alternate dose determined from Part 1, if agreed upon by the investigators and the 
Sponsor. Subjects treated in Part 3 will receive BMS-986205 at 100 mg daily and will receive
doses and schedules of nivolumab and ipilimumab selected for each tumor-specific expansion 
cohort as detailed in Section 3.1.7.
In Parts 1 and 2, Nivolumab will be administered intravenously as flat doses; either 240 mg 
Q2W for the Part 1 dose escalation and for the Part 2 dose expansion cohorts that predated
Amendment 06, or 480 mg Q4W for the Part 2 dose expansion cohorts added with or after
Amendment 06 (melanoma, NSCLC, RCC, and additional signal-seeking tumors) and the 
clinical pharmacology substudy. In Part 3, nivolumab will also be administered in flat doses for 
all cohorts at the specified doses for those cohorts.
There will be no dose escalations or reductions of nivolumab allowed once assigned. Subjects
receiving nivolumab Q2W will be dosed no less than 12 days from the previous dose and no 
more than 3 days from the scheduled dose. Subjects receiving nivolumab Q3W may be dosed 21 
days (± 3 days) from the previous dose. Subjects receiving nivolumab Q4W may be dosed 
28 days (± 3 days) from the previous dose.
For subjects receiving ipilimumab, the dosing calculations should be based on the body weight. 
If the subject’s weight on the day of the dosing differs by > 10% from the weight used to 
calculate the dose, the dose must be recalculated. All doses should be rounded up or to the 
nearest milligram per institutional standard. There will be no dose modifications of ipilimumab 
allowed. Subjects receiving ipilimumab Q3W may be dosed no less than 19 days from the 
previous dose and no more than 3 days from the scheduled dose. Subjects receiving ipilimumab 
Q6W may be dosed every 42 days (± 3 days). Subjects receiving ipilimumab Q8W may be dosed 
every 56 days (± 3 days).
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When nivolumab and ipilimumab are scheduled to be dosed on the same day, if dosing is 
delayed, both nivolumab and ipilimumab must be delayed together. If dosing is resumed after a 
dose delay, both nivolumab and ipilimumab must be resumed on the same day if the next 
scheduled day includes both nivolumab and ipilimumab administration.
There are no premedications recommended for nivolumab or ipilimumab (where applicable) on 
the first cycle. If an acute infusion reaction is noted, the subjects should be managed according to 
Section 4.7.1.
4.5.1
Dose-limiting Toxicities
For the purpose of guiding dose escalation, DLTs will be defined based on the incidence and 
grade of AEs for which no alternate cause can be identified.
Part 1: Cycle 0 (BMS-986205 monotherapy lead-in) will have a 2-week DLT evaluation period 
(DLT 1). The combination regimen will have 4-week DLT evaluation period (DLT 2). 
Therefore, the total DLT assessment period is 6 weeks in Part 1. Subjects may proceed from 
Cycle 0 to Cycle 1 at each cohort unless any of the following events are observed: any DLT, 
Grade 2 or higher immune-related AEs considered related to BMS-986205 (eg,
immune-mediated pneumonitis, colitis, hepatitis, nephritis, renal dysfunction) with the exception 
of immune-mediated hypothyroidism and hyperthyroidism, or Grade 2 AST or ALT elevation 
that does not resolve to Grade 1 within 1 week. For Grade 2 AST or ALT elevations that resolve 
to Grade 1 or baseline within 1 week, subjects can be rechallenged with BMS-986205 
monotherapy for a minimum of 5 days before proceeding to combination with nivolumab 
provided there is not a recurrence of Grade 2 event.
The DLT-evaluation interval begins on the first day of treatment and continues for 6 weeks. The
DLT 1 period is 14 days, and subjects must receive 75% of the BMS-986205 monotherapy doses 
to be considered evaluable for combination with nivolumab. The DLT 2 period is 4 weeks during 
which subjects will receive daily dosing of BMS-986205 and 2 doses of nivolumab. The total 
DLT period is 6 weeks, and subjects must have received at least 75% of BMS-986205 doses and 
2 doses of nivolumab with observation for a minimum of 5 days following the second 
combination therapy dose to be considered evaluable for dose escalation decisions. Based on the 
predicted human half-life of BMS-986205 of 23 hours, this interval is expected to cover the 
anticipated time frame for the occurrence of clinically significant immediate and early onset AEs 
related to BMS-986205 monotherapy during Cycle 0 and repeat dosing of BMS-986205 in 
combination with nivolumab in Cycle 1. 
Part 3: The DLT-assessment period is 6 weeks in Part 3 for all treatment regimens evaluated. 
The DLT-evaluation interval begins on the first day of treatment and continues for 6 weeks. 
DLT-evaluable subjects will be defined as subjects who in the 6 week DLT evaluation period 
received ≥ 75% of BMS-986205 doses and the following nivolumab and ipilimumab doses for 
each regimen:
•
Melanoma/Ipi 1Q8: 2 doses of nivolumab and 1 dose of ipilimumab, and followed for at least 
5 days after the second dose of nivolumab
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•
NSCLC/Ipi 1Q6: 2 doses of nivolumab and 1 dose of ipilimumab, and followed for at least 5 
days after the second dose of nivolumab
•
Bladder/Ipi 3Q3: 2 doses of nivolumab and 2 doses of ipilimumab, and followed for at least 5 
days after the second dose of each drug
The incidence of DLTs that occur within 6 weeks following the start of study drug will guide 
dose escalation decisions. AEs will be graded according to the NCI CTCAE v4.03. For the 
purposes of subject management, drug-related AEs occurring at any time that meet the DLT 
definition will lead to dose interruption, dose modifications, and/or permanent discontinuation of 
study drug as defined in Section 4.5.3 and Section 4.5.6. Subjects who withdraw from the study 
during the DLT evaluation interval for reasons other than a DLT may be replaced at the same 
dose level. The incidence of DLT(s) during the DLT evaluation period will be used in dose 
escalation decisions and to define the MTD. AEs occurring after the DLT period will be 
considered for the purposes of defining the MTD, 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.
AEs will be graded according to the NCI CTCAE v4. For the purpose of guiding dose escalation, 
DLTs are defined below based on the incidence and grade of AEs for which no alternative cause 
can be identified.
In addition to the criteria listed below, any drug-related toxicity that results in a subject not being 
able to receive at least 75% of the doses of BMS-986205 and all pre-specified doses (see above) 
of nivolumab and ipilimumab (where applicable) during the DLT evaluation period or causing 
greater than 2 weeks of dose delay may be classified as a DLT. 
DLTs for DLT1 and DLT2 Periods in Part 1 and the entire DLT evaluation period in Part 
3
Nonhematologic Dose-limiting Toxicity (DLT):
A. Hepatic Nonhematologic DLT
Any of the following events will be considered 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 [DILI])*
*Note that this special category of DLT uses ULN rather than Common Toxicity Criteria Grade 
for definition.
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B. Nonhepatic Nonhematologic DLT
Any of the following events will be considered a nonhepatic nonhematologic DLT:
•
Grade 2 or greater episcleritis, uveitis, 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 2 myocarditis
•
Grade 3 pneumonitis, bronchospasm, neurologic toxicity, hypersensitivity reaction, or 
infusion reaction of any duration requires discontinuation
•
Any Grade 3 or greater nondermatologic, nonhepatic, nonhematologic 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 48 hours and either resolve spontaneously or 
respond to conventional medical intervention
−
Grade 3 nausea, vomiting, or diarrhea that lasts less than 48 hours and either resolves 
spontaneously or responds to conventional medical intervention
−
Isolated Grade 3 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 site of known or 
suspected tumor)
−
Grade 3 fatigue
−
Grade 3 infusion reaction that returns to Grade 1 in less than 6 hours
C. Dermatologic DLT
•
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 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity.
•
Grade 4 rash of any duration
D. Hematologic DLT 
•
Methemoglobin levels ≥15%
•
Grade 4 neutropenia ≥5 days in duration
•
Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement
for platelet transfusion
•
Grade ≥3 febrile neutropenia for 48 hours
•
Grade ≥3 hemolysis (ie, requiring transfusion or medical intervention such as steroids)
•
Grade 4 anemia not explained by underlying disease
4.5.2
Management Algorithms for Immuno-oncology Agents
I-O agents are associated with AEs that can differ in severity and duration from AEs caused 
by other therapeutic classes. Nivolumab, ipilimumab, and BMS-986205 are considered I-O
agents in this protocol. Early recognition and management of AEs associated with I-O agents 
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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-986205 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 5.
4.5.3
Guidelines for Dose Modification
Subjects will be monitored continuously for AEs while on study drug. Subjects will be instructed 
to notify their physician immediately for any and all AEs. The criteria presented in this section 
and Table 4.5.3-1 for dose modifications for BMS-986205 are meant as general guidelines.
Dose modification may occur in the setting of lower grade AE and/or be more conservative than 
indicated in Table 4.5.3-1 based on the clinical judgment of the investigator and in consultation 
with the Sponsor/Medical Monitor.
•
Dose reductions of BMS-986205 should be to the previous lower dose level; subjects 
receiving 25 mg of BMS-986205 will not undergo any (further) dose reductions.
•
If several AEs of varying grade or severity occur simultaneously, the dose modification
applied should be the greatest reduction applicable.
•
Assessment of causality (ie, chronology, confounding factors such as disease, concomitant 
medications, diagnostic tests, and previous experience with the agent) must be determined 
and documented by the investigator prior to dose modification.
•
If the same AE recurs despite a dose reduction, a second dose reduction versus 
discontinuation of BMS-986205 will be discussed and agreed upon by the Sponsor/Medical 
Monitor and investigators, if criteria for discontinuation are otherwise not met.
•
No more than 2 dose reductions of BMS-986205 will be allowed per subject. Dose re-
escalation after a dose reduction may occur in limited circumstances (such as a change in 
attribution of an AE) after discussion and agreement of the Sponsor/Medical Monitor and 
investigators.
•
Skipped doses will not be administered within the same cycle.
•
For an AEs leading to dose modification, BMS-986205, nivolumab, and ipilimumab (where
applicable) should be interrupted to allow recovery from the AE; see Section 4.5.4for delay 
criteria.  Re-initiation of study drug cannot occur until AE decreases to ≤Grade 1 or baseline 
assessment. See Section 4.5.5 for resumption after dose delays. 
•
During the DLT evaluation period, if the dose is reduced and a subject experiences a DLT at 
the lower dose, this DLT will be attributed to the highest dose level administered.
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•
For data collection and analysis purposes, all subjects will continue to be classified by the 
original treatment arm.
Table 4.5.3-1:
Dose Modifications
Dose Modification 
Criteria for Drug-related 
Adverse Events
BMS-986205 Monotherapy 
Modification at the Next Dose (Part 1 
Only)
BMS-986205 Combination 
Modification at the Next Dose 
(Parts 1, 2 and 3)
Methemoglobin ≥15%
Decrease 1 level of BMS-986205
Interrupt dosing until improvement and 
decrease 1 level of BMS-986205 in 
combination with same dose of 
nivolumab or nivolumab and 
ipilimumab.
Methemoglobinemia with 
Grade 3 AEs such as 
hypoxia and hemolysis
Interrupt BMS-986205. Continuation of 
BMS-986205 after recovery at a lower 
dose level may be considered after 
discussion with the 
Study Director/Medical Monitor.
Subjects may proceed to get nivolumab 
monotherapy.
Interrupt BMS-986205. Continuation of 
BMS-986205 after recovery at a lower 
dose level may be considered after 
discussion with the 
Study Director/Medical Monitor.
Subjects may proceed to get nivolumab 
monotherapy or nivolumab and 
ipilimumab.
Methemoglobinemia with 
Grade 4 AEs such as 
hypoxia and hemolysis
Permanent discontinuation of 
BMS-986205. Subjects may proceed to 
get nivolumab monotherapy.
Permanent discontinuation of 
BMS-986205. However, treatment with 
nivolumab or nivolumab and 
ipilimumab may continue after 
discussion between PI and Medical 
Monitor.
QTcF > 500 msec 
confirmed by at least
1 repeat ECG and at least 
60 msec above baseline
Interrupt if needed to optimize 
electrolyte management. If persists 
after electrolyte optimization (including 
dose modification of BMS-986205, if 
necessary), discontinue.
Subjects may proceed to get nivolumab 
monotherapy.
Interrupt if needed to optimize 
electrolyte management. If persists after 
electrolyte optimization (including dose 
modification of BMS-986205, if 
necessary), discontinue.
However, treatment with nivolumab or 
nivolumab and ipilimumab may 
continue after discussion between PI 
and Medical Monitor.
Any other drug-related 
≥Grade 3 adverse event 
that does not meet
permanent discontinuation 
criteria (Section 4.5.6)
Decrease 1 level of BMS-986205
Decrease 1 level of BMS-986205 in 
combination with same dose of 
nivolumab or nivolumab and 
ipilimumab.
Grade 2 LFT abnormalities 
that do not resolve within 
1 week
Interrupt BMS-986205. Continuation of 
BMS-986205 after recovery at a lower 
dose level may be considered after 
discussion with the 
Study Director/Medical Monitor.
Subjects may proceed to get nivolumab 
monotherapy.
NA
Grade 2 LFT abnormalities 
Interrupt dosing until improvement to 
NA
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Table 4.5.3-1:
Dose Modifications
Dose Modification 
Criteria for Drug-related 
Adverse Events
BMS-986205 Monotherapy 
Modification at the Next Dose (Part 1 
Only)
BMS-986205 Combination 
Modification at the Next Dose 
(Parts 1, 2 and 3)
that resolve in 1 week
Grade 1 or baseline and resume at same 
dose. If recurrence of Grade 2 LFT 
elevations, decrease 1 level.
Abbreviations: AE = adverse event; ECG = electrocardiogram; LFT = liver function test; QTcF = QT interval 
corrected for heart rate using Fridericia’s formula; NA = not applicable; PI = principal investigator.
4.5.4
Dose Delays due to Toxicity
•
Subjects who experience a DLT must have study drug held. Subjects who are required to 
permanently discontinue all study drugs are listed in Section 4.5.6. In addition, all Grade 2 
hepatic, pulmonary, renal, gastrointestinal, and neurological AEs should be evaluated and 
managed per the toxicity management algorithms (Appendix 5). Subjects not meeting 
guidelines for permanent discontinuation will be permitted to resume therapy based on the 
criteria specified below in Section 4.5.5. Subjects eligible to resume study drug will resume 
study drug at the treatment visit following their last received study drug dose.
•
The scheduled tumor assessments (ie, CT/MRI, positron emission tomography [PET], etc.) 
will continue on the specified schedule relative to the subject’s first dose regardless of any 
treatment delay incurred.
Study treatment (BMS-986205, nivolumab and ipilimumab [where applicable]) administration 
should be delayed for the following:
•
Grade 2 non-skin, drug-related AE, with the exception of fatigue, nausea, vomiting and 
anemia
•
Grade 2 drug-related creatinine, AST, ALT and/or Total Bilirubin abnormalities
•
Grade 3 skin, drug-related AE
•
Grade 3 drug-related fatigue, nausea, vomiting, and anemia
•
Grade 3 drug-related laboratory abnormality, with the following exceptions: 
−
Grade 3 lymphopenia or asymptomatic amylase or lipase elevations do not require dose 
delay
−
Grade ≥3 AST, ALT, Total Bilirubin will require dose discontinuation in most cases (see 
Section 4.5.6 for details)
•
Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
investigator, warrants delaying the dose of study medication
In addition, only BMS-986205 should be delayed for the following:
•
Methemoglobin ≥15%
•
Clinically significant elevations in methemoglobin (generally 10% with a normal hemoglobin 
level55) with any associated Grade 3 AE (hypoxia, dyspnea, confusion, etc) attributable to 
sustained elevations of methemoglobin and not attributable to another etiology
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•
QTcF > 500 msec confirmed by at least 1 repeat ECG and at least 60 msec above baseline 
(See Appendix 8).
If nivolumab or (and ipilimumab in Part 3) dosing is delayed for reasons other than study drug 
toxicity (eg, administrative issues, holidays, etc), BMS-986205 dosing should continue 
uninterrupted.
Participants may continue to receive nivolumab (and ipilimumab in Part 3) during dose delays of 
BMS-986205 for elevations of methemoglobin and associated events, as well as QTcF 
prolongations.
For participants with methemoglobin elevations with associated Grade 3 AEs, if contribution of 
nivolumab (and ipilimumab in Part 3) to the associated AE cannot be ruled out (eg, a participant 
with dyspnea in whom pneumonitis has not yet been ruled out), nivolumab (and ipilimumab in 
Part 3)
dosing should be delayed as well. See Section
4.5.7
for
management of 
methemoglobinemia.
If BMS-986205 dosing is delayed, dose reduction may be necessary. See Section 4.5.3.
If dosing is resumed after a delay, BMS-986205 may be resumed as soon as the criteria to 
resume treatment are met (see Section 4.5.5). Nivolumab (and ipilimumab in Part 3) should be 
resumed as soon as possible after criteria to resume treatment are met but may be resumed later 
than BMS-986205 given the differences in each drug’s administration.
Participants who require delay of any study treatment should be re-evaluated weekly or more 
frequently if clinically indicated and resume dosing when criteria to resume are met.
4.5.5
Criteria to Resume Treatment
•
Subjects experiencing AEs not meeting criteria for permanent discontinuation as outlined 
in Section 4.5.6 may resume treatment with study drug under the following criteria:
•
Subjects may resume treatment with study drug when the drug-related 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 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity.
•
Grade 2 eye pain or blurred vision not meeting DLT criteria (Section 4.5.1) must resolve to 
baseline prior to resuming study drug.
•
Drug-related pulmonary toxicity, diarrhea, or colitis must have resolved to baseline before 
treatment is resumed.
•
Subjects with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement may resume treatment.
•
If the criteria to resume treatment are met, the subject should restart treatment at the next 
scheduled time point per protocol.
•
The consideration to re-initiate study drug under these exceptions will be made on a case-by-
case basis after considering the overall benefit/risk profile and in consultation between the
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investigator and the BMS Medical Monitor. 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 therapy following resolution versus discontinuing therapy 
permanently.
•
If treatment with study drug is delayed > 6 weeks from the last dose of BMS-986205 and /or 
nivolumab (and ipilimumab, where applicable), the subject must be permanently 
discontinued from study drug, except as specified in Section 4.5.3.
4.5.6
Guidelines for Permanent Discontinuation
Subjects will be required to permanently discontinue all study drugs for the following AEs:
•
Clinical deterioration, as assessed by the investigator
•
Any occurrence of serotonin syndrome
•
Any Grade 3 non-skin, drug-related AE lasting > 7 days, or recurs with the following 
exceptions for laboratory abnormalities, neurologic toxicity,
drug-related uveitis, 
pneumonitis, bronchospasm, hypersensitivity reactions, infusion reactions, endocrinopathies
(and diarrhea and colitis for subjects receiving ipilimumab):
−
Grade 3 drug-related neurologic toxicity,
uveitis, pneumonitis, bronchospasm,
myocarditis, hypersensitivity reaction, or infusion reaction of any duration requires 
discontinuation; for subjects receiving ipilimumab, Grade 3 diarrhea and colitis of any 
duration also require discontinuation
−
Grade 3 drug-related endocrinopathies, adequately controlled with only physiologic 
hormone replacement do not require discontinuation. Adrenal insufficiency requires 
discontinuation regardless of control with hormone replacement. 
−
Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation 
except:
♦Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding requires 
discontinuation
♦Any drug-related liver function test (LFT) abnormality that meets the following 
criteria require discontinuation:
o
Grade ≥3 drug-related AST, ALT or Total Bilirubin requires discontinuation*
o
Concurrent AST or ALT > 3 x ULN and total bilirubin > 2x ULN
* In most cases of Grade 3 AST or ALT elevation, study treatment will be permanently 
discontinued. If the investigator determines a possible favorable benefit/risk ratio that warrants 
continuation of study treatment, a discussion between the investigator and the BMS Medical 
Monitor/designee must occur.
•
Any Grade 4 drug-related adverse event or laboratory abnormality (including but not limited 
to creatinine, AST, ALT, or Total Bilirubin), except for the following events which do not 
require discontinuation:
−
Grade 4 neutropenia ≤7 days
−
Grade 4 lymphopenia or leukopenia or asymptomatic amylase or lipase
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−
Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 72 
hours of their onset
−
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 dosing delay lasting > 6 weeks will be cause for permanent discontinuation. 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 benefit/risk may justify continued study drug (eg, subject deriving 
clinical benefit who requires prolonged steroid taper for management of non-DLT immune-
related AEs or experiences delays for management of a non-drug-related AE).
•
Accordingly, dosing delays to allow for prolonged steroid tapers to manage drug-related AEs 
are allowed. Additionally, dosing delays > 6 weeks that occur for non-drug-related reasons 
may be allowed if approved by the BMS Medical Monitor.
•
Prior to re-initiating treatment in a subject with a dosing delay lasting > 6 weeks, the BMS
Medical Monitor must be consulted.
•
Tumor assessments should continue as per protocol even if dosing is delayed.
All subjects who discontinue investigational product should comply with protocol-specified 
follow-up procedures as outlined in Section 3.1.2. 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 either a psychiatric or physical illness).
If 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
4.5.7
Detection and Management of Methemoglobinemia
BMS-986205 may produce a p-chloroaniline metabolite. P-chloroaniline has been associated 
with the production of methemoglobin. Symptoms of methemoglobinemia are related to the lack 
of oxygen delivery to tissues and are proportional to the fraction of methemoglobin, as described 
below for subjects with normal hemoglobin levels. 
Symptoms associated with elevations of methemoglobin are as follows:
•
0% to 10% - Usually asymptomatic
•
10% to 20% - Cyanosis without other symptoms
•
20% to 50% - Headache, dyspnea, lightheadedness (possibly syncope), weakness, confusion, 
palpitations, chest pain
•
50% to 70% - Coma, seizures, arrhythmias; acidosis
•
> 70% - Usually death
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Note that subjects with anemia may experience symptoms at lower methemoglobin percentages 
than listed above, depending on the degree of anemia. 
Increasing levels of methemoglobin may confound the results of standard pulse oximeters, with 
values of around 85% reported consistently as methemoglobin levels increase, regardless of the 
true oxygen saturation.
When methemoglobinemia is suspected, part of the diagnostic work-up includes evaluation for 
other disorders that can present with a similar clinical picture, including cardiac and pulmonary 
disease. A fresh peripheral blood sample (either venous or arterial) should be sent for evaluation 
of methemoglobin levels; methemoglobin levels may vary with storage of blood.  
Testing is done at Screening, at least once each treatment cycle, and as clinically indicated. 
The following management recommendations are intended as guidelines for the investigator and 
may be modified based on institutional practices or local standard of care, as appropriate. 
Initial care includes supportive measures and the administration of supplemental oxygen. In mild 
cases, recovery often occurs simply by interrupting the administration of the offending 
medication. Concomitant medication lists should be reviewed for medications besides study 
treatment which can cause methemoglobinemia (see Appendix 10).
Further treatment is generally indicated when the methemoglobin level is above 20% or is 
associated with symptoms.
Intravenous methylene blue is the first-line antidotal agent and works by restoring the oxygen 
carrying capacity of hemoglobin by reduction of methemoglobin from its oxidized state. It is 
given as a 1% solution at a dose of 1 to 2 mg/kg. Most subjects require only 1 dose, and 
symptoms should resolve within 1 hour. Methylene blue may confound the interpretation of 
methemoglobin levels detected by co-oximetry; alternative methods should be used after 
treatment with methylene blue if methemoglobin level monitoring is required. Methylene blue 
should be used with caution in subjects with concurrent use of serotonergic psychiatric 
medications, as this could increase the risk of serotonin syndrome. 
Exchange transfusion and hyperbaric oxygen treatment are second-line options for subjects with 
severe methemoglobinemia whose condition does not respond to methylene blue or who cannot 
be treated with methylene blue. Subject
transfer should occur when life-threatening 
methemoglobinemia that is refractory to treatment occurs in a facility that cannot provide the 
appropriate critical care.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
At scheduled PK sample collection as well as on laboratory evaluation days, BMS-986205 will 
be administered to the subject in the clinical facility. At all other times throughout the study, 
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BMS-986205 will be administered on an out-subject basis, except when subjects are seen in the 
clinic for administration of nivolumab, assessment of AEs, and laboratory evaluation. Trained 
medical personnel will dispense BMS-986205 to the subjects. Treatment compliance will be 
monitored by drug accountability, as well as by recording BMS-986205 administration in the 
subject pill diary, medical record, and CRF. Subjects should bring all drug containers to each 
study visit for drug reconciliation.
4.7.1
Treatment of Drug-related Infusion Reactions
Since nivolumab and ipilimumab contain only human immunoglobulin protein sequences, they 
are unlikely to be immunogenic and induce infusion or hypersensitivity reactions. However, if 
such a reaction were to occur, it might manifest with fever, chills, rigors, headache, rash, 
pruritus, arthralgias, 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.
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 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, nonsteroidal anti-inflammatory 
drugs, narcotics, corticosteroids, bronchodilators, IV fluids); prophylactic medications indicated 
for ≤24 hours.
•
Stop the 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 ipilimumab or nivolumab, 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 nivolumab or ipilimumab
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administrations. 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 1 mg of a 1:1,000 solution for 
subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly for IV 
administration, and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV (or 
equivalent), as needed. Subject should be monitored until the investigator is comfortable that the 
symptoms will not recur. Study drug 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).
4.8
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 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.
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If conditions for destruction cannot be met, the responsible BMS study monitor will make 
arrangements for return of study drug.
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, Table 5.1-9, Table 5.1-10, Table 
5.1-11, Table 5.1-12, Table 5.1-13, Table 5.1-14, and Table 5.1-15. In limited instances, 
scheduled events can occur outside of the indicated timeframes but BMS should be notified.
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Table 5.1-1:
Screening Procedural Outline (CA017003)
Procedure
Screening
Visit 
28 days
Day-14 to 
-1 Visit
Day-1
Visit
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed 
consent is signed. Obtain subject number from IVRS.
Inclusion/Exclusion Criteria
X
Medical History
X
Also include any toxicities or allergies related to previous treatments as well 
as any history of cytochrome b5 reductase deficiency or G6PD deficiency, and 
also record any vaccination received within 30 days of first dose of study 
medication. 
Prior Systemic Therapies
X
Including prior cancer treatment regimens and medications administered 
within 4 weeks of dosing.
Tobacco History/Status
X
Archive Tumor Tissue Samples
X
A block or 20 FFPE unstained slides (generally at least 15 required). With 
Amendment 14, archival tissues from subjects in Parts 1 and 3 may be of any 
age, while for all other subjects blocks must have been obtained less than 1 
year prior to enrollment, and FFPE slides must have been cut less than 4 
months prior to enrollment
Fresh Pre-treatment Tumor Biopsy
X
All subjects in Parts 1 and 3 (as well as subjects in other parts without archival 
tissue meeting the requirements above) will be required to undergo mandatory 
pretreatment biopsies Tumor tissue is to be sent to the central laboratory. 
Safety Assessments
Physical Examination
X
If the screening PE is performed within 24 hours prior to dosing on Day 1,
then a single examination may count as both the screening and predose
evaluation.
Physical Measurements
X
Includes height and weight.
ECOG Performance Status
X
ECOG Performance Status (see Appendix 2).
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Table 5.1-1:
Screening Procedural Outline (CA017003)
Procedure
Screening
Visit 
28 days
Day-14 to 
-1 Visit
Day-1
Visit
Notes
Vital Signs
X
Includes body temperature, seated blood pressure, and heart rate. Blood 
pressure and heart rate should be measured after the subject has been resting 
quietly for at least 5 minutes. 
Oxygen Saturation
X
Pulse oximetry collected at rest. 
Revised International Prognostic 
Index at Time of Initial Diagnosis
X
For subjects with lymphoma only. Refer to Appendix 6.
Electrocardiogram
X
12-lead ECGs should be recorded after the subject has been supine for at least 
5 minutes. 
Laboratory Tests
Laboratory tests listed below must be completed within 2 weeks of Day 1,
unless otherwise noted. 
Chemistry (Excluding LFTs)
X
Includes assessments for sodium, potassium, chloride, total serum calcium, 
magnesium, bicarbonate/carbon dioxide, phosphorus, BUN, creatinine, 
creatinine clearance, fasting glucose, total protein, albumin, amylase, lipase, 
uric acid, ferritin, and LDH.
Methemoglobin
X
Methemoglobin levels to be assessed on arterial or venous blood sample 
(performed locally).
G6PD Deficiency Testing
X
To be performed locally; may be performed at any time during screening
CBC with Differential and Platelets
X
LFT Assessments
X
Includes AST, ALT, total bilirubin, direct bilirubin (only if total bilirubin is 
elevated), alkaline phosphatase, and GGT (only when alkaline phosphatase 
increases to ≥Grade 2).
PT/PTT
X
Urinalysis
X
Urine to be checked for protein, glucose, blood, leukocyte esterase, specific 
gravity, and pH. Microscopic examination of sediment will be done if blood, 
protein, or leukocyte esterase is significantly positive on dipstick.
Thyroid Function Tests
X
TSH with free T3 and T4.
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Table 5.1-1:
Screening Procedural Outline (CA017003)
Procedure
Screening
Visit 
28 days
Day-14 to 
-1 Visit
Day-1
Visit
Notes
Genetic Mutation
X
See Section 5.7. Collected as part of the medical history on appropriate CRFs.
Mutational and Viral Status
X
Document histology, EGFR, ALK, and PD-L1 status for subjects with 
NSCLC. Document BRAF and PD-L1 status for subjects with Melanoma.
SCCHN (oropharyngeal) and cervical cancer subjects only: Sites must 
submit and document prior HPV status within 28 days of dosing. See 
Inclusion Criteria (Section 3.3.1).
Lymphoma subjects only: Results of previous molecular analysis must be 
recorded in the CRFs, if available.
- Document prior EBV status if available.
- For subjects with DLBCL: May include, but are not limited to, BCL2, MYC, 
BCL6, CD10, MUM1, Ki67, BCL2 14:18 translocation, and MYC break-
apart.
CRC subjects only: Sites must submit and document prior MSI testing and 
results. See Inclusion Criteria (Section 3.3.1).
Serology
X
Within 28 days of dosing: hepatitis B surface antigen, hepatitis C antibody (if 
hepatitis C antibody is positive reflex to hepatitis C RNA) or hepatitis C RNA.
Note: Testing for HIV-1 and HIV-2 must be performed at sites where 
mandated by local requirements.
Pregnancy Test
X
WOCBP only 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 drug.
If performed within 24 hours of dosing on Cycle 0 Day 1, then Cycle 0 Day 1
pregnancy test is not required.
Follicle Stimulating Hormone
X
If needed to document postmenopausal status as defined in Section 3.3.3.
Concomitant Medications
X
Collected during the 2 weeks prior to Cycle 1 Day 1.
Clinical Complaints
X
Collected during the 2 weeks prior to Cycle 1 Day 1.
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Table 5.1-1:
Screening Procedural Outline (CA017003)
Procedure
Screening
Visit 
28 days
Day-14 to 
-1 Visit
Day-1
Visit
Notes
Adverse Event Reporting
Monitor for Serious Adverse Events
X
All SAEs must be collected from the date of subject’s written consent until 
100 days post discontinuation of nivolumab or subject’s participation in the 
study if the last scheduled visit occurs at a later time. eSAEs should be 
approved in the BMS EDC tool within 5 business days of entry.
Baseline Efficacy Assessments
See Section 5.4
Abbreviations: ALK = anaplastic lymphoma kinase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb 
Electronic Data Capture; BUN = blood urea nitrogen; CBC = complete blood count; CRC = colorectal cancer; CRF = case report form; CT = computed 
tomography; DLBCL = diffuse large B-cell lymphoma; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EGFR = epidermal growth 
factor receptor; GGT = gamma-glutamyl transferase; HIV = human immunodeficiency virus; HL = Hodgkin’s lymphoma; HPV = human papillomavirus; 
IVRS = Interactive Voice Response System; LDH = lactate dehydrogenase; LFT = liver function test; MRI = magnetic resonance imaging; MSI = 
microsatellite instability; NHL = non-Hodgkin’s lymphoma; NSCLC = non-small cell lung cancer; PD-L1 = programmed death receptor-ligand 1; PE = 
physical examination; PET = positron emission tomography; PT = prothrombin time; PTT = partial thromboplastin time; RNA = ribonucleic acid; SAE = 
serious adverse event; SCCHN = squamous cell carcinoma of the head and neck; TSH = thyroid-stimulating hormone; WOCBP = women of childbearing 
potential.
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Table 5.1-2:
On-treatment Procedure Outline (BMS-986205 Monotherapy in Part 1 Dose Escalation)
Procedure
Cycle 0
Notes
Day 1 
Day 2
Day 8
Day 14
IVRS Assignment
X
Cycle 0 only. BMS-985205 IP assignment.
