A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Tolerability of Urelumab Administered in Combination With Nivolumab in Advanced/Metastatic Solid Tumors and B-cell Non-Hodgkins Lymphoma
Phase: PHASE1
Conditions: Advanced Solid Tumors, Advanced B-cell NHL
Sponsor: Bristol-Myers Squibb

Page: 1
Protocol Number: CA186107
IND Number: 122,465
Ex-US Non-IND
EUDRACT Number 2014-002241-22
Date: 10-Jun-2014
Revised Date: 22-Mar-2017
CLINICAL PROTOCOLCA186107
A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Tolerability of 
Urelumab Administered in Combination with Nivolumab in Advanced /Metastatic Solid Tumors 
and B Cell Non-Hodgkins Lymphoma
Revised Protocol Number:06
Incorporates amendment 01 through 06, 08,and Administrative Letter 01 through 05
Medical Monitor
RolandMeier, M.D., Ph.D.
24-hr Emergency Telephone Number
USA:1-866-470-2267
International: +1-248-844-7390
Bristol-Myers Squibb Research and Development
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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) 
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that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. 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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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 06
22-Mar-2017
Incorporates Amendment 08
Amendment 08
22-Mar-2017
In order to further explore an emerging efficacy signal, additional 
patients with previously untreated metastatic melanoma (ie, no prior 
systemic anticancer therapy for unresectable or metastatic melanoma) 
subjects with PD-L1 negative tumors (<1%) will be enrolled under this 
amendment.
Revised 
Protocol 05
09-May-2016
Incorporates Amendment 06 and Administrative Letters 04 and 05
Amendment 06
09-May-2016
To include a cohort of NSCLC and melanoma subjects who have 
relapsed or are refractory to prior anti-PD-1/anti-PD-L1therapy.
Administrative 
Letter 05
01-Jun-2016
To clarify application to new cohort of subjects with NSCLC and 
melanoma who have relapsed or are refractory to prior anti-PD-1/anti-
PD-L1) therapyand exception for NSCLC and MEL subjects enrolling in 
the expansion cohorts where prior anti-PD-1 or anti-PD-L1 therapies are 
specifically required.
Administrative 
Letter 04
19-Jan-2016
Change in MM
Revised 
Protocol 04
22-Dec-2015
Incorporates Amendment 05
Amendment 05
22-Dec-2015
To expand the study population for cohort expansion to include subjects 
with follicular lymphoma and to further differentiate subjects with non-
small-cell lung cancer into two separate groups (those with no prior anti 
PD-1/anti-PD-L1 therapy and those who have relapsed or are refractory 
to prior anti-PD-1/anti-PD-L1.
Revised 
Protocol 03
30-Aug-2015
Incorporates Amendment 04 and Administrative Letter 03
Amendment 04
30-Aug-2015
Discontinue enrollment into Cohorts A, B, C, D. Implement an update to 
exclusion Criteria
Admin Letter 
03
26-Aug-2015
Discontinue enrollment into Cohorts A, B, C, D during cohort expansion
Revised 
Protocol 02
29-Jun-2015
Incorporates Amendment 03
Amendment 03
29-Jun-2015
To implement a change in duration to combination therapy anduse of 
flat dosing for subjects enrolled following approval of Revised Protocol 
02
Revised 
Protocol 01
06-Mar-2015
Incorporate Amendment 02
Amendment 02
06-Mar-2015
To implement changes to inclusion/exclusion criteria, clarify
requirements and assessments for treatment beyond disease progression
andcriteria for allowing treatment to resume after a dose delay due to 
toxicity, add time and events schedulesfor subjects eligiblefor 
retreatment, and clarifyPK sampling and biomarker assessments.
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Document
Date of Issue
Summary of Change
Adm Letter 02
21-Oct-2014
Tocorrect a typographical error and to clarify that drug preparation, 
storage, handling and dispensing of nivolumabis contained in the 
Investigator Brochure and/or pharmacy reference sheets, andthe interval 
between end of nivolumab doseand beginning of urelumab dose.
Adm Letter 01
30-Sep-2014
To correct PK sampletime points and clarifythe expected timepoints for
vital signs and observation periodof subjects post-dosing.
Original 
Protocol
10-Jun-2014
Not applicable
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SYNOPSIS
Clinical ProtocolCA186107
Protocol Title: A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Tolerability of 
Urelumab Administered in Combination with Nivolumabin Advanced /Metastatic Solid Tumors and B Cell Non-
Hodgkin
's Lymphoma
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): Each subject will be administered intravenous (IV) doses of urelumab (BMS-663513) every 4 and 
nivolumab (BMS-936558) every 2 weeks,for up to 48 weeks of study therapy.
Retreatment with the combinationat the dose and regimen assigned at study entry, within 12 months of last 
treatment with study drug, maybe permitted after discussion and agreement with the BMS Medical Monitor.
Study Phase:1/2
Research Hypothesis: 
It is anticipated that the combination of an anti-CD137 (urelumab) and an anti PD-1 antibody (nivolumab) will 
demonstrate adequate safety and tolerability atpharmacologically relevant doses, so as to permit further clinical 
testing. There is no formal primary research hypothesis for this study to be statistically tested.
Objectives: 
Primary Objective: To assess the safety and tolerability of urelumabgiven in combination with nivolumab and to 
identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination, in subjects 
with advanced (metastatic and/or unresectable) solid tumors and B cell lymphomas.
Secondary Objectives:
To assess the preliminary anti-tumor activity of the combination of urelumab and nivolumab in subjects with 
advanced solid tumors and B cell lymphomas.
To characterize the pharmacokinetics (PK) of urelumab and nivolumab when co-administered.
To monitorimmunogenicity of urelumab and nivolumab administered as combination therapy.
 
 
.
Study Design:
This is a phase 1/2 open label study.The first phase of the study will consist of a dose escalation assessment of the 
safety and tolerability of urelumab administered with nivolumab in subjects with advanced solid tumors or B-cell 
non-Hodgkin’s lymphoma (NHL). The second phase of the study will include a 2-stage cohort expansion in multiple
tumortypes (melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma,diffuse large B cell 
lymphoma, and follicular lymphoma) at the maximally tolerated dose (MTD), highest administereddose (HAD), or 
at an alternative dose/regimen as determined by the investigators and the sponsorand outlined in the Study 
Population section (Section 3.3).
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The study design schema is outlined below in Figure 1: 
Figure 1: 
Study Design Schema
Subjects will complete up to four periods of the study: 
Screening(up to 28 days):
Subjects will sign consent and be evaluated for study eligibility.
Treatment(up to a maximum of 6cycles of study therapy):
The Treatment Periodwill consist of up to 6 treatment cycles.  Each cycle is 8 weeks for a total of 48 weeks.
Nivolumab will be given every 2 weeks up to 48weeks.Urelumab will be given every 4 weeks up to 48weeks.On 
days where both study drugs are given, nivolumab will be given first followed by urelumab.
Clinical/SafetyFollow-up(100 days following study drug discontinuation):
Subjects that discontinue the treatment phase will enter the Clinical/SafetyFollow-up period, with visits scheduled 
on days 30, 60 and 100 to monitor for adverse events.
Survival/Long-Term Follow-up(survival will last up to 3 years following the first dose of study drug):
The duration of survival follow-up will be up to 3 years following the first dose of study drug. Subjects who 
discontinue study drug with ongoing SD, PR, or CR will continue to have tumor assessments completed every 
= Nivolumab/BMS-936558 dose
CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease 
Screen
Treatment Period: up to 6 treatment cycle.  Each cycle 
is 8 weeks for a total of 48 weeks.
Includes assessment between Days 49-56
Clinical Follow-up
Survival /Long 
term Follow-up 
Day -28 
1
15
2
43 49-56
Scans
= Urelumab/BMS-663513 dose
Day 29 dose applicable for Cohorts 1, 2, A, B, D
Additional cycles
-CR (see above)
-PR
-SD
-Unconfirmed PD
Clinic visits
Days 30, 60, 100 
after end of 
treatment to 
monitor for adverse 
event
Clinic visits or 
telephone 
contact every
3 months for up 
to 3 years 
following the first 
doseof study 
drug
Retreatment:
Subjects who progress within 12 months of 
completing treatment may be considered for 
retreatment with urelumab/nivolumab 
therapy, after discussion /agreement with 
medical monitor.
Treatment Completed
--Completion of 6cycles
--Confirmed PD
--PD and clinical deterioration
--Toxicity
--Confirmed CR (on an individual 
basis following consultation 
between MM and site PI)
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12weeks for the first year after discontinuation of study drug, and then continue to receive scans as per standard of 
care guidelines for follow-up or at a minimum of every 6 months for up to 3 years following the first dose of study 
drug, or until disease progression or withdrawal of consent. Subjects in the Survival/Long-termFollow-up period 
who have progression of disease will be allowed to receive tumor directed therapy as required.
Re-treatment with the combination at the dose and regimen assigned at study entry,within 12 months of last dose of 
study drug, may be permitted after discussion and agreement with the BMS Medical Monitor, provided that the 
subject continues to meet the re-treatment eligibility criteria.These subjects will complete up to 4 additional periods 
of the study:  screening, treatment, clinical follow-up, and survival/long-term follow-up.
Dose Escalation:
A 3+3+3 design will be used to assess the safety of urelumab given in combination with nivolumab. The cohorts for 
dose escalation are provided in Table 1. Potential alternate cohorts are provided in Table 3. TheDose Limiting 
Toxicity (DLT) observation period will last for 8 weeksfollowing the first dose of study medication. The DLT 
evaluation period is defined as 8 weeks after administration of the first combination dose of nivolumab and 
urelumab, and includes subjects who have had administration of at least one dose of nivolumab monotherapy during 
this interval. This interval is based upon inclusion of the earliest times to onset of clinically significant adverse 
events attributed to study drug, and also allows for a substantial amount of time for unexpected toxicities related to 
dosing regimen to emerge.
Approximately three subjects will be treated initially at each dose regimen. In order to assure sufficient evaluable 
subjects per cohort an additionalsubject may be added to a cohort (ie, enroll a fourth subject in a cohort of 3). 
Note: Should this action be taken, cohort tolerability assessment and subsequent dose escalation, if indicated, will 
occur when the minimum number of subjects required to assess tolerability have completed the 8 week DLT period. 
However, if any additional subject experiences an event that would, per protocol, result in either cohort expansion or 
the halting of dose escalation, the escalation rules as defined below in Table 2 willbe followed.
Table 1:
Doses/Regimens During Dose Escalation
Cohort 
Number
Total Subjectsa
urelumab
nivolumabb
1
n = approximately3-9
3 mg IV every 
4weeks
3 mg/kg or 240 mg IV every 
2 weeks
2
n = approximately3-9
8 mg IV every 
4weeks
3 mg/kg or 240 mg IV every 
2 weeks
Total
n = approximately 6-18
a 3-9 subjects will be enrolled during dose escalation.Additional subjects may be added for a total of up to 
12subjects per dose level
b Nivolumab 3 mg/kg will be administered for subjects enrolled prior to Revised Protocol 02.  Nivolumab 240 mg 
flat dose administered for subjects enrolled after Revised Protocol 02
After dose escalation to the next cohort, 3-9 additional subjects may be enrolled in any previously tolerated dose 
level (original 3-9 subjects from dose escalation plus additional subjects required to have a total cohort size of 12. If 
the rate of DLTs exceeds 33% in a given treatment regimen; the findings will be discussed and further enrollment 
may be interrupted for that specific treatment regimen and tumor type.If one of the planned dose cohorts is 
determined to exceed the MTD, and/or based on ongoing safety/tolerability experience through the dose escalation 
phase of the study, an alternate dose escalation schema as outlined in Table 3may be explored in consultation and 
agreement between the Sponsor and investigators.
Sentinel Subject: During dose escalation, the first subject in each cohort will receive C1D1 (eg, the first dose of 
study drugs) and be observed for 3 weeks such that one combination dose followed by one nivolumab dose are 
administered before additional subjects in the cohort receive the first dose of study drug (ie, C1D1). 
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Dose Escalation Rules:
Table 2outlines the decision rules for dose escalation based on the number of subjects and observed DLTs. No 
intra-subject dose escalation or reduction is allowed. Subjects who withdraw from the study during the DLT period 
for reasons other than a DLT may be replaced within the same dose level/regimen. Dose escalatio
n will be based on 
the number of dose limiting toxicities (DLTs) experienced during the DLT observation period
If dose escalation is terminated, then the dose or dose regimen below that which invoked the stopping rule will be 
declared the MTD.
Table 2: 
Decision Rules During Dose Escalation
Number 
of 
Evaluable 
Subjects/
Cohort
3-4
6-8
9-12
Total 
Number 
of 
Observed 
DLTs 
0 
1
2 or 
more
1 
2
3 or 
more
2
3 or 
more
Decision 
Rule
Dose 
Escalate
Enroll 
additional 
subjects at 
in cohort to 
reach at 
least 6 
subjects
Dose 
exceed
s MTD
Dose 
Escalate
Enroll 
additional 
subjects at 
in cohort 
to reach at 
least 9 
subjects
Dose 
exceed
s MTD
Dose 
Escalate
Dose 
exceed
s MTD
If either Cohort 1 or Cohort 2 exceeds the MTD, alternate treatment regimens may be explored during dose 
escalation or cohort expansion (listed in Table 3).
Table 3:
Alternate Treatment Regimens
Cohort
urelumab
nivolumaba
Ab
8 mg IV every 8 weeks
3 mg/kg or 240 mgIV every 2 weeks
Bb
8 mg IV every 8 weeks
1 mg/kg or 80 mgIV every 2 weeks
C
3 mg IV every 4 weeks
1 mg/kg or 80 mgIV every 2 weeks
Db
3 mg IV every 8 weeks
3 mg/kg or 240 mgIV every 2 weeks
a Nivolumab 1 mg/kg or 3 mg/kg will be administered for subjects enrolledprior to Revised Protocol 02. 
Nivolumab 80 mg or 240 mg flat dose administered for subjects enrolled after Revised Protocol 02
b Treatment regimen not applicable following Revised Protocol 03.
All available clinical and laboratory data observed during dose escalation will be reviewed to determine the 
alternative treatment regimen listed in Table 3 to be evaluated. The nature, time of onset, and time to resolution of 
DLTs observed will be reviewed in the context of the current safety data from the respective urelumab and 
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nivolumab trials. After review of this data, and after consultation between the investigators and the sponsor, the 
identified alternative treatment regimens may be evaluated. 
Cohort Expansion:
The purpose of the cohort expansions is to gather additional safety, tolerability, preliminary efficacy and 
pharmacodynamic information regarding the combination of urelumab and nivolumab. Once the MTD of combined 
administration of urelumab and nivolumab has been defined, cohort expansions will be initiated. 
Expansion cohorts will follow a 2-stage design as defined below in Table 4:
Table 4:
Cohort Expansion
Tumor Types
Stage 1 Expansion
Stage 2 Expansion
Non-small Cell Lung Cancer 
(NSCLC)
Up to approximately 20 subjects at 
MTDor HAD
Up to approximately 
20 subjects 
Melanoma (MEL)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 
20 subjects 
Head and Neck Squamous Cell 
Carcinoma (SCCHN)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 
20 subjects 
Diffuse Large B Cell 
Lymphoma (DLBCL)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 
20 subjects 
NSCLC (progressive or 
recurrent disease during or after 
anti-PD-1/anti-PD-L1 therapy)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 
20 subjects 
Follicular Lymphoma (FL)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 
20 subjects 
Melanoma (progressive or 
recurrent disease during or after 
an anti-PD-1/anti-PD-L1 
containing treatment regiment)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 
20 subjects
Melanoma PD-L1 negative
Up to approximately 50 subjectsat 
MTD or HAD
Stage 1 of the expansion phase will treat 20 subjectsper tumor type at the MTD and HAD as identified during dose 
escalationfollowed by Stage 2: continued enrollment of up to approximately 20 additional subjects (total of 40 
subjects per tumor type) (Stage 2) to obtain additionalsafety/efficacy data forthe combination.  
The safety, tolerability, and preliminary efficacy data from Stage 1 of the cohort expansion will be evaluated per 
tumor type and discussed by the sponsor with investigators prior to enrolling20 additional patientsduring Stage2.
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Efficacy criteria for moving to Stage 2:
A minimum of 4 out of 20 subjects should demonstrate an objective response to study therapy. In general, if 0 to 3 
responses are observed in a given tumor specific cohort during Stage 1of cohort expansion, Stage 2 will not be 
enrolled for that tumor type.Please note: Ongoing assessment of data from initial 20 patients may be used to 
consider additional enrollment in that tumor type at a later date (to consider the possibility of delayed responses).
An additional 50 treatment naïve PD-L1 negative melanoma subjects will be treated at MTD/HAD to further 
evaluate if there is an efficacy signal in this population.   Additional subjects may be enrolled and treated so as to 
accrue a minimum of 50 evaluable subjects with at least 2 on treatment scans.
Safety criteria for moving to Stage 2:
If the rate of DLTs exceeds 33% in a given tumor type; the findings will be discussed by sponsor with investigators 
and further enrollment may be interrupted for that specific tumor type.
Safety data from subjects enrolled in Stage 1 of the expansion phase will be reviewed by BMS medical and safety 
teams, and discussed with and endorsed by participating investigators, prior to moving to Stage 2of cohort 
expansion.
If the efficacy and safety data from a given tumor type meet the minimum criteria for moving forward, 
approximately 20 additional subjects will be enrolledduring Stage 2 of cohort expansion.The evaluation of data 
from Stage 1 and the decision to begin Stage 2 of the expansion phase of the study can be made up to one year 
following completion of the enrollment of Stage 1 for each individual tumor type.
Dose Limiting Toxicity: DLTs are defined in Section4.5.2.The incidence of DLTswhich occur within 8 weeks 
following the start ofstudy therapy will guide dose escalation decisions. Adverse events will be graded according to 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version4.0 (CTCAEv4). 
For the purposes of subject management, drug-related AEs occurring at any time which meet the DLT definition 
will lead to dose interruption and or permanent discontinuation of study drug as defined in Sections 4.5.5 and 4.5.7.
Duration of Study: The total time on study for any individual subject is expected to be approximately 3.1years. The 
total duration of the study is expected to be 4.5years from the time of the first visit of the first subject to the required 
survival follow-up of the last subject enrolled.
Number of Subjects: Up to approximately 260 subjects will be dosed.
Study Population:
Subjects at least 18 years old, who have histologic confirmation of a solid malignancy or B-cell NHL that is 
advanced (metastatic and/or unresectable), with measurable diseasewill be eligible to participate in the study.
For Dose Escalation: Subjects with any solid tumor type (with the exception of primary central nervous 
system tumors) and B-cell NHL are eligible to enroll.
For Cohort Expansion:Subjects must have one of the following tumor types to be eligible: NSCLC; MEL, 
SCCHN, DLBCL, or FL. 
 