Once subject eligibility has been confirmed, IVRS 
assignment can be performed within 3 days prior to 
first study drug administration. (Discuss with Sponsor 
if institutional policies and procedures require 
additional lead-time.)
Complete Physical 
Examination
Xb
Predose.
Symptom-directed 
PE
X
X
X
Predose.
Vital Signs and 
Oxygen Saturations
X
Includes temperature, seated blood pressure, and 
heart rate. Blood pressure and heart rate should be 
measured after the subject has been seated quietly for 
at least 5 minutes.
12-lead ECG
X
X
Collect triplicate ECGs on Cycle 0 Day 1 and Cycle 0 
Day 14 at -1 hour pre-dose and 2 and 4 hours post 
dose. All ECG tests during Cycle 0 will be performed 
in triplicates (eg, 1 ECG test equals 3 consecutive 
individual 12-lead ECGs performed allowing a 
5-minute window between ECGs). ECGs should be 
performed after the subject has been resting supine 
for at least 5 minutes and should be completed prior 
to any PK/PD sample blood collections when 
assessments occur at the same time points.
Laboratory Testa
Chemistry 
(Excluding LFTs)
Xb
X
X
Predose; includes assessments for sodium, potassium, 
chloride, total serum calcium, magnesium, 
bicarbonate/carbon dioxide, phosphorus, BUN, 
creatinine, glucose, total protein, albumin, amylase, 
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Table 5.1-2:
On-treatment Procedure Outline (BMS-986205 Monotherapy in Part 1 Dose Escalation)
Procedure
Cycle 0
Notes
Day 1 
Day 2
Day 8
Day 14
lipase, and LDH.
Methemoglobin
X
X*
X
X
If elevated, draw reticulocyte count, LDH, and 
haptoglobin.
Collect predose and at 2 and 4 hours postdose on 
Day 1; if elevated see Section 4.5.7.
Predose on Day 4 (±1 day).
Predose on Days 8 and 14. 
*Only collect predose on Day 2 if elevated either 2 or 
4 hours postdose evaluation on Day 1.
Additional samples as clinically indicated.
CBC with 
Differential and 
Platelets
Xb
X*
X
X
Collect predose.
If methemoglobin is elevated, collect at 2 and 4 hours 
postdose on Day 1.
Predose on Day 4 (±1 day).
*Only collect on Day 2 only if methemoglobin is 
elevated.
LFT Assessments
Xb
X
X
Collect predose. 
Includes AST, ALT, total bilirubin, direct bilirubin 
(only if total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when alkaline 
phosphatase is increased to ≥Grade 2).
Pregnancy Test 
(WOCBP)
X
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 pregnancy test is positive, hold all study drugs and
perform confirmatory testing. If pregnancy is 
confirmed, permanently discontinue all study drugs
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Table 5.1-2:
On-treatment Procedure Outline (BMS-986205 Monotherapy in Part 1 Dose Escalation)
Procedure
Cycle 0
Notes
Day 1 
Day 2
Day 8
Day 14
and immediately notify Sponsor per Section 6.5.
Concomitant 
Medication 
Assessments
X
X
X
X
Review prior to dosing.
Monitor for 
Nonserious Adverse 
Events
X
X
X
X
Nonserious AEs will be collected starting with the 
first dose of study drug and through 100 days after 
completion of study drugs (or 30 days if subject only 
received BMS-986205).
Monitor for Serious 
Adverse Events
X
X
X
X
All SAEs must be collected from the date of subject’s 
written consent until 100 days after completion of 
study drugs (or 30 days if subject only received 
BMS-986205) or subject’s participation in the study 
if the last scheduled visit occurs at a later time. 
eSAEs should be approved in the BMS EDC tool 
within 5 business days of entry.
Pharmacokinetic 
(PK) Assessments
See Section 5.5.4
Performed in all subjects.
Immunogenicity 
Assessments
See Section 5.5.4.
Performed in all subjects.
Biomarker 
Assessments
See Section 5.6 and Table 5.6-1.
See Section 5.6.
Urine for 
p-chloroaniline
See Section 5.4.
Urine (0 to 24 hours) collection start after first dose. 
An approximately 50 mL aliquot of each urine 
collection (0 to 8 hours, 8 to 24 hours) will be frozen 
for shipment.
Study Drug 
Administration
Details regarding preparation and administration are provided in the site 
training materials
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IDO1 INHIBITOR
Table 5.1-2:
On-treatment Procedure Outline (BMS-986205 Monotherapy in Part 1 Dose Escalation)
Procedure
Cycle 0
Notes
Day 1 
Day 2
Day 8
Day 14
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 administration must be performed 
daily. BMS-986205 must be administered with a light 
meal approximately the same time each day.
Pill Diary
X
Pill diary must be completed with each administered daily 
dose of BMS-986205.
Review pill diary during each visit for compliance of 
daily administration of BMS-986205. Collect pill 
diary at the completion of each cycle.
a Subjects who meet discontinuation criteria during or after Cycle 0 will have CBC with differential, platelets, methemoglobin levels, and chemistry with LFTs 
done at the EOT and during the follow-up visit at 7 days.
b For Cycle 0 Day 1 physical exam and laboratory tests do not need to be repeated if completed within the last 72 hours (for all laboratory tests).
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end of 
treatment; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; LDH = lactate 
dehydrogenase; LFT = liver function test; PE = physical examination; SAE = serious adverse event; WOCBP = women of childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
124
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
IVRS Assignment
IVRS 
Assignment
X
Q2W 
Nivo 
dosing 
only
X
Q2W Nivo 
dosing only
Once subject eligibility has been 
confirmed, IVRS assignment can be 
performed within 3 days prior to first 
study drug administration. (Discuss 
with Sponsor if institutional policies 
and procedures require additional 
lead-time.)
Safety Assessments
Complete 
Physical 
Examination
X
X
Symptom-
directed PE
X
Q2W Nivo 
dosing only
X
Revised Protocol No.: 05
Date: 29-Jun-2018
125
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
Vital Signs and 
Oxygen 
Saturations
X
X
X
X
X
Q2W Nivo 
dosing only
X
Includes temperature, seated blood 
pressure, and heart rate. Blood 
pressure and heart rate should be 
measured after the subject has been 
seated quietly for at least 5 minutes.
For nivolumab, VS should be 
obtained prior to the infusion and 
then every 30 minutes (+ 10 minutes) 
until 1 hour following completion of 
the infusion, except on Cycle 1 
Days 1 and 15 (for subjects receiving 
nivolumab 240 mg Q2W) and on 
Cycle 1 Day 1 (for subjects receiving
nivolumab 480 mg Q4W) when VS 
will be obtained until 4 hours 
following 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.
12-lead ECG
X
X
12-lead ECGs should be recorded 
after the subject has been supine for 
at least 5 minutes. ECGs must be 
collected predose on Day 1 of each 
cycle.
Revised Protocol No.: 05
Date: 29-Jun-2018
126
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
Laboratory 
Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated 
on Day 1 for Cycles 1 and onward, if completed within the last 72 hours.
All laboratory testing will be done weekly for Cycle 1 only, unless otherwise specified.
Chemistry 
(Excluding 
LFTs)
X
X
X
X
X
Q2W Nivo 
dosing only
X
Predose; includes assessments for 
sodium, potassium, chloride, total 
serum calcium, magnesium, 
bicarbonate/carbon dioxide,
phosphorus, BUN, creatinine, 
glucose, total protein, albumin, 
amylase, lipase, and LDH.
Methemoglobin
X
X
X
X
X
X
Collect predose.
Collected once per cycle from Cycle 
2 on, or more frequently as clinical
indicated.
If elevated, draw reticulocyte count, 
LDH, and haptoglobin.
CBC with 
Differential and 
Platelets
X
X
X
X
X
Q2W Nivo 
dosing only
X
Predose.
LFT 
Assessments
X
X
X
X
X
Q2W Nivo 
dosing only
X
Predose; includes AST, ALT, total 
bilirubin, direct bilirubin (only if 
total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when 
alkaline phosphatase is increased
to ≥Grade 2).
Revised Protocol No.: 05
Date: 29-Jun-2018
127
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
Thyroid 
Function Tests
X
X
X
If collected at screening do not repeat 
on Cycle 1 Day 1. Collect every 2 
cycles, predose, beginning with 
Cycle 3 Day 1 and at the end of 
treatment.
To include TSH with reflex testing to 
free T3 and free T4 if TSH abnormal. 
Results should be examined by the 
investigator or appropriate designee 
within 48 hours of dose 
administration.
Pregnancy Test 
(WOCBP)
X
Q2W 
Nivo 
dosing 
only
X
Q2W Nivo 
dosing only
X
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 pregnancy test is positive, hold all 
study drugs and perform 
confirmatory testing. If pregnancy is 
confirmed, permanently discontinue 
all study drug and immediately 
notify Sponsor per Section 6.5.
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
Q2W Nivo 
dosing only
X
X
Review prior to dosing.
Revised Protocol No.: 05
Date: 29-Jun-2018
128
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
Monitor for 
Nonserious 
Adverse Events
X
X
X
X
X
Q2W Nivo 
dosing only
X
X
Nonserious AEs will be collected 
starting with the first dose of study 
drug and through 100 days after 
discontinuation of nivolumab.
Monitor for
Serious 
Adverse Events
X
X
X
X
X
Q2W Nivo 
dosing only
X
X
All SAEs must be collected from the 
date of subject’s written consent until 
100 days post discontinuation of 
nivolumab or subject’s participation 
in the study if the last scheduled visit 
occurs at a later time. eSAEs should 
be approved in the BMS EDC tool
within 5 business days of entry.
Sample Collection
Pharmacokineti
c Assessments
See Section 5.5.4.
Immunogenicit
y Assessments
See Section 5.5.4.
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2.
Biopsy window for C1D15 is C1D15 
to C1D28.
Efficacy 
Assessments
See Section 5.4
Imaging
X
See Section 5.4
Revised Protocol No.: 05
Date: 29-Jun-2018
129
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
Study Drug 
Administratio
n
Details regarding preparation and 
administration are provided in the 
site training materials.
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 should be dispensed 
once every cycle.
BMS-986205 administration must be 
performed daily. BMS-986205 must 
be administered with a light meal 
approximately the same time each 
day.
Nivolumab 
Administration
X
Q2W 
Nivo 
dosing 
only
X
Q2W Nivo 
dosing only
For subjects receiving nivolumab 
240 mg Q2W, nivolumab should be 
dispensed at Cycle 1 Day 1 and 
Cycle 1 Day 15. Every 14 days 
during Cycles 2+.
For subjects receiving nivolumab 
480 mg Q4W, nivolumab should be 
dispensed at Day 1 of each cycle.
After the first nivolumab infusion, 
subjects should be monitored per 
local/institutional guidelines.  If no 
such guidelines exist, an observation 
period of 2 hours after the end of the 
nivolumab infusion is suggested.
Revised Protocol No.: 05
Date: 29-Jun-2018
130
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-3:
On-treatment Procedural Outline (BMS-986205 + Nivolumab Part 1 Dose Escalation and Part 2 Dose 
Expansion)
Procedure
Cycle 1 (4 weeks)
Cycles 2+ (4 weeks)
End of 
Treatmenta,b,c
Notes
Day 1
Day 8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Day 22 (+7 
days)d
Pill Diary
X
Pill diary must be completed with each administered daily dose of 
BMS-986205
X
Review pill diary during each visit 
for compliance of daily
administration of BMS-986205. 
Collect pill diary at the completion of 
each cycle and EOT.
a EOT is defined as the visit where 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, Cycle 2 
Day 22) and the start of the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
d Concomitant medication assessment and monitoring for nonserious AEs from Days 22 to 28 must be recorded on the next subject visit. for SAE, the guidance 
provided in Section 6.1 must be followed.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; 
GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working 
Group; LDH = lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = 
Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of 
childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
131
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
IVRS Assignment
IVRS Assignment
X
X
X
X
Once subject eligibility has 
been confirmed, IVRS 
assignment can be 
performed within 3 days 
prior to first study drug 
administration. (Discuss 
with Sponsor if 
institutional policies and 
procedures require 
additional lead-time.)
Safety Assessments
Complete Physical 
Examination
X
X
X
X
Predose
Symptom-directed 
PE
X
X
X
X
X
C2 
only
X
Predose
Vital Signs and 
Oxygen 
Saturations
X
X
X
X
X
X
X
X
C2 
only
X
X
Includes temperature, 
seated blood pressure, and 
heart rate. Blood pressure 
and heart rate should be 
measured after the subject 
has been seated quietly for 
at least 5 minutes.
For nivolumab and 
ipilimumab, VS should be 
obtained prior to the first 
infusion and then every 30
minutes (± 10 minutes) 
Revised Protocol No.: 05
Date: 29-Jun-2018
132
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
until 1 hour following 
completion of the last 
infusion except on Cycle 1 
Day 1 when VS will be 
obtained until 4 hours 
following completion of
both infusions.
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.
12-lead ECG
X
X
12-lead ECGs should be 
recorded after the subject 
has been supine for at least 
5 minutes. ECGs must be 
collected at predose on 
Day 1 of each cycle.
Revised Protocol No.: 05
Date: 29-Jun-2018
133
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
Laboratory Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated on 
Day 1 if completed within the last 72 hours.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
X
C2 
only
X
X
Predose; includes 
assessments for sodium, 
potassium, chloride, total 
serum calcium, 
magnesium, 
bicarbonate/carbon 
dioxide, phosphorus, BUN,
creatinine, glucose, total 
protein, albumin, amylase, 
lipase, and LDH.
Methemoglobin
X
X
X
X
X
X
X
X
C2 
only
X
X
Predose; additional 
assessments as clinically 
indicated.
If elevated, draw 
reticulocyte count, LDH, 
and haptoglobin.
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
X
C2 
only
X
X
Predose.
LFT Assessments
X
X
X
X
X
X
X
X
C2 
only
X
X
Predose; includes AST, 
ALT, total bilirubin, direct 
bilirubin (only if total 
bilirubin is elevated), 
alkaline phosphatase, and 
GGT (only when alkaline 
phosphatase is increased 
Revised Protocol No.: 05
Date: 29-Jun-2018
134
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
to ≥Grade 2).
Thyroid Function 
Tests
X
X
X
X
X
If collected at screening do 
not repeat on Cycle 1 Day 
1.
To include TSH with reflex 
testing to free T3 and free 
T4 if TSH abnormal. 
Results should be 
examined by the 
investigator or appropriate 
designee within 48 hours 
of dose administration.
Pregnancy Test 
(WOCBP)
X
X
X
X
X
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 pregnancy test is 
positive, hold all study 
drugs and perform 
confirmatory testing. If 
pregnancy is confirmed, 
permanently discontinue 
all study drug and 
immediately notify 
Sponsor per Section 6.5.
Revised Protocol No.: 05
Date: 29-Jun-2018
135
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
X
C2 
only
X
X
Review prior to dosing.
Monitor for 
Nonserious 
Adverse Events
X
X
X
X
X
X
X
X
C2 
only
X
X
Nonserious AEs will be 
collected starting with the 
first dose of study drug and 
through 100 days after 
discontinuation of 
nivolumab.
Monitor for 
Serious Adverse 
Events
X
X
X
X
X
X
X
X
C2 
only
X
X
All SAEs must be collected 
from the date of subject’s 
written consent until 100 
days post discontinuation 
of nivolumab or subject’s 
participation in the study if 
the last scheduled visit 
occurs at a later time. 
eSAEs should be approved 
in the BMS EDC tool 
within 5 business days of 
entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Revised Protocol No.: 05
Date: 29-Jun-2018
136
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2
Mandatory on-treatment 
biopsies required for all 
subject. Biopsy window for 
C1D15 is C1D15-C1D28. 
EOT biopsy is optional.
Efficacy 
Assessments
See Section 5.4
Study Drug Administration
Details regarding
preparation and 
administration are provided 
in the site training 
materials.
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 should be 
dispensed on Day 1 and 
Day 29 of each cycle.
BMS-986205 
administration must be 
performed daily. 
BMS̻986205 must be 
administered with a light 
meal approximately the 
same time each day.
Nivolumab 
Administration
X
X
X
X
Nivolumab should be 
dispensed at Day 1 and 
D29 of each cycle.
Revised Protocol No.: 05
Date: 29-Jun-2018
137
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-4:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Melanoma and 
Mixed Tumor Type 
Procedure
Cycle 1 (8 weeks)
Cycles 2+ (8 weeks)
End of 
Treatment
a,b,c
Notes
Day 
1
Day 
8
Day 
15
Day 22
(±2 days)
Day 
29
Day 36
(±2 days)
Day 43
(±2 days)
Day 
1
Day 15
(±2 
days)
Day 
29
After the first nivolumab 
infusion, subjects should 
be monitored per 
local/institutional 
guidelines.  If no such 
guidelines exist, an 
observation period of 
2 hours after the end of the 
nivolumab infusion is 
suggested.
Ipilimumab 
Administration
X
X
Ipilimumab should be 
dispensed on Day 1 of each 
cycle.
Pill Diary
X
Pill diary must be completed with each administered daily dose of BMS-986205
X
Review pill diary during 
each visit for compliance 
of daily administration of 
BMS-986205. Collect pill 
diary at the completion of 
each cycle and EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment.
b For subject 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 
the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
Abbreviations: Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb 
Electronic Data Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of 
treatment; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International 
Working Group; LDH = lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = 
Revised Protocol No.: 05
Date: 29-Jun-2018
138
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of 
childbearing potential
Revised Protocol No.: 05
Date: 29-Jun-2018
139
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-5:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): NSCLC
Procedure
Cycle 1 (6 weeks)
Cycles 2+ (6 weeks)
End of 
Treatmenta,b,c
Notes
Da
y 1
Day 
8
Day 
15
Day 
22
Day 2
9 (±2 
days)
Day 36
(±2 days)
Day 1
Day 15
(±2 days)
Day 
22
IVRS Assignment
IVRS Assignment
X
X
X
X
Once subject eligibility has been 
confirmed, IVRS assignment can 
be performed within 3 days prior 
to first study drug administration.
(Discuss with Sponsor if 
institutional policies and 
procedures require additional 
lead-time.)
Safety Assessments
Complete Physical 
Examination
X
X
X
X
Symptom-directed 
PE
X
X
X
X
C2 only
X
Vital Signs and 
Oxygen Saturations
X
X
X
X
X
X
X
C2 only
X
X
Includes temperature, seated 
blood pressure, and heart rate. 
Blood pressure and heart rate 
should be measured after the 
subject has been seated quietly for 
at least 5 minutes.
For nivolumab and ipilimumab, 
VS should be obtained prior to the 
first infusion and then every 30 
minutes (± 10 minutes) until 
1 hour following completion of 
the last infusion except on Cycle 1 
Day 1 when VS will be obtained 
until 4 hours following 
completion of both infusions.
Revised Protocol No.: 05
Date: 29-Jun-2018
140
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-5:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): NSCLC
Procedure
Cycle 1 (6 weeks)
Cycles 2+ (6 weeks)
End of 
Treatmenta,b,c
Notes
Da
y 1
Day 
8
Day 
15
Day 
22
Day 2
9 (±2 
days)
Day 36
(±2 days)
Day 1
Day 15
(±2 days)
Day 
22
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.
12-lead ECG
X
X
12-lead ECGs should be recorded 
after the subject has been supine 
for at least 5 minutes. ECGs must 
be collected at predose on Day 1 
of each cycle.
Laboratory Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated on 
Day 1 if completed within the last 72 hours.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
C2 only
X
X
Predose; includes assessments for 
sodium, potassium, chloride, total 
serum calcium, magnesium, 
bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, 
glucose, total protein, albumin, 
amylase, lipase, and LDH.
Methemoglobin
X
X
X
X
X
X
X
X
X
Predose; additional assessments as 
clinically indicated.
If elevated, draw reticulocyte 
count, LDH, and haptoglobin.
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
C2 only
X
X
Predose.
Revised Protocol No.: 05
Date: 29-Jun-2018
141
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-5:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): NSCLC
Procedure
Cycle 1 (6 weeks)
Cycles 2+ (6 weeks)
End of 
Treatmenta,b,c
Notes
Da
y 1
Day 
8
Day 
15
Day 
22
Day 2
9 (±2 
days)
Day 36
(±2 days)
Day 1
Day 15
(±2 days)
Day 
22
LFT Assessments
X
X
X
X
X
X
X
C2 only
X
X
Predose; includes AST, ALT, 
total bilirubin, direct bilirubin 
(only if total bilirubin is elevated), 
alkaline phosphatase, and GGT 
(only when alkaline phosphatase 
is increased to ≥Grade 2).
Thyroid Function 
Tests
X
X
X
X
If collected at screening do not 
repeat on Cycle 1 Day 1.
To include TSH with reflex 
testing to free T3 and free T4 if 
TSH abnormal. Results should be 
examined by the investigator or 
appropriate designee within 
48 hours of dose administration.
Pregnancy Test 
(WOCBP)
X
X
X
X
X
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 pregnancy test is positive, hold 
all study drugs and perform 
confirmatory testing. If pregnancy 
is confirmed, permanently 
discontinue all study drug and 
immediately notify Sponsor per 
Section 6.5.
Revised Protocol No.: 05
Date: 29-Jun-2018
142
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-5:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): NSCLC
Procedure
Cycle 1 (6 weeks)
Cycles 2+ (6 weeks)
End of 
Treatmenta,b,c
Notes
Da
y 1
Day 
8
Day 
15
Day 
22
Day 2
9 (±2 
days)
Day 36
(±2 days)
Day 1
Day 15
(±2 days)
Day 
22
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
C2 only
X
X
Review prior to dosing.
Monitor for 
Nonserious Adverse 
Events
X
X
X
X
X
X
X
C2 only
X
X
Nonserious AEs will be collected 
starting with the first dose of 
study drug and through 100 days 
after discontinuation of 
nivolumab.
Monitor for Serious 
Adverse Events
X
X
X
X
X
X
X
C2 only
X
X
All SAEs must be collected from 
the date of subject’s written 
consent until 100 days post 
discontinuation of nivolumab or 
subject’s participation in the study 
if the last scheduled visit occurs at 
a later time. eSAEs should be 
approved in the BMS EDC tool 
within 5 business days of entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2
Mandatory on-treatment biopsies 
required for all subject. Biopsy 
window for C1D15 is C1D15 to 
C1D28. EOT biopsy is optional.
Revised Protocol No.: 05
Date: 29-Jun-2018
143
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-5:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): NSCLC
Procedure
Cycle 1 (6 weeks)
Cycles 2+ (6 weeks)
End of 
Treatmenta,b,c
Notes
Da
y 1
Day 
8
Day 
15
Day 
22
Day 2
9 (±2 
days)
Day 36
(±2 days)
Day 1
Day 15
(±2 days)
Day 
22
Efficacy 
Assessments
See Section 5.4
Study Drug Administration
Details regarding preparation and 
administration are provided in the 
site training materials.
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 should be dispensed 
on Day 1 and Day 22 of every 
cycle
BMS-986205 administration must 
be performed daily. BMS̻986205 
must be administered with a light 
meal approximately the same time 
each day.
Nivolumab 
Administration
X
X
X
X
Nivolumab should be dispensed 
on Days 1 and 22 of each cycle.
After the first nivolumab infusion, 
subjects should be monitored per 
local/institutional guidelines.  If 
no such guidelines exist, an 
observation period of 2 hours after 
the end of the nivolumab infusion 
is suggested.
Ipilimumab 
Administration
X
X
Ipilimumab should be dispensed 
on Day 1 of each cycle.
Pill Diary
X
Pill diary must be completed with each administered daily dose of 
BMS-986205
X
Review pill diary during each visit 
for compliance of daily 
Revised Protocol No.: 05
Date: 29-Jun-2018
144
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-5:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): NSCLC
Procedure
Cycle 1 (6 weeks)
Cycles 2+ (6 weeks)
End of 
Treatmenta,b,c
Notes
Da
y 1
Day 
8
Day 
15
Day 
22
Day 2
9 (±2 
days)
Day 36
(±2 days)
Day 1
Day 15
(±2 days)
Day 
22
administration of BMS-986205. 
Collect pill diary at the 
completion of each cycle and 
EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment.
b For subject 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 
the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; GGT = 
gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working Group; LDH = 
lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = Response Evaluation 
Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of childbearing potential
Revised Protocol No.: 05
Date: 29-Jun-2018
145
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-6:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Bladder
Procedure
Cycles 1 and 2 (each 6 weeks)
Cycles 3+ (4 
weeks
End of 
Treatmenta,b,c
Notes
Day 
1
Day
8
Day
15
Day 
22
Day 29
(±2 days)
Day 36
(±2 days)
Day 
1
Day 15
(±2 
days)
IVRS Assignment
IVRS Assignment
X
X
X
Once subject eligibility has been 
confirmed, IVRS assignment can be 
performed within 3 days prior to first 
study drug administration. (Discuss 
with Sponsor if institutional policies 
and procedures require additional 
lead-time.)
Safety Assessments
Complete Physical 
Examination
X
X
X
Symptom-directed 
PE
C1
only
X
C1 only
C1 only
C3
only
X
Revised Protocol No.: 05
Date: 29-Jun-2018
146
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-6:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Bladder
Procedure
Cycles 1 and 2 (each 6 weeks)
Cycles 3+ (4 
weeks
End of 
Treatmenta,b,c
Notes
Day 
1
Day
8
Day
15
Day 
22
Day 29
(±2 days)
Day 36
(±2 days)
Day 
1
Day 15
(±2 
days)
Vital Signs and 
Oxygen Saturations
X
C1 
only
X
X
C1 only
C1 only
X
C3
only
X
Includes temperature, seated blood 
pressure, and heart rate. Blood 
pressure and heart rate should be 
measured after the subject has been 
seated quietly for at least 5 minutes.
For nivolumab and ipilimumab, VS 
should be obtained prior to the first 
infusion and then every 30 minutes 
(± 10 minutes) until 1 hour following 
completion of the last infusion except 
on Cycle 1 Day 1 when VS will be 
obtained until 4 hours following 
completion of both infusions.
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.
12-lead ECG
X
X
12-lead ECGs should be recorded 
after the subject has been supine for at 
least 5 minutes. ECGs must be 
collected at predose on Day 1 of each 
cycle.
Revised Protocol No.: 05
Date: 29-Jun-2018
147
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-6:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Bladder
Procedure
Cycles 1 and 2 (each 6 weeks)
Cycles 3+ (4 
weeks
End of 
Treatmenta,b,c
Notes
Day 
1
Day
8
Day
15
Day 
22
Day 29
(±2 days)
Day 36
(±2 days)
Day 
1
Day 15
(±2 
days)
Laboratory Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated 
on Day 1 for Cycles 1 and onward if completed within the last 72 hours.
Chemistry 
(Excluding LFTs)
X
C1 
only
X
X
C1 only
X
C3
only
X
Predose; includes assessments for 
sodium, potassium, chloride, total 
serum calcium, magnesium, 
bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, glucose, 
total protein, albumin, amylase, 
lipase, and LDH.
Methemoglobin
X
C1 
only
X
X
X
X
X
Predose; additional assessments as 
clinically indicated.
If abnormal, draw LDH, reticulocyte 
count, and haptoglobin
CBC with 
Differential and 
Platelets
X
C1 
only
X
X
C1 only
X
C3 
only
X
Predose.
LFT Assessments
X
C1 
only
X
X
C1 only
X
C3 
only
X
Predose; includes AST, ALT, total 
bilirubin, direct bilirubin (only if total 
bilirubin is elevated), alkaline 
phosphatase, and GGT (only when 
alkaline phosphatase is increased 
to ≥Grade 2).
Revised Protocol No.: 05
Date: 29-Jun-2018
148
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-6:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Bladder
Procedure
Cycles 1 and 2 (each 6 weeks)
Cycles 3+ (4 
weeks
End of 
Treatmenta,b,c
Notes
Day 
1
Day
8
Day
15
Day 
22
Day 29
(±2 days)
Day 36
(±2 days)
Day 
1
Day 15
(±2 
days)
Thyroid Function 
Tests
X
X
X
X
If collected at screening, do not repeat 
on Cycle 1 Day 1.
To include TSH with reflex testing to 
free T3 and free T4 if TSH abnormal. 
Results should be examined by the 
investigator or appropriate designee 
within 48 hours of dose 
administration.
Pregnancy Test 
(WOCBP)
X
X
X
X
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 pregnancy test is positive, hold all 
study drugs and perform confirmatory 
testing. If pregnancy is confirmed, 
permanently discontinue all study 
drug and immediately notify Sponsor 
per Section 6.5.
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
C3 
only
X
Review prior to dosing.
Monitor for 
Nonserious Adverse 
Events
X
X
X
X
X
X
X
C3 
only
X
Nonserious AEs will be collected 
starting with the first dose of study 
drug and through 100 days after 
discontinuation of nivolumab.
Revised Protocol No.: 05
Date: 29-Jun-2018
149
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-6:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Bladder
Procedure
Cycles 1 and 2 (each 6 weeks)
Cycles 3+ (4 
weeks
End of 
Treatmenta,b,c
Notes
Day 
1
Day
8
Day
15
Day 
22
Day 29
(±2 days)
Day 36
(±2 days)
Day 
1
Day 15
(±2 
days)
Monitor for Serious 
Adverse Events
X
X
X
X
X
X
X
C3 
only
X
All SAEs must be collected from the 
date of subject’s written consent until 
100 days post discontinuation of 
nivolumab or subject’s participation 
in the study if the last scheduled visit 
occurs at a later time. eSAEs should 
be approved in the BMS EDC tool 
within 5 business days of entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2
Mandatory on-treatment biopsies 
required for all subject. Biopsy 
window for C1D15 is C1D15-C1D28. 
EOT biopsy is optional.
Efficacy 
Assessments
See Section 5.4
Study Drug Administration
Details regarding preparation and 
administration are provided in the site 
training materials.
If additional treatment beyond 
48 weeks is given, additional cycles 
should follow the schedule and events 
Revised Protocol No.: 05
Date: 29-Jun-2018
150
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-6:
On-treatment Procedural Outline--Part 3 (BMS-986205, Nivolumab, and Ipilimumab): Bladder
Procedure
Cycles 1 and 2 (each 6 weeks)
Cycles 3+ (4 
weeks
End of 
Treatmenta,b,c
Notes
Day 
1
Day
8
Day
15
Day 
22
Day 29
(±2 days)
Day 36
(±2 days)
Day 
1
Day 15
(±2 
days)
of Cycle 3+ of initial treatment
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 should be dispensed on 
Day 1 and Day 22 of Cycles 1 and 2, 
and the Day 1 of Cycle 3 and beyond.
BMS-986205 administration must be 
performed daily. BMS̻986205 must 
be administered with a light meal 
approximately the same time each 
day.
Nivolumab 
Administration
80 
mg
80 
mg
480 
mg
Nivolumab should be dispensed at 
Days 1 and 22 of Cycles 1 and 2 and 
Day 1 of Cycle 3 and beyond.
After the first nivolumab infusion, 
subjects should be monitored per 
local/institutional guidelines.  If no 
such guidelines exist, an observation 
period of 2 hours after the end of the 
nivolumab infusion is suggested.
Ipilimumab 
Administration
X
X
Ipilimumab should be dispensed on 
Days 1 and 22 of Cycles 1 and 2 only.
Pill Diary
X
Pill diary must be completed with each administered daily 
dose of BMS-986205
X
Review pill diary during each visit for 
compliance of daily administration of 
BMS-986205. Collect pill diary at the 
completion of each cycle and EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment.
b For subject 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 the Week 1 Clinical/Safety Follow-up visit
Revised Protocol No.: 05
Date: 29-Jun-2018
151
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
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 Clinical/Safety Follow-up visit.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; GGT = 
gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working Group; LDH = 
lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = Response Evaluation 
Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
152
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-7:
Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
Notes
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects 
Begins After Completion of 
Clinical/Safety Follow-up 
Every 12 Weeks (± 2 weeks) 
Until 2 years After FIRST 
Dose of Study Drug and a 
Minimum of 12 months after 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (+2weeks) 
Until End of 
Survival 
Follow-up
Safety Assessments
Physical Examination 
X
X
X
Symptom-directed only.
Vital Signs
X
X
X
Includes body temperature, 
seated blood pressure, and 
heart rate. Blood pressure and 
heart rate should be measured 
after the subject has been 
seated quietly for at least 
5 minutes.
Laboratory Tests
Chemistry (Excluding 
LFTs)
X
X
X
Includes assessments for 
sodium, potassium, chloride, 
total serum calcium, 
magnesium, 
bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, 
glucose, total protein, albumin, 
amylase, lipase, and LDH.
Revised Protocol No.: 05
Date: 29-Jun-2018
153
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-7:
Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
Notes
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects 
Begins After Completion of 
Clinical/Safety Follow-up 
Every 12 Weeks (± 2 weeks) 
Until 2 years After FIRST 
Dose of Study Drug and a 
Minimum of 12 months after 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (+2weeks) 
Until End of 
Survival 
Follow-up
Methemoglobin
X
X
X
Only to be drawn if above 
ULN at last assessment; not 
required during follow-up. If 
elevated, draw reticulocyte 
count, LDH, and haptoglobin.
CBC with Differential 
and Platelets
X
X
X
If methemoglobin is elevated, 
collect this assessment at same 
time point(s) as 
methemoglobin collection.
LFT Assessment
Collect at 30, 60, and 100 days following 
the last dose of study drug. For subjects 
with LFT abnormalities following the last 
dose of study drug, consider collecting 
weekly until normalized.
Includes AST, ALT, total 
bilirubin, direct bilirubin (only 
if total bilirubin is elevated), 
alkaline phosphatase, and 
GGT (only when alkaline 
phosphatase is increased to 
≥Grade 2).
Thyroid Function Tests
X
X
X
To include TSH with reflex 
testing to free T3 and free T4
if TSH abnormal.
Revised Protocol No.: 05
Date: 29-Jun-2018
154
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-7:
Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
Notes
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects 
Begins After Completion of 
Clinical/Safety Follow-up 
Every 12 Weeks (± 2 weeks) 
Until 2 years After FIRST 
Dose of Study Drug and a 
Minimum of 12 months after 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (+2weeks) 
Until End of 
Survival 
Follow-up
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 Sponsor 
per Section 6.5.
Adverse Event Reporting and Concomitant Medication Assessments
Monitor for Nonserious 
Adverse Events
X
X
X
Nonserious AEs will be 
collected starting with the first 
dose of study drug and through 
100 days after completion of 
study drugs (or 30 days if 
subject only received BMS-
986205).
Revised Protocol No.: 05
Date: 29-Jun-2018
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Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-7:
Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
Notes
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects 
Begins After Completion of 
Clinical/Safety Follow-up 
Every 12 Weeks (± 2 weeks) 
Until 2 years After FIRST 
Dose of Study Drug and a 
Minimum of 12 months after 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (+2weeks) 
Until End of 
Survival 
Follow-up
Monitor for Serious 
Adverse Events
X
X
X
All SAEs must be collected 
from the date of subject’s 
written consent until 100 days 
after completion of study 
drugs (or 30 days if subject 
only received BMS-986205) 
or subject’s participation in the 
study if the last scheduled visit 
occurs at a later time. eSAEs 
should be approved in the 
BMS EDC tool within 
5 business days of entry.
Concomitant Medication 
Assessments
X
X
X
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.4
Immunogenicity (ADA) 
Assessments
See Section 5.4.
Efficacy Assessments
Diagnostic Imaging
X
X
See Section 5.4
Revised Protocol No.: 05
Date: 29-Jun-2018
156
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-7:
Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
Notes
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects 
Begins After Completion of 
Clinical/Safety Follow-up 
Every 12 Weeks (± 2 weeks) 
Until 2 years After FIRST 
Dose of Study Drug and a 
Minimum of 12 months after 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (+2weeks) 
Until End of 
Survival 
Follow-up
Assessment of Subject 
Survival Status
X
Subject status will be assessed 
by either a clinic visit or 
telephone contact. 
New Subsequent Anti-
cancer Therapies 
X
X
X
X
Any new anti-cancer therapies 
(including surgery and 
radiotherapy) will be recorded.
a Follow-up visits at Days 30, 60, and 100 (± 10 days) should occur after the last dose of study drug or should coincide with the date of discontinuation ± 10
days if date of discontinuation is greater than 30 days after the last dose to monitor for adverse events.
b Follow up after first dose of combination therapy, not monotherapy lead-in.
c Only for subjects with CR, PR, or SD at end of treatment.
Abbreviations: ADA = anti-drug antibody; AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
CBC = complete blood count; CR = complete response; ECOG = Eastern Cooperative Oncology Group; FU = follow-up; GGT = gamma-glutamyl transferase; 
hCG = human chorionic gonadotropin; IWG = International Working Group; LDH = lactate dehydrogenase; LFT = liver function test; PR = partial response; 
RECIST = Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; WOCBP = women of childbearing 
potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
157
Approved
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Approved
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v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-8:
Re-treatment Day 0 Procedural Outline (CA017003)
Procedure
Day 0a
Notes
Safety Assessments
Informed Consent
X
Subjects must re-consented.
Complete Physical Examination
X
If the screening PE is performed within 1 day of dosing on Cycle 1 Day 1, then a single examination
may count as both the screening and predose evaluation.
ECOG Performance Status 
X
ECOG Performance Status (Appendix 2).
Physical Measurements
X
Weight
Vital Signs
X
Includes body temperature, respiratory rate, seated blood pressure, and heart rate. Blood pressure, 
respiratory rate, and heart rate should be measured after the subject has been seated quietly for at least 
5 minutes.
Oxygen Saturation
X
Pulse oximetry collected at rest.
Electrocardiogram
X
12-lead ECG should be recorded after the subject has been supine for at least 5 minutes if not done 
within the last 30 days.
Laboratory Tests
Laboratory tests listed below must be completed within 2 weeks of re-treatment Day 1 unless 
otherwise noted.
Chemistry (Excluding LFTs)
X
Includes assessments for sodium, potassium, chloride, total serum calcium, magnesium, 
bicarbonate/carbon dioxide, phosphorus, BUN, creatinine, creatinine clearance, fasting glucose, total 
protein, albumin, amylase, lipase, uric acid, ferritin, and LDH.
Methemoglobin
X
Methemoglobin levels to be assessed on arterial or venous blood sample (performed locally).
CBC with Differential and Platelets
X
LFT Assessments
X
Includes AST, ALT, total bilirubin, direct bilirubin (only if total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when alkaline phosphatase is increased to ≥Grade 2).
Revised Protocol No.: 05
Date: 29-Jun-2018
158
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v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-8:
Re-treatment Day 0 Procedural Outline (CA017003)
Procedure
Day 0a
Notes
Urinalysis
X
Urine to be checked for protein, glucose, blood, leukocyte esterase, specific gravity, and pH. 
Microscopic examination of sediment will be done if blood, protein, or leukocyte esterase is
significantly positive on dipsticks.
Serology Tests
X
Repeat the following if > 6 months since last treatment: hepatitis B surface antigen, hepatitis C antibody 
(if hepatitis C antibody is positive reflex to hepatitis C RNA), or hepatitis C RNA.
Note: Testing for HIV-1 and HIV-2 must be performed at sites where mandated by local requirements.
Thyroid Function Tests
X
TSH with free T3 and free T4.
Pregnancy Test
X
WOCBP only, 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 drug. 
If performed within 24 hours of dosing on Cycle 1 Day 1, then Cycle 1 Day 1 pregnancy test is not 
required. 
Follicle Stimulating Hormone
X
If needed to document postmenopausal status as defined in Section 3.3.3.
Efficacy Assessments
Diagnostic Imaging
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) only required for subjects with history or symptoms of brain metastases and 
have not had brain imaging within 30 days of anticipated first study drug administration.
Bone Scan Imaging
X
As clinical indicated (eg, subjects with history or symptoms of bone metastases), but bone scans will not 
be considered a modality for assessment for measurable disease.
Clinical Drug Supplies
Subject Registration via IVRS
X
Ensure subject continues to meet eligibility for protocol treatment.
a All procedures for re-treatment eligibility will be performed within 28 days of re-treatment Day 1 dosing unless noted otherwise.
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; CRP = C-reactive 
protein; CT = computed tomography; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; GGT = gamma-glutamyl transferase; 
HIV = human immunodeficiency virus; LDH = lactate dehydrogenase; LFT = liver function test; MRI = magnetic resonance imaging; PE = physical 
examination; RNA = ribonucleic acid; TSH = thyroid-stimulating hormone; WOCBP = women of childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
159
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Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-9:
Re-treatment Procedural Outline (CA017003 Dose Escalation Part 1 and Dose Expansion Part 2)
Procedure
Cycle 1
Cycles 2+
Day 
1
Day 15 
(± 2 
days) 
Day 22-28
(± 2 days)
Day 1
Day 15 (± 
2 days)
Day 22
(± 7 days)d
End of 
Treatmenta,b,c
Notes
Safety Assessments
IVRS
X 
Q2W 
Nivo 
Dosing 
Only
X
Q2W 
Nivo 
Dosing 
Only
Once subject eligibility has been 
confirmed, IVRS assignment can 
be performed within 3 days prior 
to first study drug administration. 
(Discuss with Sponsor if 
institutional policies and 
procedures require additional lead-
time.)
Complete Physical 
Examination
X
X
Predose
Symptom-directed PE
X 
Q2W 
Nivo 
Dosing 
Only
Xa
Predose
Vital Signs
X 
Q2W 
Nivo 
Dosing 
Only
X 
Q2W 
Nivo 
Dosing 
Only
X
Includes temperature, seated blood 
pressure, and heart rate. Blood 
pressure and heart rate should be 
measured after the subject has 
been seated quietly for at least 5 
minutes.
Vital signs will be obtained at 
predose
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.
Revised Protocol No.: 05
Date: 29-Jun-2018
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-9:
Re-treatment Procedural Outline (CA017003 Dose Escalation Part 1 and Dose Expansion Part 2)
Procedure
Cycle 1
Cycles 2+
Day 
1
Day 15 
(± 2 
days) 
Day 22-28
(± 2 days)
Day 1
Day 15 (± 
2 days)
Day 22
(± 7 days)d
End of 
Treatmenta,b,c
Notes
Laboratory Tests
On-study laboratory testing (including pregnancy testing) to be done on site/local, within 24 hours prior to dosing
Chemistry (Excluding 
LFTs)
X 
Q2W 
Nivo 
Dosing 
Only
X
Q2W 
Nivo 
Dosing 
Only
X
Includes assessments for sodium, 
potassium, chloride, total serum 
calcium, magnesium, 
bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, 
glucose, total protein, albumin, 
amylase, lipase, and LDH.
Methemoglobin
X
X
Once per cycle, or more frequently 
as clinically indicated.
CBC with Differential 
and Platelets
X 
Q2W 
Nivo 
Dosing 
Only
X
Q2W 
Nivo 
Dosing 
Only
X
Predose.
Collect if methemoglobin is 
elevated when measurement is 
taken.
LFT Assessments
X
Q2W 
Nivo 
Dosing 
Only
X
Q2W 
Nivo 
Dosing 
Only
X
Predose; includes AST, ALT, total 
bilirubin, direct bilirubin (only if 
total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when 
alkaline phosphatase is increased 
to ≥Grade 2).
Thyroid Function Tests
X 
C2 and 
every 
other 
cycle
X
To include TSH with reflex testing 
to free T3 and free T4 if TSH 
abnormal. Results should be 
examined by the investigator or 
appropriate designee within 
48 hours of dose administration.
During re-treatment, collect 
thyroid function tests every 2 
cycles.
Revised Protocol No.: 05
Date: 29-Jun-2018
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-9:
Re-treatment Procedural Outline (CA017003 Dose Escalation Part 1 and Dose Expansion Part 2)
Procedure
Cycle 1
Cycles 2+
Day 
1
Day 15 
(± 2 
days) 
Day 22-28
(± 2 days)
Day 1
Day 15 (± 
2 days)
Day 22
(± 7 days)d
End of 
Treatmenta,b,c
Notes
Pregnancy Test 
(WOCBP)
X
Q2W 
Nivo 
Dosing 
Only
X
Q2W 
Nivo 
Dosing 
Only
X
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 all study drug and 
immediately notify Sponsor per 
Section 3.5.
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
Q2W 
Nivo 
Dosing 
Only
X
X
Q2W 
Nivo 
Dosing 
Only
X
X
Review prior to dosing.
Monitor for Nonserious 
Adverse Events
X
Q2W 
Nivo 
Dosing 
Only
X
X
Q2W 
Nivo 
Dosing 
Only
X
X
Nonserious AEs will be collected 
starting with the first dose of study 
drug and through 100 days after 
completion of study drugs.
Monitor for Serious 
Adverse Events
X
Q2W 
Nivo 
Dosing 
Only
X
X
Q2W 
Nivo 
Dosing 
Only
X
X
All SAEs must be collected from 
the date of subject’s written 
consent until 100 days after 
completion of study or subject’s 
participation in the study if the last 
scheduled visit occurs at a later 
time. eSAEs should be approved in 
Revised Protocol No.: 05
Date: 29-Jun-2018
162
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-9:
Re-treatment Procedural Outline (CA017003 Dose Escalation Part 1 and Dose Expansion Part 2)
Procedure
Cycle 1
Cycles 2+
Day 
1
Day 15 
(± 2 
days) 
Day 22-28
(± 2 days)
Day 1
Day 15 (± 
2 days)
Day 22
(± 7 days)d
End of 
Treatmenta,b,c
Notes
the BMS EDC tool within 5 
business days of entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Efficacy Assessments
See Section 5.4
Imaging Assessments
C2 and then every 2 
cycles
See Section 5.4
Study Drug 
Administration
Details regarding preparation and 
administration are provided in site 
training materials.
BMS-986205
Administration
X
Daily continuous dosing
BMS-986205 should be dispensed 
once every cycle.
BMS-986205 administration must 
be performed daily. BMS-986205 
must be administered with a light 
meal at approximately the same 
time each day.
Revised Protocol No.: 05
Date: 29-Jun-2018
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v
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-9:
Re-treatment Procedural Outline (CA017003 Dose Escalation Part 1 and Dose Expansion Part 2)
Procedure
Cycle 1
Cycles 2+
Day 
1
Day 15 
(± 2 
days) 
Day 22-28
(± 2 days)
Day 1
Day 15 (± 
2 days)
Day 22
(± 7 days)d
End of 
Treatmenta,b,c
Notes
Nivolumab
Administration
X 
Q2W 
nivolu
mab 
only
X
Q2W 
nivolumab
only
For subjects receiving nivolumab 
240 mg Q2W, nivolumab should 
be dispensed at Cycle 1 Day 1 and 
Cycle 1 Day 15. Every 14 days 
during Cycles 2+.
For subjects receiving nivolumab 
480 mg Q4W, nivolumab should 
be dispensed at Day 1 of each 
cycle.
After the first nivolumab infusion, 
subjects should be monitored per 
local/institutional guidelines.  If no 
such guidelines exist, an 
observation period of 2 hours after 
the end of the nivolumab infusion 
is suggested.
Pill Diary
X
Pill diary must be completed with each administered daily 
dose of BMS-986205.
X
Review pill diary during each visit 
for compliance of daily 
administration of BMS-986205. 
Collect pill diary at the completion 
of each cycle and EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment.
b For subject who complete all scheduled cycles of therapy, the EOT visit will be the same as the last scheduled and completed on-treatment visit (eg, Cycle 2 
Day 22) and the start of the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
d Concomitant medication assessment and monitoring for nonserious AEs from Days 22 to 28 must be recorded on the next subject visit. for SAE, the guidance 
provided in Section 6.1 must be followed.
Revised Protocol No.: 05
Date: 29-Jun-2018
164
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7.0
v
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CRP = C-reactive protein; ECOG = Eastern Cooperative Oncology Group; EOT = end of 
treatment; GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International 
Working Group; LDH = lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; 
RECIST = Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; WOCBP = women of childbearing 
potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
165
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-10:
Re-treatment Procedural Outline Part 3: Melanoma
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 
15
(±2 
days)
Da
y 
29
Day 
43
(±2 
days)
Day 
1
Day 
29
IVRS Assignment
IVRS Assignment
X
X
X
X
Once subject eligibility has been confirmed, IVRS assignment can 
be performed within 3 days prior to first study drug 
administration. (Discuss with Sponsor if institutional policies and 
procedures require additional lead-time.)
Safety Assessments
Complete Physical 
Examination
X
X
X
X
Symptom-directed 
PE
X
X
X
Vital Signs and 
Oxygen Saturations
X
X
X
X
X
X
X
Includes temperature, seated blood pressure, and heart rate. Blood 
pressure and heart rate should be measured after the subject has 
been seated quietly for at least 5 minutes.
For nivolumab and ipilimumab, VS should be obtained prior to the 
first infusion and then every 30 minutes (± 10 minutes) until 
1 hour following completion of the last infusion except on Cycle 1 
Day 1 when VS will be obtained until 4 hours following 
completion of both infusions.
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.
12-lead ECG
X
X
12-lead ECGs should be recorded after the subject has been supine 
for at least 5 minutes. ECGs must be collected at predose on Day 1 
of each cycle.
Revised Protocol No.: 05
Date: 29-Jun-2018
166
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v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-10:
Re-treatment Procedural Outline Part 3: Melanoma
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 
15
(±2 
days)
Da
y 
29
Day 
43
(±2 
days)
Day 
1
Day 
29
Laboratory Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated on 
Day 1 if completed within the last 72 hours.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
Predose; includes assessments for sodium, potassium, chloride, 
total serum calcium, magnesium, bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, glucose, total protein, albumin, 
amylase, lipase, and LDH.
Methemoglobin
X
X
X
X
X
X
X
Predose; additional assessments as clinically indicated.
If elevated, draw reticulocyte count, LDH, and haptoglobin.
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
Predose.
LFT Assessments
X
X
X
X
X
X
X
Predose; includes AST, ALT, total bilirubin, direct bilirubin (only 
if total bilirubin is elevated), alkaline phosphatase, and GGT (only 
when alkaline phosphatase is increased to ≥Grade 2).
Thyroid Function 
Tests
X
X
X
X
X
If collected at screening do not repeat on Cycle 1 Day 1.
To include TSH with reflex testing (free T3 and free T4). Results 
should be examined by the investigator or appropriate designee 
within 48 hours of dose administration.
Pregnancy Test 
(WOCBP)
X
X
X
X
X
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 pregnancy test is positive, hold all study drugs and perform 
confirmatory testing. If pregnancy is confirmed, permanently 
discontinue all study drug and immediately notify Sponsor per 
Section 6.5.
Revised Protocol No.: 05
Date: 29-Jun-2018
167
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-10:
Re-treatment Procedural Outline Part 3: Melanoma
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 
15
(±2 
days)
Da
y 
29
Day 
43
(±2 
days)
Day 
1
Day 
29
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
Review prior to dosing.
Monitor for 
Nonserious 
Adverse Events
X
X
X
X
X
X
X
Nonserious AEs will be collected starting with the first dose of 
study drug and through 100 days after discontinuation of 
nivolumab.
Monitor for 
Serious Adverse 
Events
X
X
X
X
X
X
X
All SAEs must be collected from the date of subject’s written 
consent until 100 days post discontinuation of nivolumab or 
subject’s participation in the study if the last scheduled visit 
occurs at a later time. eSAEs should be approved in the BMS EDC 
tool within 5 business days of entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2.
Efficacy 
Assessments
See Section 5.4
Revised Protocol No.: 05
Date: 29-Jun-2018
168
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v
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1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-10:
Re-treatment Procedural Outline Part 3: Melanoma
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 
15
(±2 
days)
Da
y 
29
Day 
43
(±2 
days)
Day 
1
Day 
29
Study Drug 
Administration
Details regarding preparation and administration are provided in the site training materials.
BMS-986205 
Administration
X
Continuous daily dosing during all 
cycles
BMS-986205 administration must be performed daily. 
BMS̻986205 must be administered with a light meal 
approximately the same time each day.
Nivolumab 
Administration
X
X
X
X
Nivolumab should be dispensed at Day 1 and D29 of each cycle.
After the first nivolumab infusion, subjects should be monitored 
per local/institutional guidelines.  If no such guidelines exist, an 
observation period of 2 hours after the end of the nivolumab 
infusion is suggested.
Ipilimumab 
Administration
X
X
Ipilimumab should be dispensed on Day 1 of each cycle.
Pill Diary
X
Pill diary must be completed with 
each administered daily dose of 
BMS-986205
X
Review pill diary during each visit for compliance of daily 
administration of BMS-986205. Collect pill diary at the 
completion of each cycle and EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment.
b For subject 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 
the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; GGT = 
gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working Group; LDH = 
lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = Response Evaluation 
Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
169
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-11:
Re-treatment Procedural Outline Part 3: NSCLC
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 
days)
Day 
1
Day 
22
IVRS Assignment
IVRS Assignment
X
X
X
X
Once subject eligibility has been confirmed, IVRS 
assignment can be performed within 3 days prior to first 
study drug administration. (Discuss with Sponsor if 
institutional policies and procedures require additional 
lead-time.)
BMS-986205 should be dispensed once every cycle.
Safety Assessments
Complete Physical 
Examination
X
X
X
X
Predose
Symptom-directed 
PE
X
X
X
Vital Signs and 
Oxygen Saturations
X
X
X
X
X
X
X
Includes temperature, seated blood pressure, and heart 
rate. Blood pressure and heart rate should be measured 
after the subject has been seated quietly for at least 5 
minutes.
For nivolumab and ipilimumab, VS should be obtained 
prior to the first infusion and then every 30 minutes 
(± 10 minutes) until 1 hour following completion of the 
last infusion except on Cycle 1 Day 1 when VS will be 
obtained until 4 hours following completion of both 
infusions.
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.
Revised Protocol No.: 05
Date: 29-Jun-2018
170
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-11:
Re-treatment Procedural Outline Part 3: NSCLC
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 
days)
Day 
1
Day 
22
12-lead ECG
X
X
12-lead ECGs should be recorded after the subject has 
been supine for at least 5 minutes. ECGs must be collected 
at predose on Day 1 of each cycle.
Laboratory Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated on 
Day 1 if completed within the last 72 hours.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
X
X
Predose; includes assessments for sodium, potassium, 
chloride, total serum calcium, magnesium, 
bicarbonate/carbon dioxide, phosphorus, BUN, creatinine, 
glucose, total protein, albumin, amylase, lipase, and LDH.
Methemoglobin
X
X
X
X
X
X
X
Predose; additional assessments as clinically indicated.
If elevated, draw reticulocyte count, LDH, and 
haptoglobin.
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
X
Predose.
LFT Assessments
X
X
X
X
X
X
X
Predose; includes AST, ALT, total bilirubin, direct 
bilirubin (only if total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when alkaline phosphatase is 
increased to ≥Grade 2).
Thyroid Function 
Tests
X
X
X
X
If collected at screening, do not repeat on Cycle 1 Day 1.
To include TSH with reflex testing (free T3 and free T4). 
Results should be examined by the investigator or 
appropriate designee within 48 hours of dose 
administration.
Pregnancy Test 
(WOCBP)
X
X
X
X
X
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.
Revised Protocol No.: 05
Date: 29-Jun-2018
171
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-11:
Re-treatment Procedural Outline Part 3: NSCLC
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 
days)
Day 
1
Day 
22
If pregnancy test is positive, hold all study drugs and 
perform confirmatory testing. If pregnancy is confirmed, 
permanently discontinue all study drug and immediately 
notify Sponsor per Section 6.5.
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
Review prior to dosing.
Monitor for 
Nonserious 
Adverse Events
X
X
X
X
X
X
X
Nonserious AEs will be collected starting with the first 
dose of study drug and through 100 days after 
discontinuation of nivolumab.
Monitor for 
Serious Adverse 
Events
X
X
X
X
X
X
X
All SAEs must be collected from the date of subject’s 
written consent until 100 days post discontinuation of 
nivolumab or subject’s participation in the study if the last 
scheduled visit occurs at a later time. eSAEs should be 
approved in the BMS EDC tool within 5 business days of 
entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2.
Efficacy 
See Section 5.4
Revised Protocol No.: 05
Date: 29-Jun-2018
172
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-11:
Re-treatment Procedural Outline Part 3: NSCLC
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 
days)
Day 
1
Day 
22
Assessments
Study Drug Administration
Details regarding preparation and administration are 
provided in the site training materials.
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 administration must be performed daily. 
BMS̻986205 must be administered with a light meal 
approximately the same time each day.
Nivolumab 
Administration
X
X
X
X
Nivolumab should be dispensed at Day 1 and D22 of each 
cycle.
After the first nivolumab infusion, subjects should be 
monitored per local/institutional guidelines. If no such 
guidelines exist, an observation period of 2 hours after the 
end of the nivolumab infusion is suggested.
Ipilimumab 
Administration
X
X
Ipilimumab should be dispensed on Day 1 of each cycle.
Pill Diary
X
Pill diary must be completed with each 
administered daily dose of BMS-986205
X
Review pill diary during each visit for compliance of daily 
administration of BMS-986205. Collect pill diary at the 
completion of each cycle and EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment0.
b For subject 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 
the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; GGT = 
gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working Group; LDH = 
Revised Protocol No.: 05
Date: 29-Jun-2018
173
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = Response Evaluation 
Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
174
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-12:
Re-treatment Procedural Outline Part 3: Bladder
Procedure
Cycles 1 and 2
Cycles 3+
End of Treatment
a,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 days)
Day 1
Day 
15
IVRS Assignment
X
X
X
X
Once subject eligibility has been confirmed, IVRS 
assignment can be performed within 3 days prior to 
first study drug administration. (Discuss with 
Sponsor if institutional policies and procedures 
require additional lead-time.)
Safety Assessments
Complete Physical 
Examination
X
X
X
Predose
Symptom-directed 
PE
X
X
C3
X
Vital Signs and 
Oxygen Saturations
X
X
X
X
X
C3
X
Includes temperature, seated blood pressure, and 
heart rate. Blood pressure and heart rate should be 
measured after the subject has been seated quietly 
for at least 5 minutes.
For nivolumab and ipilimumab, VS should be 
obtained prior to the first infusion and then every 30 
minutes (± 10 minutes) until 1 hour following 
completion of the last infusion except on Cycle 1 
Day 1 when VS will be obtained until 4 hours 
following completion of both infusions.
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.
12-lead ECG
X
X
12-lead ECGs should be recorded after the subject 
has been supine for at least 5 minutes. ECGs must be 
collected at predose on Day 1 of each cycle.
Revised Protocol No.: 05
Date: 29-Jun-2018
175
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-12:
Re-treatment Procedural Outline Part 3: Bladder
Procedure
Cycles 1 and 2
Cycles 3+
End of Treatment
a,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 days)
Day 1
Day 
15
Laboratory Tests
On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated on 
Day 1 if completed within the last 72 hours.
Chemistry 
(Excluding LFTs)
X
X
X
X
X
C3
X
Predose; includes assessments for sodium, 
potassium, chloride, total serum calcium, 
magnesium, bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, glucose, total protein, 
albumin, amylase, lipase,, and LDH.
Methemoglobin
X
X
X
X
X
X
Predose; additional assessments as clinically 
indicated.
If elevated, draw reticulocyte count, LDH, and 
haptoglobin.
CBC with 
Differential and 
Platelets
X
X
X
X
X
C3
X
Predose.
LFT Assessments
X
X
X
X
X
C3
X
Predose; includes AST, ALT, total bilirubin, direct 
bilirubin (only if total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when alkaline 
phosphatase is increased to ≥Grade 2).
Thyroid Function 
Tests
X
X
X
X
If collected at screening, do not repeat on Cycle 1 
Day 1.
To include TSH with reflex testing  to free T3 and 
free T4 if TSH abnormal. Results should be 
examined by the investigator or appropriate designee 
within 48 hours of dose administration.
Revised Protocol No.: 05
Date: 29-Jun-2018
176
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-12:
Re-treatment Procedural Outline Part 3: Bladder
Procedure
Cycles 1 and 2
Cycles 3+
End of Treatment
a,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 days)
Day 1
Day 
15
Pregnancy Test 
(WOCBP)
X
X
X
X
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 pregnancy test is positive, hold all study drugs and 
perform confirmatory testing. If pregnancy is 
confirmed, permanently discontinue all study drug 
and immediately notify Sponsor per Section 6.5.
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
C3
X
Review prior to dosing.
Monitor for 
Nonserious 
Adverse Events
X
X
X
X
X
C3
X
Nonserious AEs will be collected starting with the 
first dose of study drug and through 100 days after 
discontinuation of nivolumab.
Monitor for 
Serious Adverse 
Events
X
X
X
X
X
C3
X
All SAEs must be collected from the date of 
subject’s written consent until 100 days post 
discontinuation of nivolumab or subject’s 
participation in the study if the last scheduled visit 
occurs at a later time. eSAEs should be approved in 
the BMS EDC tool within 5 business days of entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Biomarker 
Assessments
See Section 5.6 and Table 5.6-2.
Revised Protocol No.: 05
Date: 29-Jun-2018
177
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-12:
Re-treatment Procedural Outline Part 3: Bladder
Procedure
Cycles 1 and 2
Cycles 3+
End of Treatment
a,b,c
Notes
Day 
1
Day 8
(±2 days)
Day 
22
Day 29
(±2 days)
Day 1
Day 
15
Efficacy 
Assessments
See Section 5.4
Study Drug Administration
Details regarding preparation and administration are 
provided in the site training materials.
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 administration must be performed 
daily. BMS̻986205 must be administered with a 
light meal approximately the same time each day.
Nivolumab 
Administration
80 
mg
80 
mg
480 
mg
Nivolumab should be dispensed at Days 1 and 22 of 
Cycles 1 and 2 and Day 1 of Cycle 3 and beyond.
After the first nivolumab infusion, subjects should 
be monitored per local/institutional guidelines.  If no 
such guidelines exist, an observation period of 
2 hours after the end of the nivolumab infusion is 
suggested.
Ipilimumab 
Administration
X
X
Ipilimumab should be dispensed on Days 1 and 22 of 
Cycles 1 and 2 only.
Pill Diary
X
Pill diary must be completed with each 
administered daily dose of BMS-986205
X
Review pill diary during each visit for compliance of 
daily administration of BMS-986205. Collect pill 
diary at the completion of each cycle and EOT.
a EOT is defined as the visit where decision is made to discontinue the subject from treatment.
b For subject 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 the Week 1 Clinical/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 Clinical/Safety Follow-up visit.
Revised Protocol No.: 05
Date: 29-Jun-2018
178
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; GGT = 
gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working Group; LDH = 
lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = Response Evaluation 
Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of childbearing potential.
Revised Protocol No.: 05
Date: 29-Jun-2018
179
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-13:
Re-treatment Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects Begins After 
Completion of Clinical/Safety 
Follow-up Every 12 Weeks (± 2 
weeks) until 2 Years After First 
Dose of Study Drug and a 
Minimum of 12 months After 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (± 2 weeks) 
Until End of 
Survival 
Follow-up
Notes
Safety Assessments
Physical Examination
X 
X 
X 
Symptom directed 
only.
Vital Signs
X 
X 
X 
.
Includes body 
temperature, seated 
blood pressure, and 
heart rate. Blood 
pressure and heart 
rate should be 
measured after the 
subject has been 
seated quietly for at 
least 5 minutes
Laboratory Tests
Chemistry (Excluding 
LFTs)
X
X
X
Includes assessments 
for sodium, 
potassium, chloride, 
total serum calcium, 
magnesium, 
bicarbonate/carbon 
dioxide, phosphorus, 
BUN, creatinine, 
glucose, total protein, 
albumin, amylase, 
lipase, and LDH, 
Revised Protocol No.: 05
Date: 29-Jun-2018
180
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-13:
Re-treatment Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects Begins After 
Completion of Clinical/Safety 
Follow-up Every 12 Weeks (± 2 
weeks) until 2 Years After First 
Dose of Study Drug and a 
Minimum of 12 months After 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (± 2 weeks) 
Until End of 
Survival 
Follow-up
Notes
excluding AST, 
ALT, total bilirubin, 
direct bilirubin (only 
if total bilirubin is 
elevated), alkaline 
phosphatase, and 
GGT (only when 
alkaline phosphatase 
is increased 
to ≥Grade 2).
Methemoglobin
X
X
X
Only to be if above 
ULN at last 
assessment; not 
required during 
follow-up. 
CBC with Differential and 
Platelets
X
X
X
If methemoglobin is 
elevated, collect this 
assessment at same 
time point(s) as 
methemoglobin 
collection.
LFT Assessment
Collect at 30, 60, and 100 days following the 
last dose of study drug. For subjects with 
LFT abnormalities following the last dose of 
study drug, consider collecting weekly until 
normalized.
Includes AST, ALT, 
total bilirubin, direct 
bilirubin (only if total 
bilirubin is elevated), 
alkaline phosphatase, 
Revised Protocol No.: 05
Date: 29-Jun-2018
181
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-13:
Re-treatment Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects Begins After 
Completion of Clinical/Safety 
Follow-up Every 12 Weeks (± 2 
weeks) until 2 Years After First 
Dose of Study Drug and a 
Minimum of 12 months After 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (± 2 weeks) 
Until End of 
Survival 
Follow-up
Notes
and GGT (only when 
alkaline phosphatase 
is ≥Grade 2).
Thyroid Function Tests
X
X
X
To include TSH with 
reflex testing (free T3 
and free T4).
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 
Sponsor per 
Section 6.4.
Adverse Event Reporting and Concomitant Medication Assessments
Monitor for Nonserious 
Adverse Events
X
X
X
Nonserious AEs will 
be collected starting 
with the first dose of 
Revised Protocol No.: 05
Date: 29-Jun-2018
182
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-13:
Re-treatment Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects Begins After 
Completion of Clinical/Safety 
Follow-up Every 12 Weeks (± 2 
weeks) until 2 Years After First 
Dose of Study Drug and a 
Minimum of 12 months After 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (± 2 weeks) 
Until End of 
Survival 
Follow-up
Notes
study drug and 
through 100 days 
after completion of 
study drugs (or 
30 days if subject 
only received 
BMS-986205).
Monitor for Serious 
Adverse Events
X
X
X
All SAEs must be 
collected from the 
date of subject’s 
written consent until 
100 days after 
completion of study 
drugs (or 30 days if 
subject only received 
BMS-986205) or 
subject’s 
participation in the 
study if the last 
scheduled visit 
occurs at a later time. 
eSAEs should be 
approved in the BMS 
EDC tool within 
5 business days of 
entry.
Revised Protocol No.: 05
Date: 29-Jun-2018
183
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-13:
Re-treatment Follow-up Procedural Outline (CA017003)
Procedure
Clinical/Safety Follow-up
Survival/Long-term Follow-up
Response 
Follow-upc
FU 1
30 daysa
(± 10 days) 
FU 2
60 days 
(± 10 days)
FU 3
100 days 
(± 10 days)
All Subjects Begins After 
Completion of Clinical/Safety 
Follow-up Every 12 Weeks (± 2 
weeks) until 2 Years After First 
Dose of Study Drug and a 
Minimum of 12 months After 
LAST Dose of Study Drugb
Begins After 
Completion of 
Safety Follow-
up (± 2 weeks) 
Until End of 
Survival 
Follow-up
Notes
Concomitant Medication 
Assessments
X
X
X
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity (ADA) 
Assessments
See Section 5.5.4
Efficacy Assessments
Diagnostic Imaging
X
X
See Section 5.4
Assessment of Subject 
Survival Status
X
Subject status will be 
assessed by either a 
clinic visit or 
telephone contact.
New Subsequent Anti-
cancer Therapies 
X
X
X
X
Any new anti-cancer
therapies (including 
surgery and 
radiotherapy) will be 
recorded.
a Follow-up visits at Days 30, 60, and 100 (± 10 days) should occur after the last dose of study drug or should coincide with the date of discontinuation ±  10
days if date of discontinuation is greater than 30 days after the last dose to monitor for adverse events.
b Follow up after first dose of combination therapy, not monotherapy lead-in.
Revised Protocol No.: 05
Date: 29-Jun-2018
184
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v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
c Only for SD, PR, and CR subjects at end of study.
Abbreviations: ADA = anti-drug antibody; AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
CBC = complete blood count; CR = complete response; CRP = C-reactive protein; ECOG = Eastern Cooperative Oncology Group; FU = follow-up; 
GGT = gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IWG = International Working Group; LDH = lactate dehydrogenase; LFT = liver 
function test; PR = partial response; RECIST = Response Evaluation Criteria In Solid Tumors; SAE = serious adverse event; SD = stable disease; TSH = thyroid-
stimulating hormone; WOCBP = women of childbearing potential
.
Revised Protocol No.: 05
Date: 29-Jun-2018
185
Approved
7.0
v
Approved
1.0
v


Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-14:
On-treatment Procedure Outline QTc Substudy (Monotherapy BMS-986205)
Procedure
Cycle 0
Notes
Day -1
Day 1 
Day 2
Day 8
Day 14
IVRS Assignment
X
Cycle 0 only. BMS-985205 IP 
assignment.
Once subject eligibility has been 
confirmed, IVRS assignment can be 
performed within 3 days prior to first 
study drug administration. (Discuss with 
Sponsor if institutional policies and 
procedures require additional lead-time.)
Complete Physical 
Examination
X b
Predose
Symptom-directed 
PE
X
X
X
Predose
Vital Signs and 
Oxygen Saturations
X
Includes temperature, seated blood 
pressure, and heart rate. Blood pressure 
and heart rate should be measured after 
the subject has been seated quietly for at 
least 5 minutes.
12-lead ECG
(Holter)
X
X
12-lead continuous ECG (Holter) 
monitoring will be started no later than 1 
hour predose and continue until at least 
6.5 hours postdose. From these 
recordings, after transmission to the 
central ECG laboratory, triplicate ECGs 
will be extracted during a 5-minute 
sampling period starting at the nominal 
times specified. Each 5-minute sampling 
period should be preceded by at least 10 
minutes of rest in a supine position, 
which would be continued until the end 
of the 5-minute sampling period.
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CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-14:
On-treatment Procedure Outline QTc Substudy (Monotherapy BMS-986205)
Procedure
Cycle 0
Notes
Day -1
Day 1 
Day 2
Day 8
Day 14
12-lead ECGs
X
X
For monitoring subject safety, at least 
5 minutes after the end of triplicate ECG 
period at 4 hours post dose on Cycle 0 
Days 1 and 14, the site’s standard ECG 
machine will be connected using dual-
snap electrodes without interrupting the 
Holter monitoring.
Laboratory Testa On-study laboratory tests (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be repeated on Day 1 
for Cycles 1 and onward, if completed within 72 hours. All laboratory testing will be done weekly for Cycle 1 only, unless otherwise specified.
Chemistry 
(Excluding LFTs)
Xb
X
X
Predose; includes assessments for 
sodium, potassium, chloride, total serum 
calcium, magnesium, 
bicarbonate/carbon dioxide, phosphorus, 
BUN, creatinine, glucose, total protein, 
albumin, amylase, lipase, and LDH.
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Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-14:
On-treatment Procedure Outline QTc Substudy (Monotherapy BMS-986205)
Procedure
Cycle 0
Notes
Day -1
Day 1 
Day 2
Day 8
Day 14
Methemoglobin
X
X*
X
X
If elevated, draw reticulocyte count, 
LDH, and haptoglobin.
Collect at predose and 2 and 4 hours 
postdose on Day 1; if elevated see 
Section 4.5.7.
*Only collect predose on Day 2 if 
elevated either 2 or 4 hours postdose 
evaluation on Day 1. 
Please collect predose on Day 4 (±1
Day).
Predose on Days 8 and 14.
Additional collections as clinically 
indicated.
CBC with 
Differential and 
Platelets
Xb
X
X
X
Collect predose.
If methemoglobin is elevated, collect at 
2 and 4 hours postdose on Day 1.
Collect on Day 2 only if methemoglobin 
is elevated.
Please collect predose on Day 4 (±1
Day). 
LFT Assessments
Xb
X
X
Includes AST, ALT, total bilirubin, 
direct bilirubin (only if total bilirubin is 
elevated), alkaline phosphatase, and 
GGT (only when alkaline phosphatase is 
increased to ≥Grade 2).
Revised Protocol No.: 05
Date: 29-Jun-2018
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Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-14:
On-treatment Procedure Outline QTc Substudy (Monotherapy BMS-986205)
Procedure
Cycle 0
Notes
Day -1
Day 1 
Day 2
Day 8
Day 14
Pregnancy Test 
(WOCBP)
X
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 pregnancy test is positive, hold all 
study drugs and perform confirmatory 
testing. If pregnancy is confirmed, 
permanently discontinue all study drug 
and immediately notify Sponsor per 
Section 6.5.
Concomitant 
Medication 
Assessments
X
X
X
X
Review prior to dosing.
Monitor for 
Nonserious Adverse 
Events
X
X
X
X
Nonserious AEs will be collected 
starting with the first dose of study drug 
and 30 days after discontinuation of 
study drug.
Monitor for Serious 
Adverse Events
X
X
X
X
All SAEs must be collected from the 
date of subject’s written consent until 30 
days post discontinuation of study drug
or subject’s participation in the study if 
the last scheduled visit occurs at a later 
time. eSAEs should be approved in the 
BMS EDC tool within 5 business days 
of entry.
Pharmacokinetic 
(PK) Assessments
X
See Table 5.5.4.3-1 for details on PK 
collection
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CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-14:
On-treatment Procedure Outline QTc Substudy (Monotherapy BMS-986205)
Procedure
Cycle 0
Notes
Day -1
Day 1 
Day 2
Day 8
Day 14
Study Drug 
Administration
Details regarding preparation and administration are provided in the site 
training materials
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 administration must be 
performed daily. BMS-986205 must be 
administered with a light meal 
approximately the same time each day.
Pill Diary
X
Pill diary must be completed with each administered 
daily dose of BMS-986205
Review pill diary during each visit for 
compliance of daily administration of 
BMS-986205. Collect pill diary at the 
completion of each cycle.
a Subjects who meet discontinuation criteria during or after Cycle 0 will have CBC with differential, platelets, methemoglobin levels, and chemistry with LFTs 
done at the EOT and during the follow-up visit at 7 days.
b For Cycle 0 Day 1, laboratory tests and physical exam do not need to be repeated if completed within the last 72 hours (for all laboratory tests).
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; ECG = electrocardiogram; EOT = end of treatment; GGT = gamma-glutamyl transferase; 
hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; LDH = lactate dehydrogenase; LFT = liver function test; PE = physical 
examination; SAE = serious adverse event; WOCBP = women of childbearing potential.
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CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-15:
On-treatment Procedural Table for QTc Substudy (BMS-986205 + Nivolumab)
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 1
Day 
8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Days 22
(+7 days)d
IVRS Assignment
IVRS 
Assignment
X
X
Once subject eligibility has been 
confirmed, IVRS assignment can be 
performed within 3 days prior to first 
study drug administration. (Discuss 
with Sponsor if institutional policies 
and procedures require additional 
lead-time.)
For subjects receiving nivolumab 
480 mg Q4W, nivolumab should be 
dispensed at Day 1 of each cycle.
Safety Assessments
Complete 
Physical 
Examination
X
X
Symptom-
directed PE
X
X
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CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-15:
On-treatment Procedural Table for QTc Substudy (BMS-986205 + Nivolumab)
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 1
Day 
8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Days 22
(+7 days)d
Vital Signs and 
Oxygen 
Saturations
X
X
X
X
X
X
Includes temperature, seated blood 
pressure, and heart rate. Blood 
pressure and heart rate should be 
measured after the subject has been 
seated quietly for at least 5 minutes. 
For nivolumab, VS should be 
obtained prior to the infusion and 
then every 30 minutes (+ 10
minutes) until 1 hour following 
completion of the infusion, except on 
Cycle 1 Days 1 and 15 (for subjects 
receiving nivolumab 240 mg Q2W) 
and on Cycle 1 Day 1 (for subjects 
receiving nivolumab 480 mg Q4W) 
when VS will be obtained until 
4 hours following 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.
12-lead ECG
X
X
12-lead ECGs should be recorded 
after the subject has been supine for 
at least 10 minutes. ECGs must be 
collected predose on Day 1 of each 
cycle.
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CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-15:
On-treatment Procedural Table for QTc Substudy (BMS-986205 + Nivolumab)
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 1
Day 
8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Days 22
(+7 days)d
Laboratory 
Tests
On-study laboratory testing (including pregnancy testing) to be done on site/local. Laboratory tests do not need to be 
repeated on Day 1 for Cycles 1 and onward, if completed within the last 72 hours.
All laboratory testing will be done weekly for Cycle 1 only, unless otherwise specified.
Chemistry 
(Excluding 
LFTs)
X
X
X
X
X
X
Predose; includes assessments for 
sodium, potassium, chloride, total 
serum calcium, magnesium, 
bicarbonate/carbon dioxide, 
phosphorus, BUN, creatinine, 
glucose, total protein, albumin, 
amylase, lipase, and LDH.
Methemoglobin
X
X
X
X
X
X
Collect predose Cycle 1 Days 1, 8, 
15, 22, each subsequent Cycle Day 1 
and EOT.
If elevated, draw reticulocyte count, 
LDH, and haptoglobin.
Additional collections to be drawn as 
clinically indicated.
CBC with 
Differential and 
Platelets
X
X
X
X
X
X
Predose.
LFT 
Assessments
X
X
X
X
X
X
Predose; includes AST, ALT, total 
bilirubin, direct bilirubin (only if 
total bilirubin is elevated), alkaline 
phosphatase, and GGT (only when 
alkaline phosphatase is increased 
to ≥Grade 2).
Thyroid 
Function Tests
X
X
X
If collected at screening, do not 
repeat on Cycle 1 Day 1. Collect 
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CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-15:
On-treatment Procedural Table for QTc Substudy (BMS-986205 + Nivolumab)
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 1
Day 
8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Days 22
(+7 days)d
every 2 cycles, predose, beginning 
with Cycle 3 Day 1 and at the end of 
treatment.
To include TSH with reflex testing 
(free T3 and free T4). Results should 
be examined by the investigator or 
appropriate designee within 48 hours 
of dose administration.
Pregnancy Test 
(WOCBP)
X
X
X
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 pregnancy test is positive, hold all 
study drugs and perform 
confirmatory testing. If pregnancy is 
confirmed, permanently discontinue 
all study drug and immediately 
notify Sponsor per Section 6.5.
Adverse Event Reporting and Concomitant Medication Assessments
Concomitant 
Medication 
Assessments
X
X
X
X
X
X
X
X
Review prior to dosing.
Monitor for 
Nonserious 
Adverse Events
X
X
X
X
X
X
X
X
Nonserious AEs will be collected 
starting with the first dose of study 
drug and through 100 days after 
completion of study drugs (or 30 
days if subject only received BMS-
Revised Protocol No.: 05
Date: 29-Jun-2018
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Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-15:
On-treatment Procedural Table for QTc Substudy (BMS-986205 + Nivolumab)
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 1
Day 
8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Days 22
(+7 days)d
986205).
Monitor for
Serious Adverse 
Events
X
X
X
X
X
X
X
X
All SAEs must be collected from the 
date of subject’s written consent 
until 100 days after completion of 
study drugs (or 30 days if subject 
only received BMS-986205) or 
subject’s participation in the study if 
the last scheduled visit occurs at a 
later time. eSAEs should be 
approved in the BMS EDC tool 
within 5 business days of entry.
Sample Collection
Pharmacokinetic 
Assessments
See Section 5.5.4
Immunogenicity 
Assessments
See Section 5.5.4
Efficacy 
Assessments
See Section 5.4
Revised Protocol No.: 05
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Clinical Protocol
CA017003
BMS-986205
IDO1 INHIBITOR
Table 5.1-15:
On-treatment Procedural Table for QTc Substudy (BMS-986205 + Nivolumab)
Procedure
Cycle 1
Cycles 2+
End of 
Treatmenta,b,c
Notes
Day 1
Day 
8
Day 
15 
Day 
22 
Day 1 
Day15 
(±2 days)
Days 22
(+7 days)d
Study Drug 
Administration
Details regarding preparation and 
administration are provided in the 
site training materials.
BMS-986205 
Administration
X
Continuous daily dosing during all cycles
BMS-986205 administration must be 
performed daily. BMS-986205 must 
be administered with a light meal 
approximately the same time each 
day.
Nivolumab 
Administration
X
X
After the first nivolumab infusion, 
subjects should be monitored per 
local/institutional guidelines.  If no 
such guidelines exist, an observation 
period of 2 hours after the end of the 
nivolumab infusion is suggested.
Pill Diary
X
Pill diary must be completed with each administered daily 
dose of BMS-986205
X
Review pill diary during each visit 
for compliance of daily 
administration of BMS-986205. 
Collect pill diary at the completion 
of each cycle and EOT.
a EOT is defined as the visit where 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, Cycle 2 
Day 22) and the start of the Week 1 Clinical/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), does not need to be repeated, and will be considered the start of the Week 1 Clinical/Safety Follow-up visit.
d Concomitant medication assessment and monitoring for nonserious AEs from Days 22 to 28 must be recorded on the next subject visit. for SAE, the guidance 
provided in Sectio 6.1 must be followed.
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CA017003
BMS-986205
IDO1 INHIBITOR
Abbreviations: AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMS EDC = Bristol-Myers Squibb Electronic Data 
Capture; BUN = blood urea nitrogen; CBC = complete blood count; CR = complete response; ECG = electrocardiogram; EOT = end of treatment; GGT = 
gamma-glutamyl transferase; hCG = human chorionic gonadotropin; IVRS = Interactive Voice Response System; IWG = International Working Group; LDH = 
lactate dehydrogenase; LFT = liver function test; PE = physical examination; Q2W = every 2 weeks; Q4W = every 4 weeks; RECIST = Response Evaluation 
Criteria In Solid Tumors; SAE = serious adverse event; TSH = thyroid-stimulating hormone; VS = vital signs; WOCBP = women of childbearing potential.
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CA017003
BMS-986205
IDO1 INHIBITOR
5.1.1
Retesting During Screening or Lead-in Period
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 may be 
needed to identify whether repeat testing of any particular parameter is clinically relevant.
Retesting is limited to these specific laboratory parameters and/or assessments.
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 available a well-calibrated scale for 
recording body weight, a 12-lead ECG machine, and a calibrated sphygmomanometer and 
thermometer for vital signs assessments. A current and fully-stocked (advanced cardiac life 
support or basic cardiac life support) cart will be immediately available on the premises. The site 
will have urine collection containers, a refrigerated centrifuge, a monitored and alarmed 
refrigerator, and freezer (-20°C or below), as well as containers and dry ice for shipment and 
storage of blood and urine samples. The site will provide all materials required for accurate 
source documentation of study activities and for housing the subjects during the study. BMS will 
supply study medications. 
BMS will provide a BMS-approved protocol and any amendments or administrative letters (if 
required) and IB. CRFs (electronic or hard copy) will be provided by BMS. BMS/The Central 
Laboratory will provide labels and tubes for the collection of blood samples for PK/biomarker 
 analysis.
Additionally, the IVRS manual and pharmacy manual will also be provided. 
5.3
Safety Assessments
AEs will be assessed continuously during the study and for 100 days after the last dose of study 
drug. AEs will be evaluated according to the NCI CTCAE v4.03 and should be followed per 
requirements in Sections 6.1.1 and 6.2.1. AEs will be coded using the most current version of 
Medical Dictionary for Regulatory Activities (MedDRA) 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 detailed in Section 5.1.
5.3.1
Imaging Assessment for the Study
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the study investigator as per 
standard medical/clinical judgment
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BMS-986205
IDO1 INHIBITOR
5.3.2
Laboratory Test Assessments
A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests performed up to Day -1 must be available prior to dosing. The 
following clinical laboratory tests will be performed:
Hematology
Hemoglobin
Hematocrit
Total leukocyte count, including differential
Platelet count
Methemoglobin
Reticulocyte counts and haptoglobin (at baseline and reflex when methemoglobin is elevated)
Ferritin (at Screening)
Glucose 6-Phosphate Dehydrogenase deficiency testing (at screening)
Serum Chemistry
Aspartate aminotransferase
Alanine aminotransferase
Total bilirubin
Direct bilirubin
Alkaline phosphatase
Lactate dehydrogenase
Creatinine
Blood urea nitrogen
Uric acid 
Glucose (Fasting at screening only)
Amylase
Lipase 
Gamma-glutamyl transferase only when 
alkaline phosphatase is ≥Grade 2
Total Protein
Albumin
Sodium
Potassium
Chloride
Calcium
Phosphorus
Magnesium
Creatinine clearance (CrCl)- screening only
Bicarbonate/carbon dioxide
Urinalysis (at screening )
Protein
Glucose
Blood
Leukocyte esterase
Specific gravity
pH
Other: 
24 hour urine collection for testing of p-chloroaniline
Serology 
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BMS-986205
IDO1 INHIBITOR
Serum for hepatitis C antibody (if Hepatitis C antibody is positive reflex to hepatitis C RNA) or 
hepatitis C RNA, hepatitis B surface antigen, HPV status, HIV-1 and HIV-2 antibodies. (Testing 
for HIV-1 and HIV-2 must be performed at sites where mandated by local requirements)
Other Analyses
Pregnancy test (WOCBP only) 
TSH with reflex to free T3 and free T4 as applicable.
FSH (if needed to document postmenopausal status as defined in Section 3.3.3)
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).
5.3.2.1
Microsatellite Instability Testing
MSI-H (Microsatellite Instability High) in tumors refers to changes in 2 or more of the 
5 National Cancer Institute-recommended panels of microsatellite markers in tumor tissue. The 
original (1997) Bethesda guidelines proposed a panel of five microsatellite markers for the 
uniform analysis of MSI in HNPCC. This panel, which is referred to as the Bethesda panel, 
included 2 mononucleotide (BAT-25 and BAT-26) and 3 dinucleotide (D5S346, D2S123, and 
D17S250) repeats56. Individual testing sites may utilize a slightly different panel of markers
incorporating alternative mononucleotide or dinucleotide markers. Regardless of the panel of 
markers, samples with instability in 0 or 1 marker are designated as non-MSI-H (nMSI-H). 
Those with one unstable marker are designated as MSI-Low (MSI-L). Samples with no 
detectable alterations are MSI-stable (MSS). Samples with detectable alterations in two or more 
markers are considered MSI-High (MSI-H).
5.4
Efficacy Assessments
Assessment of tumor response will be reported by the investigator and recorded on the CRF for 
appropriate populations of subjects as defined by RECIST v1.1 (see Appendix 3) for subjects 
with solid tumors and IWG (see Appendix 4) for subjects with HL and NHL. Investigators will 
also report the number and size of new lesions that appear while on study.
For subjects with lymphoma with bone marrow involvement at screening, a bone marrow biopsy 
and aspirate will be required to confirm a CR.
Body Imaging
CT with contrast is the preferred modality (MRI if CT is not feasible). Assessment should 
include the chest/abdomen/pelvis at a minimum; and other known/suspected sites of disease 
should be performed.
Disease assessment with CT and/or MRI as appropriate will be performed at baseline and as 
follows:
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BMS-986205
IDO1 INHIBITOR
•
Parts 1, and Part 2: end of Cycle 2 and then every 8 weeks throughout the treatment period.
•
Part 3:
−
Melanoma/ Ipi 1Q8: At Week 12 (± 1 week) and then every 8 weeks (± 1 week)
throughout the treatment period.
−
NSCLC/ Ipi 1Q6: At Week 6 (± 1 week) and then every 6 weeks (± 1 week) throughout 
the treatment period
−
Bladder/ Ipi 3Q3: At Week 6 (± 1 week) and then every 6 weeks (± 1 week) throughout
the treatment period up to 24 weeks, after which they will occur every 12 weeks
(± 1 week) throughout the treatment period.
−
Mixed Tumor Type/ Ipi 1Q8: At Week 8 (± 1 week) and then every 8 weeks (± 1 week) 
throughout the treatment period.
These efficacy assessment schedules were selected to allow for more direct comparisons of anti-
tumor activity in this study to those of historical comparators for each tumor type.
For all study parts, assessments will be performed every 12 weeks for the first year after the EOT 
visit and then every 6 months thereafter, up to 2 years following the EOT visit. Efficacy 
assessments should continue until disease progression, the completion of follow-up, or until 
subjects withdraw from the study. 
For subjects with HL and NHL, PET will be performed at baseline and in order to confirm a CR. 
Disease assessments at other time points may be performed as clinically indicated.
Brain Imaging
Brain imaging is only required at screening for subjects with known history or symptoms of 
brain metastases and who have not had brain imaging within 30 days of anticipated first study 
drug administration).  After screening, brain imaging is required only as clinically indicated.
Bone Scan
Bone scan may be performed as clinically indicated at baseline (eg, subjects with history of 
symptoms of bone metastases), but bone scans will not be considered a modality for assessment 
for measurable disease.  After baseline, bone scan are required only as clinically indicated
Imaging Modalities
For all the solid tumor types subjects, the following imaging assessments should be performed at 
study-specified schedule: CT of the chest, CT or MRI of the abdomen, pelvis, and other known 
sites of disease, which is also summarized Table 5.4-1:
•
CT scans should be acquired with slice thickness of 5 mm or less with no intervening gap 
(continuous) 
•
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 and other sites of disease may be 
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BMS-986205
IDO1 INHIBITOR
obtained. MRIs should be acquired with slice thickness of 5 mm or less with no gap 
(continuous).
•
PET alone will not be considered for the disease assessment. Complementary CT and/or MRI 
or biopsy must be performed in such cases. 
Note: Use of CT component of a PET/CT scanner: Combined modality scanning, such as
with FDG-PET/CT, is increasingly used in clinical care and is a modality/technology that is 
in rapid evolution; therefore, the recommendations outlined here may change rather quickly 
with time. At present, low-dose or attenuation correction CT portions of a combined FDG-
PET/CT are of limited use in anatomically-based efficacy assessments, and it is, therefore, 
suggested that they should not be substituted for dedicated diagnostic contrast enhanced CT 
scans for anatomically-based RECIST (Appendix 7) measurements. However, if a site can 
document that the CT performed as part of a FDG-PET/CT is of identical diagnostic quality 
to a diagnostic CT (with IV and oral contrast), then the CT portion of the FDG-PET/CT can 
be used for RECIST 1.1 measurements. Note, however, that the FDG-PET portion of the CT 
introduces additional data which may bias an investigator if it is not routinely or serially 
performed. 
For subjects with lymphomas, FDG PET-CT (or PET-MRI, or PET with CT/MRI) may be 
performed for tumor response assessment throughout the study. If CT performed as part of FDG 
PET-CT is of comparable quality to a diagnostic CT (+/- IV contrast), the adequate dose CT of 
the FDG PET-CT can be used for tumor measurements, otherwise additional diagnostic quality 
CT should be obtained, ideally with oral and intravenous contrast.
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Table 5.4-1:
Acceptable Imaging Assessment Methods for Different Anatomic 
Regions
Anatomic Region
Preferred Method
Alternative Methods
Chest, abdomen, and pelvis
Note: Scan must cover lung apices 
to diaphragm, diaphragm through 
entire liver, and to below the pubic 
symphysis
CT with IV contrast
For chest:
•
CT without contrast can be 
used only if the subject has a 
clinical contraindication for 
iodine-based IV contrast (eg, 
hypersensitivity, 
renal 
insufficiency)
For abdomen and pelvis:
•
MRI with gadolinium-based 
IV 
contrast 
is 
the 
first 
alternative 
method 
if 
the 
subject
has 
a 
clinical 
contraindication for iodine-
based IV contrast
•
CT without contrast can be 
used as the second alternative 
method only if the subject has 
a clinical contraindication for 
both 
contrast-enhanced 
CT 
and MRI.
Brain
MRI with IV contrast
•
CT with IV contrast is the first 
alternative 
method 
if 
IV 
gadolinium 
is 
clinically 
contraindicated. 
•
MRI without contrast can be 
used as a second alternative 
method if a subject has clinical 
contraindications 
for 
both 
contrast-enhanced 
CT 
and 
MRI
Bone
Bone scintigraphy
PET (18F-fluoride NaF or FDG) 
and 99m Technetium SPECT
In all study parts, scans will be collected centrally and may be reviewed by a blinded 
independent central review (BICR) at a later date, or at any time during the study per Sponsor 
request.
5.4.1
Primary Efficacy Assessment
The primary efficacy assessments will include the ORR (eg, PR + CR rate), duration of response 
(DoR), and progression-free survival rate (PFSR) at time points (eg, 24 weeks) based on 
assessment of tumor response using RECIST v1.1 or IWG criteria for selected expansion cohorts 
in Part 2 and cohorts in Part 3.
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5.4.2
Secondary Efficacy Assessments
The efficacy assessments will include the ORR (eg, PR + CR rate), DoR, and PFSR at time
points (eg, 24 weeks) based on assessment of tumor response using RECIST v1.1 or IWG 
criteria for dose escalation (Part 1) and the clinical pharmacology substudy.
5.5
Pharmacokinetic Assessments
5.5.1
Pharmacokinetic Assessment following BMS-986205 Monotherapy 
PK of BMS-986205
 will be derived from plasma concentration 
versus time and urinary excretion data. Individual subject PK parameter values will be derived 
by noncompartmental methods by a validated PK analysis program. Actual times will be used for 
the analyses.
The PK parameters to be assessed for BMS-986205 following multiple dose administration in 
Cycle 0 during the dose escalation phase and QTc substudy include but not limited to the 
following:
Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(TAU)
Area under the concentration-time curve in 1 dosing interval
Ctrough
Trough observed plasma concentration at the end of the dosing interval
CLT/F
Apparent total body clearance
Vss/F
Apparent volume of distribution at steady-state
AI
Accumulation index, calculated based on ratio of AUC(TAU) and 
Cmax at steady state to after the first dose
%UR24
Percent urinary recovery over 24 hours
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5.5.2
Pharmacokinetic Assessment following Combination Therapy of BMS-
986205 and Nivolumab
Plasma samples for BMS-986205 will be collected for all subjects receiving combination 
treatment of BMS-986205 and nivolumab. Plasma concentration data will be tabulated using 
summary statistics. These data, together with data from the monotherapy, may also be pooled 
with other datasets for PPK analysis, which will be presented in a separate report.
Serum samples for nivolumab 
 immunogenicity assessments will be collected for all 
subjects receiving combination treatment of BMS-986205 and nivolumab. End-of-infusion and 
trough (Ctrough) concentrations will be tabulated using summary statistics. These data may also 
be pooled with other datasets for PPK analysis, which will be presented in a separate report.
5.5.3
Pharmacokinetic Assessment following Combination Therapy of BMS-
986205, Nivolumab, and Ipilimumab
Serial plasma samples for BMS-986205 
 will be collected for all subjects 
in the safety cohort receiving combination treatment of BMS-986205, nivolumab and 
ipilimumab. The PK parameters to be assessed for BMS-986205 
 