 
 
 
  
 
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A fresh biopsy is required to determine PD-L1 status prior to treatment into the PD-L1 
negative, treatment-naive melanoma cohort.
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational [Medicinal] 
Products (Non-IP/Non-IMP) as listed:
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Study Drug for CA186107
Medication 
Potency 
IP/Non-IP 
Urelumab (BMS-663513)
5mg/mL
IP
Nivolumab (BMS-936558)
10 mg/mL
IP
Study Assessments: 
Safety Outcome Measures:  Safety assessments will be based on medical review of adverse event reports and the 
results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests. The incidence of 
observed adverse events will be tabulated and reviewed for potential significance and clinical importance. Adverse 
events will be assessed continuously during the study and for 100 days after the last treatment. Both AEs and 
laboratory tests will be graded using the NCI CTCAEv4.
Efficacy Measures: 
In solid tumor patients, disease assessment with computed tomography (CT) and/or magnetic resonance 
imaging (MRI), as appropriate, will be performed at baseline and every 8 weeks until confirmed disease 
progression, at the completion of follow-up, or untilsubjects withdraw from the study. Tumor responses will be 
derived for appropriate populations of subjects as defined by RECIST v1.1 based on recorded tumor 
measurements (see Appendix 1). 
For lymphomas, the primary efficacy assessment is objective response rate (ORR), defined as a subject 
achieving either a partial remission (PR) or complete remission (CR) according to the revised International 
Working Group Criteria for non-Hodgkin Lymphoma (Revised Response Criteria for Malignant Lymphoma, 
Cheson BD, J Clin Onc,2007 Feb 10;25(5):579-86. Epub2007Jan 22, [Appendix 2]).The primary efficacy 
assessment, along with the secondary endpoints of duration of OR, complete remission rate (CR), and 
progression free survival (PFS) will be performed based on investigators assessments.Subjects will be assessed 
for response by imaging (spiral CT/MRI) beginning at week 8 and follow the schedule shown in Table 5.1-2 
and Table 5.1-3 until disease progression. A PET scan is required to confirm CR. Subjects eligible for 
re-treatment will be assessed for response by imaging (spiral CT/MRI) beginning at week 8 and follow the 
schedule shown in Table 5.1-5and Table 5.1-6until disease progression.
At the sponsor’s discretion, scans and measurements may be collected and reviewed by independent 
radiologists at a later date, or at any time during the study.
Pharmacokinetic Measures: The nivolumab pharmacokinetic concentrations will be measured at specified time 
pointsto derive the PK parameters (Ceoinf, Ctrough, Cmax, Tmax, AUC [0-T], AUC[TAU]). Pharmacokinetic 
serum concentrations of urelumab will be measured at specified time points to derive PK parameters (Ceoinf, Cmax, 
Ctrough, Tmax, AUC[0-T], AUC[TAU]).
Immunogenicity Measures:Serum samples to evaluate development of positive anti-drug antibody (ADA) response 
to urelumab and nivolumab will be collected at specified time points.
Biomarker Measures: The sample collection and biomarker assessment strategy is designed to address the key 
questions listed below regarding the actions of urelumab and nivolumab and the simultaneous modulation of the 
innate and adaptive immune systems.
Does concurrent blockade of the PD-1 pathway and costimulation with anti-CD137 agonistic antibody affect
aspects of innate and adaptive immunity that lead to enhancement of clinical activity (versus activity previously 
observed using either agent alone)?
Are there pre-treatment markers expressed in blood or tumor tissue (eg, PD-L1; CD137) that associate with
clinical outcomes?
Does the combination of CD137 agonism with PD-1 blockade enhance anti-PD-1-and/or anti-CD137-mediated 
pharmacodynamic effects (versus effects previously observed using either agent alone)?
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Separate whole blood samples (PAXgene) will be obtained at baseline and at multiple times during treatment to 
monitor pharmacodynamic changes in expression of immunoregulatory genes including immunoglobulins, 
interferon-inducible genes, and genes associated with major immune cell subtypes.
Whole Blood -for PBMC-based cytometry: Cytometry will be used to assess baseline and serial on 
treatment alterations in composition/activation status of lymphocyte subsets present in peripheral blood 
mononuclear cell preparations (PBMCs). 
Serum:To understand the prevalence of circulating proteins and the impact they may have on the clinical 
activity and/or safety of nivolumab-urelumab treatment, the protein concentrations of a panel of cytokines, 
chemokines, and other relevant immunomodulatory, serum-soluble factors will be investigated by ELISA 
and/or other relevant multiplex-based protein assay methods. 
Statistical Considerations:
Sample Size Determination:
Dose escalation:As this is a Phase 1/2 dose escalation trial, the sample size at each dose cannot be determined 
exactly, as it depends on the number of observed toxicities. Approximately 3 to9 subjects are expected to be treated 
during dose escalation in each cohort, and up to 12 subjects may be dosed at selected cohorts.
Cohort Expansion: 
Stage 1: During Stage 1 of thecohort expansion,approximately 20 subjectsin each tumor typewill be treated atthe 
MTD/HAD dose level and schedule. With a sample size of approximately 20subjects in each treatment regimen, it 
is intended to provide a general picture of the safety of each regimen. For example, if a low grade adverse event 
were observed in 3or fewer patients, the 90% 1-sided upper confidence interval would be 30%.
Stage 2: During Stage 2 of cohort expansion, up to approximately 20 additional subjects will be treated in each
tumor type. This will allow for further establishment of the safety profile of the combination and a preliminary 
assessment of efficacy. A total of 40 subjects (20from Stage 1 and 20 from Stage 2) is based on achieving a higher 
precision. If in a cohort of 40 subjects 12, 15, or 18 responses are observed, then the lower limit of the one-sided 
90% exact binomial CI for the ORR is 20%, 27%, and 34% respectively. These calculations are based on the 
Clopper-Pearson method for exact confidence intervals. If the true ORR in a tumor type is 50%, then with 40 
subjects in a tumor typethere is 96% chance of observing at least 15responses, and 87% chance of observing at 
least 17responses, and there is 8% chance of observing 15 or fewer responses (false negative rate).
An additional 50 treatment naïve PD-L1 negative melanoma subjects will be treated at MTD/HAD to further 
evaluate if there is an efficacy signal in this population.   Additional subjects may be enrolled and treated so as to 
accrue a minimum of 50 evaluable subjects with at least 2 on treatment scans.  These 50 PD-L1 negative melanoma 
patients will be combined for analysis with approximately 18 PD-L1 negative melanoma patients from Cohort 2 for 
a total of 68 PD-L1 negative melanoma patients.  Assuming an ORR of approximately 56%, a minimum of 38/68 
responders would provide a 95% Clopper-Pearson confidence interval with a lower limit above 42%.
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Endpoints:
Primary Endpoint:Safety as measured by the rate of adverse events (AEs) and serious adverse events (SAEs), is the 
primary endpoint of this Phase 1/2 study. All subjects who receive at least one (full or partial) dose of urelumab or 
nivolumab will be evaluated for safety during treatment and for up to 100 days in follow-up.
Secondary Endpoints:
Efficacy:Best overall response (BOR), objective response rate (ORR), duration of response,and progression 
free survival rate(PFSR) will be assessed based on RECIST v1.1 in subjects with solidtumors, and based on 
investigator assessment per revised IWGcriteria in subjects with lymphomas.
Pharmacokinetics: Urelumab and nivolumab maximum concentration (Cmax[µg/mL]),end of infusion 
concentration (Ceoinf),time to maximum concentration (Tmax[hr])trough concentration(Ctrough [µg/mL]) 
and area under the curve (AUC[0-T] and AUC[TAU][µg.hr/mL])will be evaluated using non-compartmental 
analysis in all treated subjects with adequate serum concentration data.
Immunogenicity:Occurrence of specificADA to urelumab and nivolumab will be determined.
 
 
 
 
 
 
Statistical Analysis:
Safety:All recorded adverse events will be listed and tabulated by system organ class, preferred term, tumor type, 
and treatment arm. The most current version of MedDRA will be used for coding.Vital signs and clinical laboratory 
test results will be listed and summarized by tumor type and treatmentarm.Any significant physical examination 
findings and results of clinical laboratory tests will be listed.ECG results will be evaluated by the investigator; 
clinically significant abnormalitieswill be listed.
Pharmacokinetics:Summary statistics will be tabulated for the pharmacokinetic parameters by tumor type, dose, 
regimen,study dayand time on urelumab PK subjects and nivolumab PK subjects where data is available. This data 
may also be pooled with other datasets for population PK analysis which will be part of a separate report.
Immunogenicity Analyses:A listing will be provided of all available immunogenicity data.Additionally, a listing of 
immunogenicity data from those subjects with at least one positive ADAat any time point will be provided.The 
frequency of subjects with at least one positive ADA assessment, and frequency of subjects who develop ADA after 
a negative baseline assessment will be provided.To examine the potential relationship between immunogenicity and 
safety, the frequency and type of AEs of special interest may be examined by overall immunogenicity status.
Efficacy Analyses:Individual BOR, duration of response and PFS will be listed using RECIST v1.1 criteriain solid 
tumors and investigator assessed revised IWG criteria in lymphomas.BOR outcomes will be tabulated by tumor 
type and treatment arm. The ORR and PFS rate (eg, at 24 weeks) and the corresponding confidence interval will be 
provided by tumor type and treatment.The duration of response and PFS will be estimated by Kaplan-Meier 
methodology by tumor type, depending on data availability.PFS rates at 24weeks will be similarly estimated, based 
onKaplan-Meier methodology.Presentations of efficacy will include subjects in cohort expansion and subjects in 
dose escalation matching those in cohort expansion by tumor type and treatment.Individual changes in the tumor 
burden over time will be presented graphically within a tumor type.Landmark overall survival will also be assessed 
as part of exploratory efficacy analysis, by Kaplan-Meier plots and medians for each tumor type.
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TABLE OF CONTENTS 
 
 
TITLE PAGE 
................................................................................................................ 
DOCUMENT HISTORY 
.............................................................................................. 
SYNOPSIS
 ....................................................................................................................
 
TABLE OF CONTENTS 
.............................................................................................. 
 
 
 
 
...... 
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 Clinical Pharmacology and Safety 
.......................................................... 
1.4.3.1 Pharmacokinetics of urelumab and nivolumab .............................. 
1.4.4 Immunogenicity of Urelumab .................................................................. 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
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 Period 
...................................................................................... 
3.1.2 Treatment Period 
..................................................................................... 
3.1.3 Clinical/Safety Follow-up 
........................................................................ 
3.1.4 Survival/Long-Term Follow-up ............................................................... 
3.1.5 Dose Escalation 
....................................................................................... 
3.1.6 Cohort Expansion 
.................................................................................... 
3.1.6.1 Stage 1 Cohort Expansion .............................................................. 
3.1.6.2 Stage 2 Cohort Expansion .............................................................. 
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 ........................................................... 
 
 
 
 
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3.5 Discontinuation of Subjects from Treatment 
.................................................... 
3.5.1 Treatment Beyond Disease Progression 
.................................................. 
3.5.1.1 Discontinuation due to further progression 
.................................... 
3.5.1.2 Assessment schedule for the subjects with post-progression 
treatment
 ...............................................................................................
 
3.6 Post Study Drug Follow-up .............................................................................. 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up 
.................................................................................... 
4 STUDY DRUG 
.......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.2 Noninvestigational Product 
............................................................................... 
4.3 Storage and Dispensing..................................................................................... 
4.3.1 BMS-663513 (urelumab) ......................................................................... 
4.3.2 BMS-936558 (nivolumab) 
........................................................................ 
4.4 Method of Assigning Subject Identification 
..................................................... 
4.5 Selection and Timing of Dose for Each Subject 
............................................... 
4.5.1 Antiemetic Premedications ...................................................................... 
4.5.2 Dose Limiting Toxicities 
.......................................................................... 
4.5.3 Management Algorithms for Immuno-Oncology Agents 
......................... 
4.5.4 Guidelines for Dose Modification 
............................................................ 
4.5.4.1 Dose Reductions.............................................................................. 
4.5.5 Dose Delays Due To Toxicity .................................................................. 
4.5.6 Criteria to Resume Treatment 
.................................................................. 
4.5.7 Guidelines for Permanent Discontinuation 
............................................. 
4.5.8 Retreatment with Study Therapy 
.............................................................. 
4.5.9 Treatment of Drug Related Infusion Reactions ....................................... 
4.6 Blinding/Unblinding 
......................................................................................... 
4.7 Treatment Compliance 
...................................................................................... 
4.8 Destruction of Study Drug 
................................................................................ 
4.9 Return of Study Drug 
........................................................................................ 
5 STUDY ASSESSMENTS AND PROCEDURES 
..................................................... 
5.1 Flow Chart/Time and Events Schedule 
............................................................. 
5.1.1 Retesting During Screening Period 
......................................................... 
5.2 Study Materials 
................................................................................................. 
5.3 Safety Assessments 
........................................................................................... 
5.3.1 Hepatotoxicity Assessment 
....................................................................... 
5.3.2 Imaging Assessment for the Study............................................................ 
5.3.3 Laboratory Test Assessments 
................................................................... 
5.4 Efficacy Assessments 
........................................................................................ 
5.5 Pharmacokinetic Assessments 
.......................................................................... 
5.5.1 Pharmacokinetics: Collection and Processing 
........................................ 
5.5.2 Pharmacokinetic Sample Analyses 
.......................................................... 
5.5.3 Labeling and Shipping of Biological Samples 
......................................... 
5.6 Biomarker Assessments 
.................................................................................... 
 
 
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5.8 Outcomes Research Assessments ..................................................................... 
5.9 Other Assessments 
............................................................................................ 
5.9.1 Immunogenicity 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 Laboratory Test Result Abnormalities 
.............................................................. 
6.4 Pregnancy 
.......................................................................................................... 
6.5 Overdose 
........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) 
..................................................... 
6.7 Other Safety Considerations 
............................................................................. 
6.7.1 Treatment Algorithms for Drug-related Adverse Events 
......................... 
6.7.2 Rapid Notification of Other Adverse Events of Interest 
........................... 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination 
............................................................................... 
8.1.1 Dose Escalation 
....................................................................................... 
8.1.2 Cohort Expansion 
.................................................................................... 
8.1.2.1 Stage 1 
............................................................................................. 
8.1.2.2 Stage 2: 
........................................................................................... 
8.2 Populations for Analyses 
.................................................................................. 
8.3 Endpoint Definitions 
......................................................................................... 
8.3.1 Primary Endpoint(s) ................................................................................ 
8.3.2 Secondary Endpoints ............................................................................... 
8.3.2.1 Efficacy Endpoints 
.......................................................................... 
8.3.2.2 Pharmacokinetics (PK) 
................................................................... 
8.3.2.3 Immunogenicity 
............................................................................... 
 
8.4 Analyses 
............................................................................................................ 
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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 
................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.7 Other Analyses 
......................................................................................... 
8.5 Interim Analyses 
............................................................................................... 
9 STUDY MANAGEMENT
 ........................................................................................
 
9.1 Compliance 
....................................................................................................... 
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 RECIST 1.1 
........................................................................................... 
APPENDIX 2 INTERNATIONAL WORKING GROUP CRITERIA FOR 
NONHODGKIN LYMPHOMA 
............................................................................. 
APPENDIX 3 MANAGEMENT ALGORITHMS FOR IMMUNO-ONCOLOGY 
AGENTS
 .................................................................................................................
 
APPENDIX 4 ECOG PERFORMANCE STATUS 
..................................................... 
APPENDIX 5 REVISED INTERNATIONAL PROGNOSTIC INDEX (IPI) SCALE
................................................................................................................................. 
APPENDIX 6 INTERNATIONAL PROGNOSTIC INDEX FOR FOLLICULAR 
LYMPHOMA
 .........................................................................................................
 
 
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Yervoy(ipilimumab). In the largest survival analysis of the anti-CTLA-4 monoclonal antibody 
to date, patients receiving ipilimumab 22% of patients were alive at 3 years, no deaths being 
reported beyond 7 years and median 7-year overall survival was 17%.
9Yet, 5-year survival rates 
for distant stage diseases are 15%,
10and recurrent and/or metastaticmalignant melanoma remains 
largely a fatal disease.
11Moreover, only around 50% of patients carry the BRAFV600E mutation 
sensitive to targeted agents like Zelboraf(vemurafenib), Debrafenib and Trametinib.With the 
recent health authority approvals of Opdivo and Keytruda for patients with metastatic melanoma, 
treatment options for patients who relapse following treatment with anti-PD-1 or anti-PD-L1 
therapies will become increasingly important.
Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death in the US. In 2014, an estimated 224,210 new 
cases will be diagnosed, and 159,260 deaths are estimated to occur because of the disease 
accounting for 27% of all deaths due to cancer.
1Most lung cancers (∼ 80%) arenon-small-cell 
lung cancers.12Of these patients, more than 65% present with locally advanced or metastatic 
disease.13 Despite treatment with platinum- and taxane-based chemotherapy, patients with 
metastatic NSCLC have a median survival of approximately 12 months,14and a 5-year survival 
rate of approximately 15%.
15Even though there has been an increase in the number of treatment 
options available for patients with NSCLC, there has been little overall survival (OS) improvement 
from several new agents such as pemetrexed, erlotinib and bevacizumab beyond very small 
subpopulations. Therapeutic options for mutation wild-type NSCLC are particularly limited after 
failure of front-line chemotherapy. 
Overall, 
this group of patients only has an OS of about 8 months 
after progression from platinum agents. Once resistance to tyrosine kinase inhibitors (TKIs) 
occurs, the patients who have EGFR mutations or ALK translocations will have a rapid disease 
progression. Therefore, the majority of NSCLC cases remain a disease withhigh burden and unmet 
medical need.Anti-PD-1 therapies have recently been approved by the US FDA and the European 
Medicines Agency (EMA) for the treatment of advanced NSCLC. With these recent approvals, 
patients who relapse following treatment with anti-PD-1 or anti-PD-L1 therapies will become an 
important new patient category which will require new treatment options.
Head and Neck Carcinoma Squamous Cell (SCCHN)
Head and neck cancer (HNC) is the sixth most common cancer, with a worldwide incidence of at 
least a half a million.16,17The vast majority of cases are squamous cell carcinoma of the head and 
neck (SCCHN), which account for 3% to 4% of all cancers in the US.18,19In 2013 in the United 
States, the American Cancer Society estimates 53,640 new cases are diagnosed and approximately 
11,520 deaths due to this cause occur yearly.
20HNCs describe malignancies of the upper 
aerodigestive tract which include squamous cell carcinomas (SCCHN) of the oral cavity, 
nasopharynx, pharynx and larynx. Smoking and tobacco products, alcohol use, and infection with 
human papillomavirus (HPV) are among the major risk factors, however, a shift in SCCHN 
epidemiology in recent decades has been observed. Tobacco-and alcohol-related disease has 
declined while HPV-driven malignancies have increased.
21 Approximately 10-20% of 
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recurrent/metastatic SCCHN is HPV+.22,23 Epidemiological tracking of HPV-driven HNCs 
suggest that patients with HPV positive (HPV+) tumors have better response rates and survival 
after treatment.24
Treatment of recurrent or metastatic disease involves a multimodal approach including surgery, 
use of cytotoxic chemotherapies such as methotrexate, organoplatinum compounds, fluorouracil 
(5-FU), or taxanes, combination with the biologic agent cetuximab and radiation. Despite the 
availability of these multimodal and novel approaches in management, prognosis has been poor 
for patients with disease recurrence after therapy with curative intent, with median survival for 
patients with locoregionally recurrent or metastatic disease, treated with palliative chemotherapy 
alone, being only 8–10 months.25Metastatic or recurrent SCCHN remains an area of high unmet 
medical need and patients who progress after treatment (refractory or platinum-resistant disease) 
have the worst prognosis with median OS of 3-4months and 1 year survival rate of < 5%.26In 
conclusion, there is no effective standard of care that provides survival benefits beyond 
4-6months in second line platinum refractory recurrent or metastatic SCCHN. New therapeutic 
options are needed for this patient group.
Diffuse Large B-Cell Lymphoma (DLBCL):
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults in 
the United States with a projected estimate of 22,390 new cases and almost 10,000projected deaths 
in 2013.27 With standard therapy, including rituximab (anti-CD20) and an anthracycline 
containing regimen, around 60-70% of patients are alive without lymphoma with a median follow-
up of at least 4 years.28Therefore, despite improvements in overall survival of patients with 
DLBCL with the routine addition of rituximab, 30-40% of patients have disease that is either 
refractory to initial therapy or relapses after standard therapy
.
29
Relapsed/refractory DLBCL is treated with chemotherapy and rituximab but is a therapeutic option 
only in the approximately 50% patients who are eligible for intensive therapy. Those who are 
ineligible for an aggressive approach due to other co-morbidities, poor performance status, 
advanced age, or refusal are considered incurable. Of the patients eligible for high-dose 
chemotherapy, only 50% demonstrate chemosensitive disease such that they can go on to an 
autologous stem cell transplant (ASCT). About 50% of responders to a second chemotherapy 
regimen followed by ASCT maintain their response at 2 years.30
Treatment options following failure of ASCT are limited for patients with DLBCL. Optimal 
management strategies for these patients have yet to be established and outcomes for patients 
requiring subsequent lines of therapy post ASCT remain particularly poor.31
Patients who successfully undergo an ASCT still have an unacceptably high rate of disease 
recurrence. For non-transplant candidates who fail second line therapy or relapse post-transplant, 
therapy is palliative.
29Without transplant, chemotherapy provides short-term disease control in 
relapsed/refractory DLBCL. Primary refractory subjects are unlikely to achieve CR with a second 
chemotherapy regimen and following relapse, a second remission is usually not durable. Therefore, 
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more effective therapies are needed in the relapsed/refractory setting and an agent or combination 
of agents that could overcome that subsequent refractory state could be a valuable new strategy in 
this population. 
Follicular Lymphoma (FL)
FL is the second most common lymphoma in the United States and Western Europe, accounting 
for approximately 20% of NHL (overall) and themajority of low-grade lymphomas. In Europe, 
the incidence is 2.18/105 persons/year32and the median age at diagnosis of 60 years, slight female 
predominance (M:F ratio 1:1.7).33Conventional therapy for FL is not curative. Therefore, new, 
more effective therapies are needed. The safety and effectiveness of rituximab in relapsed, 
refractory Low-Grade or Follicular, CD20-Positive, B-Cell NHL were demonstrated in 3 single-
arm studies enrolling 296 subjects. Despite the fact that most subjects respond to initialtherapy 
(with 40-80% CR),34depending upon the regimen used, and that rituximab has activity as a 
single agent, nearly all subjects later develop progressive disease. Also, up to 10% are refractory 
to their initial treatment. Therefore, new, more effective therapies that potentiate, and perhaps 
create more durable responses to rituximab, are needed.
CD137 (4-1BB) and Urelumab (BMS-663513)
CD137 (4-1BB or TNFRSF9), a TNF superfamily Type 1 membrane glycoprotein receptor, is 
expressed on the surface of lymphoid organs and can be detected on activated T cells (CD4+ and 
CD8+), activated NK cells, natural killer T (NKT) cells, regulatory T cells, activated thymocytes, 
intraepithelial lymphocytes and eosinophils.35,36CD137 is not detected on the surface of resting 
Tand B lymphocytes or activated B lymphocytes.
37,38CD137 expression has now also been 
reported on splenic, follicular, and GM-CSF-stimulated bone marrow (BM) dendritic cells (DC) 
as well as on BM derived mast cells and DCs.39,40,41The natural ligand for CD137 is designated 
as CD137L, a TNF superfamily Type II membrane glycoprotein.42CD137L is expressed on the 
surface of activated T lymphocytes, macrophages, monocytes, DCs and B lymphocytes. In 
addition to its role on effector cells, signaling through CD137 enhances the ability of CD137 
positive DCs to potentiate T cell responsivenessto alloantigens.
43More recent evidence suggests 
that CD137 expressed on tumor-associated endothelial cells play a role in augmenting T cell 
trafficking into tumors.
44
Urelumab is a fully human agonistic mAb specific to the human CD137 receptor (4-1BB). 
Urelumab activates the CD137 pathway and provides a strong costimulatory signal to Tcells and 
NK cells, resulting in enhanced cytokine production (chiefly IFN), survival and proliferation. 
Consequently, urelumab can enhance the function of antigen-specific T cells and mediate clinical 
antitumor activity by enhancing the host antitumor immune response.
Urelumab is the first agonistic anti CD137 antibody studied in humans. By the end of 2008, 
fourstudies in humans had been conducted using urelumab: 2 monotherapy studies (a Phase 1 
study, CA186001, in subjects with solid malignancies and a Phase 2 study, CA186006, in subjects 
with advanced melanoma) and 2 phase 1 combination therapy studies [CA186004 (which 
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combined urelumab with carboplatin and paclitaxel in subjects with solid malignancies) and 
CA186005 (which combined urelumab with radiation and carboplatin plus paclitaxel in subjects 
with non small cell lung cancer)]. In total, 291 subjects including 273 subjects treated with 
monotherapy and 18 subjects treated on the combination trials have received urelumab treatment 
in these 4studies. Hepatotoxicity, was the most frequent clinically important toxicity.
On 18-Nov-2008, a fatal case of drug-related hepatotoxicity was reported in a subject receiving 
urelumabmonotherapy at a dose of 5 mg/kg administered every 3 weeks on study CA186006. A 
second case of fatal, drug-related hepatotoxicity was reported on 30-Nov-2008 in a subject with 
melanoma treated with urelumab at a dose of 1 mg/kg administered every 3 weeks. On 
05-Dec-2008, the sponsor suspended treatment of subjects with urelumab on all ongoing studies 
at the time (CA186001, CA186004, CA186005, and CA186006).
Although a maximum tolerated dose (MTD) of urelumab administered intravenously on an every 
3 week schedule was not formally defined during dose escalation studies, the subsequent 
evaluation of hepatoxicity observed across the program suggested that the occurrence and severity 
of hepatoxicity was substantially increased at doses 1 mg/kg. A urelumab dose of <1mg/kg 
(ie,0.1 mg/kg or 0.3 mg/kg every 3 weeks) resulted in infrequent Grade 3 hepatotoxicity 
(ALT0/41 [0%]; AST 1/41 [2.4%]; total bilirubin 0/41 [0%]), whereas a urelumab dose of 
>1mg/kg every 3 weeks resulted in more frequent Grade 3 hepatotoxicity (ALT 43/189 
[22.8%]; AST 39/189 [20.6%]; total bilirubin 8/189 [4.2%]). The frequency and severity of 
hepatotoxicity reached a plateau at doses > 1 mg/kg. [Note: for consistency, subjects on a q 3 week 
schedule only are compared here]. Those results suggest the multi-treatment MTD is < 1 mg/kg 
administered every 3 weeks.
In addition, anti-tumor activity as well as pharmacodynamic activi
ty was observed across a wide 
dose range of Urelumab (0.1 to 10mg/kg).
Based upon review of these prior findings and the rare incidence of hepatotoxicity at doses below 
1 mg/kg (described above), the Food and Drug Administration (FDA) lifted the clinical hold on 
30-Jun-2011 and now a new Phase 1 monotherapy study, CA186011, is currently enrolling 
subjects. This study is a dose-escalation study at the 0.1 mg/kg and 0.3 mg/kg doses exploring the 
safety, tolerability, pharmacokinetics (PK), and immunoregulatory activity of IV urelumab in 
subjects with advanced and/or metastatic solid tumors or relapsed/refractory B-cell NHL. Dose 
escalation for study CA186011 has been completed with both doses with no DLTs at either dose.
PD-1 (CD279) and Nivolumab (BMS-936558)
Programmed Cell Death 1 (PD-1) is a cell surface signaling receptor that plays a critical role in 
the regulation of T cell activation and tolerance.45It is a type I transmembrane protein and together 
with BTLA, CTLA-4, ICOS and CD28, comprise the CD28 family of T cell co-stimulatory 
receptors. PD-1 is primarily expressed on activated T cells, B cells, and myeloid cells.
46It is also 
expressed on natural killer (NK) cells47. Binding of PD-1 by its ligands PD-L1 and PD-L2, results 
in phosphorylation of the tyrosine residue in the proximal intracellular immune receptor tyrosine 
inhibitory domain, followed by recruitment of the phosphatase SHP-2, eventually resulting in 
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1.3
Objectives(s)
1.3.1
Primary Objectives
To assess the safety and tolerability of urelumab given in combination with nivolumab and to 
identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the 
combination, in subjects with advanced (metastatic and/or unresectable) solid tumors and B cell 
lymphomas.
1.3.2
Secondary Objectives
The secondary objectives are as follows:
To assess the preliminary anti-tumor activity of the combination of urelumab and nivolumab 
in subjects with advanced solid tumors and B cell lymphomas.
To characterize the pharmacokinetics (PK) of urelumab and nivolumab when co-administered.
To monitor immunogenicity of urelumab and nivolumab administered as combination therapy.
 
 
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1.4
Product Development Background
Data for urelumab and nivolumab follows with additional data also available in the respective 
Investigator Brochures.
1.4.1
Pharmacology
Urelumab (BMS-663513)
Urelumab is a fully human agonist IgG4κ isotype monoclonal antibody specific to the human 
CD137 receptor. Urelumab has a molecular weight of 150 kDa. Antibodies to the human 
CD137receptor do not cross-react with the murine receptor and vice-versa. Therefore, an 
anti-murine CD137 receptor antibody homolog, BMS-469492, was used for evaluation in murine 
tumor models. Both urelumab and BMS-469492 (mouse anti-CD137) are agonistic antibodies 
which do not block the interaction of CD137 with its ligand, CD137L. Both the human and the 
mouseanti-CD137 antibodies increase IFNγ secretion from T cells activated with anti-CD3 in an 
in vitro functional assay. 
The functional effects of urelumab on human and monkey T cells and peripheral blood 
mononuclear cells (PBMC) were determined by measuring IFNγ production by human T cells or 
monkey PBMC from healthy donors that were stimulated with anti-CD3 antibody (0.5-1g/mL) 
± anti-human CD137 antibodies. Urelumab demonstrated co-stimulatory properties yielding 
higher levels of IFNγ in human and monkey cells compared to controls (anti-CD3 +/ control IgG).
Endogenous CD137 provides a co-stimulatory signal to T cells which results in enhancement of 
T-cell survival, T-cell proliferation and cytokine synthesis. To determine whether urelumab 
agonist antibody could elicit these same biologic effects, human T cells stimulated with anti-CD3 
urelumab at concentrations known to induce IFNsynthesis were stained with annexin-V and 
propidium iodide to determine the number of live cells (Annexin-V/Propidium iodide negative) 
and with cyclin D2 to assay the cell cycle status of treated cells. Concentrations of urelumab 
ranging from 0.4 -10μg/mL resulted in an increase in the number of live cells by approximately 
1.8 to 2-fold, and yielded a significant increase in the number of cyclin D2 expressing T cells by 
2.5 to 3-fold), confirming the costimulatory effect of urelumab.
Nivolumab (BMS-936558)
Nivolumab is a fully human, IgG4 (kappa) isotype monoclonal antibody that binds to PD-1 with 
nanomolar affinity (KD = 3.06 nM) and a high degree of specificity, thus precluding binding to its 
ligands PD-L1 and PD-L2. Nivolumab does not bind other related family members, such as BTLA, 
CTLA-4, ICOS or CD28. Pre-clinical testing of nivolumab demonstrated that binding to PD-1 
results in enhanced T cell proliferation and release of interferon-gamma (IFN-gamma) in vitro.
1.4.2
Toxicity
Urelumab (BMS-663513)
Intravenous administration of urelumab to monkeys at single doses up to 100 mg/kg (AUC(0-INF) 
534,000 g h/mL) or repeated doses up to 100 mg/kg (AUC833,000 g h/mL), every two weeks 
for up to 9 month, did not result in drug-related toxicity. In mice, the liver was identified as the 
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principal target organ with the murine homolog BMS-469492. The liver lesion occurred after 
single exposures to BMS-469492 at doses 0.2 mg/kg and was characterized as minimal to 
moderate subacute inflammation of the liver and hepatocellular necrosis. Alanine or aspartate 
aminotransferases (ALT or AST) were generally sensitive and specific markers of this injury. 
Based upon the results from investigative studies the liver lesion was consistent with local 
IFN--mediated injury and likely represents a mechanism-related effect of CD137 modulation in 
mice. The NOEL for liver inflammation in mice was achieved following a single dose of 
BMS-469492 at 0.1 mg/kg. No therapeutic window for this toxicity exists in the mouse efficacy 
models. No liver toxicity was observed in the monkey studies with urelumab. 
Multiple-dose administration of the murine homolog BMS-469492 in mice induced liver and skin 
toxicities. There was minimal to moderate chronic inflammation and hepatocellular single-cell 
necrosis, increased ALT and AST, and pigment within Kupffer cells. The severity of the reversible 
hepatotoxicity in mice did not progress with increasing dose level, increasing number of doses, or 
with different dose frequencies. The NOEL for liver inflammation with multiple-dose 
administration of BMS-469492 to mice was not determined. The hepatic toxicity was not 
exacerbated by co-administration of known inflammatory agents, such as lipopolysaccharide 
(LPS) or acetaminophen (APAP). Instead, pre-treatment with BMS-469492 showed a trend to 
prevent or dampen the acute centrilobular hepatocellular necrosis induced by APAP. For further 
details on these studies, please refer to the Investigator Brochure.
Nivolumab (BMS-936558)
Toxicologystudies in cynomolgus monkeys revealed that nivolumab was well tolerated at doses 
up to 50 mg/kg given twice weekly for 27 doses. Drug related findings were limited to a reversible 
decrease in triiodothyronine (T3) by 28%, 
 