 following multiple dose administration in combination with nivolumab and 
ipilimumab include but are not limited to:
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Cmax
Maximum observed plasma concentration
Tmax
Time of maximum observed plasma concentration
AUC(TAU)
Area under the concentration-time curve in 1 dosing interval
Ctrough
Trough observed plasma concentration at the end of the dosing interval
CLT/F
Apparent total body clearance
Vss/F
Apparent volume of distribution at steady-state
AI
Accumulation index, calculated based on ratio of AUC(TAU) and 
Cmax at steady state to after the first dose
Plasma samples for BMS-986205 and serum samples for 
 
nivolumab and ipilimumab immunogenicity assessments will be collected for all subjects in the 
expansion cohort receiving the combination treatment. Plasma concentration data for 
BMS-986205 
 
 will be tabulated using summary statistics. These data may also be pooled with other 
datasets for PPK analysis, which will be presented in a separate report.
5.5.4
Pharmacokinetics: Collection and Processing
5.5.4.1
BMS-986205 Monotherapy and in Combination with Nivolumab (Parts 1 
and 2)
Detailed sampling schedules to be followed for the assessment of PK and immunogenicity for all 
analytes in Parts 1 and 2 of the study are provided in this section. All time points are relative to 
the start of BMS-986205 dosing. Predose samples should be taken within 30 minutes before the 
start of BMS-986205 administration.
 
Further details of sample collection, 
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processing, and shipment will be provided in the laboratory procedures 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 5.5.4.1-1:
Pharmacokinetic, ADA/Immunogenicity for BMS986205 
 (Dose Escalation Part 1 and 
Dose Expansion Part 2)
Study Day of 
Sample 
Collection
Event
Time 
(Relative To 
BMS-986205 
Dose)
Hour: Min
BMS-986205 
 
Plasma 
Sample
BMS-986205 
Biotransform
ation Sample
BMS-986205 
 
 
Urine Sample
Nivolumab 
ADA Sample
Cycle 0 a
C0D1
Predose
0
X
X
X
1
X
X
0-8 h
2
X
3
X
4
X
6
X
8
X
C0D2
Predose
0
X
X
8-24 h
C0D8
Predose
0
X
C0D14
Predose
0
X
X
1
X
X
2
X
X
3
X
4
X
X
6
X
X
8
X
X
CD015
Predoseb
X
X
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Table 5.5.4.1-1:
Pharmacokinetic, ADA/Immunogenicity for BMS986205 
 (Dose Escalation Part 1 and 
Dose Expansion Part 2)
Study Day of 
Sample 
Collection
Event
Time 
(Relative To 
BMS-986205 
Dose)
Hour: Min
BMS-986205 
 
Plasma 
Sample
BMS-986205 
Biotransform
ation Sample
BMS-986205 
 
 
Urine Sample
Nivolumab 
ADA Sample
Cycle 1
C1D1
Predose
0c
X
X
X
EOId
1.0
X
2.5-4
X
C1D15
Predosee
0
X
Cycle 3
C3D1
Predose
0
X
X
EOI
1.0
X
2.5-4
X
Cycle 5
Every 4 Cycles 
from C5D1 f
Predose
0
X
X
EOI
1.0
X
EOT and FU
EOT
X
X
FU g
X
X
a Dose escalation only.
b This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 0 Day 14 if Cycle 1 Day 1 does not occur on the next day of Cycle 0 Day 
14.
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c This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 0 Day 14 if Cycle 1 Day 1 does not occur on the next day of Cycle 0 
Day 14.
d This sample should be taken immediately prior to stopping the nivolumab 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.
e If biopsy does not occur on C1D15, than an additional predose PK sample should be collected on the day of biopsy. 
f For subjects who will not receive additional treatment beyond Cycle 12, follow the EOT and FU schedules
g First 2 follow-up visits. 
Abbreviations: ADA = anti-drug antibody; ECG = electrocardiogram; EOI = end of infusion; EOT = end of treatment; FU = follow-up; PK = pharmacokinetic.
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Table 5.5.4.1-2:
Pharmacokinetic and ADA Sampling Schedule for BMS-986205 
 
 for Re-treatment
Study Day of 
Sample 
Collection
Event
Time 
(Relative to 
BMS-986205
Dose)
Hour: Min
BMS-986205
 
Plasma Sample
Nivolumab 
ADA Sample
1
Predose
0
X
X
113a
Predose
0
X
X
EOT and FU
EOT
X
X
FUb
X
X
a Day 113 of retreatment = C5D1 of retreatment.
b First 2 follow-up visits (up to 100 days from end of treatment visit)
Abbreviations: ADA = anti-drug antibody; EOT = end of treatment; FU = follow-up
5.5.4.2
BMS-986205 in Combination with Both Nivolumab and Ipilimumab 
(Part 3)
Detailed sampling schedules to be followed for the assessment of PK and immunogenicity for all 
analytes in Part 3 of the study are provided below. All time points are relative to the start of 
BMS-986205 dosing. Predose samples should be taken within 30 minutes before the start of 
BMS-986205 administration. 
 
 
 
Further details of sample collection, processing, and shipment will 
be provided in the laboratory procedures 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 5.5.4.2-1:
Pharmacokinetic, ADA/Immunogenicity Assessments for Melanoma and Mixed Tumor Type Cohorts 
in Part 3
Study Day of 
Sample 
Collections
(1 Cycle = 
8 Weeks)
Event
Time
(Relative to 
BMS-986205 
Dose)
Hour: Min
BMS-986205 
 
 
Plasma Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C1D1
Predose
0
X
X
X
Nivo EOI
1
X
Ipi EOI
2
X
3a
X
4a
X
6a
X
8a
X
C1D2
Predoseb
0a
X
C1D15
Predosec
0
X
1a
X
2a
X
3 a
X
4a
X
6a
X
8a
X
C1D16 a
Predosed
0
X
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Table 5.5.4.2-1:
Pharmacokinetic, ADA/Immunogenicity Assessments for Melanoma and Mixed Tumor Type Cohorts 
in Part 3
Study Day of 
Sample 
Collections
(1 Cycle = 
8 Weeks)
Event
Time
(Relative to 
BMS-986205 
Dose)
Hour: Min
BMS-986205 
 
 
Plasma Sample
Nivolumab 
ADA Sample
Ipilimumab 
ADA Sample
C2D1
Predose
0
X
X
X
Nivo EOI
1
X
Ipi EOI
2
X
Every 2 Cycles 
starting C4D1e
Predose
0
X
X
X
EOT
X
X
X
FUf
X
X
X
a Safety cohort only
b This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 1 Day 1
c If biopsy does not occur on C1D15, collect an additional Predose PK sample on the day of the biopsy.
d This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 1 Day 15.
e For subjects who will not receive additional treatment beyond Cycle 6, follow the EOT and FU schedules at the end of Cycle 6
f First 2 follow-up visits.
Abbreviations: ADA= anti-drug antibody; C=cycle; D= day; Ipi=ipilimumab; EOI = end of infusion; EOT = end of treatment; FU = follow-up; Nivo=nivolumab; 
PK = pharmacokinetic
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Table 5.5.4.2-2:
Pharmacokinetic, ADA/Immunogenicity Assessments for NSCLC 
Cohorts in Part 3
Study Day 
of Sample 
Collections
(1 Cycle = 
6 Weeks)
Event
Time
(Relative to 
BMS-98620
5 Dose)
Hour: Min
BMS-98620
5
 
 
Plasma 
Sample
Nivoluma
b ADA 
Sample
Ipilimuma
b ADA 
Sample
C1D1
Predose
0
X
X
X
Nivo EOI
1
X
Ipi EOI
2
X
3a
X
4a
X
6a
X
8a
X
C1D2
Predoseb
0a
X
C1D15
Predosec
0
X
1a
X
2a
X
3a
X
4a
X
6a
X
8a
X
C1D16a
Predosed
0
X
C2D1
Predose
0
X
X
X
Nivo EOI
1
X
Ipi EOI
2
X
Every 
3 Cycles 
starting 
C5D1e
Predose
0
X
X
X
EOT
X
X
X
FUf
X
X
X
a Safety cohort only
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b This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 1 Day 1.
c If biopsy does not occur on C1D15, collect an additional Predose PK sample on the day of the biopsy.
d This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 1 Day 16.
e For subjects who will not receive additional treatment beyond Cycle 8, follow the EOT and FU schedules at the 
end of Cycle 8.
f First 2 follow-up visits
Abbreviations: ADA= anti-drug antibody; C=cycle; D= day; Ipi=ipilimumab; EOI = end of infusion; EOT = end of 
treatment; FU = follow-up; Nivo=nivolumab; PK = pharmacokinetic
Table 5.5.4.2-3:
Pharmacokinetic, ADA/Immunogenicity Assessments for Bladder 
Cohorts in Part 3
Study Day 
of Sample 
Collections
(1 Cycle = 
6 Weeks
for C1 and 
C2, 
4 Weeks 
for C3+)
Event
Time
(Relative to 
BMS-98620
5 Dose)
Hour: Min
BMS-98620
5
 
 
Plasma 
Sample
Nivoluma
b ADA 
Sample
Ipilimuma
b ADA 
Sample
C1D1
Predose
0
X
X
X
Nivo EOI
1
X
Ipi EOI
2
X
3a
X
4a
X
6a
X
8a
X
C1D2
Predoseb
0a
X
C1D15c
Predose
0
X
1a
X
2a
X
3a
X
4a
X
6a
X
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Table 5.5.4.2-3:
Pharmacokinetic, ADA/Immunogenicity Assessments for Bladder 
Cohorts in Part 3
Study Day 
of Sample 
Collections
(1 Cycle = 
6 Weeks
for C1 and 
C2, 
4 Weeks 
for C3+)
Event
Time
(Relative to 
BMS-98620
5 Dose)
Hour: Min
BMS-98620
5
 
 
Plasma 
Sample
Nivoluma
b ADA 
Sample
Ipilimuma
b ADA 
Sample
8a
X
C1D16a
Predosed
0
X
C2D1
Predose
0
X
X
X
Nivo EOI
1
X
Ipi EOI
2
X
C3D1
Predose
0
X
X
X
Nivo EOI
1
X
Every 
4 Cycles 
starting 
C7D1e
Predose
0
X
X
EOT
X
X
X
FUf
X
X
X
a
Safety cohort only
b This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 1 Day 1
c If biopsy does not occur on C1D15, collect an additional Predose PK sample on the day of the biopsy.
d This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 1 Day 15
e For subjects who will not receive additional treatment beyond Cycle 11, follow the EOT and FU schedules at the 
end of Cycle 11
f First 2 follow-up visits 
Abbreviations: ADA= anti-drug antibody; C=cycle; D= day; Ipi=ipilimumab; EOI = end of infusion; EOT = end of 
treatment; FU = follow-up; Nivo=nivolumab; PK = pharmacokinetic
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Table 5.5.4.2-4:
Pharmacokinetic and ADA Assessments During Re-Treatment in 
Part 3
Study Day 
of Sample 
Collection
Event
Time 
(Relative to 
BMS-
986205
Dose)
Hour: Min
BMS-
986205
 
Plasma 
Sample
Nivolumab 
ADA 
Sample
Nivolumab 
ADA 
Sample
1
Predose
0
X
x
x
113a
Predose
0
X
x
x
EOT and FU
EOTb
X
x
x
FU
X
x
x
a Day 113 of retreatment = C5D1 of retreatment.
Abbreviations: ADA = anti-drug antibody; EOT = end of treatment; FU = follow-up.
b First 2 follow-up visits 
5.5.4.3
Pharmacologic Substudy
Table 5.5.4.3-1 lists the ECG and PK sampling schedules to be followed for the QTc substudy. 
Twelve-lead continuous ECG (Holter) will be used in the QTc substudy. Each ECG time point 
will be collected in triplicates. ECGs should be performed after the subject has been resting 
supine for at least 10 minutes and should be completed prior to any PK/PD sample blood 
collections when assessments occur at the same time points. All serial ECGs will be transmitted 
to a central laboratory for measurement of intervals and classification of ECG abnormalities.
Following Cycle 0, subjects in the QTc SubStudy will follow the sampling schedule as outlined 
in Table 5.5.4.1-1 for subsequent treatment cycles.
Table 5.5.4.3-1:
Serial ECG and Pharmacokinetic Collection Schedule for QTc 
Substudy (Baseline and Cycle 0)
Study Day of 
Sample Collection
Event
Time 
(Relative to BMS-
986205 Dose)
Hour: Min
ECG Collectiona
BMS-986205
 
 Plasma 
Sample
-1 (ECG baseline)b
(Predose)c
-0:45
X
1:45
X
2:45
X
3:45
X
5:45
X
C0D14
Predose
-0:45
X
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Table 5.5.4.3-1:
Serial ECG and Pharmacokinetic Collection Schedule for QTc 
Substudy (Baseline and Cycle 0)
Study Day of 
Sample Collection
Event
Time 
(Relative to BMS-
986205 Dose)
Hour: Min
ECG Collectiona
BMS-986205
 
 Plasma 
Sample
Predose
0
X
1
X
1:45
X
2
X
2:45
X
3
X
3:45
X
4
X
5:45
X
6
X
8
X
C0D15
Predosed
0
X
a See Table 5.1-15 for detailed instructions on ECG collections.
b Allowed up to 5 days prior to the start of cycle 0
c No drug is given on the Day-1 visit; Event and Times listed for this visit are intended to approximate the same 
time as on the treatment day (C0D14)
d This sample should be taken 24 hours after the previous BMS-986205 dose on Cycle 0 Day 14 if Cycle 1 Day 1 
does not occur on the next day of Cycle 0 Day 14.
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5.5.5
Pharmacokinetic Sample Analyses
The plasma and urine samples of BMS-986205
 will be analyzed by 
validated liquid chromatography-mass spectrometry (LC-MS) assays, and serum samples of 
anti-nivolumab antibody will be analyzed by validated immunoassays. 
 
 
5.5.6
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 procedure manual.
5.6
Biomarker Assessments
Blood and tumor samples will be collected at the times indicated in Table 5.6-1 for the 
measurement of biomarkers relevant to dose selection
 
. Further details of blood and tumor collection and processing will be provided to 
the site in the procedure manual.
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Table 5.6-1:
BMS-986205 Plus Nivolumab Dose Escalation Part 1 Biomarker Sampling Schedule
Study 
Daya
Time 
(Event)
Hour
Time 
(Relative to 
Dosing)
Hour: Min
PD Serum 
Sample for 
Kynurenine
Metabolite
PD Tumor 
Biopsy
Screening 
D-28 to 
Day -1
0 (predose)
C0D1
0 (predose)
00:00
X
Xb
C0D1
6
6:00
X
C0D2
0 (predose)
00:00
X
C0D8
0 (predose)
00:00
X
C1D1
0 (predose)
00:00
X
C1D15
0 (predose)
00:00
X
Xb,c
C2D1
0 (predose)
00:00
X
C3D1
0 (predose)
00:00
X
b Pre- and on-treatment biopsies are mandatory for subjects in Part 1. Additional subjects may be added to dose levels 1 and 2 for pre and on-treatment biopsies 
if initial PK/PD analyses suggests these dose levels are biologically active.
c C1D15 biopsy specimens may be obtained within a collection window of C1D15 through C1D28 for all subjects. PD serum
 
 C1D15 samples should be collected on day of biopsy if possible.
Abbreviations: C = cycle; D = day; 
PD = pharmacodynamics.
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Table 5.6-2:
Dose Expansion Part 2 Biomarker Sampling Schedule
Study Day
Time 
(Event)
Hour
Time 
(Relative to 
Dosing)
Hour: Min
PD Serum 
Sample for 
Kynurenine
Metabolite
PD 
Tumor 
Biopsy
Screening D-28 to Day -
1
0
(predose)
Xb
C1D1
0
(predose)
00:00
X
C1D8c
0
(predose)
00:00
X
C1D15
0
(predose)
00:00
X
Xb
C2D1
0
(predose)
00:00
X
C3D1
0
(predose)
00:00
X
Unscheduled/EOT/at 
progressiond
Xe
Xe
b Pre-treatment biopsies are required for participants that do not have sufficient archival tissue. On-treatment biopsies will be mandatory for all subjects. 
Additional subjects may be added to dose levels 1 and 2 for mandatory pre and on-treatment biopsies if initial PK/PD analyses suggests these dose levels are 
biologically active.
c C1D8 visit is not required during retreatment.
d Unscheduled visit included to allow for biopsy and biomarker collection at beginning of re-treatment or at progression.
e Tumor biopsy is optional at the unscheduled visit. If tumor biopsy is collected, PD serum
 samples should be collected 
on the same day.
Abbreviations: C = cycle; D = day; 
 EOT = end of treatment; PD = pharmacodynamics
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Table 5.6-3:
Part 3 Biomarker Sampling Schedule: Melanoma, NSCLC, and Bladder
Study Day
Time
(Event)
Hour
Time
(Relative to 
Dosing)
Hour: Min
PD Serum 
Sample for 
Kynurenine 
Metabolite
PD 
Tumor 
Biopsy
Screening D-28 to 
Day-1
0 (predose)
Xa
C1D1
0 (predose)
00:00
X
C1D8
0 (predose)
00:00
X
C1D15
0 (predose)
00:00
X
Xa
C2D1
0 (predose)
00:00
X
C3D1
0 (predose)
00:00
X
Unscheduled/EOT/
at progressionb
Xc
Xc
a Pre- and on-treatment biopsies will be mandatory for Part 3; C1D15 biopsy may be obtained between C1D15 and C1D28.
b Unscheduled visit included to allow for biopsy and biomarker collection at beginning of re-treatment or at progression.
c Tumor biopsy is optional at the unscheduled visit. If tumor biopsy is collected, PD serum
samples should be collected 
on the same day.
Abbreviations: C = cycle; D = day; 
 EOT = end of treatment; PD = pharmacodynamics.
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5.7
 Biomarker Assessments
5.7.1
Peripheral Blood Markers
5.7.1.2
Serum 
 for Kynurenine and Related 
Metabolites
Serum 
 will be collected from all subjects at time points as indicated in Table 
5.6-1, Table 5.6-2, and Table 5.6-3. 
 
Levels of kynurenine, tryptophan, and related metabolites in serum will be determined by LC-
MS analysis. Serum levels will be measured on serum frozen after collection from subjects. 
 
 
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5.7.2
Tissue Markers from Fresh Tumor Biopsies
 
 
 
 
With 
Amendment 14, all subjects in Parts 1 and 3 (as well as subjects in other parts without archival 
tissue meeting the requirements above) will be required to undergo mandatory pre-treatment 
biopsies. All subjects will be required to undergo an on-treatment biopsy at acceptable clinical
risk as judged by the investigator. Please notify the BMS Medical Monitor if biopsy on-treatment 
may pose unacceptable clinical risk, or if tumor at the time of on-treatment biopsy is not 
accessible for sampling.
An optional specimen (not mandatory) at the time of disease progression or during another 
clinically meaningful event (eg, response or AE) may be collected.
Where possible, biopsied lesions should be distinct from index lesions being evaluated for 
radiological response. Biopsies may be excisional, incisional, or core needle. Excisional biopsies 
are strongly encouraged where feasible. Biopsies from previously irradiated lesions are only 
suitable if they subsequently progressed. Baseline samples may be obtained at any time 
following other screening procedures and prior to first dose of study drug (administered on Cycle 
0 Day 1 in Part 1 or Cycle 1 Day 1 in Parts 2 and 3). In limited circumstances, recent fresh 
samples (frozen and FFPE) obtained prior to start of screening that meet biomarker requirements 
of the study as determined by the Study Director or Medical Monitor may be substituted for fresh 
biopsies, after permission from the Study Director or Medical Monitor is obtained. Cycle 1 Day 
15 specimens may be obtained within a collection window of Cycle 1 Day 15 through 
Cycle 1 Day 28. 
As described previously, complete instructions on the collection, processing, handling, and 
shipment of all biomarker specimens will be provided in a separate procedure manual. Please 
refer to this manual for information pertaining to the collection and processing of tissue via 
biopsy or core needle. Collection procedures at baseline and on-treatment (and at progression) 
should be completed on a single, appropriately accessible lesion, when applicable. In the case 
that the lesion sampled at baseline is no longer accessible or within acceptable clinical risk to 
re-biopsy during study (at Cycle 1 Day 15 or at progression), tissue from alternative lesion(s) 
may be obtained. This should be documented. Immediate confirmation for presence of viable 
tumor cells from collected tissue samples is strongly recommended. If adequate tissue is not 
obtained following initial passages of the needle, repeat passages may be required.
Subjects whose baseline or on-treatment biopsy yields inadequate tissue quantity or quality (lack 
of tumor) will be allowed to continue in the study 
 
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 If tissue obtained from a large proportion of 
subjects is deemed inadequate for testing (eg, possesses low tumor cell content), additional 
subjects may be enrolled in an attempt to obtain tissue specimens better-suited for testing.
5.7.2.1
Tumor Kynurenine and Related Metabolites
Tumor levels of kynurenine, tryptophan, and related metabolites will be measured in fresh frozen 
tumor biopsies collected at baseline and on treatment. Kynurenine, tryptophan, and related 
metabolites will be assessed by LC-MS methods. On-treatment reduction in tumor kynurenine 
level is the predicted effect of IDO1 inhibition.
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5.7.3
Tissue Markers from Archived Tumor Samples
Submission of baseline tumor tissue sample is mandatory from all patients. Tumor tissue samples 
at baseline should be either archival tumor FFPE, FFPE slides and/or fresh biopsy in FFPE block
- specified with cohort. One FFPE block of < 1 year old or 20 slides (fewer slides may be 
acceptable with the approval of the medical monitor, but generally 15 will be required) of less 
than 4 months old will be requested from patients with no mandatory fresh biopsy requirement at 
baseline; archival samples from subjects in Parts 1 and 3 are not subject to these time limitations 
as these subjects will also undergo fresh pretreatment biopsies. These specimens will be 
submitted for central PD-L1 immunohistochemistry (IHC) in melanoma and NSCLC patients. 
The pre-treatment tumor samples must be a core biopsy, punch biopsy, excisional biopsy, or 
surgical specimen. Fine needle aspirates or other cytology specimens are insufficient for 
enrollment. Tumor samples obtained from bone lesion are not acceptable. 
Molecular characterization of archival specimens will be similar to the characterizations 
described above (IHC
) but are likely to focus on the expression of PD-L1 
 
as candidate markers associated with response to combination therapy. 
 