.
Preliminary new non-clinical safety findings of adverse pregnancy outcomes and infant losses in 
the absence of overt maternal toxicity have been reported.
66The findings of increased late stage 
pregnancy loss and early infant deaths/euthanasia in nivolumab exposed pregnant monkeys 
suggest a potential risk to human pregnancy if there is continued treatment with nivolumab during 
pregnancy.
1.4.3
Clinical Pharmacology and Safety
Urelumab (BMS-663513)
Four studies in humans havebeen conducted using urelumab: 2 monotherapy studies (a Phase 1 
study, CA186001, in subjects with solid malignancies and a Phase 2 study, CA186006, in subjects 
with advanced melanoma) and 2 combination therapy phase 1 studies [CA186004 (combining 
urelumabwith carboplatin and paclitaxel in subjects with solid malignancies) and CA186005 
(combining urelumab with radiation and carboplatin with paclitaxel in subjects with non small cell 
lung cancer)]. In total, 291 subjects including 273 subjects treated with monotherapy and 
18subjects treated on the combination trials have received urelumab treatment in these 4 studies.
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Of the 273 subjects treated with urelumab in monotherapy studies, drug-related AEs were reported 
in 216 (79.1%) subjects. Drug-related Grade 3 AEs were reported in 75 (27.5%) subjects. The 
most frequently reported drug-related AEs (>10% of subjects) were fatigue, increased AST 
(23.4%), increased ALT (22.7%), fatigue (22.7%), rash (18.3%), nausea (13.5%), pruritus 
(11.7%), pyrexia (11.3%), decreased appetite (11.3%), and diarrhea (11%). Other drug-related 
AEs included headache, decreased platelets, asthenia, neutropenia, febrile neutropenia, and 
thrombocytopenia.
A maximum tolerated dose of urelumab administered intravenously on an every 3 week schedule 
was not formally defined during dose escalation studies. On 18-Nov-2008, a fatal case of 
drug-related hepatotoxicity was reported in a subject receiving urelumab monotherapy at a dose 
of 5mg/kg administered every 3 weeks on study CA186006. A second case of fatal, drug-related 
hepatotoxicity was reported on 30-Nov-2008 in a subject with melanoma treated with urelumab at 
a dose of 1 mg/kg administered every 3 weeks. On 05-Dec-2008, the sponsor suspended treatment 
of subjects with urelumab on all ongoing studies at the time (CA186001, CA186004, CA186005, 
and CA186006). 
After review and presentation of data to the FDA showing the significantly improved hepatic 
safety profile at doses below 1 mg/kg versus that of doses at or above 1 mg/kg, the clinical hold 
was lifted in June 2011 and subjects are currently being treated at doses below 1 mg/kg. 
CA186011, the Phase 1 monotherapy study exploring doses of 0.1 mg/kg and 0.3 mg/kg, has 
completed the dose escalation portion with no DLTs at either dose.
A case of potential drug-induced liver injury (DILI) occurred in study CA186011 in a subject 
treated at 0.3 mg/kg dose.
53Per guidance in that protocol, enrollment in the 0.3 mg/kg dose level 
was halted and 0.3 mg/kg urelumab was determined to exceed the MTD and the 0.1 mg/kg dose 
level was selected for expansion.
Evaluation of the safety data revealed that drug-related hepatotoxicity is the most frequent 
clinically significant drug-related AE experienced among subjects treated with urelumab and is 
dose and schedule dependent. Exposure response analysis revealed that the occurrence and severity 
of hepatoxicity may be correlated with exposure (Cavg) and is substantially increased at doses 
1mg/kg. Doses of urelumab <1mg/kg every 3 weeks resulted in a low frequency of Grade 3 
hepatotoxicity [0 Grade 3 ALT and 1 Grade 3 AST (2.3%) of 44 subjects] whereas an urelumab 
dose of 1 mg/kg every 3weeks resulted in more frequent Grade 3 hepatotoxicity [43 Grade 
3 ALT (22.8%) and 39Grade 3 AST (20.6%) of 189 subjects]. (see Figure1.1.1-1).
Nivolumab (BMS-936558)
The overall safety experience with nivolumab, as monotherapy or in combination with other 
therapeutics, is based on experience in approximately 1,500 subjects treated to date. For 
monotherapy, the safety profile is similar across tumor types. The one exception is pulmonary 
inflammation AEs which may be numerically greater in subjects with NSCLC because in some 
cases it can be difficult to distinguish between nivolumab related and unrelated causes of 
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pulmonary symptoms and radiographic changes. There was no pattern in the incidence, severity, 
or causality of AEs to nivolumab dose level.
In several ongoing clinical trials, the safety of nivolumab in combination with other therapeutics 
such as ipilimumab, cytotoxic chemotherapy, anti-angiogenics and targeted therapies is being 
explored. Most studies are ongoing and as such, the safety profile of nivolumab combinations 
continues to evolve. The most advanced combination under development is nivolumab and 
ipilimumab in subjects with MEL. Thus far, the combination of both agents results in a safety 
profile with similar types of AEs as either agent alone, but in some cases with greater frequency.
Overall, the safety profile of nivolumab monotherapy as well as combination therapy is 
manageable and generally consistent across completed and ongoing clinical trials with no MTD 
reached at any dose tested, up to 10 mg/kg. There was no pattern in the incidence, severity, or 
causality of AEs to nivolumab dose level. Most AEs were low grade (grade 1 to grade 2) with 
relatively few related high grade (grade 3 to grade 4) AEs. Most high grade events were 
manageable with the use of corticosteroids or hormone replacement therapy for endocrinopathies. 
Management algorithms including the use of immunosuppressive agents, such as corticosteroids, 
infliximab, etc., are provided in Appendix 3. Nivolumab should not be used in subjects with active 
autoimmune disease given the mechanism of action of the antibody.
Nivolumab has demonstrated clinical activity in response evaluable subjects witha variety of solid 
tumor malignancies in the following studies:
1) completed Phase 1 single-dose (MDX1106-01): n = 37 subjects with prostate cancer, MEL, 
NSCLC, RCC,and CRC
2) ongoing Phase 1 multi-dose, dose escalation study with nivolumab monotherapy 
(CA209003/MDX1106-03): NSCLC n = 129, MEL n = 107, RCCn=34subjects
3) ongoing Phase 1b study with nivolumab in combination with ipilimumab 
(CA209004/MDX1106-04): MEL n = 82 subjects
4) ongoing Phase 1 study with nivolumab monotherapy or in combination with platinum-based 
chemotherapy or erlotinib (CA209012): NSCLC, monotherapy n = 20, combination therapy n 
= 77 subjects
In addition, monotherapy or combination trials with nivolumab are on-going for subjects with 
SCCHN,67HCC,68CRC69, GBM
70, and NHL.
71,72
Updated overall clinical experience for nivolumab is available in the current version of the 
Investigator’s Brochure.
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1.4.3.1
Pharmacokinetics ofurelumab and nivolumab
Urelumab (BMS-663513)
The CA186001 first-in-human study showed that over the dose range studied (0.3 mg/kg to 
15mg/kg), urelumab concentrations were quantifiable within approximately 0.5 hour and peak 
concentrations occurred between 1 and 5 hours. The CA186001 and CA186011 studies showed 
that at 0.1 and 0.3 mg/kg (the dose range to be tested in this study), the mean serum elimination 
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half-life of urelumab in subjects with solid malignancies was approximately 125-135 hours 
(5.2-5.6 days). Serum urelumab Cmax and AUC increased in proportion to dose when 
administered at 0.1 to 0.3 mg/kg.
Nivolumab (BMS-936558)
A single dose pharmacokinetic analysis of 39 subjects with cancer given nivolumab at 0.3, 1, 3,
and 10 mg/kg revealed that the median T
maxacross single doses ranged from 1.6 to 3 hours with 
individual values ranging from 0.9 to 7 hours. The pharmacokinetics of nivolumab were linear in 
the range of 0.3 to 10 mg/kg with dose proportional increases in maximum serum concentration 
(C
max) and area under the concentration-time curve from time zero to infinity (AUCINF), with low 
to moderate inter-subject variability observed at each dose level. The mean terminal elimination 
half-life of nivolumab was 17 to 25 days, which is consistent with the half-life of endogenous 
IgG4. Both the elimination and distribution of nivolumab were independent of the dose.
1.4.4
Immunogenicity of Urelumab
Data from previous studies indicate that the overall rates of immunogenicity in patients treated 
with urelumab range from 11% (CA186001) to 27% (CA186006).
1.5
Overall Risk/Benefit Assessment
Subjects who have advanced solid tumors or B-cell NHL have extremely poor prognosis with 
limited curative options as stated in Section 1.
29,31Nivolumab has demonstrated clinical activity 
in subjects with advanced NSCLC, RCC, MEL andlymphomas among other tumors. 
Nivolumab monotherapy has demonstrated clinical activity across several tumor types, including 
advanced, previouslytreated melanoma. The combination of nivolumab and urelumab has the 
potential for increased benefit compared to nivolumab monotherapy.
Nivolumab has also demonstrated a manageable safety profile. The most common AEs included 
fatigue, rash, pruritus, diarrhea, and nausea. Side effects of nivolumab therapy may include those 
associated with immune mediated activation, such as thyroiditis and transaminitis. In addition, 
<1% subjects who developed pneumonitis have died. To mitigate risk to subjects management 
algorithms for nivolumab-related adverse events from prior collective nivolumab experience have 
been included (Appendix 3).
Pharmacodynamic evidence of biologic activity was noted with urelumab monotherapy doses 
ranging from 0.1 mg/kg to 10 mg/kg. Clinical anti-tumor activity was also noted in subjects treated 
at urelumab doses starting ata 0.1 mg/kg dose in the Phase 1 monotherapy studies. Among solid 
tumors, anti-tumor activity was manifested in both objective responses and stable disease. All 
objective responseswere observed in subjects with melanoma, and subjects with RCCand ovarian 
cancer were noted to have stable disease. 
In study CA186006,one subject with metastatic melanoma developed a complete response and 
7of 41 showed stable disease. The complete response seen at 0.1 mg/kg and similar stable disease 
rates at 0.1 mg/kg and 1.0 mg/kg in study CA186006 suggest that there is anti-tumor activity at 
the initial dose level of 0.1 mg/kg. The similar stable disease rates of 1.0 mg/kg q3w and 1.0mg/kg 
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q6w in study CA186006 suggest that a less frequent dosing interval may not impact efficacy, but 
may improve the safety profile. Pharmacodynamic evidence of biologic activity was also observed 
across the same dose range. In hematologic malignancies, objective responses were observed in 
10subjects with B-cell NHL treated at 0.3 mg/kg, including one completeresponse based on 
preliminary data from CA186011 (Part 3 of cohort expansion).
Taken together, these data provide evidence for further evaluation of the potential benefit of 
urelumab in combination nivolumab in solid tumors and B-cell NHL (in particular patients with 
the DLBCL or FLsubtypesof B-cell NHL).
Hepatotoxicity is the most frequent clinically significant drug-related AE experienced among 
subjects treated with urelumab and is dose and potentially schedule dependent. However, the risk 
of hepatotoxicity at doses being tested in the current study (flat dose of 8 mg) is expected to be 
very low (Sections1.1.1and 1.4.3). In a prior monotherapy study (CA186006), that evaluated a 
dose of 0.1 mg/kg of urelumab which correlates with 8 mg flat dose, only 1 event of drug-related 
Grade 3 AST elevation was noted in the 41 subjects treated at the 0.1 mg/kg dose, and no other 
Grade 3 hepatic events occurred at this dose. In addition, in the ongoing monotherapy study 
CA186011 (Part 4 initiated in May 2014) exploring the 0.1 mg/kg dose of urelumab, no hepatic 
DLTs were observed during the dose escalation period with this dose, and no Grade3 hepatic 
events were noted in subjects subsequently dosed at 0.1 mg/kg urelumab (preliminary safety data). 
The possibility exists that the combination of urelumab and nivolumab will be more hepatotoxic 
than urelumab monotherapy, but this isconsidered unlikely since nivolumab monotherapy has not 
been associated with any significant hepatotoxicity. However, since this is an experimental study, 
the study protocol has been designed to minimize the risk of potential synergistic hepatotoxicity 
orunanticipated adverse events as follows:
1) Enrollment Criteria (Section 3.3.1) have been strictly chosen to minimize inclusion of 
subjects with underlying potential for increased hepatotoxicity from urelumab. Subjects with 
disease characteristics that could predispose to higher risk of morbidity during conduct of the 
study ie, patients with history of any hepatitis [eg, alcoholic or non-alcoholic steatohepatitis 
(NASH), drug-related, auto-immune] will be excluded from participation.
The safety monitoring plan will require weekly liver function tests (LFTs) including AST, ALT 
alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and totalbilirubin during 
treatment with urelumab (Table5.1-1), and weekly for the first 8 weeks following last 
treatment with urelumab (Table5.1-3). As detailed in Section5.3.1and Hepatotoxicity 
management algorithm (Appendix 3):
Management of LFT Elevations: 
Subjects experiencing Grade 3 elevations in ALT, AST, or total bilirubin will 
be discontinued.
Subjects experiencing ALT or AST > 3x ULN with concurrent total bilirubin 
>2xULN and fulfilling Hy’s law criteria will be discontinued. If 2events of Hy’s 
Law (ALT or AST > 3 X ULN and concurrent T Bili > 2 X ULN) occurs at any 
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point in the study the entire cohort and all cohorts above will be considered to 
exceed the MTD and no subject will receive further doses at or above that dose 
level.
Subjects experiencing Grade 2 elevations in ALT, AST or total bilirubin will have 
the next planned dose delayed until ALT, AST, and total bilirubin resolve to 
Grade 1 
2) Hepatotoxicity management algorithm: To mitigate risk to subjects who develop 
drug-related hepatotoxicity, specific guidelines and algorithm for management of 
hepatotoxicity (see Appendix 3), with links to online resources with a comprehensive listing 
of potentially hepatotoxic agents are included in this protocol.
Screening tests, and clinical and laboratory safety assessments will also be performed on an 
ongoing basis and monitored closely. In addition, the AEs and SAEs will be reviewed by the 
Medical Monitor/Study Director and the Pharmacovigilancegroup to look for trends and safety 
issues. It is possible that unforeseen, unknown, or unanticipated reactions may occur since 
urelumab is an investigational product.
In addition to the potential risk associated with administration of study drugs, there is also some 
risk associated with tumor biopsies, including bleeding, infection and pain. While there is no direct 
benefit to subjects who undergo these procedures, there is the distinct possibility that the data 
generated from these samples will guide the further development of these compounds and may be 
of direct benefit for others with advanced solid tumors.
Preliminary data in 138 patients treated with urelumab and nivolumab as of the clinical cutoff date 
of30-Sep-2016, revealed that the most frequent TRAE was fatigue (31%); grade 3/4 ALT/AST 
elevations (2%/2%) and TRAEs leading to discontinuation (6%) were infrequent. No treatment-
related deaths were reported. Twenty-five of 124 evaluable patients treated with the combination 
had objective responses (melanoma, n=23; SCCHN, n=1, NSCLC, n=1). The ORR in melanoma 
was 50% (23/46) including 9/18 of subjects with PD-L1 negative tumors by IHC.
There remains a significant unmet need for curative options in the tumor types being evaluated in 
this studyincluding PD-L1 negative melanoma where the objective response rate to anti-PD-1 
monotherapy is ~30-35%. Overall, the data indicate a favorable benefit/risk profile for the 
evaluation of a combination of urelumab with nivolumab in this study since the availability of 
moreeffective therapies or combination of agents would be of great benefit to these patients 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 European Union Directive 2001/20/EC and the United States Code of Federal 
Regulations, Title 21, Part 50 (21CFR50).
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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 Investigator Brochure or product 
labeling information to be provided to subjects and any updates. 
The investigator or BMS should provide the IRB/IEC with reports, updates and other information 
(eg, expedited safety reports, amendments, and administrative letters) according to regulatory 
requirements or institution procedures.
2.3
Informed Consent
Investigators must ensure that subjects are clearly and fully informed about the purpose, potential 
risks, and other critical issues regarding clinical studies in which they volunteer to participate. 
In situations where consent cannot be given to subjects, their legally acceptable representatives (as 
per country guidelines) are clearly and fully informed about the purpose, potential risks, and other 
critical issues regarding clinical studies in which the subject volunteers to participate. 
BMS will provide the investigator with an appropriate (ie, Global or Local) sample informed 
consent form(s) whichwill include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
Provide a copy of the consent form(s) and written information about the study in the language 
in which the subject is most proficient prior to clinical study participation. The language must 
be non-technical and easily understood. 
Allow time necessary for subject or subject
's legally acceptable representative to inquire about 
the details of the study.
Obtain an informed consent signed and personally dated by the subject or the subject
's legally 
acceptable representative and by the person who conducted the informed consent discussion. 
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Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent 
form(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.
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 beobtained from the subject.
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject
's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject
's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject
's willingness to continue participation in the study. This communication should be 
documented. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects
' signed ICF and, in the 
US, the subjects’ signed HIPAA Authorization.
The consent form(s) must also include a statement that BMS and regulatory authorities have direct 
access to subject records. 
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 1/2 open label study. The first phase of the study will consist of a dose escalation 
assessment of the safety and tolerability of urelumab administered with nivolumab in subjects with 
advanced solid tumors or B-cell NHL. The second part of the study will include a 2-stage cohort 
expansion in multipletumor types (MEL, NSCLC, SCCHN, DLBCLandFL). Expansion cohorts 
will be explored at the maximally tolerated dose (MTD), highest administered dose (HAD), or at 
an alternative dose/regimen as determined by the investigators and the sponsor. The eligibility for 
the selected tumor types for the cohort expansions are listed in Study Population (Section3.3).
Subjects will complete up to four periods of the study (Screening, Treatment, Clinical/Safety
Follow-up, Survival/Long-term Follow-up): The total time on study for any individual subject is 
expected to be approximately 3.1 years. 
3.1.1
Screening Period
The screening period will last for 28 days. Screening period begins by establishing the subject’s 
initial eligibility and signing of the informed consent form (ICF). Subject is enrolled using the 
Interactive Voice Response System (IVRS). 
3.1.2
Treatment Period
The Treatment Period will consist of up to 6 treatment cycles.  Each cycle is 8 weeks for a total of 
48 weeks. Nivolumab will be given every 2 weeks; urelumab will be given every 4weeks. 
Subjects 
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completing approximately 48weeks of initial treatment withongoing disease control (CR, PR or 
SD) will be followed to monitor the duration of their disease control and may be eligible for 
retreatment if their disease progresses within 12 months following treatment discontinuation (see 
Protocol Section4.5.8for retreatment).
Treatment cycles are comprised of 4 doses of nivolumab per cycle and 2 doses of urelumab per 
cycle. Nivolumab will be administered on Days 1, 15, 29, and 43 and urelumab will be 
administered on Days 1 and 29 of each treatment cycle depending on the treatment cohort. On 
days where both study drugs are given, nivolumab will be given first followed by urelumab at least
30 minutes aftercompletion of the nivolumabinfusion.
Following each treatment cycle, the decision to treat a subject with additional cycles ofstudy 
therapy, up to a maximum of 6 cycles,will be based on tumor assessment (evaluation performed 
between Days 49 and 56 of each cycle and completed before the first dose in the next cycle). 
Tumor progression or response endpoints will be assessed usingRECIST 1.1 criteria for solid 
tumors(Appendix 1)and revised International Working Group (IWG) Criteria for non-Hodgkin 
Lymphoma73 (Appendix 2) for lymphomas. Treatment beyond initial investigator-assessed 
progression (either clinical or radiographic) is permitted only if the subject has an 
investigator-assessed clinical benefit and is tolerating study drug. Subjects with a response of 
unconfirmed PD, SD, PR, or CR at the end of a given cycle will continue to the next treatment 
cycle. Subjects will generally be allowed to continue study therapy until the first occurrence of 
either: 1)completion of the maximum number of cycles, 2) confirmed PD, 3) clinical deterioration 
suggesting that no further benefit from treatment is likely, 4) intolerability to therapy; or 5) the 
subject meets criteria for discontinuation of study therapy as outlined in protocol Sections 3.5and 
4.5.7. Individual subjects with confirmed CR (or a stable and confirmed PR which, in the 
investigator’s opinion, represents the maximum expected benefit for the subject) will be given the 
option to discontinue study therapy prior to 12 months on a case by case basis after specific 
consultation and agreement between the investigator and BMS MM in settings where benefit/risk 
justify discontinuation of study therapy. 
3.1.3
Clinical/Safety Follow-up
Subjects that discontinue the treatment phase will enter the Clinical/SafetyFollow-up period. 