 
 
 
 
Note that HPV status, a known prognostic factor for cervical cancer and SCCHN, will be 
monitored via CRF. When HPV status is unknown for cervical or SCCHN (oropharyngeal
primary location) cancer subjects, HPV status (and type) may be assessed/confirmed 
retrospectively using archival and/or fresh specimens. Analyses may include p16 IHC and/or 
HPV detection methods such as, but not limited to, in situ hybridization and PCR-based 
techniques.
5.8
Outcomes Research Assessments
Not applicable.
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6
ADVERSE EVENTS
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing 
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 AEs. The causal relationship can be 1 of the following:
•
Related: There is a reasonable causal relationship between study drug administration and the 
AE.
•
Not related: There is not a reasonable causal relationship between study drug administration 
and the AE.
The term “reasonable causal relationship” means there is evidence to suggest a causal 
relationship. 
AEs 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 1 or more AEs.)
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 
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•
is an important medical event (defined as a medical event[s] that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent 1 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 DILI is also considered an important medical event (see 
Section 6.7 for the definition of potential DILI).
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study 
drug is an SAE.
Although pregnancy, overdose, cancer, and potential drug 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 drug (eg, death is an 
endpoint; if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as an 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 colorectaloscopy)
−
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
and for 30 days post discontinuation of study drug for subjects not receiving combination 
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therapy. 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. 
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 SAE.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. 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.
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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
Adverse Events of Special Interest
Adverse events of special interest (AEOSI) have been defined for this protocol which require 
expedited reporting by the investigator of these adverse events to BMS. These are:
•
Hemophagocytic lymphohistiocytosis (HLH; also known as histiocytosis haematophagic)
•
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
These AEOSI, whether related or not related to study drug, must be reported to BMS or designee 
within 24 hours of awareness of the event.  These AEOSI are medically important events and are 
therefore considered SAEs. The reporting system for SAEs should be used (see Section 6.1.1).
Both HLH and DRESS syndrome may both pose diagnostic challenges due to varying clinical 
manifestations and signs and symptoms that may overlap with other clinical events. To assist 
investigators in identifying constellations of clinical symptoms that may be consistent with one 
of these diagnoses, standardized scoring criteria are provided in Appendix 12. Formal evaluation 
and documentation of diagnostic scores based on these systems is not required; investigators 
should use their best clinical judgement as informed by these provided criteria to determine if a 
subject has experienced one of these AEOSI.
6.4
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:
•
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).
6.5
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 + 30 days after nivolumab administration (for a total of 23 weeks post-treatment 
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completion), 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).
If the investigator determines a possible favorable benefit/risk ratio that warrants continuation of 
study treatment, or re-initiation of study treatment, a discussion between the investigator and the 
BMS Medical Monitor/designee must occur. If, for whatever reason, the pregnancy has ended, 
confirmed by negative serum pregnancy test, treatment may be resumed (at least 3 weeks and not 
greater than 6 weeks after the pregnancy has ended), following approvals of subject /sponsor 
/IRB/EC, as applicable.
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 subject should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.6
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important. Overdoses meeting the regulatory 
definition of SAE must be reported as an SAE (see Section 6.1.1 for reporting details).
In the event of an overdose the investigator/treating physician should:
1) Contact the Medical Monitor/designee immediately
2) Closely monitor the subject for AEs/SAEs and laboratory abnormalities
3) Document the quantity of the excess dose as well as the duration of the overdosing in the 
CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor/designee based on the clinical evaluation of the subject.
6.7
Potential Drug-induced Liver Injury
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. All occurrences of potential DILIs, 
meeting the defined criteria, must be reported as SAEs (see Section 6.1.1 for reporting details).
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Potential DILI is defined as: 
1) Aminotransaminases (ALT or AST) elevation > 3 times ULN
AND 
2) Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated serum alkaline 
phosphatase)
AND 
3) No other immediately apparent possible causes of aminotransaminases elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic or biliary 
obstruction caused by tumor.
6.8
Other Safety Considerations
Any significant worsening noted during interim or final PEs, ECG, x-ray filming, or any other 
potential safety assessment required or not required by protocol should also be recorded as a 
nonserious AE or SAE, 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 (Part 1)
As a Phase 1 dose escalation trial, the sample size at each dose in these arms depends on 
observed toxicity and posterior inference. For BMS-986205 in combination with nivolumab 
(with BMS-986205 lead-in), approximately 30 subjects are expected to be treated during the 
dose escalation phase. Initially, approximately 3 subjects will be treated at the starting dose 
levels of BMS-986205 in combination with nivolumab. Due to the potential for early 
discontinuation, an additional subject(s) may be enrolled to ensure approximately 3 evaluable 
subjects at each dose level.
During the dose escalation phase, once a dose level has been decided, a set of approximately 
3 subjects will be treated at that specified dose level. Cohort-tolerability assessment and 
subsequent dose recommendation will occur when 2 evaluable subjects within a set have 
completed a 6-week DLT evaluation period (2 weeks of monotherapy lead-in plus 4 weeks of 
combination treatment). If the potential DLT occurring in any third evaluable subject regarding 
the 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 sponsor and investigators. Continuous re-assessment of dose recommendation by 
BLRM in the lead-in phase and BLRM-Copula in the combination phase will be carried out at 
each dose level.
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Additional increments of approximately 3 evaluable subjects will be treated in recommended 
dose levels per BLRM-copula model during the dose escalation phase. At least 6 DLT-evaluable 
subjects will be treated in the selected dose cohort(s) chosen for expansion. Due to the 
BMS-986205 lead-in period, more than 3 subjects per cohort may be treated per BMS-986205 
dose level considering potential DLTs happened within lead-in period.
Up to 12 additional subjects may be treated at any dose level below the estimated MTD/MAD 
for further evaluation of safety and pharmacodynamic/PK parameters as required. 
8.1.2
Dose Expansion (Part 2)
Dose expansions of BMS-986205 administered in combination with nivolumab in 
8 disease-restricted populations, and subjects in 1 mixed cohort of additional signal-seeking 
tumor types will be included. The following 7 tumor-specific cohorts will be classified into 3 
categories according to different sample size modeling settings: SCCHN and bladder cancer in a 
group; cervical cancer, DLBCL, melanoma with prior anti-PD-(L)1 therapy, NSCLC with prior 
anti-PD-(L)1 therapy, and pancreatic cancer in a different group; and melanoma with prior anti-
PD-(L)1 and anti-CTLA-4 therapy in another group. The two last groups will be analyzed using 
a Simon 2-stage design. 
A Simon 2-stage (optimal) design will be used as a guide for many of the tumor-specific cohorts 
(see below for exceptions). The 2-stage design with a reasonable FPR and FNR, based on 
assumptions of true (target) and historic ORR for each indication, will provide guidance for the 
total sample size for these cohorts. The sample size and operational characteristics of using a 
2-stage design are provided in Table 8.1.2-1, although not used for hypothesis testing. For 
example, guided by, initially, a minimum of 10 subjects for the SCCHN tumor type will be 
treated in Stage 1 for an initial evaluation of efficacy. Assuming the true response rate is 50% 
when treated with BMS-986205 in combination with nivolumab, if there are 2 or fewer 
responses in 10 treated subjects, the cohort would likely not be considered as efficacious. The 
probability of early stopping for futility is approximately 53% in this case if in fact the treatment 
is inefficacious. The totality of efficacy data and response profile will be considered while 
making the decision to terminate. Enrollment will be continued during initial efficacy evaluation 
(ie, with the indicated number of subjects at Stage 1) to ensure that additional subjects are 
enrolled to account for unexpected trial impact, such as response non-evaluable subjects due to 
early drop-out, design parameter change (eg, historical rate update), and so on.
For an expansion cohort of approximately 35 subjects in the cervical, melanoma: prior 
anti-PD-(L)1, pancreatic, NSCLC: prior anti-PD-(L)1, and DLBCL cohorts, and an 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% confidence interval 
(CI) for the ORR is 11% (higher than historical ORR of 10%). The CI is calculated using the 
Clopper-Pearson method.
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For an expansion cohort of approximately 27 subjects in the bladder and SCCHN tumors and 
assumed true response rate of 50%, there is a 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, 40% 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 the Clopper 
Pearson method.
For an expansion cohort of approximately 37 subjects with melanoma with prior anti-PD-(L)1 
and anti-CTLA-4 therapy, and an assumed true response rate of 20%, there is a 85% chance of 
observing at least 5 responses (in other words, the FNR is 15%). If the true response rate is only 
5% rather than 20%, then there is a 14% chance that there will be at least 5 responses in 
37 subjects (in other words, FPR is 14%). Also, if 5 responses are observed (eg, 14% observed 
response rate), the lower bound of the 80% CI for the ORR is 7% (higher than historical ORR of 
5%). The CI is calculated using the Clopper-Pearson method. 
The Simon 2-stage design will not be used for the mixed cohort of additional signal-seeking 
tumor types in Part 2. Approximately 35 to 40 subjects will be enrolled to allow for the 
exploration of early efficacy signals seen during the dose escalation portion of the trial as well as 
potential signals arising from ongoing trials of other IDO1 inhibitors in combination with 
anti-PD-(L)1. A 2-stage design will also not be utilized for the RCC and I-O naïve melanoma 
and NSCLC cohorts, as nivolumab is already an established standard of care in these settings. 
Approximately 40 subjects will be enrolled in each of these cohorts to allow for the exploration 
of early efficacy signals of BMS-986205 in combination with nivolumab. 
Approximately 16 melanoma I-O naïve BRAF mutant subjects’ post-BRAF inhibitor therapy 
will be randomized into 2 cohorts and will either be treated with nivolumab or nivolumab in 
combination with BMS-986205, but will not be used for formal statistical comparison.
Table 8.1.2-1:
Dose Expansion: Example of Simon 2-stage Design 
Characteristics
Expansion Cohort
Historic 
ORR
(%)
Target 
ORR
(%)
Stage 1
/Total N
Stage 1 
Responses 
Futility 
Boundary
Alpha/
Power
(%)
Probability 
of Early 
Stopping
(%)
Cervical, Melanoma: 
Prior anti-PD-(L)1, 
Pancreatic NSCLC: 
Prior anti-PD-(L)1, 
and DLBCL
10
30
12/35
1
10/90
66
Bladder and SCCHN
25
50
10/27
2
10/90
53
Melanoma: Prior anti-
PD-(L)1 and 
anti-CTLA-4
5
20
12/37
0
10/90
54
*Note: For the melanoma, prior anti-PD-(L)1, and prior anti-PD-(L)-1/anti-CTLA-4 cohorts, the analysis will be 
focused on approximately 35 subjects who are BRAF (wild-type) WT.  
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Abbreviations: CTLA-4 = cytotoxic T lymphocyte-associated antigen 4; DLBCL = diffuse large B cell lymphoma; 
I-O = immuno-oncology; NSCLC = non-small cell lung cancer; PD-1 = programmed cell death; 
PD-L1 = programmed death receptor-ligand 1; PD-(L)1 = either PD-1 or PD-L1; ORR = objective response rate; 
SCCHN = squamous cell carcinoma of the head and neck..
8.1.3
Combination with Both Nivolumab and Ipilimumab (Part 3)
The combination of BMS-986205 with nivolumab and ipilimumab in Part 3 will be evaluated in 
2 parts, the safety evaluation phase and the cohort expansion phase of the combination in 
melanoma, NSCLC, and bladder cancer as well as a mixed tumor type cohort.
All safety cohorts will begin with an assessment of safety and tolerability of the triplet 
combination regimen in a limited number of subjects, including a sentinel subject. As described 
in Section 3.1.1.2, the NSCLC and melanoma regimen cohorts will begin enrollment first, 
followed by the bladder regimen cohort once safety and tolerability has been established in either 
NSCLC or melanoma. Initially, approximately 3 subjects will be treated at the selected dose 
combination of BMS-986205 with nivolumab and ipilimumab. Due to the potential for early 
discontinuation, an additional subject(s) may be enrolled to ensure approximately 3 DLT 
evaluable subjects. Initial safety assessment to allow enrollment in the bladder safety cohort will 
occur when at least 2 evaluable subjects in either the NSCLC or melanoma safety cohorts have 
completed a 6-week DLT evaluation period (see Section 4.5.1 for criteria for DLTs). In the 
melanoma and NSCLC safety evaluation cohorts, if the potential DLT occurring in any third 
evaluable subject regarding the specific dose combination does not influence the 
recommendation by BLRM (-Copula) to open enrollment in the bladder safety cohort, then the 
bladder safety cohort may proceed with enrollment without waiting for the third subject to 
complete the corresponding DLT observation period. After the initial subjects in each treatment 
regimen are evaluated, additional increments of approximately 3 to 6 subjects will be treated in 
the same safety cohort as per BLRM-copula model recommendation that the dose combination is 
safe. At least 6 DLT-evaluable subjects will be treated and assessed in the selected dosing 
regimen safety cohort before starting enrollment in the expansion cohort for that tumor 
type/regimen. Up to 12 DLT-evaluable subjects in total may be treated in the safety evaluation 
cohort for each tumor type at the dose selected for expansion cohorts for evaluation of safety and 
pharmacodynamic/PK parameters as required. BLRM (-copula) will be used to monitor the 
safety of the triplet dose combination on an ongoing basis. If, at any time, the aggregate rate of 
treatment related toxicities meeting DLT criteria within an individual treatment tumor 
type/regimen exceeds 33% across all subjects treated in the safety evaluation and dose expansion 
cohorts, the findings will be discussed and further enrollment may be interrupted. At that time, 
depending on the nature and grade of the toxicities and after assessing the risk/benefit ratio, a 
new dose(s) of BMS 986205 for subjects within that dosing regimen may be initiated at a 
previously tested lower dose level or at a dose level intermediate to previously tested lower dose 
levels.
Once the initial safety and tolerability has been established independently for each regimen 
based on safety cohort evaluations, enrollment will begin of subjects into expansion cohorts for 
further evaluation of safety and tolerability, as well as preliminary evaluation of anti-tumor 
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efficacy. In the expansion cohorts, BMS 986205 will be administered at a dose determined to be 
tolerable in combination with each nivolumab and ipilimumab regimen. Each BMS-986205 and 
nivolumab/ipilimumab combination regimen will be evaluated in tumor-specific cohorts based 
on the tumor type evaluated in the safety cohorts. The Ipi 1Q8 regimen will also be evaluated in 
a mixed tumor-type cohorts which may incorporate tumor types evaluated in Part 2 Dose 
Escalation. This 40 subject cohort is used to obtain preliminary safety, PK, and PD data for the 
triplet combination in other tumor types.
As all subjects in the melanoma, NSCLC, and bladder disease-specific cohorts will be receiving 
agents (nivolumab and ipilimumab) with known efficacy, a single-stage design will be utilized 
for each of these tumor types. Approximately 40 subjects will be enrolled in each of the 
following cohorts: melanoma PD-L1 positive, melanoma PD-L1 negative, NSCLC PD-L1 
positive, NSCLC PD-L1 negative and bladder, mixed tumor type to allow for the exploration of 
early efficacy signals of BMS-986205 in combination with both nivolumab and ipilimumab in 
relevant subpopulations. In each NSCLC expansion cohort, approximately 10 subjects will be 
IO-treatment naive, 25 will be treatment-naive, and 5 IO-therapy experienced. In the melanoma 
cohorts, approximately 35 will be treatment-naïve in the advanced setting and 5 will be 
IO-therapy experienced in each cohort. In the bladder expansion cohort in Part 3, at least 30 
subjects will be IO-therapy naive.
The anti-tumor activity of the expansion cohorts will be continuously monitored in all subjects 
who are evaluable for response using the measurements described in Section 8.3.1. In the 
NSCLC cohort, 16 of 25 responses for the treatment naïve subjects would result in 80% CIs for 
an ORR that is strictly higher than the historical rate of 45.3%.60 In the melanoma cohort, 22 of 
35 responses for the treatment naïve subjects would result in 80% CIs for ORRs that are strictly 
higher than the historical rates of 580.0%.28 In the bladder cohort, 16 of 30 responses would 
result in 80% CI for ORR that is strictly higher than the historical rate of 38.5%.61 The CIs are 
calculated using the Clopper-Pearson method.
8.2
Populations for Analyses
1) All Enrolled Subjects: All subjects who have signed an ICF and are registered into the IVRS.
2) All Treated Subjects: All subjects who received at least 1 dose of study drug.
3) The PK dataset includes all available concentration-time data from the subjects who received 
any BMS-986205 or nivolumab or ipilimumab.
4) The Immunogenicity dataset consists of all available immunogenicity data from the subjects 
who receive nivolumab or ipilimumab and have a baseline and at least 1 post-treatment 
immunogenicity measurement.
5) The Biomarker dataset includes all available biomarker data from the subjects who receive 
any study drug.
Analyses of safety, extent of exposure, biomarkers, PK, efficacy, and pharmacodynamics will be 
based on all treated subjects.
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8.3
Endpoints
8.3.1
Primary Endpoint(s)
•
The primary objective of this study is to establish safety, tolerability, and the 
MTD/MAD/alternate dose. 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 the 
NCI CTCAE v4.03.
•
The co-primary objective, anti-tumor activity of BMS-986205 in combination with 
nivolumab in Part 2 (dose expansion) and BMS-986205 in combination with both nivolumab 
and ipilimumab in Part 3, will be measured by ORR, DoR, and PFSR based on RECIST v1.1 
for solid tumors or IWG for blood tumor. For Parts 1 and 2, disease assessment with CT 
and/or MRI as appropriate will be performed at baseline, end of Cycle 2, and every 8 weeks. 
For Part 3, in the melanoma cohorts, the first tumor assessment will occur at Week 12 (± 1 
week); subsequent imaging will be every 8 weeks thereafter during the treatment period; for 
NSCLC, imaging assessments will occur every 6 weeks during the treatment period; for 
bladder, imaging assessments will occur every 6 weeks during the treatment period up to 24 
weeks, and then occur every 12 weeks thereafter during the treatment period. For all study 
parts, assessments continue every 12 weeks for the first year after the EOT visit, and then 
every 6 months thereafter, up to 2 years following the EOT visit until disease progression per 
RECIST v1.1 or IWG, or until confirmed disease progression for subjects treated beyond
progression (defined as an additional 10% or greater increase in tumor burden volume from 
time of initial progression including all target lesions and new measurable lesions), at the 
completion of follow-up, or until subjects withdraw from the study.
•
Best overall response (BOR) is defined as the best response designation over the study as a 
whole, recorded between the dates of first dose until the last tumor assessment prior to 
subsequent therapy. CR or PR determinations included in the BOR assessment must be 
confirmed by a second scan performed no less than 4 weeks after the criteria for response are 
first met. For those subjects who have surgical resection, only presurgical tumor assessments 
will be considered in the determination of BOR.
•
ORR is defined as the proportion of all treated subjects whose BOR is either a CR or PR.
•
DoR, 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, 1 year, and 2 years: The proportion of treated subjects remaining 
progression free and surviving at 24 weeks, 1 year, and 2 years if sufficient data are 
available. The proportion will be calculated by the Kaplan-Meier estimate, which takes into 
account censored data.
8.3.2
Secondary Endpoint(s)
8.3.2.1
Pharmacokinetics
For the first secondary objective (PK), selected BMS-986205 parameters, such as Cmax, Tmax,
AUC(TAU), Ctrough, CLT/F, CLR/F, Vss/F, AI, %UR24,
 
from concentration-time 
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data during BMS-986205 monotherapy and concentrations at end of infusion and Ctrough during 
combination treatment. Concentrations at end of infusion and Ctrough for nivolumab and 
ipilimumab (where applicable) will be assessed during combination treatment (see Section 5.5).
8.3.2.2
Pharmacodynamics
The second secondary objective of pharmacodynamics, assessed by change from baseline for 
serum kynurenine and percent change from baseline, will be summarized.
8.3.2.3
Efficacy
The BOR, ORR, DoR, and PFS rates at pre-specified time points based on RECIST v1.1 and 
IWG will be the secondary efficacy endpoints for dose escalation and clinical pharmacology 
substudies.
8.3.2.4
Immunogenicity
The third secondary objective of immunogenicity will be assessed by the frequency of positive 
anti-drug antibody (ADA) to nivolumab or ipilimumab.
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, height, and body mass index will be tabulated.
8.4.2
Efficacy Analyses
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 v1.1 for solid tumors and IWG 
for blood tumor.
To describe the anti-tumor activity of BMS-986205 in combination with nivolumab and in 
combination with both nivolumab and ipilimumab, ORR will be calculated. ORR and 
corresponding 2-sided exact 95% CI by the Clopper and Pearson method will be provided by 
treatment, and/or dose level and tumor type (if appropriate). Median DoR and corresponding 
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2-sided 95% CI may be reported by treatment, and/or dose level and tumor type (if appropriate). 
DoR 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 90% CI will be derived based on the Greenwood formula.
 
8.4.3
Safety Analyses
All recorded AEs will be listed and tabulated by system organ class, preferred term, treatment
arm, and dose level and coded according to the most current version of MedDRA. Vital signs 
and clinical laboratory test results will be listed and summarized by treatment. Any significant 
PE findings and clinical laboratory results will be listed. 
8.4.4
Pharmacokinetic Analyses
All individual PK parameters will be listed for each analytic 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(TAU), Ctrough, CLT/F, and CLR/F, after multiple-dose PK. Medians and ranges 
will be presented for Tmax. Means and standard deviations will be presented for all other PK 
parameters. 
BMS-986205 dose dependency will be assessed in dose escalation lead-in. To describe the 
dependency on dose of BMS-986205, scatter plots of Cmax and AUC(TAU) versus dose may be 
provided for each day measured. 
 
 
 
 
 
Urinary recovery data of BMS-986205 will be listed if available. Cumulative amount and 
cumulative percent recovered per interval will be summarized. Plots of individual cumulative 
percent of dose recovered in urine versus end of interval time will be provided. Mean plots of 
cumulative percent of dose recovered in urine versus end of interval time will also be provided. 
8.4.5
Biomarker Analyses
Summary statistics for biomarkers and their corresponding changes (or percent changes) from 
baseline will be tabulated by planned study day and dose in each arm. The time course of 
biomarker measures will be investigated graphically. If there is indication of meaningful pattern 
over time, further analysis (eg, by linear mixed model) may be performed to characterize the 
relationship. Methods such as, but not limited to, logistic regression will be used to explore 
possible associations between biomarker measures from peripheral blood or tumor biopsy and 
clinical outcomes.
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8.4.7
Outcomes Research Analyses
Not applicable.
8.4.8
Other Analyses 
Not applicable.
8.4.9
Immunogenicity Analyses
A listing of all available immunogenicity data will be provided by treatment, dose, and 
immunogenicity status. The frequency of subjects with a baseline and/or at least 1 positive ADA 
assessment of nivolumab and/or ipilimumab will be summarized.
8.4.10
ECG Analyses
Summary statistics will be presented for each ECG parameter (heart rate, QTcF, PR, and QRS) 
and the corresponding changes from baseline by dose and time points. Scatter plots of change 
from baseline values in each ECG parameter versus the nearest corresponding plasma drug 
concentrations will be presented. The plot of ΔQTcF versus drug concentrations will include the 
estimated linear regression taken from the results of fitting a random intercept and slope model 
(mixed model). The frequency of subjects’ maximum recorded postdose QTcF, PR, QRS, and 
ΔQTcF will be tabulated by treatment and summarized.
 
Additional ECG data and time matched 
concentrations may be pooled from other studies to perform an integrated analysis. The results of 
the analysis will be reported separately.
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 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to study subjects. 
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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. Certain CRF pages and/or electronic files may serve as the 
source documents.
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 procedures, 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 the 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 BA/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 paper or 
electronic SAE form and Pregnancy Surveillance form, respectively. 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, including any paper or electronic 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:
•
External principal investigator designated at protocol development
•
National coordinating investigator 
•
Study steering committee chair or their designee
•
Subject recruitment (eg, among the top quartile of enrollers)
•
Involvement in trial design
•
Regional representation (eg, among top quartile of enrollers from a specified region or 
country)
•
Other criteria (as determined by the study team)
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For this single site protocol, the principal investigator for the site will sign the clinical study 
report.
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 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 subject. 
This does not mean periodic abstinence (eg, calendar, 
ovulation, symptothermal, profession of abstinence for entry 
into a clinical trial, postovulation methods) or withdrawal, 
which are not acceptable methods of contraception. Women
must continue to have pregnancy tests. Acceptable alternate 
methods of highly or less effective contraceptive methods
must be discussed in the event that the subject chooses to 
forego complete abstinence.
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11
LIST OF ABBREVIATIONS
Term
Definition
ADA
anti-drug antibody
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
AI
accumulation index
AJCC
American Joint Committee on Cancer
ALK
anaplastic lymphoma kinase
ALT
alanine aminotransferase
APC
antigen-presenting cell
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-24h)
area under the concentration-time curve from time zero to 24 hours 
postdose
AUC(0-T)
area under the concentration-time curve from time zero to the time of the 
last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in 1 dosing interval
AUEC
area under the effect curve
BCRP
breast cancer resistance protein
BDC
bile duct-cannulated
BLRM
Bayesian Logistic Regression Method
BMS
Bristol-Myers Squibb
BMS EDC
Bristol-Myers Squibb Electronic Data Capture
BOR
best overall response
BSEP
bile salt export pump
BUN
blood urea nitrogen
C24
observed plasma concentration at 24 hours
Cavgss
average steady-state concentrations
CBC
complete blood count
CI
confidence interval
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Term
Definition
CrCl
creatinine clearance
CLR/F
apparent renal clearance 
CLT/F (or CLT)
apparent total body clearance
Cmax
maximum observed plasma concentration
Cmin1
trough concentration after the first dose
Cmaxss
steady-state peak concentration
Cminss
trough steady-state concentration
CNS
central nervous system
CR
complete response
CRC
colorectal cancer
CRF
case report form
CRP
C-reactive protein
CT
computed tomography 
CTA
clinical trial agreement
CTLA-4
cytotoxic T lymphocyte-associated antigen 4
Ctrough
trough observed plasma concentration at the end of the dosing interval
%CV
coefficient of variation
 
CYP
cytochrome P450
DL-1
dose level-1
DDI
drug-drug interaction
DILI
drug-induced liver injury
DLBCL
diffuse large B-cell lymphoma
DLT
dose limiting toxicity
DoR
duration of response
EC50
half maximal effective concentration
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group 
eCRF
electronic case report form
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Term
Definition
EDC
electronic data capture
EGFR
epidermal growth factor receptor
EMH
extramedullary hematopoiesis
EOI
end of infusion
EOT
end of treatment
EU
European Union
FDA
Food and Drug Administration
FNR
false negative rate
FPR
false positive rate
FSH
follicle stimulating hormone
FU
follow-up
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GM
geometric mean
hCG
human chorionic gonadotropin
HDPE
high-density polyethylene
HEK293
human embryonic kidney 293
HED
human equivalent dose
hERG
human ether-à-go-go-related gene 
HIV
human immunodeficiency virus
HL
Hodgkin’s lymphoma
HNSTD
highest non-severely toxic dose
HPV
human papillomavirus
hWB
human whole blood
IC50
half maximal inhibitory concentration
ICF
informed consent form
IDO1
indoleamine 2,3-dioxygenase 1
HRT
hormone replacement therapy
IB
Investigator’s Brochure
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Term
Definition
ICH
International Conference on Harmonisation 
IEC
Independent Ethics Committee
IFNγ
interferon-gamma
IgG4
immunoglobulin G4
IHC
Immunohistochemistry
IMP
investigational medicinal products
I-O
immuno-oncology
IP
investigational product
IRB
Institutional Review Board
IUD
intrauterine devices
IV
intravenous
IVRS
Interactive Voice Response System
IWG
International Working Group
KI
inhibitor concentration corresponding to the half-maximal rate of
inactivation
Kd
dissociation constant
LC-MS
liquid chromatography-mass spectrometry
LDH
lactate dehydrogenase
LFT
liver function test
MAD
maximum administered dose
MATE1
multidrug and toxin extrusion 1
MCV
mean corpuscular volume
MCHC
mean corpuscular hemoglobin concentration
MedDRA
Medical Dictionary for Regulatory Activities
MLR
mixed lymphocyte reaction
MM
Medical Monitor
 