Subjects must be followed for at least 100 days after the last dose of therapy. Follow-up visits 
should occur at Days 30, 60 and 100 (7 days) after the last dose or coinciding with the date of 
discontinuation (7 days) if date of discontinuation is greater than 30 days after the last dose to 
monitor for adverse events. All subjects will be required to complete the 3 clinical safety follow-up 
visits regardless of whether they start new anti-cancer therapy, 
except those subjects who withdraw 
consent for study participation.
3.1.4
Survival/Long-Term Follow-up
After completion of the Clinical/SafetyFollow-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 assesssurvival status. The duration of survival follow-up will be 
3years following the first dose of study drug. 
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Subjects who discontinue study drug with ongoing SD, PR, or CR will continue to have tumor 
assessments completed every 12 weeks for the first yearafter discontinuation of study drug, and 
then continue to receive scans as per standard of care guidelines for follow-up or at a minimum of 
every 6 months up to 3 years following the first dose of study drug, or until disease progression or 
withdrawal of consent.
Subjects in the Survival/Long-termFollow-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.
A study schematic is presented below in Figure 3.1.4-1:
Figure 3.1.4-1:
Study Schematic
3.1.5
Dose Escalation
A 3+3+3 design will be used to assess the safety of urelumab given in combination with 
nivolumab. The cohorts for dose escalation are provided in Table 3.1.5-1. The Dose Limiting 
Toxicity (DLT) observation period will last for 8 weeks following the first dose of study 
medication. The DLT evaluation period will be defined as 8 weeks after administration of the first 
combination dose of nivolumab and urelumab, and includes subjects who have had administration 
= Nivolumab/BMS-936558 dose
CR = complete response; PR = partial response; SD = stable disease; PD = progressive disease 
Screen
Treatment Period: up to 6 treatment cycles.  Each cycle 
is 8 weeksfor a total of 48 weeks.
Includes assessment between Days 49-56
Clinical Follow-up
Survival /Long 
term Follow-up 
Day -28 
1
15
29 43 49-56
Scans
= Urelumab/BMS-663513 dose
Day 29 dose applicable for Cohorts 1, 2, A, B, D
Additional cycles
-CR (see above)
-PR
-SD
-Unconfirmed PD
Clinic visits
Days 30, 60, 100 
after end of 
treatment to 
monitor for adverse 
event
Clinic visits or 
telephone 
contact every
3 months for up 
to 3 years 
following the first 
dose of study 
drug
Retreatment:
Subjects who progress within 12 months of 
completing treatment may be considered for 
retreatment with urelumab/nivolumab 
therapy, after discussion /agreement with 
medical monitor.
Treatment Completed
--Completion of 6cycles
--Confirmed PD
--PD and clinical deterioration
--Toxicity
--Confirmed CR (on an individual 
basis following consultation 
between MM and site PI)
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of at least one dose of nivolumab monotherapy during this interval. This interval is based upon 
inclusion of the earliest times to onset of clinically significant adverse events attributed to study 
drug, and also allows for a substantial amount of time for unexpected toxicities related to the 
dosing regimen to emerge.
Approximately three subjects will be treated initially at each dose regimen. In order to assure a 
sufficient number of evaluable subjects in each cohort an additional subject may be added to a 
cohort (ie, enroll a fourth subject in a cohort of 3). For example, if 4 subjects are treated in the 
cohort, the decision to enroll additional patients or escalate will be made after the 3rd evaluable 
patient completes the DLT window. In this situation, if the decision is made to remain at the same 
dose level and the 4th patient is evaluable, he/she will be included as part of the 2nd cohort at that 
dose level.
Note: (i) Should this action be taken, cohort tolerability assessment and subsequent dose 
escalation, if indicated, will occur when the minimum number of evaluable subjects required to 
assess tolerability have completed the 8 week DLT period. (ii) If any additional subject experiences 
an event that would, per protocol, 
result in either cohort expansion or the halting of dose escalation, 
the escalation rules as defined below in Table 3.1.5-2will be followed. 
Table 3.1.5-1:
Dosages during Dose Escalation
Cohort
Total Subjectsa
urelumab
nivolumabb
1
n = approximately 3-9
3 mg IV every 4 weeks
3 mg/kg or 240 mg IV 
every 2 weeks
2
n = approximately 3-9
8 mg IV every 4 weeks
3 mg/kgor 240 mgIV 
every 2 weeks
Total
n = approximately 6-18
a 3-9 subjects will be enrolled during dose escalation. Additional subjects may be added to each dose level for a total 
of up to 12 subjects per dose level
b Nivolumab 3 mg/kg will be administered for subjects enrolledprior to Revised Protocol 02. Nivolumab 240mg 
flat dose administered for subjects enrolled after Revised Protocol 02.
After dose escalation to the next cohort, 3-9 additional subjects may be enrolled in any previously 
tolerated (as defined by the dose escalation decision rules in Table 3.1.5-2) dose level (original 3-9 
subjects from dose escalation plus additional subjects required to have a total cohort size of 12).If 
the rate of DLTs exceeds 33% in a given treatment regimen,the findings will be discussed and 
further enrollment may be interrupted for that specific treatment regimen and tumor type.
If one of the planned dose cohorts is determined to exceed the MTD, and/or based on ongoing 
safety/tolerability experience through the dose escalation phase of the study, an alternate dose 
escalation schema as outlined in Table 3.1.5-3may be explored in consultation and agreement 
between the Sponsor and investigators.
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Sentinel Subject:During dose escalation, the first subject treated at each dose level will receive 
C1D1 (eg,the first dose of study drugs) and will be observed for 3 weeks such that one 
combination dose followed by one nivolumab dose are administered before additional subjects in 
the cohort receive the first dose of study drug (ie,C1D1).
Dose Escalation Rules:Tableoutlines the decision rules for dose escalation based on the number 
of subjects and observed DLTs. No intra-subject dose escalation or reduction is allowed. Subjects 
who withdraw from the study during the DLT period for reasons other than a DLT may be replaced 
within the same dose level/regimen. Dose escalation will be based on the number of dose limiting 
toxicities (DLTs) experienced during the DLT observation period.
If dose escalation is terminated, then the dose or dosing regimen below thatwhichinvoked the 
stopping rule will be declared the MTD.
Table 3.1.5-2:
Decision Rules During Dose Escalation
Number of 
Evaluable 
Subjects/
Cohort
3-4a
6-8
9-12
Total 
Number of 
Observed 
DLTs 
0 
1
2 or 
more
1
2
3 or 
more
2
3 or 
more
Decision 
Rule
Dose 
Escalate
Enroll 
additional 
subjects in 
cohort to 
reach at 
least 6 
subjects
Dose 
exceeds 
MTD
Dose 
Escalate
Enroll 
additional 
subjects at in 
cohort to 
reach at least 
9subjects
Dose 
exceeds 
MTD
Dose 
Escalate
Dose 
exceeds 
MTD
a If 4 subjects are enrolled in a cohort, the decision to enroll additional patients or escalatewill be made after the 3rd 
evaluable subject completes the DLT window. In this situation, if the decision is made to remain at the same dose 
level and the 4th subject is evaluable, he/she will be included as part of the 2nd cohort at that dose level
If either Cohort 1 or Cohort 2 exceeds the MTD, alternate treatment regimens may be explored 
during dose escalation or cohort expansion (listed in Table 3.1.5-3).
Table 3.1.5-3:
Alternate Treatment Regimens
Cohort Designation
urelumab
nivolumaba
Ab
8 mg IV every 8 weeks
3 mg/kg or 240 mg IV every 
2weeks
Bb
8 mg IV every 8 weeks
1 mg/kg or 80 mg IV every 2 weeks
C
3 mg IV every 4 weeks
1 mg/kg or 80 mg IV every 2 weeks
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Table 3.1.5-3:
Alternate Treatment Regimens
Cohort Designation
urelumab
nivolumaba
Db
3 mg IV every 8 weeks
3 mg/kg or 240 mg IV every 2 
weeks
a Nivolumab 1 mg/kg or 3 mg/kg will be administered for subjects enrolledprior to Revised Protocol 02. Nivolumab 
80 mg or 240 mg flat dose administered for subjects enrolled after Revised Protocol 02
b Dosing regimen not applicable following Revised Protocol 03 (Dated 31-Aug-2015)
All available clinical andlaboratory data observed during dose escalation will be reviewed to 
determine the alternative treatment regimen listed in Table 3.1.5-3to be evaluated. The nature, 
time of onset, and time to resolution of DLTs observed will be reviewed in the context of the 
current safety data from the respective urelumab and nivolumab trials. After review of this data, 
and after consultation between theinvestigators and the sponsor, the identified alternative 
treatment regimens may be evaluated. 
3.1.6
Cohort Expansion
The purpose of cohort expansion is to gather additional safety, tolerability, preliminary efficacy 
and pharmacodynamic information regarding the combination of urelumab and nivolumab. Once 
the safety profile of all doses tested has been characterized and the MTD of combined 
administration of urelumaband nivolumab has been defined, cohort expansions will be initiated at 
the MTD, the HAD, or an alternate dose, if recommended by the investigators and the sponsor. 
Treatment doses in the cohort expansion groups will not exceed the HAD. The cohort expansion 
phase will follow a 2-stage designas outlined below in Table 3.1.6-1.
Table 3.1.6-1:
Cohort Expansion
Tumor Types
Stage 1 Expansion
Stage 2 Expansion
Non-small Cell Lung Cancer 
(NSCLC)
Up to approximately 20 subjects at 
MTDor HAD
Up to approximately 20 additional 
subjects
Melanoma (MEL)
Up to approximately 20 subjects at 
MTDorHAD
Up to approximately 20 additional 
subjects
Head and Neck Squamous Cell 
Carcinoma (SCCHN)
Up to approximately 20 subjects at 
MTDorHAD
Up to approximately 20 additional 
subjects
Diffuse Large B Cell Lymphoma 
(DLBCL)
Up to approximately 20 subjects at 
MTDorHAD
Up to approximately 20 additional 
subjects
NSCLC (progressive or recurrent 
disease during or after anti-PD-
1/anti-PD-L1 therapy)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 20 subjects
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Table 3.1.6-1:
Cohort Expansion
Tumor Types
Stage 1 Expansion
Stage 2 Expansion
Follicular Lymphoma (FL)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 20 subjects
Melanoma (progressive or recurrent 
disease during or after an 
anti-PD-1/anti-PD-L1 containing 
treatment regimen)
Up to approximately 20 subjects at 
MTD or HAD
Up to approximately 20 subjects
Melanoma PD-L1 negative
Up to approximately 50 subjectsat 
MTD or HAD
3.1.6.1
Stage 1 Cohort Expansion
Stage 1 of the expansion phase willtreat 20subjects per tumor typeat the MTD or HAD as 
identified during dose escalation followed by continued enrollment of up to approximately 
20additional subjects (total of 40 subjects per tumor type)(Stage 2)to obtain additional
safety/efficacydata forthe combination. The safety, tolerability, and preliminary efficacy data 
from Stage 1 of the cohort expansion will be evaluated per tumor type and discussed by the sponsor 
with investigators prior to enrolling20 additionalpatients during Stage 2.
Efficacy criteria for moving to Stage 2:
In order to enroll additional patients inStage 2 of cohort expansion a minimum of 4 out of 
20subjects in the first stage of cohort expansion need to demonstrate an objective response to 
study therapy. In general, if 0 to 3 responses are observedin a given tumor specific cohort during 
Stage 1of cohort expansion,Stage 2 will not be enrolled for that tumor type.Please note: Ongoing 
assessment of data from the initial 20 patients may be used to consider additional enrollment in 
that tumor type at a later date (to consider the possibility of delayed responses).
An additional 50 treatment naïve PD-L1 negative melanoma subjects will be treated at MTD/HAD 
to further evaluate if there is an efficacy signal in this population.   Additional subjects may be 
enrolled and treated so as to accrue a minimum of 50 evaluable subjects with at least 2 on treatment 
scans.
Safety criteria for moving to Stage 2:
If the rate of events that would qualify as DLTs exceeds 33% fora particular tumor type; the 
findings will be discussed by sponsor with investigators and further enrollment may be interrupted 
for subjects with that tumor type.
Safety data from subjects enrolled in Stage 1 of the expansion phase will be reviewed by BMS 
medical and safety teams, and discussed with and endorsed by participating investigators, prior to 
moving toStage 2of cohort expansion. 
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If the efficacy and safety data from a given tumor type meet the minimum criteria for moving 
forward, approximately 20 additional subjects will be enrolled during Stage 2 of cohort expansion. 
The evaluation of data from Stage 1 and the decision to begin Stage 2 of the expansion phase of 
the study can be made up to one year following completion of the enrollment of Stage 1 for each 
individual tumor type.
In the instance of unforeseen toxicity in a single expansion cohort, BMS will review the aggregate 
safety data both within a tumor type and across tumor types to determine if all subjects should 
have the dose reduced or treatment modified,or if the reduction should apply to only the specific 
tumor type. A decision on the impact of toxicity in one tumor-specific cohort across the program 
will be made based on the nature and severity of toxicity and feedback from participating 
investigators
3.1.6.2
Stage 2 Cohort Expansion
To evaluate additional safety, tolerability, 
and preliminary efficacy of the combination of urelumab 
and nivolumab, up to approximately 20 additional subjects will be enrolled following evaluation 
of the data from Stage 1 of Cohort Expansion.
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 study drug. Study drug would be provided via anextension 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 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
Forentry 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 informed consent form prior to the performance of any 
study-related procedures that are not considered part of standard of care.
2) Target Population
a) Subjects must have histologic or cytologic confirmation of a malignancy that is advanced 
(metastatic and/or unresectable):
i) Dose Escalation:
(1).All solid tumor and B-cell NHL histologies will be permitted during dose 
escalation, except for subjects with primary CNS tumors, CNS lymphoma or with 
CNS metastases as the only site of active disease.
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(2).Subjects must have received and thenprogressed, or been intolerant to, at least one 
standard treatment regimen in the advanced or metastatic setting, if such a therapy 
exists. Subjects who refuse or are ineligible for standard therapy will be allowed to 
enroll provided their refusal/ineligibility is documented in medical records.
ii)Cohort Expansion
(1).The following tumor types will be permitted during cohort expansion:
a. Non Small Cell Lung Cancer (NSCLC). 
No prioranti-PD-1/anti-PD-L1 therapy
i.
Must have recurrent or progressive disease during or after platinum 
doublet-based chemotherapy for advanced or metastatic disease OR must 
have recurrent or progressive disease within six months after completing 
platinum-based chemotherapy for local disease.
ii.
Subjectswith non-squamous histologymust have known EGFR and ALK 
status. 
iii.
Subjects with an activating EGFR mutation must have received an EGFR 
tyrosine kinase inhibitor.
iv.
Subjects with an ALK translocation must have received an ALK inhibitor.
b. Melanoma(MEL)
i.
Not applicable.
ii.
Subjects must have known BRAF V600mutation status or consent to 
BRAF V600 mutation testing per local institutional standards during the 
Screening Period.
iii.
Histologically confirmed unresectable Stage3 or Stage 4 melanoma as 
per American Joint Committee on Cancer (AJCC)staging system
iv.
Treatment naive subjects (ie, no prior systemic anticancer therapy for 
unresectable or metastatic melanoma).
1. Note: Prior adjuvant or neoadjuvant melanoma therapy is permitted if
it was completed at least 4 weeks or 5 half-life times (whichever is 
shorter) prior to randomization and all related adverse events have 
either returned to baseline or stabilized.
c. Headand Neck Squamous Cell Carcinoma (SCCHN)
i.
Histologically confirmed incurable locally advanced, recurrent or 
metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not 
amenable to local therapy with curative intent (surgery or radiation 
therapy with or without chemotherapy).
ii.
Confirmation of tumor HPV status: Prior testing results are acceptable if 
known. 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.
iii.
Tumor progression or recurrence within 6 months of last dose of platinum 
therapy in the adjuvant (ie,with radiation after surgery), primary (ie, with 
radiation), recurrent, or metastatic setting. Clinical progression after 
platinum therapy is an allowable event for entry and is defined as 
progression of a lesion at least 10 mm in size that is amenable to caliper 
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measurement (eg,superficial skin lesion as per RECIST 1.1) or a lesion 
that has been visualized and photographically recorded with 
measurements and shown to have progressed.
iv.
Prior curative radiation therapy must have been completed at least4 
weeks prior to study drug administration. Prior focal palliative 
radiotherapy must have been completed at least 2 weeks before study drug 
administration.
d. Tumor Biopsy confirmation of relapsed or refractory DLBCL, or transformed 
lymphoma (TL), prior to the initiation of study drug. 
i.
TL is limited to DLBCL. Subjects with Grade 3b follicular lymphoma are 
excluded.
ii.
DLBCL or TL should be pathologically confirmed by standard 
immunohistochemical or flow cytometric techniques.
iii.
Documentation of the above should be present in the subject’s medical 
record.
iv.
Prior treatment as defined below;
1. Subjects with relapsed DLBCL or TL after high-dose conditioning 
chemotherapy andASCT, or
2. Subjects with relapsed or refractory DLBCL or TL after at least 1 prior 
multi-agent chemotherapy regimen if ASCT ineligible. Ineligibility 
for ASCT will be determined using local institutional criteria.
Definition of Relapsed DLBCL
the appearanceof new lesions > 6 months after obtaining a CR
an increase 50% in the size of previously involved sites > 6 
months after completing planned therapy
Definition of Refractory DLBCL
< 50% decrease in lesion size after planned therapy,
the appearance of newlesions during therapy or < 6 months after 
completion of planned therapy
an increase of 
50% in the size of previously involved sites during 
therapy or < 6 months after completion of planned therapy.
v.
Measurable disease: Subjects must have at least one lesion that is 
>15mm (1.5cm) in the longest diameter on cross-sectional imaging and 
measureable in two perpendicular dimensions per computed tomography 
(spiral CT) or MRI
e. Non Small Cell Lung Cancer (NSCLC).Subjects with progressive or recurrent 
disease (per RECIST v1.1) during or after anti-PD-1 or anti-PD-L1 therapy:
i.
Must have received platinum based chemotherapy for advanced or 
metastatic disease; or locally advanced disease
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ii.
A minimum of 5 subjects in Part 1 of Cohort Expansion should have 
squamous histology
iii.
Subjects with non-squamous histology must have known EGFR and ALK 
status. 
iv.
Subjects with an activating EGFR mutation must have received an EGFR 
tyrosine kinase inhibitor.
v.
Subjects with an ALK translocation must have received an ALK inhibitor.
vi.
Must have received anti-PD-1/anti-PD-L1 treatment as most recent 
therapy and have progressed during or after therapy. 
vii.
The last dose of prior anti-PD-1/anti-PD-L1 treatment 28 days from 
initiation of study therapy.
viii.
No more than 25% of NSCLC subjects (5 during stage 1 and 5 during 
stage 2 of cohort expansion) will be enrolled with primary refractory 
disease (ie, a BOR of PDper RECIST v1.1). The remaining subjects in 
the cohort will be subjects with relapsed disease (ie, SD, PR or CR but 
progressing on therapy).
f. Follicular Lymphoma (FL)
i.
Tumor biopsy confirmation of relapsed or refractory FL must be obtained 
prior to the initiation of study drug.
1. Grade 1, 2, or 3a FL without pathologic evidence of transformation.
2. FL should be pathologically confirmed by standard 
immunohistochemical or flow cytometric techniques.
3. Documentation of the above should be present in the subject’s medical 
record.
4. Treatment of FL consisting of 2 prior treatment lines; each of the 2 
prior treatment lines must include CD20 antibody and/or an alkylating 
agent (eg, bendamustine, cyclophosphamide, ifosfamide, melphalan, 
chlorambucil, busulfan, nitrosoureas). At least one of the prior 
treatment lines must include rituximab.
NOTE: Separate lines of therapyare defined as 2 regimens separated 
by disease progression, relapsed disease, or refractory disease.
ii.
Definition of Relapsed FL
1. The appearance of new lesions > 6 months after obtaining a CR
2. An increase 50% in the size of previously involved sites > 6 months 
after completing planned therapy.
iii.
Definition of Refractory FL
1. < 50% decrease in lesion size after planned therapy
2. The appearance of new lesions during therapy or < 6 months after 
completion of planned therapy
3. An increase of 50% in the size of previously involved sites during 
therapy or < 6 months after completion of planned therapy
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g. Melanoma (MEL) Subjects with progressive or recurrent disease (per RECIST 
v1.1) during or after anti-PD-1 or anti-PD-L1 therapy:
i.
Subjects must have known BRAF V600 mutation status or consent to 
BRAF V600 mutation testing per local institutional standards during the 
Screening Period.
ii.
Histologically confirmed unresectable Stage 3 or Stage 4 melanoma as 
per American Joint Committee on Cancer (AJCC) staging system
iii.
Must have received anti-PD-1/anti-PD-L1 with or without anti-CTLA4 
treatment as most recent therapy and have progressed during or after 
therapy. 
iv.
The last dose of prior anti-PD-1/anti-PD-L1 treatment 28 days from 
initiation of study therapy.
v.
No more than 25% of MEL subjects (5 during stage 1 and 5 during stage 
2 of cohort expansion) will be enrolled with primary refractory disease 
(ie, a BOR of PD per RECIST v1.1). The remaining subjects in the cohort 
will be subjects with relapsed disease (ie, SD, PR or CR but progressing 
on therapy).