 
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Term
Definition
 
MRI
magnetic resonance imaging
mRNA
messenger ribonucleic acid
MSI
Microsatellite Instability
MSI-H
Microsatellite Instability High
MTD
maximum tolerated dose
NA
not applicable
NAFLD
nonalcoholic fatty liver disease
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse 
Events
NHL
non-Hodgkin’s lymphoma
NOAEL
no-observed adverse effect level
NSCLC
non-small cell lung cancer
OATP
organic anion transporting polypeptide
OCT1
organic cation transporting polypeptide
ORR
objective response rate
Pc
permeability coefficient
PCR
polymerase chain reaction
PD
progressive disease
PD-1
programmed cell death-1
PD-L1
programmed death receptor-ligand 1
PD-(L)1
either PD-1 or PD-L1
PE
physical examination
PET
positron emission tomography
PFSR
progression-free survival rate
P-gp
P-glycoprotein
PI
principal investigator
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Term
Definition
PID
subject identification number
PK
pharmacokinetic(s)
PPK
population pharmacokinetics
PR
partial response
PT
prothrombin time
PTT
partial thromboplastin time
Q2W
every 2 weeks 
Q4W
every 4 weeks
QD
quaque die, once daily
QTcF
QT interval corrected for heart rate using Fridericia’s formula
RBC
red blood cell
RECIST
Response Evaluation Criteria In Solid Tumors
RCC
renal cell carcinoma
RNA
ribonucleic acid
SAE
serious adverse event
SD
stable disease
SCCHN
squamous cell carcinoma of the head and neck
STD10
severe toxicity to 10%
TCGA
The Cancer Genome Atlas
T-HALF
apparent terminal phase half-life
Tmax
time of maximum observed plasma concentration
Treg
regulatory T cells
TSH
thyroid-stimulating hormone
ULN
upper limit of normal
%UR24
Percent urinary recovery over 24 hours
US
United States
Vss/F (or Vss)
apparent volume of distribution at steady state
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Term
Definition
Vz/F (or Vz)
volume of distribution of terminal phase (if IV and if multi-exponential 
decline)
WBC
white blood cell
WOCBP
women of childbearing potential
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12
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expression, serum profiling for immune markers, and multiplex tissue immunohistochemistry 
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19 Beatty G et al. Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics 
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22 Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits 
T cell activation. Nat Immunol 2001;2:261-8.
23 Carter LL, Fouser LA, Jussif J, et al. PD-1: PD-L1 inhibitory pathway affects both CD4+ and 
CD8+ T cells and is overcome by IL-1. Eur J Immunol 2002;32:634-43.
24 Barber DL, Wherry EJ, Masopust D et al. Restoring function in exhausted CD8 T cells 
during chronic viral infection. Nature 2006;439:682-7.
25 Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nature 
2012;12:252-64.
26 BMS-936558 Investigator Brochure v14. Document Control No. 930038243.
27 Opdivo European Union Summary of Product Characteristics. Updated 2016 Nov 8.
28 Opdivo (nivolumab) US Prescribing Information. Bristol-Myers Squibb Company; Revised 
2018.
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29 T Kim, Amaria EN, Spencer C, et al. Combining targeted therapy and immune checkpoint 
inhibitors in the treatment of metastatic melanoma. Cancer Biol Med 2014;11:237-246.
30 Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients 
with metastatic melanoma. N Engl J Med. 2010;363(8):711; PMID20525992.
31 Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with 
advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a 
randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015;16:375-84.
32 Larkin J, Hodi FS, Wolchok JD. Combined nivolumab and ipilimumab or monotherapy in 
untreated melanoma. N Engl J Med. 2015;373(13):1270-1. doi: 10.1056/NEJMc1509660. No 
abstract available. PMID:26398076.
33 Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in 
untreated melanoma. N Engl J Med. 2015;372(21):2006-17. doi: 10.1056/NEJMoa1414428. 
Epub 2015 Apr 20. PMID:25891304.
34 Spigel DR, Reckamp KL, Rizvi NA, et al. J Clin Oncol 33:5s, 2015 (suppl; abstr8009).
35 Paz-Ares L, Horn L, Borghaei H, et al. J Clin Oncol 33, 2015 (suppl; abstrLBA109).
36 Hellmann et al. Lancet Oncol 2017; 18: 31–41. Published Online. December 5, 2016. 
http://dx.doi.org/10.1016/S1470-2045(16)30624-6.
37 Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally 
advanced and metastatic urothelial carcinoma who have progressed following treatment with 
platinum-based chemotherapy: a single-arm, multicentre, Phase 2 trial. Lancet 
2016;387:1909-20.
38 Sharma P, Bono P, Kim JW, et al. Efficacy and safety of nivolumab monotherapy in 
metastatic urothelial cancer (mUC): results from the phase 1/2 CheckMate 032 study 
[abstract]. J Clin Oncol 2016;34 suppl; abs 4501, oral presentation.
39 Galsky M, Retz M, Siefker-Radtke A, et al. Efficacy and safety of nivolumab monotherapy 
in patients with metastatic urothelial cancer (mUC) who have received prior treatment: 
Results from the Phase 2 CheckMate 275 study. Presented at: 2016 ESMO Congress; 
October 7-11, 2016; Copenhagen, Denmark. Abstract LBA31.
40 Carthon BC, Wolchok JD, Yuan J, et al. Preoperative CTLA-4 blockade: tolerability and 
immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res 
2010;16:2861-71.
41 Althammer, S., K. Steele, et al. 31st Annual Meeting and Associated Programs of the Society 
for Immunotherapy of Cancer (SITC 2016): late breaking abstracts. Journal for 
ImmunoTherapy of Cancer 4(2):91.
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42 Ipilimumab Investigator Brochure, Version No 19, Bristol Myers Squibb, 2016; Document 
Control No. 930017531.
43 BMS-986205(IDO) Biopharmaceutics Report: Non-clinical tablet and Capsule Performance 
(DPST-BMS-986205). Bristol-Meyers Squibb Company; 2017. Document Control No. 
950068203. 
44 Hejtmancik MR, Trela BA, Kurtz PJ et al. Comparative gavage 
subchronic toxicity studies of o-chloroaniline and m-chloroaniline in 
F344 rats and B6C3F1 mice. Tox Sci 2002;69,234-43.
45 Chhabra RS, Thompson M, Elwell MR, et al. Toxicity of 
p-chloroaniline in rats and mice. Food and Chem Tox 1990;28:717-22.
46 BMS-986205: Nonclinical evaluation of the pharmacokinetics and metabolism of 
BMS-986205. Bristol-Myers Squibb Company; 2015. Document Control No. 9300.
47 BMS-986205: Lead profiling report. Bristol-Myers Squibb Company; 2015. Document 
Control No. 9300.
48 Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res 
1993;10:1093-5.
49 Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for 
management. J Cardiothorac Vasc Anesth. 2014;28:1043-7.
50 para-Chloroaniline. International Agency for Research on Cancer - Summaries and 
Evaluations 1993; 57:305. 
51 Luke J, Gelmon K, Pachynski R, et al. Preliminary antitumor and immunomodulatory 
activity of BMS-986205, an optimized indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, in 
combination with nivolumab in patients with advanced cancers. SITC 2017.
52 Gibney, G et al. European Journal of Cancer, Volume 51, S106-S107.
53 Jordan RC, Lingen MW, Perez-Ordonez B, et al. Validation of methods for oropharyngeal 
cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 
2012;36:945-54
54 US Department of Agriculture, Agricultural Research Service. USDA National Nutrient 
Database for Standard Reference, Release 28; 2015 Nutrient Data Laboratory Home Page. 
Available from: http://www.nal.usda.gov/ndb/search.
55 Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for
management. J Cardiothorac Vasc Anesth 2014;28:1043-7.
56 Umar A, Boland Cr, Terdiman JP, et al. Revised Bethesda Guidelines for Hereditary 
Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability. J Nat 
Cancer Inst 2004;96:261-68.
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60 Hellmann MD, Ciuleanu T-E, Pluzanski A, et al. Nivolumab Plus Ipilimumab in Lung 
Cancer with a High tumor Mutational Burden. N Engl J Med. 2018; 378:2093-2104
61 Sharma P, Callahan MK, Calvo E, et al. Efficacy and Safety of Nivolumab Plus Ipilimumab 
in Metastatic Urothelial Carcinoma: First Results from the Phase I/II CheckMate 032 Study. 
Journal of ImmunoTherapy of Cancer. 2016; 4(Suppl 2):O3 
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APPENDIX 1
STATISTICAL METHODOLOGY
Statistical Details for Bayesian Logistic Regression Model (BLRM and BLRM-Copula) and 
Priors for Dose Escalation and Safety Monitoring
1
MODEL SETUP FOR BMS-986205 LEAD-IN (MONOTHERAPY)
1.1
Monotherapy Methodology Description 
An adaptive 2-parameter Bayesian Logistic Regression Model (BLRM) guided by the escalation 
with overdose control (EWOC) principle1,2,3 will be used to guide the dose escalation of 
BMS-986205 alone in the lead-in phase for dose recommendation during dose escalation. 
The BLRM will be fitted on the dose limiting toxicity (DLT) data for BMS-986205 within the 
2 weeks lead-in throughout the dose escalation to model the dose-toxicity relationship of 
BMS-986205 in the lead-in phase. 
The dose-toxicity relationships for BMS-986205 alone follow a logistic model as follows:
݈݋݃݅ݐሺ݌௜ሻൌ݈݋݃ሺߙଵሻ൅ߚଵ݈݋݃ሺ݀ଵ௜݀ଵ
כ
൘ሻ
Note that the ߙଵand ߚଵparameters are assumed positive, and ݀ଵ
כ is the reference dose for 
BMS-986205 (please refer to the meaning of ߙଵ
and ߚଵin Section 1.2.1 for detailed 
implementation).
1.2
Prior Specification for BMS-986205 Monotherapy 
The Bayesian approach requires the specification of prior distributions for model parameters,
which include parameters (ߙଵ, ߚଵ) for BMS-986205. The prior distributions for BMS-986205 
single agent activity were derived using a weakly informative prior based on published 
indoleamine 2,3-dioxygenase (IDO) clinical trial data4 as well as discussion with the Bristol-
Myers Squibb (BMS) clinical team.
Derivation of prior distribution of these parameters is provided in the following subsections.
1.2.1
Prior Derivation for BMS-986205 Parameters (࢒࢕ࢍሺࢻ૚ሻ, ࢒࢕ࢍሺࢼ૚ሻ)
A weakly informative prior will be used for parameters (ߙଵ, ߚଵ) for BMS-986205 to reflect the 
potential of different toxicity of BMS-986205 from historical IDO data and to allow for 
considerable prior uncertainty. 
Further details are provided below.
Weakly Informative Prior
The median DLT rate at the reference dose (BMS-986205 at 800 mg QD) was assumed to be 
30%, ie, mean (log(ߙଵ)) = -0.847.
A doubling in dose was assumed to double the odds of DLT, ie, mean(log(ߚଵ)) = 0.
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The standard deviation of log(ߙଵ) was set to 0.722 using the following steps:
•
Toxicity probability range was set to be [5%, 80%], then the toxicity interval would be 
logit(0.8)-logit(0.05) = 4.33.
•
To cover 99.7% of the variance, the toxicity interval will cover 6*sd(log(ߙଵ)).
Correspondingly, the standard deviation of log(ߚଵ) was set to 1, which allows for considerable 
larger prior uncertainty for the dose toxicity.
1) The correlation between log(ߙଵ) and log(ߚଵ) was set to 0.
2) Log(ߙଵ) and log(ߚଵ) follow bivariate normal distribution.
Table 1:
Prior Distribution for Model Parameters for BMS-986205
Parameter
Means
Standard Deviations
Correlation
log(ߙଵ), log(ȕ1)
(-0.847, 0)
(0.722, 1)
0
2
MODEL SETUP FOR BMS-986205 AND NIVOLUMAB COMBINATION 
2.1
Methodology Description for Combination therapy
Toxicity profiles of both BMS-986205 monotherapy and nivolumab monotherapy will be 
incorporated to develop the combination model framework. A copula-type model will be utilized 
to cover all general combination cases, including additive and synergistic effects. The 
combination of 2 treatments will be explored using a Bayesian hierarchical model by utilizing 
the toxicity profiles of single agents as prior marginal profiles for the combination. The 
following copula-type model5 will be used.
݌௜௝ൌ1 െ݁ݔ݌ሺെ൤ሼെ݈݋݃ሺ1 െ݌௜
௠ሻሽ
ଵఊ
ൗ൅൛െ݈݋݃ሺ1 െݍ௝
௡ሻൟ
ଵఊ
ൗ൨
ఊ
ሻ,
Where ݌௜is the pre-specified best guess toxicity probability for agent A, ݍ௝is the pre-specified 
best guess toxicity probability for agent B, and ݉and ݊characterize the individual drug effect 
and ߛcharacterizes drug-drug interactive effect.
The joint toxicity framework models toxicity rates of both agents as well as their interaction 
effects in a 7-parameter hierarchical model, where each of the monotherapy dose-toxicity 
relationship will be characterized by a 2-parameter BLRM model (see Section 1.1). There are 3
additional parameters for the copula-type model, 1 for each agent as well as 1 for the interaction 
term. A dose-toxicity surface will be characterized for different dose combinations of these 2
agents. 
As there is currently no historical data/prior knowledge to indicate how much information to be 
borrowed for each of the single agents, parameters m and n are both set to be 1, meaning 
borrowing 100% of the information from the 2 agents. The above formula is then simplified into 
a 5-parameter model as follows:
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݌௜௝ൌ1 െ݁ݔ݌ሺെ൤ሼെ݈݋݃ሺ1 െ݌௜ሻሽ
ଵఊ
ൗ൅൛െ݈݋݃ሺ1 െݍ௝ሻൟ
ଵఊ
ൗ൨
ఊ
Since only a fixed nivolumab dose (240 mg) will be used in BMS-986205 and nivolumab 
combination, this surface will be simplified into a 2-dimensional dose-toxicity curve. Posteriors 
for the corresponding 5 parameters (2 logistic regression parameters [ߙଵ, ߚଵ] for BMS-986205
and 2 logistic regression parameters for Nivolumab [ߙଶ, ߚଶ] as well as 1 interaction parameter for 
the copula-type model [ߛ, which will be discussed in detail in the following session]) will be fit 
into the in-house developed model, which implements the above described theoretical setup.
2.2
Priors Specification for Combination Studies
2.2.1
Prior for BMS-986205
Posterior information on (log(Į1) and log(ȕ1)) from the lead-in part of the study will be used as 
marginal BMS-986205 prior for combination with nivolumab. This prior information is not 
pre-specified and will be continuously updated when additional toxicity (DLT) information from 
the lead-in is available. In the simulation (see Section 2.4), the prior of BMS-986205 as 
described in Section 1.2.1(Table 1) is used for illustration purposes, as no real-time DLT data are 
available at this time.
2.2.2
Prior Derivation for Nivolumab Parameters (log(Į2),log(ȕ2)) 
Similar to BMS-986205 monotherapy in the lead-in phase, the logistic model for nivolumab is as 
follows:
݈݋݃݅ݐ൫ݍ௝൯ൌ݈݋݃ሺߙଶሻ൅ߚଶ݈݋݃ሺ݀ଶ௝
݀ଶ
כ
൘
ሻ, where ܽଶ, ߚଶ  > 0.
Note that the ߙଶand ߚଶparameters are assumed positive, and ݀ଶ
כ is the reference dose for 
nivolumab. 
The toxicity profile of nivolumab has been studied in several studies. A bivariate normal prior 
for the nivolumab model parameters (log(Į2), log(ȕ2)) was obtained by extracting a posterior of 
nivolumab using DLT and safety data from the Study CA209003, which is used later as the 
meta-analytical-predictive (MAP) prior for nivolumab. 
The MAP prior for the model parameters (log(Į2), log(ȕ2)) was obtained in the following steps.
First, a prior distribution for nivolumab was developed:
•
The median DLT rate at the reference dose (3 mg/kg every 2 weeks) was assumed to be 10%, 
ie, mean (log(Į2)) = logit(1/10) = log(1/9) = -2.197.
•
A doubling in dose was assumed to double odds of DLT, ie, mean(log(ȕ2)) = 0.
•
The standard deviation of log(Į2) was set to 2, and the standard deviation of log(ȕ2) to 1, 
which allows for considerable prior uncertainty for the dose-toxicity profile.
•
The correlation between log(Į2),and log(ȕ2) is assumed to be 0 (assuming independence of 
log(Į2) and log(ȕ2)).
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•
In addition, heterogeneity between the historical study and current study was incorporated 
using a meta-analytic predictive approach, by defining between-trial standard deviations Ĳ1
and Ĳ2 for log(Į2) and log(ȕ2), respectively. The between-trial variability is assumed to be 
moderate. Therefore, Ĳ1 and Ĳ2 were set to follow a log-normal distribution with mean 
log(0.25) and log(0.125), respectively, with a common standard deviation log(2)/1.96.
With this prior, the clinical trial data below were used to generate the posterior for nivolumab, 
which is then used as the MAP prior for this study. 
Table 2:
Data from Single Agent Nivolumab Study CA209003
Dose of Nivolumab (mg/kg)
Every 2 Weeks
No. of DLTs/No. of Evaluable Patients in Escalation Phase
0.1
0/3
0.3
0/3
1
0/3
3
0/3
10
1/6
Abbreviation: DLT = dose limiting toxicity.
Table 3:
Prior Distribution for Model Parameters for Nivolumab
Parameter
Means
Standard Deviations
Correlation
log(Į2), log(ȕ2)
(-3.269, -0.152)  
(1.186, 0.771)  
-0.369
Note: Nivolumab prior information was based on mg/kg dosing instead of flat dosing. If real 
pharmacokinetic (PK) data from this study show difference from mg/kg assumption, the 
nivolumab prior will be revisited and modified accordingly.
2.2.3
Prior for Interaction Parameters for Joint Toxicity of BMS-986205 and 
Nivolumab Combination
A gamma prior distribution for the interaction parameter ߛis derived to reflect the current 
uncertainty about the toxicity profile of the combination of BMS-986205 and nivolumab. 
Although no PK drug-drug interaction is expected, the possibility of significant positive 
interaction between BMS-986205 and nivolumab cannot be totally excluded. The interaction 
parameter ߛwas chosen accordingly but with a degree of uncertainty in order to allow for the 
possibility that the interaction may be positive or negative. Therefore, the following assumptions
are made for the interaction parameter:
•
ߛfollows a gamma distribution and with a mean centered at 1.1, which means the 
combination of 2 agents only has a little bit of synergistic effect.
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•
The 97.5 percentile of ߛis log(3), ie, 3-fold increase in odds of DLT due to interaction over 
independence at the combination starting dose.
This assumes, a priori, that there is a small synergistic interaction but also allows for the 
potential of significant synergism of the toxic profiles. It also does not completely ignore the 
possibility of antagonism since we consider 40% prior probability that ߛis less than 1.
2.3
Parameters for Dose Recommendation Decision for the Lead-in Phase 
and Combination Phase
Dose recommendation for BMS-986205 alone and in combination with nivoluamb will be based 
on inference from Bayesian posterior, and the probability that the true DLT rate for each dose 
lies in one of the following categories:
•
[0,16%) under-dosing
•
[16%,35%) targeted toxicity
•
[35%,100%] excessive toxicity
Following the principle of EWOC, after gaining information of each cohort of subjects, the 
candidate doses are the ones fulfilling the overdose criterion that there is less than 35% chance of 
excessive toxicity. Only the candidate doses will be considered for the next dose decision by 
Investigators and BMS study personnel based on a synthesis of all relevant data available from 
all dose levels evaluated in the ongoing study.  
Any information on the dose-DLT relationship generated by publicly available IDO clinical trial 
data as well as nivolumab prior data from Study CA209003 will be incorporated into the prior 
distribution before the first dose-escalation decision is made within this study in order to reflect 
all relevant information at that time.
The
final recommended maximum tolerated dose (MTD)/maximum administered dose
(MAD)/alternate dose of BMS-986205 in combination with nivolumab for cohort expansion will 
be based on the recommendation from the BLRM-copula model and a synthesis of all the data 
available on all dosed subjects, including clinical and laboratory safety assessments and PK and 
pharmacodynamic and efficacy data from all treated patients at each dose level up to the 
MTD/MAD. For further details of the BLRM-copula model and results under a variety of 
scenarios, refer to the simulation results in Section 2.4.
2.4
Operating Characteristics
The BLRM and BLRM-copula models should make reasonable decisions during a study based 
on the observed toxicities particularly in early cohorts. After completion of a given cohort, the 
decision to dose escalate and actual dose chosen for the subsequent cohort will depend on the 
recommendation of the BLRM (-copula) EWOC principle and medical review of all relevant 
data available up to date. Operating characteristics of BMS-986205 in combination with 
nivolumab using BLRM-copula models are shown in this section with simulation results. The 
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provisional dose levels for BMS-986205 are 25, 50, 100, 200, 400, 600, and 800 mg. Nivolumab 
is fixed at a 240-mg flat dose.
In order to show how the design performs, 4 hypothetical scenarios were investigated (please 
refer to Table 3 for more details):
•
Scenario 1: General dose-DLT relationship with the assumption that the increased dose will 
have increased DLT rates, with the highest dose reaching the target toxicity rate (Additive)
•
Scenario 2: All higher toxicity rates 50% higher than the additive scenario 1 along with 
increased dose levels, with the highest dose toxicity level above 33% (Synergistic)
•
Scenario 3: All dose levels with toxicities 25% lower than the additive scenario 1 (Cancel 
effect)
•
Scenario 4: All dose levels with toxicities 50% lower than the additive scenario 1 (Strong 
Cancel effect)
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Table 4:
Toxicity Rates for Each Scenario Across All 7 Pre-specified Dose Levels
Scenario/Dose Level
25 mg BMS-
986205 
+ 
240 mg 
Nivolumab
50 mg BMS-
986205 
+ 
240 mg 
Nivolumab
100 mg BMS-
986205 
+ 
240 mg 
Nivolumab
200 mg BMS-
986205 
+ 
240 mg 
Nivolumab
400 mg BMS-
986205 
+ 
240 mg 
Nivolumab
600 mg BMS-
986205 
+ 
240 mg 
Nivolumab
800 mg BMS-
986205 
+ 
240 mg 
Nivolumab
Scenario 1
Additive
0.05
0.06
0.09
0.13
0.21a
0.27a
0.33a
Scenario 2
Synergistic
0.08
0.09
0.14
0.2a
0.32a
0.41
0.5
Scenario 3
Cancel effect
0.04
0.05
0.07
0.1
0.15
0.2a
0.25a
Scenario 4
Strong Cancel effect
0.02
0.03
0.04
0.06
0.09
0.13
0.15
a Doses with true toxicity rate within the target toxicity interval [16%, 35%).
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Simulation Parameters
One thousand trial simulations were used for each scenario. The number of subjects to be treated 
in each patient cohort in a specific dose level and the stopping rules used to declare MTD were 
defined as:
I.
Fixed cohort size: 3
II.
Probability of overdosing: <35%
III.
Maximum number of subjects treated: 30
IV.
Probability of target toxicity: >50%
V.
Minimum number of subjects treated at a given dose level in order to declare MTD: 6
All simulations were run using in house-developed code via R and Openbugs, and EAST 6.3.1®
software.
Simulation Results
Operating characteristics from the simulations were reviewed to assess the relative performance 
under each true scenario. The metrics reviewed are:
1. Percentage of trials with MTD being selected at dose levels with the pre-specified 
toxicities fall within the range of [16%, 35%) (Correct MTD)
2. Percentage of trials with MTD being selected at dose levels with the pre-specified 
toxicities fall within the range of [35%, 100%] (MTD Too High)
3. Percentage of trials with MTD being selected at dose levels with the pre-specified 
toxicities fall with the range of [0%, 16%) (MTD Too Low)
4. Percentage of trials with MTD being selected at the dose level with the pre-specified 
toxicity most closest to 33% and ≤33% (MTD Point)
5. The 25% quantile of 1000 trials’ fitted MTDs derived by solving the logistic regression 
formula using posterior medians of parameters, as well as 33% as target DLT rate (Fitted 
MTD)
6. Percentage of trials stopped before declaring MTD due to the reason that MTD is below 
the lowest dose level (simulation parameter II) (EWOC Stop)
7. Percentage of trials stopped due to reaching the probability cutoff of posterior percentage 
fall in the target toxicity range (simulation parameter IV) and a minimum sample size of 
N = 6 at the declared MTD (simulation parameter V) (Target Range Stop)
8. Percentage of trials stopped due to reaching the maximum assigned sample size of N = 30 
(simulation parameter III) (MaxN Stop)
9. Average sample size for each scenario (Average Sample Size)
Below summarizes the simulated operating characteristics of the model for the 4 different 
scenarios studied. One thing to note is that the following simulation results are only for 
illustrative purposes. This might not fully represent real trial conduction scenarios due to 
software/current programming code limitations as well as not considering the clinical team’s 
decision overwriting BLRM-copula recommendation based on the totality of data.
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Table 5:
Simulation Results for Operating Characteristics
MTD Range
Point Estimate
Good Stopping
Bad 
Stopping
Average 
Sample 
Size
Correct 
MTD 
(%)
MTD 
Too 
High
(%)
MTD 
Too 
Low 
(%)
MTD 
Point
(%)
Fitted MTD 
(True MTD) 
(mg)
EWOC 
Stop
(%)
Target 
Range 
Stop
(%)
MaxN 
Stop 
(%)
Scenario 1: Additive
90.7
0
8.7
24.2
771.1 (800)
0.6
99.3
0.1
12.7
Scenario 2: Synergistic
83.2
12
3.4
46.1
640.4 (400, 600)a
1.4
98.5
0
13.6
Scenario 3: Cancel effect
88.3
0
11.6
37.4
850.4 (>800)
0.1
99.8
0.1
12.2
Scenario 4: Strong Cancel
effect
NAb
0
99.9
62.6
1030.9 (>>800)
0.1
99.9
0
11.7
a Means the true MTD falls into the range between 400 and 600 mg.
b NA because pre-specified toxicity are all below [16%, 35%) target toxicity range.
Abbreviations: EWOC = escalation with overdose control; MTD = maximum tolerated dose; NA = not applicable.
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Overall, from the scenarios illustrated above, it can be shown that the model performs very well 
under the hypothetical scenarios investigated. The model allows for high MTD identification 
accuracy (using the MTD range), a small average sample size (less than half of the proposed 
sample size), a high probability of good stopping with great confidence (> 98%), and a low 
probability of bad stopping (~ 0%) when all of the subjects have been used. 
In this simulation, different angles have been investigated regarding the performance of the 
model in terms of identifying the true MTDs under different scenarios. For scenario 1, the MTD 
point estimate is the lowest (24.2%) across all 4 scenarios. This means the dose level (800 mg) 
corresponding to the toxicity rate of 0.33 has only been identified 24.2% times as the MTD 
among all 1000 simulations. When it comes to the “correct MTD” (considering the MTD range), 
which is the accumulated percentages, scenario 1 is the highest among all 4 scenarios (90.7%). 
This can possibly be attributed to the simulation set-up on pre-specified toxicity rates. The 
toxicity levels are relatively similar to each other among the last 3 higher dose levels in scenario 
1, where 400 mg is associated with a toxicity rate of 0.21, 600 mg with a toxicity rate of 0.27,
and 800 mg with a toxicity rate of 0.33, all falling within the target interval of [16%,35%). This 
could also be explained by the model fitted MTD (771.1 mg), which is slightly lower than the 
true MTD of 800 mg. To improve the model’s performance under such scenario, dose levels with 
similar toxicity rates might be combined or dose levels might be assigned with more 
distinguishable toxicity rates
For “MTD too high” cases, scenarios 1, 3, and 4 show no possibility of overdosing. On the other 
hand, scenario 2 shows a rate of 12% of overdosing. This is matching with the model fitted MTD 
at 640.4 mg, which falls out of the range of the hypothetical true MTD (between 400 and 
600 mg). The slightly higher estimated MTD might be ascribed to the deviation of the prior 
distribution from the true underlying dose-DLT relationship. There is only 30% of the DLT rate 
assumed as current prior at the reference dose level of 800 mg, which is much lower than the true
toxicity rate (50%) at this dose level. As in all parametric models, the prior distribution plays an 
important role in the performance of the BLRM-copula model under each scenario. 
For “MTD too low” cases, scenarios 1, 2, and 3 show very low percentages of under-dosing (all 
< 12%), which is consistent with the hypothetical Pr (DLT). This also benefits from the properly 
defined overdose control probability of (Pr(overdose) < 35%). In scenario 4, a very strong cancel 
effect has been investigated with the highest toxicity level set as 0.15. In this case, the “fitted 
MTD” of 1030.9 mg could provide more guidance for the clinical team during trial conduction.
Different reasons for stopping have been investigated to obtain a deeper understanding of the 
operating
characteristics
of the BLRM-copula model. The performance of a “Good 
Stopping/Target Range Stop” (a stop due to high confidence about the recommended MTD fall 
in the pre-specified target toxicity interval) is good across all 4 scenarios (all high above 98%). 
Another indicator of a “Good Stopping” is the EWOC Stop; the overdosing control is low 
(< 2%) across all 4 scenarios. Low values are good because all of the toxicities among the 4 
scenarios that correspond to the starting dose are low (ranging from 0.02 to 0.08). Therefore, the 
chance of stopping early and declaring the MTD lower than the pre-specified lowest dose level 
should rarely happen. This is consistent with our hypothetical scenarios. Additionally, “Bad 
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Stopping” due to reaching the maximum pre-assigned sample size (max N = 30) is around 0 for 
all 4 scenarios, which is ideal for early phase trials. 
The average sample size from all 1000 simulations for each scenario is below or equal to 14, 
which is less than the pre-specified maximum sample size (N = 30). To control the possible 
heterogeneity between the prior distribution and the underlying true dose-DLT relationship, more 
information from the current study is warranted. Increasing the “total maximum number of 
subjects” for the trial or adding a stopping rule for the “maximum number of subjects enrolled 
for a next to-be dose level,” or adding a restriction for “dose skipping,” might be implemented 
during the conduction of the trial to gain more information from the trial. Also, intermediate dose 
levels and/or flexible cohort sizes might be investigated in the real study.
3
MODEL SETUP FOR BMS-986205, NIVOLUMAB AND IPILIMUMAB 
COMBINATION 
3.1
Methodology Description for Triplet Combination therapy
Toxicity profiles of BMS-986205 monotherapy, nivolumab and ipilimumab monotherapy will be 
incorporated to develop the triplet combination model framework. A copula-type model will be 
utilized to cover all general combination cases, including additive and synergistic effects. The 
combination of 3 treatments will be explored using a Bayesian hierarchical model by utilizing 
the toxicity profiles of single agents as prior marginal profiles for the combination. The 
following copula-type model6 will be used.
݌௜௝௞ൌ1 െ݁ݔ݌ሺെ൤ሼെ݈݋݃ሺ1 െ݌௜
௠ሻሽ
ଵఊ
ൗ൅൛െ݈݋݃ሺ1 െݍ௝
௡ሻൟ
ଵఊ
ൗ൅ሼെ݈݋݃ሺ1 െݎ௞
௧ሻሽ
ଵఊ
ൗ൨
ఊ
ሻ,
Where ݌௜is the pre-specified best guess toxicity probability for agent A, ݍ௝is the pre-specified 
best guess toxicity probability for agent B and ݎ௞is the pre-specified best guess toxicity 
probability for agent C. Here ݉, ݊and ݐcharacterize the individual drug effect and 
ߛcharacterizes drug-drug interactive effect.
The joint toxicity framework models toxicity rates of both agents as well as their interaction 
effects in a multi-parameter hierarchical model, where each of the monotherapy dose-toxicity 
relationship will be characterized by a 2-parameter BLRM model (see Section 1.1). There are 4 
additional parameters for the copula-type model, 1 for each agent as well as 1 for the interaction 
term. A dose-toxicity surface will be characterized for different dose combinations of these 3 
agents. 
As there is currently no historical data/prior knowledge to indicate how much information to be 
borrowed for each of the single agents, parameters m, n and t are both set to be 1, meaning 
borrowing 100% of the information from all 3 agents. The above formula is then simplified into 
a 7-parameter model as follows:
݌௜௝௞ൌ1 െ݁ݔ݌ሺെ൤ሼെ݈݋݃ሺ1 െ݌௜ሻሽ
ଵఊ
ൗ൅൛െ݈݋݃ሺ1 െݍ௝ሻൟ
ଵఊ
ൗ൅ሼെ݈݋݃ሺ1 െݎ௞ሻሽ
ଵఊ
ൗ൨
ఊ
Since only a fixed nivolumab and ipilimumab dose will be used in BMS-986205, nivolumab and 
ipilimumab combination, in each safety cohort, this surface will be simplified into a 2-
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dimensional dose-toxicity curve. Posteriors for the corresponding 7 parameters (2 logistic 
regression parameters [ߙଵ, ߚଵ] for BMS-986205, 2 logistic regression parameters for Nivolumab 
[ߙଶ, ߚଶ] and 2 logistic regression parameters for Ipilimumab [ߙଷ, ߚଷ] as well as 1 interaction 
parameter for the copula-type modelሾߛ, which will be discussed in detail in the following 
session]) will be fit into the in-house developed model, which implements the above described 
theoretical setup.
3.2
Priors Specification for Combination Studies
3.2.1
Prior for BMS-986205
Posterior information on (log(Į1), log(ȕ1)) from the BMS 986205 lead-in and BMS 986205 and 
nivolumab combination part of the study will be used as marginal BMS-986205 prior for 
combination of BMS 986205 with nivolumab and ipilimumab. This prior information is not 
pre-specified and will be continuously updated when additional toxicity (DLT) information from 
the study is available.
3.2.2
Prior for Nivolumab
Posterior information on (log(Į2), log(ȕ2)) from the BMS 986205 and nivolumab combination 
part of the study will be used as marginal nivolumab prior for combination of BMS 986205 with 
nivolumab and ipilimumab. This prior information is not pre-specified and will be continuously 
updated when additional toxicity (DLT) information from the study is available.
3.2.3
Prior Derivation for Ipilimumab Parameters (log(Į3),log(ȕ3)) 
Similar to nivolumab monotherapy in the two drug combination part, the logistic model for 
ipilimumab is as follows:
݈݋݃݅ݐሺݎ௞ሻൌ݈݋݃ሺߙଷሻ൅ߚଷ݈݋݃ሺ݀ଷ௞݀ଷ
כ
൘
ሻ, where ܽଷ, ߚଷ  > 0.
Note that the ߙଷand ߚଷparameters are assumed positive, and ݀ଷ
כ is the reference dose for 
ipilimumab. 
The toxicity profile of ipilimumab has been studied in several studies. A bivariate normal prior 
for the ipilimumab model parameters (log(Į3), log(ȕ3)) was obtained by extracting a posterior of 
ipilimumab using safety data from multiple studies, which is used later as the meta-analytical-
predictive (MAP) prior for ipilimumab. Since DLT information from ipilimumab studies was not 
available, incidence of treatment-related Grade 3-4 AEs from various Phase 2/3 ipilimumab 
studies at BMS in subjects with previously treated or untreated advanced melanoma was used in 
lieu of DLT rate in order to derive the prior for the BLRM parameters, (log(ߙଷ),log(ߚଷ)): a Phase 
3 study of ipilimumab administered at 3 mg/kg vs 10 mg/kg (CA184169, N=360 per arm), a 
Phase 2 study of multiple doses of ipilimumab monotherapy (CA184022, N=71 per arm), a 
Phase 3 study in HLA-A*0201positive subjects (MDX010-20, ipilimumab 3 mg/kg monotherapy 
arm with N=131), and data from other various Phase 2 studies (N=111 for pooled 3 mg/kg; 
N=325 for pooled 10 mg/kg). 
The following steps describe how this MAP component is obtained.
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First, a prior distribution for ipilimumab was developed:
•
The median toxicity rate at the ipilimumab reference dose (10 mg/kg Q3W) was assumed to 
be 30%, i.e., mean (log(ߙଷ)) = logit(0.30)= -0.847.
•
A doubling in dose was assumed to double the odds of DLT, i.e. mean (log(ߚଷ)) = 0.
•
The standard deviation of log(ߙଷ) was set to 2, and the standard deviation of log(ߚଷ) was set 
to 1, which allows for considerable prior uncertainty for the dose-toxicity profile.
•
The correlation between log(ߙଷ) and log(ߚଷ) was assumed to be 0 (assuming independence 
of log(ߙଷ) and log(ߚଷ)).
•
In addition, heterogeneity between the historical study and the current study was 
incorporated using a meta-analytic predictive approach, by defining between-trial standard 
deviations Ĳ1 and Ĳ2 for log(ߙଷ) and log(ߚଷ), respectively. The between-trial variability is 
assumed to be moderate. Therefore, Ĳ1 and Ĳ2 were set to follow a log-normal distribution 
with mean log(0.25) and log(0.125) respectively with a common standard deviation 
log(2)/1.96.
With this prior, the clinical trial data below were used to generate the posterior for ipilimumab, 
which is then used as the MAP prior for this study. 
Table 6:
Data from Phase 2/3 ipilimumab studies
Dose of Ipilimumab (mg/kg)
Toxicity (percentage [number of subjects/total subjects]) a
0.3
10% (7/72)
3
18% (119/675)
10
32% (242/760)
a % of subjects with treatment-related Grade 3-4 AEs
Table 7:
MAP prior distribution for model parameters of Ipilimumab
Parameter
Means