h. Melanoma (MEL) Subjects with PD-L1 negative
i.
Fresh, pre-treatment biopsies are required.
ii.
Subjects must have known BRAF V600 mutation status or consent to 
BRAF V600 mutation testing per local institutional standards during the 
Screening Period.
iii.
Histologically confirmed unresectable Stage3 or Stage 4 melanoma as 
per American Joint Committee on Cancer (AJCC) staging system
iv.
Treatment naive subjects (ie, no prior systemic anticancer therapy for 
unresectable or metastatic melanoma).
1. Note: Prior adjuvant or neoadjuvant melanoma therapy is permitted if 
it was completed at least 4 weeks or 5 half-life times (whichever is 
shorter) prior to randomization and all related adverse events have 
either returned to baseline or stabilized.  However, no prior therapy 
with immune checkpoint inhibitors (eg, anti-PD-1, anti-PD-L1, anti 
LAG 3 and anti-CTLA4); immune costimulatory molecules (eg, anti-
CD137, anti-OX40, anti GITR); anti-cancer vaccines (eg, Provenge, 
MAGE-3); or otherimmune modulating monoclonal antibodies is 
permitted.
v. Subjects must be PD-L1 negative (PD-L1 tumor cell expression <1%) based 
on  IHC testing performed by a BMS selected vendor on a fresh tumor sample 
collected during the screening period. 
b) Presence of at least one lesion with measurable disease, which is distinct from the biopsy 
lesion,as defined by RECIST v1.1 for solid tumors or revised IWG criteria for B-cell NHL 
for response assessment. The only exception permissible is in sole accessible, bulky 
DLBCL lesions that are >5cm in largest diameter. Lesions meeting this criterion can be 
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biopsied and followed as an index lesion. Subjectswith 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.
c) Subjects must consent to allow the acquisition of existing formalin-fixed 
paraffin-embedded (FFPE) material, either a block or at least 10-15 unstained slides, for 
performance of correlative studies:
i) For NSCLC(noprior anti-PD-1/anti-PD-L1), tissue must have been collected within 6 
months of trial entry. 
ii)For other solid tumor types, tissue may have been collected at any time prior to first 
dose of study drug.
iii)The solid tumor tissue specimen must be a core needle biopsy, 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. Note: 
For DLBCLandFLsubjects only, FNA specimens are mandatory. FNA specimens 
may be omitted only in cases where a portion of the excisional biopsy specimen will 
be available for protocol-specified cytometry assessments (SeeSection 5.7.2). Biopsies 
of bone lesions that do not have a soft tissue component or decalcified bone tumor 
samples are also not acceptable 
iv)For subjects with no available archived specimen, a fresh tumor biopsy may be 
collected to fulfill this criterion.
v) For subjects with NSCLC (relapsed/refractory to prior anti-PD-1/anti-PD-L1), tissue 
must have been collected after progression from prior anti-PD-1/anti-PD-L1.
d) The first 20 subjectswith MEL and SCCHN in the Stage 1 of the expansion will be required 
to undergo mandatory pre-treatment and on-treatment biopsies in the cohort expansion 
phase at acceptable clinical risk as judged by the investigator. Biopsies in the MEL and 
SCCHN cohortsmust be excisional, incisional, or core needle biopsies. The biopsy lesion 
must be distinct from a target lesion.
e) All subjects in the DLBCL and FLexpansion cohortswill be required to undergo 
mandatory pre-treatment biopsies and the first 20 subjects in Stage 1 of the expansion phase 
will be required to undergo mandatory on-treatment biopsies withadequate tissue 
collection to perform specified analyses. The biopsy lesion must be distinct from an index 
lesion. Note: The only exception permissible is in sole accessible, bulky lesions that are 
>5cm in largest diameter. Lesions meeting this criterioncan be biopsied and followed as 
an index lesion.
f) ECOG status of 0 or 1.
g) Adequate organ function for subjects with solid tumor histologies as defined by the 
following(institutional levels of lab normal values based on ethnicity will be allowed for 
WBC, ANC, and Hemoglobin):
i) WBC 2000/L (stable off any growth factor within 4 weeks of first study drug 
administration)
ii)Neutrophils 1500/L (stable off any growth factor within 4 weeks of first study drug 
administration)
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iii)Platelets 100x103/L (transfusion to achieve this level is not permitted within 
2weeks of first study drug administration)
iv)Hemoglobin 8.5 g/dL (transfusion to achieve this level is not permitted within 
2weeks of first study drug administration)
v) Creatinine 1.5x ULN
vi)ALT and AST 3x ULN
vii)Total bilirubin 1.5x ULN (except subjects with Gilbert’s Syndrome who must have 
normal direct bilirubin)
viii)
Normal thyroid function, subclinical hypothyroidism (TSH<10 mIU/mL) or have 
controlled thyroid disorder
h) Adequate organ function for subjects with B-cell NHL malignancies as defined by the 
following:
i) Absolute Neutrophil Count 750/μL (no WBC growth factors for prior 14days)
ii)Platelets 50 x103/μL (no platelet transfusions for prior 14 days)
iii)Hemoglobin >8.0 g/dL (no RBC transfusions for prior 7 days)
iv)Serum creatinine 1.5 x ULN or creatinine clearance (CrCl) 40 mL/min (measured 
using the Cockcroft-Gault formula below):
Female CrCl = 
(140 -age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dL
Male CrCl =
(140 -age in years) x weight in kg x 1.00 
72 x serum creatinine in mg/dL
v) AST/ALT 3 x ULN
vi)Total Bilirubin 1.5 x ULN (except subjects with Gilbert’s Syndrome, who canhave 
total bilirubin < 3.0 mg/dL).
i) Ability to comply with treatment, PK and PD sample collection,and required study follow-
up.
3) Age, Sex, and Reproductive Status
a) Males and Females, 18
b) Women of childbearing potential (WOCBP) must have a negative serum orurine 
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24hours 
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 5 half-lives of study drug plus 30 days (duration of 
ovulatory cycle) for a total of 23 weeks post-treatment completion.
e) Males who are sexually active with WOCBP must agree to follow instructions for 
method(s) of 
contraception for the duration of treatment with study drug(s) plus 5half-lives 
of study drug(s) plus 90 days (duration of sperm turnover) for a total of 31weeks post 
treatment completion.
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f) Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However they 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. Highly effective methods of contraception have 
a failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to the use of two methods of contraception, with one method 
being highly effective and the other method being either highly effective or less effective as listed 
below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
Male condoms with spermicide
Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, 
injectables, implants and intrauterine devices (IUDs) such as Mirenaby WOCBP subject or 
male subject’s WOCBP partner
IUDs, such as ParaGard
Tubal ligation
Vasectomy
Complete abstinence*
*Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an 
acceptable form of contraception for all study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed 
in the event that the subject chooses to forego complete abstinence.
LESS EFFECTIVE METHODS OF CONTRACEPTION
Diaphragm with spermicide
Cervical cap with spermicide
Vaginal sponge
Male condom without spermicide
Progestin only pills by WOCBP subject or male subject’s WOCBP partner 
Female condom*
* A male and female condom must not be used together
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3.3.2
Exclusion Criteria
1) Target Disease Exceptions
a) Subjects with known or suspected central nervous system (CNS) metastases or with the 
CNS as the only site of disease are excluded. Subjects with CNS lymphoma 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 (or4weeks of observation if no intervention is 
clinically indicated), and off of steroids for at least 2 weeks,and no new or progressive 
neurological signs and symptoms. Please note: for 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) Participation in any prior clinical study with ipilimumab, or with nivolumab including 
subjects in comparator arms, in which overall survival is listed as the primary or co-primary 
endpoint and which has not completed analysis based on the primary endpoint. Exception: 
I-O experienced NSCLC and melanoma cohort (prior antibody therapy of anti-CTLA-4 
and/or anti-PD-1 or anti-PDL-1).
d) Subjects who have received nivolumab are not eligible to be enrolledwith the exception 
for those NSCLC and MEL subjects enrolling in the expansion cohorts where prior 
anti-PD-1 or anti-PD-L1 therapies are specifically required.
2) Medical History and Concurrent Diseases
a) Subjects with a prior malignancy are excluded, except adequately treated basal cell or 
squamous cell skin cancer, localized prostate cancer, carcinoma in situ of the cervix, or 
insitu ductal or lobular carcinoma of the breast. Subjects with other second malignancies 
diagnosed more than 2years ago who have received therapy with curative intent with no 
evidence of disease during the interval who are considered by the investigator to present a 
low risk for recurrence will be eligible.
b) Prior organ allograft or allogeneic bone marrow transplantation
c) 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 patients with a history of Grave’s disease (subjects with 
suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid 
peroxidase antibodies and thyroid stimulating immunoglobulin prior to randomization),
psoriasis not requiring systemic treatment, or conditions not expected to recur are permitted 
to enroll.
d) 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.
e) Uncontrolled or significant cardiovascular disease including, but not limited to any of the 
following:
i) myocardial infarction or stroke/TIA within the past 6 months
ii)uncontrolled angina within the past 3 months
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iii)any history of clinically significant arrhythmias (such as ventricular tachycardia, 
ventricular fibrillation or torsades de pointes)
iv)QTc prolongation > 480 msec
v) history of other clinically significant heart disease (ie, cardiomyopathy, congestive 
heart failure with NYHA functional classification III-IV, pericarditis, significant 
pericardial effusion)
vi)requirement for daily supplemental oxygen therapy
f) History of any chronic hepatitis as evidenced by:
i) Positive test for hepatitis B surface antigen (HBsAg)
ii)Positive test for qualitative hepatitis C viral load (by 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.
iii)History of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, 
or previous grade 3-4 drug-related hepatitis) or any form chronic liver disease will be 
excluded.
g) 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).
h) Evidence or history of active or latent tuberculosis infection including PPD recently 
converted to positive; chest x-ray with evidence of infectious infiltrate; recent unexplained 
changes in fever/chill patterns.
i) Any significant acute or chronic medical illness.
j) Any major surgery within 4 weeks of study drug administration.
k) Subjects who are unable to undergo venipuncture and/or to tolerate venous access.
l) Known current drug or alcohol abuse
m) Any other sound medical, psychiatric and/or social reason as determined by the 
investigator.
3) Prohibited Prior Treatments and/or Therapies
a) Prior therapy with immune checkpoint inhibitors (eg, anti-PD-1, anti-PD-L1, anti-LAG-3); 
immune costimulatory molecules (eg, anti-CD137, anti-OX40, anti-GITR); anti-cancer 
vaccines (eg, Provenge, MAGE-3); or other immune modulating monoclonal antibodies. 
Prior anti-CTLA4 is permitted. Prior anti-PD-1/anti-PD-L1 therapy is permitted for the 
NSCLC cohort described in Protocol inclusion criteria 2(a)(ii)(1)(e) above.
b) Subjectswho have received prior anti-CTLA4 therapy:
i) Prior anti-CTLA4 therapy withindays from the first day of study therapy.
ii)Subjects who have received prior anti-CTLA4 blockade and experienced the following 
immune-mediated adverse events:
(1).Grade 3 or > pneumonitis, hepatitis, colitis, ocular events;
(2).Any CNS event regardless of severity;
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(3).Any immune-mediated adverse event requiring additional immunosuppressive 
therapy beyond steroids for management.
c) Any anti-cancer therapy (eg, chemotherapy, biologics, vaccines, radiotherapy, or hormonal 
treatment) including investigational drugs within 4 weeks prior to the first dose of study 
drug administration, with the exception of GnRH agonist therapy for subjects with prostate 
cancer.Prior palliative or targeted radiotherapy must have been completed at least 2 weeks 
prior to the first dose of study drug.
d) Use of non-oncology vaccines containing live virus for prevention of infectious diseases 
within 12 weeks prior to study drug. The use of the inactivated seasonal influenza vaccine 
(Fluzone®) is allowed.
e) Use of growth factors, including, but not limited to, granulocyte-colony stimulating factor 
(G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF) or erythropoietin 
within 4 weeks prior to the first dose of study drug. Note: Subjects with DLBCLonly: use 
of G-CSFor GM-CSFwithin 2 weeksprior to first dose of study drug(Section 3.3.12h(i)).
f) Use of pRBC or platelet transfusion within 2 weeks for solid tumors and 7 days for B-cell 
NHL prior to the first dose of study drug.
g) Subjects with a condition requiring systemic treatment with either corticosteroids (>10mg 
daily prednisone equivalents) or other immunosuppressive medications within 14days of 
study drug administration. Inhaled or topical steroids, and adrenal replacement doses 
>10mg daily prednisone equivalents are permitted in the absence of active autoimmune 
disease.
h) Chronic Obstructive Pulmonary Disease requiring recurrent steroids bursts or chronic 
steroids at doses greater than 10mg/day of prednisone or the equivalent
i) Subjects receiving RANK-L inhibitors or bisphosphonates are permitted. It is 
recommended that dosing of these agents begins at least 4 weeks prior to the expected first 
dose of study drug or after end of first cycle of treatment.
j) Use of any medicinal herbal preparations within 2 weeks prior to the first dose of study 
drug unless prescribed by the treating physician.
k) 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). Eligibility of subjects with prior Grade 3 checkpoint therapy-related 
immune adverse events, will be considered on a case-by-case basis after discussion with 
the MM (eg,asymptomatic isolated grade 3 lipase elevations without clinical or 
radiological features of pancreatitis will be permitted to enroll).
l) Subjects who experienced prior non-life threatening checkpoint therapy-related
immune-mediated adverse events must have confirmed recovery (resolve to baseline or 
Grade 1) from these events at thetime of study entry, asdocumented by improvement of 
clinical symptoms, abnormal findings on physical examination, and/or associated 
laboratory abnormalities.
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4) Physical and Laboratory Test Findings
a) 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.
b) Positive tests for hepatitis B virus surface antigen, hepatitis B core antibody,or hepatitisC 
RNA (Subjects with positive hepatitis C antibody and negative quantitative hepatitisC by 
PCR are eligible.)Additional testing or substitute testing per institutional guidelines to rule 
out infectionis permitted.
5) Allergies and Adverse Drug Reaction
a) History of allergy to components of urelumab or nivolumab, (eg, history of severe 
hypersensitivity reactions to drugs formulated with polysorbate 80).
6) Sex and Reproductive Status
a) Women who are pregnant or are breastfeeding.
7) 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.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and to ensure 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
Women of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 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 duration of the washout 
period below are suggested guidelines and the investigators should use their judgment in checking 
serum FSH levels. If the serum FSH level is >40 mIU/mLat any time during the washout period, 
the woman can considered postmenopausal. 
1 week minimum for vaginal hormonal products, (rings, creams, gels)
4 week minimum for transdermal products
8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
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3.4.2.1
Permitted Therapy
Subjects are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). 
Immunosuppressive agents and the use of systemic corticosteroids are permitted in the context of 
treating adverse events. Subjects receiving corticosteroids for treatment of drug-related adverse 
events must be at < 10 mg/day prednisone or equivalent prior to re-initiation of study therapy. 
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 non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by a 
contact allergen) is permitted.
Subjects receiving corticosteroid treatmentfor adverse events from prior immunotherapy must 
have completed steroid tapers for treatment of these adverse events by aminimum of 14days prior 
to commencing treatment with study therapy.
Subjects may continue to receive hormone replacement therapy.
RANK-L inhibitors and bisphosphonates are permitted as clinically indicated but should be 
avoided, if possible, prior to completion of cycle 1.
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Palliative and supportive care for disease related symptoms may be offered to all subjects on the 
trial after 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 treatment during 
radiation or surgery.
3.5
Discontinuation of Subjects from Treatment
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 stopstudy treatment and/or participation in the study;
Any clinical adverse event (AE), laboratory abnormality, or intercurrent illness which, in the 
opinion of the investigator indicates that continued participation in the study is not in the best 
interest of the subject;
Termination of the study by Bristol-Myers Squibb (BMS);
Loss of ability to freely provide consent through imprisonment or involuntary incarceration for 
treatment of either a psychiatric or physical (eg, infectious disease) illness;
Pregnancy;
Documented and confirmed disease progression as defined by RECIST or IWG criteria 
(seeAppendices 1 and 2)unless subject meets criteria for treatment beyond progression (See 
Section 3.5.1);
Clinical deterioration while receiving active study therapy that in the opinion of the 
investigator indicates that continued participation in the study is not in the best interest of the 
subject;
Discretion of the investigator;
Inability to comply with the protocol requirements;
Protocol defined reasons for discontinuation (see Section 4.5.7).
The investigator must notify the BMS Medical Monitor/designee in the event a female subject 
becomes pregnant within 24 hours and submit information to WWS on the pregnancy form within 
24 hours. The study drug should be discontinued after pregnancy has been confirmed.
All subjects who discontinue should comply with protocol specified follow-up procedures as 
outlined in Table5.1-3. The only exception to this requirement is when a subject withdraws 
consent for all study procedures or loses the ability to consent freely (ie, is imprisoned or 
involuntarily incarcerated for the treatment of either a psychiatric orphysical 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 case report form (CRF) page.
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3.5.1
Treatment Beyond Disease Progression
As described in Section1.1.2accumulating evidence indicates a minority 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 1.1 defined PD, or 
progression defined by relapsed disease (after CR) or progressive disease (after PR, SD) per 2007 
IWG criteria, as long as they meet the following criteria:
Investigator-assessed clinical benefit, and do not have 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 
urelumab/nivolumab treatment, using an ICF describing any reasonably foreseeable risks or 
discomforts, or other alternative treatment options.
The assessment of clinical benefit should take into account whether the subject is clinically 
deteriorating and unlikely to receive further benefit from continued treatment. All decisions to 
continue treatment beyond initial progression must be discussed with the BMS Medical Monitor 
and an assessment of the risk/benefit of continuing with study therapy must be documented in the 
study records. Subjects will be re-consentedto explain the rationale for this ongoing treatment.
3.5.1.1
Discontinuation due to further progression
Subjects should discontinue study therapy upon further evidence of further progression, defined 
as an additional 10% or greater increase in tumor burden volume from 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 post-progression assessment.
Any new lesion considered non-measurable at the time of initial progression may become 
measurable and therefore must be included in the tumor burden measurement as follows:
For solid tumors: New lesions are considered measurable at the time of initial progression if the 
longest diameter is at least 10 mm (except for pathological lymph nodes, which musthave a short 
axis of at least 15mm). 
For B-cell NHL: New lesions are considered measurable at the time of initial progression if the 
long axis is more than 15 mm regardless of the short axis. If a lymph node has a long axis of 11 to 
15mm, it should only be considered measurable if its short axis is more than 10 mm.
For statistical analyses that include the investigator-assessed progression date, subjects who 
continue treatment beyond initial investigator-assessed, RECIST 1.1-defined progression will be 
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considered to have investigator-assessed progressive disease at the time of the initial progression 
event.
3.5.1.2
Assessment schedule for the subjects with post-progression treatment
Subjects should continue to receive monitoring according to the On-Treatment Assessments in 
Table5.1-2and Table5.1-5. Radiographic assessment by CT (preferred) or MRI described in 
Section5.4and Table5.1-2are required when subjects continue post-progression treatment. For 
subjectswith B-cell NHL, study termination can be based on investigator-assessed evidence of 
clinical progression. FDG-PET scans for subjectswith B-cell NHL are not mandated after 
investigator-assessed progression, but can be performedand results collected.
For subjects that discontinue post-progression treatment, no additional radiographic assessments 
will be required.
 
 
 
 
 
.
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 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 three documented phone calls, 
faxes, or emails as well as lack of response by subject to one registered mail letter. All attempts 
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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 a 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
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and can consist of the following:
All products, active or placebo, being tested or used as a comparator in a clinical trial
Study required premedication 
Other drugs administered as part of the study that are critical to claims of efficacy 
(eg,background therapy, rescue medications)
Diagnostic agents: (such as glucose for glucose challenge) given as part of the protocol 
requirements must also be included in the dosing data collection
The study treatments include BMS-663513 and BMS-936558. Table 4-1below indicates the dose 
level to be used for each panel.
Table 4-1:
Treatment Administration
Cohort
Urelumab (BMS-663513)
Subjects Enrolled Prior to 
Revised Protocol 02
Subjects Enrolled After 
Revised Protocol 02
Nivolumab (BMS-936558)
Nivolumab (BMS-936558)
1
3 mg IV every 4 weeks
3 mg/kg IV every 2 weeks
240 mg IV every 2 weeks
2
8 mg IV every 4 weeks
3 mg/kg IV every 2 weeks
240 mg IV every 2 weeks
Aa
8 mg IV every 8 weeks
3 mg/kg IV every 2 weeks
240 mg IV every 2 weeks
Ba
8 mg IV every 8 weeks
1 mg/kg IV every 2 weeks
80 mg IV every 2 weeks
C
3 mg IV every 4 weeks
1 mg/kg IV every 2 weeks
80 mg IV every 2 weeks
Da
3 mg IV every 8 weeks
3 mg/kg IV every 2 weeks
240 mg IV every 2 weeks
a Dosing regimen not applicable following Revised Protocol 03 (Dated 31-Aug-2015)
Product description and storage information is described in Table 4-2.
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Expansion cohorts will be treated at the highesttested dose or a different dose level as selected by 
the sponsor.
For treatment visits where both BMS-663513 and BMS-936558 are administered, BMS-936558 
will be administered first followed by BMS-663513 at least30 minutes after completion of the 
BMS-936558 infusion. Detailed administration instructions will be provided separately via site 
training materials.
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Table 4-2:
Study Drugs for CA186107
Product Description 
Class and Dosage Form
Potency
IP/Non-IMP
Blinded or 
Open Label
Packaging/Appearance
Storage Conditions
(per label)
Urelumab 
(BMS-663513-01) 
Injection (for IV 
Infusion)
5 mg/ mL
IP
Open Label
3 mL fill in a 5 mL vial/
1 vial/carton
A clear colorless to pale 
yellow solution which 
may contain particulates
Store refrigerated, 
2°-8° C,
(36° -46° F) Protect 
from Light, Protect 
from Freezing.
Nivolumab
(BMS-936558-01)
Injection, 100 mg/vial
(10 mg/mL)
10 mg/mL
IP
Open Label
10 mLvial
Box
Clear to opalescent, 
colorless to pale yellow 
liquid. May contain light 
(few) particulates
Store 2-8 Degrees C 
(36-46 Degrees F); 
Protect from Light; 
Protect from Freezing
Protect from Shaking.
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined as follows:
A pharmaceutical form of an active substance or placebo being tested or used as a reference in a 
clinical study, including products already with a marketing authorization but used or assembled 
(formulated or packaged) in a way different from the authorized form, or used for an unauthorized 
indication, or when used to gain further information about the authorized form.
The investigational product should be storedin 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 product(s) is/are: urelumab (BMS-663513)and nivolumab 
(BMS-936558).
4.2
Noninvestigational 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 as 
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, do not dispense the study drug and 
contact BMS 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 that 
includes all processes required toensure 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).
Infusion-related supplies (eg, IV bags, in-line filters, 0.9% NaCl solution) will not be supplied by 
the sponsor and should be purchased locally if permitted by local regulations.
For non-investigational product, if marketed product is utilized, it should be stored in accordance 
with the package insert, summary of product characteristics (SmPC), or similar.
Please refer to the current version of the Investigator Brochure/pharmacy reference sheets for 
complete storage, handling, and preparation information for BMS-663513 (urelumab) and 
BMS-936558 (nivolumab)
4.3.1
BMS-663513 (urelumab)
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 
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regarding the quality or appearance of the study drug arise, the study drug should not be dispensed 
and contact BMS immediately.
Investigational product documentation must be maintained that includes all processes required to 
ensure drug is accurately administered. This includes documentation of drug storage, 
administration and, as applicable, storage temperatures, reconstitution, and use of required 
processes (eg, required diluents, administration sets).
As with all injectable drugs, care should be taken when handling and preparing urelumab.
Whenever possible, urelumab should be prepared in a laminar flow hood or safety cabinet using 
standard procedures for the safe handling of intravenous agents applying aseptic techniques. 
Gloves are required.
If urelumab solution comes in contact with the skin or mucosa, immediately and thoroughly wash 
with soap and water.
Urelumab injection is an isotonic solution that may be diluted to concentrations between 
0.05mg/mL and 1 mg/mL using sterile disposable syringes prior to administration by IV infusion. 
Solutions of urelumab injection may foam; therefore, shaking and excessive agitation of vials 
should be avoided. Gentle swirling and inversion of the vials is recommended prior to dilution. 
The urelumab drug product solution may be diluted with 0.9% sodium chloride injection normal 
saline (NS), United States Pharmacopeia, in non-PVC/non-DEHP IV bags. The product must be 
infused using a volumetric pump at the protocol specific dose(s) and rate(s) through a sterile, non-
pyrogenic, non-PVC/non-DEHP, IV infusion set containing a 0.2m polyethersulfone in-line 
filter. It is not to be administered as IV push or bolus injection. Care must be taken to assure 
sterility of the prepared solutions, since the drug product does not contain any antimicrobial 
preservatives or bacteriostatic agents. The diluted solutions may be stored for up to 4 hours at 
ambient room temperature/room light, or for up to 24 hours in a refrigerator 2°C to 8°C (36°F to 
46°F), but must be infused within each timeframe, respectively.
The infusion rates should be maintained at either 1.0 mL/min for the 60 minute infusion or at 
0.5mL/min if the rate has been reduced by half due to an infusion reaction. A minimum of 10mL 
normal saline flush should be given at the end of the infusion. For convenience the infusion times 
and volumes for the various cohorts are listed below and should be used accordingly:
Dose escalation and dose expansion cohorts 8 mg or 3 mg dose per subject
Infusion volume: 60 mL
Infusion time: 60 min (1 mL/min)
Sample calculation for required volume of urelumab based on dose:
Subject at 8 mg dose
Total dose: 8 mg
Volume urelumab: 8 mg / (5 mg/mL) = 1.6 mL
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For non-investigational product, if marketed product is utilized, it should be stored in accordance 
with the package insert, summary of product characteristics (SmPC), or similar.
4.3.2
BMS-936558 (nivolumab)
Nivolumab vials must be stored at a temperature of 2°C to 8°C and should be protected from light 
and freezing. If stored in a glass front refrigerator, vials should be stored in the carton. 
Recommended safety measures for preparation and handling of nivolumab include laboratory 
coats and gloves.
For details on drug preparation, storage, handling and dispensing of nivolumab, please refer to the 
BMS-936558 (nivolumab) Investigator Brochure and/or pharmacy reference sheets.
Nivolumab is to be administered as a 60-minute IV infusion. When both study drugs are to be 
administered on the same day, separate infusion bags and filters must be used for each infusion. 
Nivolumab is to be administered first followed by urelumab at least 30 minutes after completion 
of the nivolumab infusion. The nivolumab infusion must be promptly followed by a saline flush 
to clear the line of nivolumab before starting the urelumab infusion. 
Detailed administration instructions will be provided separately via site training materials.
4.4
Method of Assigning Subject Identification
CA186107 is an open label study. Subjects will undergo screening evaluations to determine 
eligibility within 28 days prior to dosing. Enrolled subjects, including those not dosed, will be 
assigned sequential subject numbers starting with 00001, eg, 00001, 00002, 00003, 
...00010. 
Those 
enrolled subjects meeting inclusion and exclusion criteria will be eligible to be treated and 
increasing sequentially with each additional enrolled subject. The subject number will be assigned 
by the Sponsor via Interactive Voice Response System (IVRS) once the subject signs the informed 
consent form. Each subject will then be identified by a distinct patient identification number (PID) 
which is comprised of the site number and the subject number. For example, the first subject 
screened (ie, enrolled) at site number 1, will have a PID of 0001 00001. The Investigator or 
designee will register thesubject following the enrollment procedures established by BMS. The 
following information is required for registration:
Date of birth
Gender
Date of Informed Consent
Diagnosis (Expansion Phase only)
Tumor Type (Expansion Phase only)
Enrolled subjects meeting all eligibility criteria will be assigned to a dose cohort. 
Specific instructions for using IVRS will be provided to the investigational sites in a separate 
document.
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4.5
Selection and Timing of Dose for Each Subject
Each subject will be assigned to a specific dose level as listed in Table 4-1in sequential order 
during dose escalation. Subjects in cohort expansion will be treated at the MTD, the HAD, or at 
an alternate dose, if recommended by the investigators and the sponsor.
Dosing calculations for nivolumab should be based on the body weight assessed at Day 1 per
Table5.1-1. If the subject’s weight on the day of dosing differs by >10% from the weight used to 
calculate the dose, the dose must be re-calculated. All doses should be rounded to the nearest 
milligram. There will be no dose escalations or reductions of nivolumab allowed once assigned. 
Subjects may be dosed no less than 12days from the previous dose. There are no premedications 
recommended for nivolumab on the first cycle. If an acute infusion reaction is noted, the subjects 
should be managed according to Section 4.5.9.
Following implementation of revised protocol 02, nivolumab will be administered as flat dosing 
at the doses listed in Table 4-1.
Urelumab will be administered as flat dosing at the doses listed in Table 4-1.
4.5.1
Antiemetic Premedications
Antiemetic premedications should not be routinely administered prior to dosing of study drug. See 
Section 4.5.9for subsequent premedication recommendations following a nivolumab-related 
infusion reaction.
4.5.2
Dose Limiting Toxicities
Adverse events will be gradedaccording to the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE)Version 4.0(v4.0).
Non-hematologic Dose-Limiting Toxicity (DLT):
A. Hepatic Non-Hematologic DLT
Any one of the following study drug-related events will be considered a hepatic DLT:
Any grade 3 elevation of AST, ALT or T bili
Grade 2 AST or ALT with symptomatic liver inflammation (eg, right upper quadrant 
tenderness, jaundice, pruritus)
AST or ALT > 3 x ULN and concurrent total bilirubin > 2 x ULN without initial findings of 
cholestasis (elevated serum alkaline phosphatase(ALP) (ie,findings consistent with Hy’s law
or FDA definition of potential drug-induced liver injury or pDILI)*
*[Note that this special category of DLT uses ULN rather than CTC Grade for definition]
NOTE: Subjects who experience a DLT that is considered related only to urelumab may be allowed 
to continue nivolumab monotherapy following resolution of the event. This will be determined 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 treatment with nivolumab 
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monotherapy (eg, subjects with asymptomatic, isolated grade 3 ALT and/or AST elevation that 
responds rapidly to short 2-3 weeks course of steroid therapy).
B. Non-Hepatic Non-Hematologic DLT
Any of the following events will be considered a Non-Hepatic Non-Hematologic DLT:
Any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to topical 
therapy and does not improve to Grade 1 severity within 2 weeks OR requires systemic 
treatment
Grade 3 drug-related uveitis, pneumonitis, bronchospasm, neurologic toxicity, hypersensitivity 
reaction, or infusion reaction of any duration requires discontinuation
Any Grade 3 or greater non-dermatologic, non-hepatic non-hematologic study drug-related 
toxicity will be considered a dose-limiting toxicity with the following specific EXCEPTIONS:
o 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
o Grade 3 nausea, vomiting or diarrhea that lasts less than 48 hours, and either 
resolves spontaneously or responds to conventional medical intervention
o Isolated Grade 3 elevation of amylase or lipase not associated with clinical or 
radiographic evidence of pancreatitis
o Isolated Grade 3 fever not associated with hemodynamic compromise 
(eg,hypotension, clinical or laboratory evidence of impaired end-organ perfusion)
C. Dermatologic DLT
Grade 3/4 rash if no improvement (ie,resolution to Grade 1) after a 1-2 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
D. Hematologic DLT (study drug-related)
Grade 4neutropenia 7 days in duration
Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement 
for platelet transfusion
Grade 3 febrile neutropenia for 72 hours
Grade 3 hemolysis (ie, requiring transfusionor medical intervention such as steroids)
Grade 4 anemia not explained by underlying disease
4.5.3
Management Algorithms for Immuno-Oncology Agents
Immuno-oncology (I-O) agents are associated with adverse events that can differ in severity and 
duration fromadverse events caused by other therapeutic classes. Nivolumab and urelumab are 
considered immuno-oncology agents in this protocol. Early recognition and management of 
adverse events associated with immuno-oncology agents may mitigate severe toxicity. 
Management algorithms have been developed to assist investigators in assessing and managing 
the following groups of adverse events:
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Gastrointestinal
Renal
Pulmonary
Hepatic
Endocrinopathies
Skin
Neurological
The algorithms recommended for utilization in this protocol are included in Appendix 3.
4.5.4
Guidelines for Dose Modification
Intrasubject dose escalation or reduction of urelumab and nivolumab is not permitted in this study 
in order to allow better evaluation of extended safety and efficacy at individual dose levels and 
schedules.
4.5.4.1
Dose Reductions
No dose reductions of either urelumab or nivolumab are permitted in this study.
4.5.5
Dose Delays Due To Toxicity
Subjects who experience a DLT must have study drug held. Subjects who are required to 
permanently discontinue both study drugs are listed in Section 4.5.7. In addition, all Grade2 
hepatic, pulmonary, renal, gastrointestinal, and neurological adverse events should be evaluated 
and managed per the toxicity management algorithms (Appendix 3). Subjects not meeting 
guidelines for permanent discontinuation will be permitted to resume therapy based on the criteria 
specified below in Section 4.5.6. Subjects eligible to resume study therapy will resume study 
therapy at the treatment visit following their last received study medication dose.
Depending on the dosing schedule (See Table5.1-2and Table5.1-5), if there is a delay in dosing 
of combination dose (same day dose of urelumab and nivolumab) of between 1 -26 days 
(forsubjects receiving the combination dose every 4 weeks), the procedures at the original 
scheduled visit should be performed as soon as possible. If the delay is more than 26, the visit and 
dose will be considered missed; the procedures at the next scheduled visit should be performed, 
and subsequent combination doses will follow at 4. 
Depending on the dosing schedule (See Table5.1-2and Table5.1-5), if there is a delay in dosing 
of nivolumab of between 1 -12 days, the procedures at the original scheduled visit should be 
performed as soon as possible. If the delay is more than 12 days, the visit and dose will be 
considered missed; the procedures at the next scheduled visit should be performed, and subsequent 
nivolumab doses will follow every 2 weeks. 
Whereas the general guidance on dose delays as above will normally apply to all subjects, 
extensions to the period of dose delays may be grantedfor individual subjects on a case by case 
basis after specific consultation and agreement between the investigator and BMS Medical 
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Monitor in settings where benefit/risk may justify continued study therapy (eg,subject deriving 
clinical benefit who requires prolonged steroid taper for management of non-DLT drug-related 
adverse events, or experiences delays for management of a non-drug-related AE).
The end of cycle disease assessments (ie, CT/MRI, PET, etc) will continue on an every 8weeks 
schedule relative to the subject’s 1st dose regardless of any treatment delay incurred.
4.5.6
Criteria to Resume Treatment
Subjects experiencing AEs not meeting criteria for permanent discontinuation as outlined in 
Section 4.5.7may resume treatment with study medication 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;
Subjects with Grade 2 uveitis or eye pain or blurred vision not meeting DLT criteria 
(Section 4.5.2) must resolve to baseline prior to resuming study therapy;
Drug-related pulmonary toxicity, diarrhea, or colitis, must have resolved to baseline before 
treatment is resumed;
Drug-related endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment.
NOTE: Subjects who experience a DLT that is considered related only to urelumab may be allowed 
to continue nivolumab monotherapy following resolution of the event. This will be determined 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 treatment with nivolumab 
monotherapy (eg, subjects with asymptomatic, isolated grade 3 ALT and/or AST elevation that 
responds rapidly to short 2-3 weeks course of steroid therapy).
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 therapy under these exceptions will be made on a case by 
case basis after considering the overall benefit/risk profile and in consultation between the 
investigator and the study sponsor. Any adverse event with clinical risk will be assessed on a case 
by case basis with the investigator and the BMS Medical Monitor to determine the risks and 
benefits of continuing on therapy following resolution versus discontinuing therapy permanently.
If treatment with study medication is delayed > 6 weeks, the subject must be permanently 
discontinued from study therapy, except as specified in Section 4.5.7). 
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4.5.7
Guidelines for Permanent Discontinuation
Subjects will be required to permanently discontinue both study drugs for the following adverse 
events:
A. Any drug related AE occurring at any time that meets DLT criteria as outlined in Section4.5.2
will require permanent discontinuation with the following exceptions:
a) grade 3 diarrhea, nausea, vomiting, or abdominal pain that returns to grade 1 or baseline 
within 3 days with medical intervention;
b) grade 3 pruritus or rash that returns to grade 1 or baseline within 7 days or baseline with 
medical intervention;
c) grade 4 electrolyte abnormalities that < 72 hours in duration;
d) grade 4 neutropenia 7 days in duration;
e) grade 4 increase in amylase or lipase that is not associated with clinical or radiographic 
evidence of pancreatitis;
f) grade 4 lymphopenia < 5 days in duration.
NOTE: Subjects who experience a DLT that is considered related only to urelumab may be allowed 
to continue nivolumab monotherapy following resolution of the event. This will be determined 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 treatment with nivolumab 
monotherapy (eg, subjects with asymptomatic, isolated grade 3 ALT and/or AST elevation that 
responds rapidly to short 2-3 weeks course of steroidtherapy).
Any dosing delay lasting > 6 weeks will be cause for permanent discontinuation with the following 
exceptions:
Dosing delays to allow for prolonged steroid tapers to manage drug-related adverse events are 
allowed. Prior to re-initiating treatmentin a subject with a dosing delay lasting >6weeks, the 
BMS Medical Monitormust be consulted. Tumor assessments should continue as per protocol 
even if dosing is delayed. 
Prior to re-initiating treatment in a subject with a dosing delay lasting > 6 weeks, the BMS 
Medical Monitor must be consulted. Dosing delays > 6 weeks that occur for non-drug-related 
reasons may be allowed if approved by the BMS Medical Monitor. Whereas the general 
guidance on dose delays as above will normally apply to all subjects, extensionsto the period 
of dose delays may be granted for individual subjects on a case by case basisafter specific 
consultation and agreement between the investigator and BMS Medical Monitorin settings 
where benefit/risk may justify continued study therapy (eg,subject deriving clinicalbenefit 
who requires prolonged steroid taper for management of non-DLT irAEs, or experiences
delays for management of a non-drug-related AE). 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 5. The only exception to this requirement is when a 
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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 treatment 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 case report form(CRF) page.
4.5.8
Retreatment with Study Therapy
The consideration to re-initiate study therapy under these exceptions will be made on a case by 
case basis after considering the overall benefit/risk profile and in consultation between the 
investigator and the study sponsor. Any adverse event with clinical risk will be assessed on a case 
by case basis with the investigator and the BMS Medical Monitorto determine the risks and 
benefits of continuing on therapy following resolution versus discontinuing therapy permanently.
Subjects who have completed all 6 cycles of treatment and who experience disease progression 
during the follow-up period after having experienced initial disease control (CR, PR or SD) within 
12 months of last treatment with study therapy may be permitted re-initiation of study therapy at 
their original dose regimen after discussion and agreement with the BMS Medical Monitor. 
Subjects entering this phase will follow the Time and Events schedule as outlined in Table5.1-4, 
Table5.1-5, and Table5.1-6. Samples for PK and ADAwill be collected as perTable 5.5.1-3, 
select samples for PD (PBMCs, serum cytokine samples, flow panel samples) willbe collectedas 
outlined in Table 5.7-.
Subjects undergoing retreatment of study therapy should continue to meet the eligibility criteria 
with respect to laboratory parameters andorgan function at the time study drug resumes and should 
not have experienced a DLT that would require permanent discontinuation of study therapy. 
Screening procedures that need to be repeated are outlined in Table5.1-4.Subjects will continue 
to receive study therapy at the same dose levels as assigned at study start. Additional, separate, 
safety and efficacy listings will be presented for those subjects who reinitiated study therapy.
Subjects who achieve CR during initial therapy and chose to come off therapy for reasons other 
than toxicity, will be continue to be followed and will be allowed to be re-treated within 12months 
of administration of last dose of study drug.
Subjects who experience DLT will not be eligible for retreatment, except as outlined in 
Section4.5.2.
4.5.9
Treatment of Drug Related Infusion Reactions
Since nivolumab and urelumab contain only human immunoglobulin protein sequences, it is 
unlikely to be immunogenic and induce infusion or hypersensitivity reactions. However, if such a 
reaction were to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, 
arthralgias, 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 v4.0guidelines.
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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 50mg (orequivalent) 
and/or acetominophen/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, non-steroidal anti-inflammatory drugs, 
narcotics, corticosteroids, bronchodilators, IV fluids]; prophylactic medications indicated for 
24hours).
Stop the infusion, begin an IV infusion of normal saline, and treat the subject with 
diphenhydramine 50 mg IV (or equivalent) and/or acetominophen/paracetamol 325 to 1000mg; 
remain at bedside and monitor subject until resolution of symptoms. Corticosteroid or 
bronchodilator therapy may also be administered as appropriate. If the infusion is interrupted, then 
restart the infusion at 50% of the original infusion rate when symptoms resolve; if no further 
complications ensue after 30 minutes, the rate may be increased to 100% of the original infusion 
rate. Monitor subject closely. If symptoms recur then no further study drug will be administered 
at that visit. Administer diphenhydramine 50 mg IV, and remain at bedside and monitor the subject 
until resolution of symptoms. The amount ofstudy drug infused must be recorded 
on the electronic 
case report form (eCRF). The following prophylactic premedications are recommended for future 
infusions: diphenhydramine 50 mg (or equivalent) and/or paracetamol 325 to 1000mg 
(acetaminophen) should be administered at least 30 minutes before additional study drug 
administrations. If necessary, corticosteroids (recommended dose: up to 25 mg of IV 
hydrocortisone or equivalent) may be used.
For Grade 3 or Grade 4 symptoms:(Severe reaction, Grade 3: prolonged [ie, 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 1:1,000solution 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 
(orequivalent), 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 
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symptoms (eg, appearance of a localized or generalized pruritus within 1 week after treatment), 
symptomatic treatment may be given (eg,oral antihistamine, or corticosteroids).
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Study drug will be administered in the clinical facility. The investigator or their designated study 
personnel will maintain a log (Drug Accountability Log) of all study drugs received, dispensed 
and destroyed. The investigator and the study personnel will ensure that each subject receives the 
calculated dose of the study drug based on body weight.
Drug supplies will be inventoried and accounted for throughout the study. The Drug 
Accountability Log will be reviewed by the study monitor during site visits and at the completion 
of the study. Any discrepancy should be brought to the attention of the sponsor.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially-used study drug containers, vials and syringes may be destroyed on site. 
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 SOPs and a copy provided to BMS upon request.
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposalvendor 
must be documented.
Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
If conditions for 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 provi
ded that appropriate records of disposal are 
kept.
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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 BMS Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have beenestablished according to applicable federal, state, local, 
and institutional guidelines and procedures, and provi
ded that appropriate records of disposal are 
kept. 
Arrangements for the return of the study drug will be made by the responsible Study
 Monitor.
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v