Standard deviations
Correlation
(log(ߙଷ), log(ߚଷ))
(-0.797, -0.588)
(0.405, 0.255)
0.072
Note: Ipilimumab prior information stated here is based on different dosing schedules than the 
ones being used in Part 3 combination. If real safety and pharmacokinetic (PK) data from this 
study show difference, the prior will be revisited and modified accordingly. 
3.2.4
Updated Marginal Posterior for BMS-986205, Nivolumab and Ipilimumab 
from Ongoing Studies
As multiple nivolumab and ipilimumab combinations studies in different indications with similar 
dosing schedule to Part 3 triplet combinations are ongoing, the final nivolumab and/or 
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ipilimumab marginal prior used in triplet combination may be further updated to incorporate 
recent safety information if available during the study.
3.2.5
Prior for Interaction Parameters for Joint Toxicity of BMS-986205, 
Nivolumab and Ipilimumab Combination
A gamma prior distribution for the interaction parameter ߛis derived to reflect the current 
uncertainty about the toxicity profile of the combination of BMS-986205, nivolumab and 
ipilimumab. Although no PK drug-drug interaction is expected, the possibility of significant 
positive interaction between BMS-986205, nivolumab and ipilimumab cannot be totally 
excluded. The interaction parameter ߛwas chosen accordingly but with a degree of uncertainty 
in order to allow for the possibility that the interaction may be positive or negative. Therefore,
the following assumptions are made for the interaction parameter:
•
ߛfollows a gamma distribution and with a mean centered at 1.1, which means the 
combination of 2 agents only has a little bit of synergistic effect.
•
The 97.5 percentile of ߛis log(3), ie, 3-fold increase in odds of DLT due to interaction over 
independence at the combination starting dose.
This assumes, a priori, that there is a small synergistic interaction but also allows for the 
potential of significant synergism of the toxic profiles. It also does not completely ignore the 
possibility of antagonism since we consider 40% prior probability that ߛis less than 1.
As specified in Section3.2.1, 3.2.2 and 3.2.4, recent safety information from other parts of the 
current study as well as multiple ongoing nivolumab and ipilimumab combinations studies may 
be used to update the prior distributions for the marginal of the individual drugs. Similarly, the 
interaction parameter may also be updated based on current safety data on an ongoing basis.
3.3
Safety Monitoring Examples with BLRM (-Copula) for BMS-986205, 
Nivolumab and Ipilimumab Combination
In order to provide a comprehensive view of the dynamics of the models, although no study data 
from triplet combination are available at this point, prior information is used to illustrate 
hypothetical scenarios. For the simplicity of illustration purposes, a static cohort size of 3 
subjects is applied for the initial safety cohort. BLRM -Copula models are also designed to fit 
various different cohort sizes, adaptively, and will be used for safety monitoring on a continued 
basis. 
During safety monitoring, posterior probabilities will be updated whenever new DLT 
information are available. The following two visualization plots will be used to reflect the real 
time dose-DLT relationship, to quantify benefit (in the form of target dosing) and risk (in the 
form of overdosing and underdosing) during model’s recommendation process, and to facilitate 
clinical team’s interpretation of the model recommendations for the final decision making:
•
Dose-DLT profile for the entire dose range of BMS-986205. The doses ranging between 0 
mg and 800 mg (Figure 1).
•
Stacking histograms displaying predictive probabilities on DLT rates classified into 3 
different categories (Underdosing, Target dosing and Overdosing) (Figure 2).
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Figure 1: 
Dose-DLT profile after incorporating prior information
Interpretation and usage of Figure 1:
Figure 1 is a snapshot of the dose-DLT profile with prior information only. The dose-DLT 
profile is captured with a continuous dose spectrum ranging from 0 mg to 800 mg. For each dose 
within the range, there is a corresponding distribution of the predicted DLT rates calculated from 
the samples of the model parameters. This figure will be updated each time new DLT 
information becomes available. In Figure 1, there are 3 different quantiles (2.5%, 50%, and 
97.5%) plotted to characterize the current trend of the toxicity profile (as shown by the 50% 
quantile), as well as the variation of the dose-DLT profile (as shown by the 2.5% percentile and 
the 97.5% percentile), according to the accumulation of DLT data from all previous and current 
dose levels. The toxicity boundaries (0.16 and 0.35) are illustrated in two dotted horizontal lines 
to benchmark the way in which the dose-DLT profile is trending. From this plot, based on only 
the prior information for the individual drugs, for BMS-986205 doses 25mg, 50mg, 100mg, 
200mg and 400mg, the median dose-DLT curve lies between the pre-specified toxicity interval 
limits of 16% and 35%. 
If the proposed triplet combination is found to have safety concerns, and is considered 
intolerable, lower dose levels can also be identified using different boundary cutoffs from this 
plot. For example, using the 50% percentile curve (green line), which represents the median DLT 
distribution for each dose level, a potential lower dose level corresponding to a pre-specified 
DLT rate could be determined and used as a new dose. 
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Figure 2:
Stacking histogram after incorporating prior information to classify 
predicted DLT rates into 3 categories (Underdosing, Target Dosing 
and Overdosing)
Interpretation and usage of Figure 2:
Figure 2 is a snapshot of stacking histogram with all prior information available. This figure will 
also be updated each time new DLT information becomes available.
When evaluating the dose levels based on prior information or current safety data, the model will 
first exclude doses that are intolerable from consideration (with overdosing probabilities > 35%, 
the rate that has been specified for BMS-986205 combination). All of the remaining doses will 
be considered “tolerable”, however the model will also identify the dose that maximizes the 
probability of being within the target toxicity range (DLT rate of 16% up to 35%). 
As illustrated in Figure 2, based on the prior information, the distribution of predicted DLT rates 
will be characterized into possibilities falling into 3 different categories. First, dose levels of 400, 
600mg and 800 mg are considered unsafe according to the higher-than-cutoff (0.35) overdosing 
probabilities. Among the remainder of tolerable dose levels (25 mg, 50 mg, 100 and 200 mg), 
using the BLRM-Copula model the dose level that maximizes the probability of being within the 
target dosing interval can also be identified. Here dose level 200 mg is associated with the 
highest target dosing probability of 40% compared with other dose levels.
Similarly (although not shown on Figure 2), according to the rules specified above, the model 
could possibly recommend to de-escalate to a lower dose level than current treated dose level or 
extend the current dose level. Please refer to description of Figure 1 for details on how to specify 
potential lower dose levels.
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4
REFERENCES
1
Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with 
overdose control. Stat Med 1998;17:1103–20.
2
Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to 
phase I cancer trials. Stat Med 2008;27:2420–39.
3
Neuenschwander B, Capkun-Niggli G, Branson M, et al. Summarizing historical information 
on controls in clinical trials. Clin Trials 2010;7:5-18.
4
Newton R, Scherle P, Bowman K, et al. ASCO oral presentation; 2012.
5
Yin G, Yuan Y. Bayesian dose finding in oncology for drug combinations by copula 
regression. J R Stat Soc Ser C Appl Stat 2009;58(2):211–24. ISSN 1467-9876. doi: 
10.1111/j.1467-9876.2009.00649.x.
6
Yin G, Yuan Y. Bayesian dose finding in oncology for drug combinations by copula 
regression. J R Stat Soc Ser C Appl Stat 2009;58(2):211–24. ISSN 1467-9876. doi: 
10.1111/j.1467-9876.2009.00649.x.
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APPENDIX 2
ECOG PERFORMANCE STATUS
ECOG PERFORMANCE STATUSa
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair
5
Dead
a Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, and Carbone PP. Toxicity and Response 
Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5: 649-655.
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APPENDIX 3
RECIST 1.1
1
ASSESSMENT OF OVERALL TUMOR BURDEN AND MEASURABLE 
DISEASE
Only subjects with measurable disease at baseline should be included in protocols where 
objective tumor response is the primary endpoint. In studies where the primary endpoint is tumor 
progression (either time to progression or proportion with progression at a fixed date), the 
protocol must specify if entry is restricted to those with measurable disease or whether subjects 
having non-measurable disease only are also eligible.
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 
tomography (CT) scans have slice thickness greater than 5 mm, the minimum size for a 
measurable lesion should be twice the slice thickness.
At baseline, tumor lesions/lymph nodes will be categorized as 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 the following minimum size:
•
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 exam (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 short axis when assessed by CT scan (CT scan slice thickness 
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 skin or lung, or abdominal masses/abdominal organomegaly identified by 
physical exam that is 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 exam.
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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.
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 exam 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 the 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.
1.4.2.6
Tumor markers 
Tumor markers alone cannot be used to assess objective tumor response.
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), be 
representative of all involved organs, and should lend themselves to reproducible repeated
measurements.
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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 
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.
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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 then is as follows:
•
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 time points specified in the protocol. 
CR:  Disappearance of all non-target lesions and normalization of tumor marker level. 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) and/or maintenance of tumor 
marker level above the normal limits.
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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 the 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 the 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, ie, an increase in tumor burden representing 
an additional 73% increase in ‘volume’ (which is equivalent to a 20% increase diameter in a 
measurable lesion). Examples include an increase in a pleural effusion from ‘trace’ to ‘large’, 
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 CR. 
3.3
New Lesions
The appearance of new malignant lesions denotes disease progression. The finding of a new 
lesion should be unequivocal, ie, not attributable to differences in scanning technique, change in 
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imaging modality, or findings thought to represent something other than tumor (for example, 
some ‘new’ bone lesions may be simply healing or flare of pre-existing lesions). This is 
particularly important when the subject’s baseline lesions show PR or CR. 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 the 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 pre-existing 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
Time Point Response
A response assessment should occur at each time point 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 time point.
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Table 4.1-1:
Time Point 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
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, NE = not evaluable.
4.1.1
Missing assessments and not evaluable designation
When no imaging/measurement is done at all at a particular time point, the subject is not 
evaluable (NE) at that time point. If only a subset of lesion measurements are made at an 
assessment, the case is also considered NE at that time point, unless a convincing argument can 
be made that the contribution of the individual missing lesion(s) would not have changed the 
assigned time point response.
4.1.2
Confirmation Scans
•
Verification of Response: Confirmation of PR and CR is required at least 4 weeks later to 
ensure that the responses identified are not the result of measurement error.
4.2
Best Overall Response: All Time Points
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 objectively documented progression 
per RECIST Criteria or subsequent cancer therapy, whichever happens first taking into account 
any requirement for confirmation. 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 time points with subsequent confirmation. 
CR or PR may be claimed only if the criteria for each are met at a subsequent time point as 
specified in the protocol (generally 4 weeks later). 
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In this circumstance, the best overall response can be interpreted as specified in Table 4.2-1.
When SD is believed to be the 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 6–8 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 Time Point
Subsequent Time Point
CR
CR
CR
CR
PR
SD, PD or PRa
CR
SD
SD provided minimum criteria for 
SD duration met, otherwise, PD
CR
PD
SD provided minimum criteria for 
SD duration met, otherwise, PD
CR
NE
SD provided minimum criteria for 
SD duration met, otherwise NE
PR
CR
PR
PR
PR
PR
PR
SD
SD
PR
PD
SD provided minimum criteria for 
SD duration met, otherwise, PD
PR
NE
SD provided minimum criteria for 
SD duration met, otherwise NE
NE
NE
NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, NE = not evaluable.
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). 
Best response would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be 
claimed when subsequent scans suggest small lesions were likely still present and in fact the subject had PR, not 
CR at the first time point. Under these circumstances, the original CR should be changed to PR and the best 
response is PR.
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 disease or PD is objectively 
documented (taking as reference for PD the smallest measurements recorded on study).
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that recurrent disease is objectively documented.
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4.3.2
Duration of Stable Disease
SD 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).
CR (Complete Remission)
The designation of CR requires the following:
1. Complete disappearance of all detectable clinical evidence of disease and disease-related 
symptoms, if present before therapy.
a) Typically FDG-avid lymphoma: in patients with no pretreatment PET scan or when the 
PET scan was positive before therapy, a post-treatment residual mass of any size is 
permitted as long as it is PET negative.
b) Variably FDG-avid lymphomas/FDG avidity unknown: in patients without a pretreatment 
PET scan, or if a pretreatment PET scan was negative, all lymph nodes and nodal masses 
must have regressed on CT scan to normal size (≤1.5 cm in their greatest transverse 
diameter for nodes > 1.5 cm before therapy). Previously involved nodes that were 1.1 to 
1.5 cm in their long axis and > 1.0 cm in their short axis before treatment must have 
decreased to ≤1.0 cm in their short axis after treatment.
2. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical 
examination or CT scan, should not be palpable on physical examination and should be 
considered normal size by imaging studies, and nodules related to lymphoma should 
disappear. However, determination of splenic involvement is not always reliable because a 
spleen considered normal in size may still contain lymphoma, whereas an enlarged spleen 
may reflect variations in anatomy, blood volume, the use of hematopoietic growth factors, or 
causes other than lymphoma.
3. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have 
cleared on repeat bone marrow biopsy. The biopsy sample on which this determination is 
made must be adequate (with a goal of > 20 mm unilateral core). If the sample is 
indeterminate by morphology, it should be negative by immunohistochemistry. A sample that 
is negative by immunohistochemistry but demonstrates a small population of clonal 
lymphocytes by flow cytometry will be considered a CR until data become available 
demonstrating a clear difference in patient outcome.
PR (Partial Remission)
The designation of PR requires all of the following:
1. At least a 50% decrease in the sum of the product of the diameters (SPD) of up to 6 of the 
largest dominant nodes or nodal masses. These nodes or masses should be selected according 
to all of the following: they should be clearly measurable in at least 2 perpendicular 
dimensions; if possible, they should be from disparate regions of the body; and they should 
include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
2. No increase should be observed in the size of other nodes, liver, or spleen.
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3. Splenic and hepatic nodules must regress by ≥50% in their SPD or, for single nodules, in the 
greatest transverse diameter.
4. With the exception of splenic and hepatic nodules, involvement of other organs is usually 
assessable, and no measurable disease should be present.
5. Bone marrow assessment is irrelevant for the determination of a PR if the sample was 
positive before treatment. However, if positive, the cell type should be specified 
(eg, large-cell lymphoma or small neoplastic B cells). Patients who achieve a CR by the 
above criteria but have persistent morphologic bone marrow involvement will be considered 
partial responders. When the bone marrow was involved before therapy and a clinical CR 
was achieved but with no bone marrow assessment after treatment, patients should be 
considered partial responders.
6. No new sites of disease should be observed.
7. FDG:
a) Typically FDG-avid lymphoma: for patients with no pretreatment PET scan or if the PET 
scan was positive before therapy, the post-treatment PET should be positive in at least 
1 previously involved site.
b) Variably FDG-avid lymphomas/FDG-avidity unknown: for patients without a 
pretreatment PET scan, or if a pretreatment PET scan was negative, CT criteria should be 
used. In patients with follicular lymphoma or mantle-cell lymphoma, a PET scan is only 
indicated with 1 or at most 2 residual masses that have regressed by > 50% on CT; those 
with more than 2 residual lesions are unlikely to be PET negative and should be 
considered partial responders.
SD (Stable Disease)
SD is defined as the following:
1. A patient is considered to have SD when he or she fails to attain the criteria needed for a CR 
or PR but does not fulfill those for PD (see Relapsed Disease [after CR]/PD [after PR, SD]).
2. Typically FDG-avid lymphomas: the PET should be positive at prior sites of disease with no 
new areas of involvement on the post-treatment CT or PET scan.
3. Variably FDG-avid lymphomas/FDG-avidity unknown: for patients without a pretreatment 
PET scan or if the pretreatment PET was negative, there must be no change in the size of the 
previous lesions on the post-treatment CT scan.
PD: Relapsed Disease (after CR)/PD (after PR, SD)
Lymph nodes should be considered abnormal if the long axis is > 1.5 cm regardless of the short 
axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if 
its short axis is > 1.0. Lymph nodes ≤1.0 x ≤1.0 cm will not be considered abnormal for relapse 
or PD.
1. Appearance of any new lesion > 1.5 cm in any axis during or at the end of therapy, even if 
other lesions are decreasing in size. Increased FDG uptake in a previously unaffected site 
should only be considered relapsed or PD after confirmation with other modalities. In 
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patients with no prior history of pulmonary lymphoma, new lung nodules identified by CT 
are mostly benign. Thus, a therapeutic decision should not be made solely on the basis of the 
PET without histologic confirmation.
2. At least a 50% increase from nadir in the SPD of any previously involved nodes, or in a 
single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be 
considered PD, a lymph node with a diameter of the short axis of < 1.0 cm must increase by 
≥50% and to a size of 1.5 × 1.5 cm or > 1.5 cm in the long axis.
3. At least a 50% increase in the longest diameter of any single previously identified node 
> 1 cm in its short axis.
4. Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion 
was PET positive before therapy unless the lesion is too small to be detected with current 
PET systems (< 1.5 cm in its long axis by CT).
Measurable extranodal disease should be assessed in a manner similar to that for nodal disease. 
For these recommendations, the spleen is considered nodal disease. Disease that is only 
assessable (eg, pleural effusions, bone lesions) will be recorded as present or absent only, unless, 
while an abnormality is still noted by imaging studies or physical examination, it is found to be 
histologically negative.
In clinical trials where PET is unavailable to the vast majority of participants, or where PET is 
not deemed necessary or appropriate for use (eg, a trial in patients with MALT lymphoma), 
response should be assessed as above, but only using CT scans. However, residual masses should 
not be assigned CRu status but should be considered PRs.
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APPENDIX 4
INTERNATIONAL WORKSHOP GROUP RESPONSE CRITERIA 
FOR NHL (2014)1
Table 1:
Revised Criteria for Response Assessment
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Reference:
1 Cheson BD, et al: Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-
Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32:3059-68. 
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APPENDIX 5 
MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens.
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated.
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The 
oral equivalent of the recommended intravenous doses may be considered for ambulatory 
patients with low-grade toxicity. The lower bioavailability of oral corticosteroids should be taken 
into account when switching to the equivalent dose of oral corticosteroids.
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended. 
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used.
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APPENDIX 6
REVISED INTERNATIONAL PROGNOSTIC INDEX (IPI) SCALE*
Composite score was determined by assigning 1 point for each of the following factors:
•
Age > 60 years
•
ECOG PS > 2
•
Elevated Serum LDH
•
More than 1 extranodal site
•
Stage III/IV disease (Ann Arbor staging)
*Sehn LH, Berry B, Chhanabhai M, et al. The revised International Prognostic Index (R-IPI) is a 
better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma 
treated with R-CHOP. Blood 2007 109: 1857-1861
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APPENDIX 7
CYP3A4, CYP1A2 AND CYP2B6 GUIDANCE
The lists below are not meant to be all inclusive. Please consult individual drug labels for further 
information. Additional information is also available at:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio
nsLabeling/ucm093664.htm
Table 1:
Classification of In Vivo Inhibitors of CYP Enzymes
CYP 
Enzymes
Strong Inhibitorsa
≥5-fold Increase in AUC
or > 80% Decrease in CL
Moderate Inhibitorsb
≥2 but < 5-fold Increase 
in AUC or 50-80% 
Decrease in CL
Weak Inhibitorsc
≥1.25 but < 2-fold Increase in 
AUC or 20-50% Decrease in 
CL
CYP3A
Boceprevir, clarithromycin, 
conivaptan, grapefruit juice,d
indinavir, itraconazole, 
ketoconazole, lopinavir/ritonavir, 
mibefradil,e nefazodone, 
nelfinavir, posaconazole, 
ritonavir, saquinavir, telaprevir, 
telithromycin, voriconazole
Amprenavir, aprepitant, 
atazanavir, ciprofloxacin, 
darunavir/ritonavir, 
diltiazem, erythromycin, 
fluconazole, 
fosamprenavir, grapefruit 
juice,d imatinib, 
verapamil
Alprazolam, amiodarone, 
amlodipine, atorvastatin, 
bicalutamide, cilostazol, 
cimetidine, cyclosporine, 
fluoxetine, fluvoxamine, 
ginkgo,f goldenseal,f isoniazid, 
nilotinib, oral contraceptives, 
ranitidine, ranolazine, 
tipranavir/ritonavir, zileuton
CYP1A2
ciprofloxacin, enoxacin,
fluvoxamineg, zafirlukast
methoxsalen, mexiletine, 
oral contraceptives
acyclovir, allopurinol, 
cimetidine, peginterferon alpha-
2a, piperine, zileuton
Please note that this is not an exhaustive list.
a A strong inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a substrate for that CYP 
by equal or more than 5-fold.
b A moderate inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate 
for that CYP by less than 5-fold but equal to or more than 2-fold.
c A weak inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate for 
that CYP by less than 2-fold but equal to or more than 1.25-fold.
d The effect of grapefruit juice varies widely among brands and is concentration, dose, and preparation dependent. 
Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain preparation was used 
(eg, high dose, double strength) or as a “moderate CYP3A inhibitor” when another preparation was used (eg, low 
dose, single strength).
e Withdrawn from the United States market because of safety reasons.
f Herbal product.
g Strong inhibitor of CYP1A2 and CYP2C19, and moderate inhibitor of CYP2D6 and CYP3A
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450.
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Table 2:
Classification of In Vivo Inducers of CYP Enzymes
CYP 
Enzymes
Strong Inducers
≥80% Decrease in AUC
Moderate Inducers
50-80% Decrease in AUC
Weak Inducers
20-50% Decrease in AUC
CYP3A
Avasimibe,a
carbamazepine, phenytoin, 
rifampin, St. John’s wortb
Bosentan, efavirenz, 
etravirine, modafinil, 
nafcillin
Amprenavir, aprepitant, 
armodafinil, echinacea,c
pioglitazone, prednisone, 
rufinamide
CYP1A2
Phenytoind, rifampine, 
ritonavirf, smoking, 
teriflunomide
Please note that this is not an exhaustive list.
a Not a marketed drug.
b The effect of St. John’s wort varies widely and is preparation dependent.
c Herbal product.
d Strong inducer of CYP3A and moderate inducer of CYP1A2, CYP2C19.
e Strong inducer of CYP2C19, CYP3A, and moderate inducer of CYP1A2, CYP2B6, CYP2C8, 
CYP2C9.
f Strong inducer of CYP2C19 and moderate inducer of CYP1A2, CYP2B6, CYP2C9.
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450.
Table 3:
Examples of Sensitive In Vivo CYP Substrates and CYP 
Substrates with Narrow Therapeutic Range
CYP 
Enzymes
Sensitive Substratesa
Substrates with Narrow 
Therapeutic Rangeb
CYP3A
Alfentanil, aprepitant, budesonide, buspirone, conivaptan, 
darifenacin, darunavir, dasatinib, dronedarone, eletriptan, 
eplerenone, everolimus, felodipine, indinavir, fluticasone, 
lopinavir, lovastatin, lurasidone, maraviroc, midazolam, 
nisoldipine, quetiapine, saquinavir, sildenafil, simvastatin, 
sirolimus, tolvaptan, tipranavir, triazolam, vardenafil
Alfentanil, astemizole,c cisapride,c 
cyclosporine, dihydroergotamine, 
ergotamine, fentanyl, pimozide, 
quinidine, sirolimus, tacrolimus,
terfenadinec
CYP2B6
Bupropion, efavirenz
Please note that this is not an exhaustive list.
a Sensitive CYP substrates refers to drugs whose plasma AUC values have been shown to increase 5-fold or higher 
when co-administered with a known CYP inhibitor.
b CYP substrates with narrow therapeutic range refers to drugs whose exposure-response relationship indicates that 
small increases in their exposure levels by the concomitant use of CYP inhibitors may lead to serious safety 
concerns (eg, Torsades de Pointes).
c Withdrawn from the United States market because of safety reasons.
Abbreviations: AUC = area under the concentration-time curve; CYP = cytochrome P450.
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APPENDIX 8
MEDICATIONS ASSOCIATED WITH QT PROLOGATION
The list below is not meant to be all inclusive. Please consult individual drug labels for further 
information.
quinidine, procainamide, disopyramide,
amiodarone, sotalol, ibutilide, dofetilide,
erythromycins, clarithromycin,
chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide,
cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
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APPENDIX 9
P-GP AND BCRP GUIDANCE
The list below is not meant to be all inclusive. Please consult individual drug labels for further 
information. Additional information is also available at:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio
nsLabeling/ucm080499.htm
Table 1:
Examples of In Vivo Substrates for Selected Transporters
Transporter
Gene
Substrate
P-gp
ABCB1
Aliskiren, ambrisentan, colchicine, dabigatran etexilate, 
digoxin, everolimus, fexofenadine, imatinib, lapatinib, 
maraviroc, nilotinib, posaconazole, ranolazine, saxagliptin, 
sirolimus, sitagliptin, talinolol, tolvaptan, topotecan
BCRP
ABCG2
Methotrexate, mitoxantrone, imatinib, irrinotecan, lapatinib, 
rosuvastatin, sulfasalazine, topotecan
Please note that this is not an exhaustive list.
Abbreviations: BCRP = breast cancer resistance protein; P-gp = P-glycoprotein.
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APPENDIX 10
AGENTS KNOWN TO CAUSE METHEMOGLOBINEMIA
Acetanilid
p-Amino salicylic acid
Aniline, aniline dyes
Benzene derivatives
Clofazimine
Chlorates
Chloroquine
Dapsone
Local anesthetic agents 
Benzocaine 
Lidocaine 
Prilocaine 
Menadione
Metoclopramide
Methylene blue*
Naphthoquinone
Naphthalene
Nitrites 
Amyl nitrite 
Farryl nitrite 
Sodium nitrite 
Nitroglycerin 
Nitric oxide 
Nitrobenzene
Paraquat
Phenacetin
Phenazopyridine
Primaquine
Rasburicase
Resorcinol
Sulfonamides
While methylene blue is a recognized treatment for methemoglobinemia, it is an agent with oxidant potential (and 
may worsen the clinical situation) since in individuals with glucose-6-phosphate dehydrogenase deficiency, it 
induces acute hemolysis that can further decrease oxygen delivery to the tissues. Paradoxically, in high doses,
methylene blue can also increase methemoglobinemia.
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APPENDIX 11
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP
•
Premenarchal
•
Premenopausal female with 1 of the following:
−
Documented hysterectomy
−
Documented bilateral salpingectomy
−
Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
•
Postmenopausal female
−
A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 
years in the absence of other biological or physiological causes. In addition, females 
under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 
40 mIU/mL to confirm menopause.
CONTRACEPTION GUIDANCE FOR FEMALE PARTICIPANTS OF CHILD BEARING 
POTENTIAL
One of the highly effective methods of contraception listed below is required during study 
duration and until the end of relevant systemic exposure, defined as 5 months after the end of 
study treatment.*
Note: Hormone-based contraceptives are not considered highly effective methods of 
contraception for WOCBP participants recieving BMS-986205. 
Highly Effective Contraceptive Methods That Are User Dependent 
Failure rate of <1% per year when used consistently and correctly.a
•
Not for WOCBP participants recieving BMS-986205: Combined (estrogen- and 
progestogen-containing) hormonal contraception associated with inhibition of ovulationb 
−
oral 
−
intravaginal 
−
transdermal 
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Not for WOCBP participants recieving BMS-986205: Progestogen-only hormonal 
contraception associated with inhibition of ovulationb 
−
oral 
−
injectable 
Highly Effective Methods That Are User Independent
•
Not for WOCBP participants recieving BMS-986205: Implantable progestogen-only 
hormonal contraception associated with inhibition of ovulation b
•
Intrauterine device (IUD)c
•
Bilateral tubal occlusion
•
Not for participants receiving BMS-986205: Vasectomized partner 
A vasectomized partner is a highly effective contraception method for provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
•
Sexual abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study drug. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.
•
It is not necessary to use any other method of contraception when complete abstinence is 
elected. 
•
WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in Section 2. 
•
Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence 
NOTES: 
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical 
studies. 
b Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy 
of the contraceptive method.  Hormonal contraception is permissible only when there is sufficient evidence 
that the IMP and other study medications will not alter hormonal exposures such that contraception would be 
ineffective or result in increased exposures that could be potentially hazardous.  In this case, alternative 
methods of contraception should be utilized. 
c Intrauterine devices and intrauterine hormone releasing systems are acceptable methods of contraception in the 
absence of definitive drug interaction studies when hormone exposures from intrauterine devices do not alter 
contraception effectiveness. The absence of such interactions is not known for BMS-986205 when 
administered with nivolumab. Therefore, for participants of child-bearing potential who receive these 2 
medications, intrauterine hormone releasing systems are not acceptable methods of contraception.
Unacceptable Methods of Contraception*
•
Male or female condom with or without spermicide.  Male and female condoms cannot be 
used simultaneously
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•
Diaphragm with spermicide
•
Cervical cap with spermicide
•
Vaginal Sponge with spermicide
•
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action
•
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
•
Withdrawal (coitus interruptus).
•
Spermicide only
•
Lactation amenorrhea method (LAM)
* Local laws and regulations may require use of alternative and/or additional 
contraception methods.
CONTRACEPTION GUIDANCE FOR MALE PARTICIPANTS WITH PARTNER(S) OF 
CHILD BEARING POTENTIAL.
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to the following during the treatment and until the end of relevant systemic exposure.
•
Inform any and all partner(s) of their participation in a clinical drug study and the need to 
comply with contraception instructions as directed by the investigator.
•
Male participants are required to use a synthetic or latex male condom for any sexual activity 
with WOCBP for the study duration and until end of relevant systemic exposure defined as 7 
months after the end of study treatment.
•
Female partners of males participating in the study to consider use of effective methods of 
contraception until the end of relevant systemic exposure, defined as 7 months after the end 
of treatment in the male participant.
•
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent 
from sexual activity or use a synthetic or latex male condom during each episode of sexual 
activity for the duration of study treatment, and until 7 months after the end of study 
treatment. 
•
Refrain from donating sperm for the duration of the study treatment and until 7 months after 
the end of study treatment.
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 6.5 and the Appendix for Adverse Events and Serious 
Adverse Events Definitions and procedures for Evaluating, Follow-up and Reporting.
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APPENDIX 12
DIAGNOSTIC CRITERIA FOR HLH AND DRESS SYNDROME
Jordan et al. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041. Epub 2011 Aug 9.
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Kardaun et al., Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS SHBr J Dermatol. 2007 
Mar;156(3):609-11.
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