Clinical Protocol
CA186107
BMS-663513
urelumab
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule
Study assessments and procedures for initial treatment are presented in Table5.1-1, Table5.1-2, and Table5.1-3. Study assessments for 
re-treatment are presented in Table5.1-4,Table5.1-5, and Table5.1-6.
Table5.1-1: 
Screening Procedural Outline (CA186107) -Initial Treatment
Procedure
Screening
Visit (Day -28 to 
Day 1)
Notes
Eligibility Assessments
Informed Consent
X
A subject is considered enrolled only when a protocol-specific informed consent is 
signed. Contact IVRS to obtain study subject number. Study allows for re-enrollment of 
a subject that has discontinued the study as a pre-treatment failure. If re-enrolled, the 
subject must be re-consented and assigned a new subject number from IVRS.
Inclusion/Exclusion Criteria
X
Medical History
X
Include any toxicity or allergy-related to previous treatments. Includes more detailed 
medical history of risk factors for potential events such as pulmonary-related events.
Tobacco and Alcohol History/Status
X
Document subject’s history and current status of tobacco and alcohol use
Tumor tissue acquisition
X
For patients with solid tumors (except for Melanoma PD-L1 negative cohort):
Tumors may be archival.1 paraffin block or 10 -15 FFPE unstained slides identified and 
shipped to the Central Lab prior to dosing. BMS Medical Monitor approval is required 
for subjects for whom tissue is not available. 
For patientsin the Melanoma PD-L1 negative cohort:A fresh tumor biopsy is 
required.  1 paraffin block or 10 -15 FFPE unstained slides to be shipped directly to the 
BMS selected vendor for testing prior to dosing.  
Safety Assessments
Physical Examination (PE)
X
If the screening PE is performed within 24hours of dosing on Cycle 1Day 1 then a 
single exam may count as both the screening and pre-dose evaluation.
Performance Status
X
ECOG Performance Status (Appendix 4).
Physical Measurements
X
Includes height, weight.
Revised Protocol No.: 06
Date: 22-Mar-2017
81
610
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-1: 
Screening Procedural Outline (CA186107) -Initial Treatment
Procedure
Screening
Visit (Day -28 to 
Day 1)
Notes
Vital Signs
X
Includes body temperature, seated blood pressure, heart rate and respiratory rate. Blood 
pressure, heart rate and respiratory rate should be measured after the subject has been 
seated quietly for at least 5 minutes.
Oxygen Saturation
X
Pulse oximetry collected at rest. Oxygenlevels will be used in combination with clinical 
signs and symptoms and radiographic images to evaluate pulmonary/respiratory status. 
Changes in O2 levels will not be used in isolation to document or diagnosis pulmonary 
toxicity.
Revised International Prognostic 
Index (IPI) and Follicular Lymphoma 
International Lymphoma Index 
(FLIPI) at time of initial disease 
diagnosis
X
For subjects with B-cell NHL only. Refer to Appendix 5
Electrocardiogram (ECGs)
X
12-lead ECG; ECGs should be recorded after the subject has been supine for at least 5 
minutes
Chest Radiograph
X
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, 
carbon dioxide, phosphorus, BUN, creatinine, fasting glucose, total protein, albumin, 
amylase, lipase, CRP, ferritin, uric acid, and LDH.
CBC w/differential & platelets
X
LFT assessments
X
AST, ALT, alkaline phosphatase, total bilirubin, and GGT 
Urinalysis
X
Urine to be checked for protein, glucose, blood, leukocyte esterase, specific gravity and 
pH. Microscopic examination of sediment if blood, protein, or leukocyte esterase 
positive on dipstick.
PT/PTT
X
Thyroid Function Tests (TFT)
X
TSH with free T3 and free T4
Revised Protocol No.: 06
Date: 22-Mar-2017
82
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Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-1: 
Screening Procedural Outline (CA186107) -Initial Treatment
Procedure
Screening
Visit (Day -28 to 
Day 1)
Notes
Human Papillomavirus Status
X
SCCHN subjects only. Sites must submit and document prior HPV statuswithin 28 days 
of dosing. For subjects with unknown status, tumor tissue will be required, per inclusion 
criteria. Subjects must consent to HPV testing.
Epstein-Barr Virus (EBV) Status
X
For subjectswith B-cell NHLonly. Sites must submit and document prior EBV status 
within 28 days of dosing. For subjects with unknown status, tumor tissue will be 
required, per inclusion criteria. Subjects must consent to EBV testing.
Document mutational status
X
Document EGFR and ALK for subjects with NSCLC. Document BRAF for subjects with 
MEL. 
Document lymphoma risk 
classification
X
For subjects with B-cell NHL. May include, but are not limited to BCL2, MYC, BCL6, 
CD10, MUM1, Ki67, BCL2 14:18 translocation, and MYC break-apart.
Serology Tests
X
Within 28 days of dosing: Hep A IgM, Hep B surface antigen, Hep C antibody, Hepatitis 
C viral load Note: Testing for HIV-1, HIV-2 must be performed at sites where mandated 
by local requirements
Serum Pregnancy Test
X
WOCBP onlyatscreening and within 24 hours prior todosing.Theserum pregnancy 
test may be completed on the first day of treatment provided the resultsare available 
before the start of study therapy. 
Minimum test sensitivity of at least 25 IU/L required.
FSH
X
Female 55 with amenorrhea to confirm menopausal status-See Section3.3.3
 
 
Assessment of Signs and Symptoms
X
Collected for the period 2 weeks prior to Cycle 1 Day 1
Adverse Event Reporting
Monitor for Serious Adverse Events
X
All SAEs must be collected starting at the time the subject signs informed consent and 
through 100 days post discontinuation of dosing or completion of the subject’s 
participation in the study if the last scheduled visit occurs at a later time.
Revised Protocol No.: 06
Date: 22-Mar-2017
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Approved
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1.0
v
612

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-1: 
Screening Procedural Outline (CA186107) -Initial Treatment
Procedure
Screening
Visit (Day -28 to 
Day 1)
Notes
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) for subjects with history or symptoms of brain metastases or 
who have not had brain imaging within 30 days of anticipated first study drug 
administration.
PET Scan
X
Required at screening for subjects with B-cell NHL only
Bone Scan
X
As clinical indicated (ie, 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
Revised Protocol No.: 06
Date: 22-Mar-2017
84
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Approved
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1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-2: 
On Treatment Procedural Outline (CA186107) -Initial Treatment
Procedure
Cycles 1-6
Notes
D 1a
(-2 days)
D 15
(2 days)
D 29
(2 days)
D 43
(2 days)
D 49-56
Safety Assessments
Targeted Physical Examination 
(PE)
X
A targeted (symptom-directed) physical examination performed by the 
investigator or designee is required at each subsequent visit.
Performance Status
X 
X 
X 
X
ECOG score prior to dosing (Appendix 4)
Physical Measurements
X 
X 
X 
X
Weight only prior to dosing
Vital Signs
X 
X 
X 
X
Vital signs (body temperature, seated blood pressure, heart rate and 
respiratory rate) will be obtained before the BMS-936558 infusion, after 
the BMS-936558 infusion, before the BMS-663513, and after the 
BMS-663513 infusion. 
Subjects must be observed for 30 minutes after the BMS-663513 infusion 
before discharge. If any vital sign is abnormal at the final check, the subject 
must be observed further for a period of time, as clinically indicated.
The start and stop time of the study drug infusion should be documented. If 
there are any new or worsening clinically significant changes since the last 
examination, report changes on the appropriate non-serious or serious 
adverse event page.
See Section 4.5.9for treatment of infusion reaction.
Non-Serious Adverse Events
X 
X 
X 
X
Non-serious AEs will be collected starting with the first dose of study 
medication and through 100 days after discontinuation of dosing.
Serious Adverse Events
X 
X 
X 
X
All SAEs must be collected starting at the time a subject signs informed 
consent and through 100 days after discontinuation of dosing. SAEs should 
be approved in TAO within 5 business days of entry
Electrocardiogram (ECGs)
X
12-lead ECG (if performed on same day as study drug administration it is 
to be performed prior to dosing).
Revised Protocol No.: 06
Date: 22-Mar-2017
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930152107
1.0
v
614

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-2: 
On Treatment Procedural Outline (CA186107) -Initial Treatment
Procedure
Cycles 1-6
Notes
D 1a
(-2 days)
D 15
(2 days)
D 29
(2 days)
D 43
(2 days)
D 49-56
Chest Radiograph
As clinically indicated.
Oxygen Saturation Levels
X 
X 
X 
X
Collect pulse oximetry at rest prior to dosing.
Laboratory Tests
X 
X 
X 
X
On study labs (including pregnancy testing) to be done on site/local. 
Within 72 hrs prior todosing
Chemistry (excluding LFTs)
X 
X 
X 
X
Includes assessments for sodium, potassium, chloride, total serum calcium, 
magnesium, carbon dioxide, phosphorus, BUN, creatinine, glucose, total 
protein, albumin, amylase, lipase, CRP, ferritin,LDH.
CBC with differential & platelets
X 
X 
X 
X
Should also be collected at each timepoint where samples for 
immunophenotyping are collected as listed in Table 5.7-1
LFT assessments
Weekly during treatment with urelumab 
and for 8 weeks following last urelumab 
dose then Days 1, D15, D29 and D43 of 
each subsequent cycle
Includes AST, ALT, total bilirubin, alkaline phosphatase and GGT.
LFTs will be monitored weekly duringtreatment with urelumab and for 
8weeks following the last dose of urelumab 
TFT
X
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.
Urinalysis
X 
X 
X 
X
Urine to be checked for protein, glucose, blood, leukocyte esterase, specific 
gravity and pH. Microscopic examination of sediment if blood, protein, or 
leukocyte esterase positive on dipstick.
Pregnancy Serum or Urine Test for 
WOCBP
X 
X 
X 
X
Urine or Serum within 24 hours prior to treatment, the minimum sensitivity 
of the pregnancy test must be 25 IU/L or equivalents of HCG. If pregnancy 
test is positive, subject must not receive study drug. Pregnancy test must be 
performed at a minimum of every 4 weeks in the event of dosing delays.
Sample Collection
Pharmacokinetic (PK) Assessments
See Table 5.5.1-1
Revised Protocol No.: 06
Date: 22-Mar-2017
86
615
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-2: 
On Treatment Procedural Outline (CA186107) -Initial Treatment
Procedure
Cycles 1-6
Notes
D 1a
(-2 days)
D 15
(2 days)
D 29
(2 days)
D 43
(2 days)
D 49-56
Immunogenicity Assessments 
See Table 5.5.1-1
Biomarker Assessments
See Table 5.7-1and Table 5.7-2
Efficacy Assessments
Diagnostic Imaging
X
By methods used at baseline.  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
As clinically indicated
Bone Scan
X
As clinically indicated 
PET Scan
X
Required to confirm a CR for subjects with B-cell NHL
Bone marrow aspirate and biopsy
X
Required to confirm CR in subjects with B-cell NHL with bone marrow 
disease at screening
Clinical Drug Supplies
BMS-936558 Administration
X 
X 
X 
X
BMS-663513 Administration 
(Cohort 1, 2, C)
X
X
Cohort 1,2, C 
To start administration no sooner than 30 minutes after completion of the 
BMS-936558 infusion
Abbreviations: D =Day
a Day 1 of each cycle except where noted
Revised Protocol No.: 06
Date: 22-Mar-2017
87
616
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-3:
Follow-up Procedural Outline (CA186107)
Procedure
Clinical/SafetyFollow-up
Survival/
Long-Term 
Follow-up
Notes
1
30 daysa
(7 days)
2
60 days
(7 days)
3
100 days
(7 days)
every 
12weeks
(2 weeks)
Safety Assessments
Physical Examination (PE)
X
X
X
Vital Signs
X
X
X
Includes body temperature, seated blood pressure, 
heart rate and respiratory rate. Blood pressure, heart 
rate and respiratory rate should be measured after the 
subject has been seated quietly for at least 5 minutes.
Performance Status
X
X
X
ECOG score (Appendix 4)
Monitor for non-Serious Adverse 
Events
X
X
X
Non-serious AEs will be collected starting with the 
first dose of study medication and through 100 days 
after discontinuation of dosing.
Monitor for Serious Adverse Events
X
X
X
All SAEs must be collected starting at the time a 
subject signs informed consent and through 100days 
after discontinuation of dosing. SAEs should be 
approved in TAO within 5 business days of entry of 
entry
Laboratory Tests
Chemistry (excluding LFTs)
X
X
X
Includes assessments for sodium, potassium, chloride, 
total serum calcium, magnesium, carbon dioxide, 
phosphorus, BUN, creatinine, glucose, total protein, 
albumin, amylase, lipase, CRP, ferritin, and LDH.
Revised Protocol No.: 06
Date: 22-Mar-2017
88
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Approved
930152107
1.0
v
617

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-3:
Follow-up Procedural Outline (CA186107)
Procedure
Clinical/SafetyFollow-up
Survival/
Long-Term 
Follow-up
Notes
1
30 daysa
(7 days)
2
60 days
(7 days)
3
100 days
(7 days)
every 
12weeks
(2 weeks)
CBC with differential & platelets
X
X
X
Should also be collected at each timepoint where 
samples for immunophenotyping are collected as listed 
in Table 5.7-1
LFT assessment
Weekly for 8 weeks following last 
urelumab ( if applicable) and at 30 Day, 60 
Day, 100 Day follow-up
LFTs will be monitored weekly for 8weeks following 
the last dose of urelumab. Includes AST, ALT, total 
bilirubin, alkaline phosphatase and GGT
TFT
X
X
X
To include TSH with reflex testing (free T3 and 
freeT4). 
Urinalysis
X
X
X
Urine to be checked for protein, glucose, blood, 
leukocyte esterase, specific gravity and pH. 
Microscopic examination of sediment if blood, 
protein, or leukocyte esterase positive on dipstick.
Pregnancy Serum or Urine Test 
For WOCBP
X
X
X
The minimum sensitivity of the pregnancy test must be 
25 IU/L or equivalents of HCG.
SampleCollection
Pharmacokinetic (PK) Assessments
X
X
X
See Table 5.5.1-1
Immunogenicity (ADA) 
Assessments
X
X
X
See Table 5.5.1-1
Revised Protocol No.: 06
Date: 22-Mar-2017
89
618
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-3:
Follow-up Procedural Outline (CA186107)
Procedure
Clinical/SafetyFollow-up
Survival/
Long-Term 
Follow-up
Notes
1
30 daysa
(7 days)
2
60 days
(7 days)
3
100 days
(7 days)
every 
12weeks
(2 weeks)
Efficacy Assessments
Diagnostic Imaging
X
X
By method used at baseline. 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.
Subjects who discontinue the clinical/safetyfollow-up 
phase of the trial with ongoing SD, PR, or CR will 
continue to have tumor imaging completed every 
12weeks for the first year following the 
Clinical/SafetyFollow-up period and then as per 
standard of care (minimum of every 6 months) until 
disease progression or withdrawal of consent 
Survival Status
Assessment Subject Survival Status
X
Subject status will be assessed by either a clinic visit 
or telephone contact every 12 weeks (2weeks) for 
up to 3 years following the first dose of study drug. 
The nature and start dates of any new therapies during 
this period will be recorded.
a Follow-up visits at Days 30, 60 and 100 (days) should occur after the last dose or coinciding with the date of discontinuation days if date of discontinuation 
is greater than 30 days after the last dose to monitor for adverse events.
Revised Protocol No.: 06
Date: 22-Mar-2017
90
619
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-4: 
Retreatment Screening Procedural Outline (CA186107)
Procedure
Screening
Visit 
(Day -28 
to -1)
Notes
Eligibility Assessments
Safety Assessments
Physical Examination (PE)
X
If the screening PE is performed within 24 hours of dosing on Cycle 1Day 1 then a single exam may 
count as both the screening and pre-dose evaluation.
Performance Status
X
ECOG Performance Status (Appendix 4).
Physical Measurements
X
Weight.
Vital Signs
X
Includes body temperature, seated blood pressure, heart rate and respiratory rate. Blood pressure, heart 
rate and respiratory rate should be measured after the subject has been seated quietly for at least 5 
minutes.
Oxygen Saturation
X
Pulse oximetry collected at rest. Oxygen levels will be used in combination with clinical signs and 
symptoms and radiographic images to evaluate pulmonary/respiratory status. Changes in O2 levels will 
not used in isolation to document or diagnosis pulmonary toxicity.
Revised International Prognostic 
Index (IPI) and Follicular Lymphoma 
International Prognostic Index 
(FLIPI)
X
For subjects with B-cell NHL only. Refer to Appendix 5
Electrocardiogram (ECGs)
X
12-lead ECG; ECGs should be recorded after the subject has been supine for at least 5 minutes if not 
done within the last 6 months
Laboratory Tests
Laboratory tests listed below must be completed within 2 weeks of Retreatment Day 1 unless 
otherwise noted
Chemistry (Excluding LFTs)
X
Includes assessments for sodium, potassium, chloride, total serum calcium, magnesium, carbon dioxide, 
phosphorus, BUN, creatinine, fasting glucose, total protein, albumin, amylase, lipase, CRP, ferritin, uric 
acid, and LDH.
CBC w/differential & platelets
X
LFT assessments
X
AST, ALT, alkaline phosphatase, total bilirubin, and GGT 
Revised Protocol No.: 06
Date: 22-Mar-2017
91
620
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-4: 
Retreatment Screening Procedural Outline (CA186107)
Procedure
Screening
Visit 
(Day -28 
to -1)
Notes
Urinalysis
X
Urine to be checked for protein, glucose, blood, leukocyte esterase, specific gravity and pH. 
Microscopic examination of sediment if blood, protein, or leukocyte esterase positive on dipstick.
PT/PTT
X
Serology Tests
X
Repeat the following if >6 months since last treatment: Hep B surface antigen, Hep C antibody, 
Hepatitis C viral load Note: Testing for HIV-1, HIV-2 must be performed at sites where mandated by 
local requirements 
Thyroid Function Tests (TFT)
X
TSH with free T3 and free T4
SerumPregnancy Test
X
WOCBP only. 
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) for subjects with history or symptoms of brain metastases or who have not had 
brain imaging within 30 days of anticipated first study drug administration.
PET Scan
X
As clinically indicated for subjects with B-cell NHL
Bone Scan
X
As clinical indicated (ie, 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.
Revised Protocol No.: 06
Date: 22-Mar-2017
92
621
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-5:
Retreatment Procedural Outline (CA186107)
Procedure
Cycles 1-6
Notes
D 1a
(-2 days)
D 15
(2 days)
D 29
(2 days)
D 43
(2 days)
D 49-56
Safety Assessments
Physical Examination (PE)
X
A targeted (symptom directed)PEperformed by the investigator or 
designee is required at each subsequent visit.
Performance Status
X 
X 
X 
X
ECOG score prior to dosing (Appendix 4)
Physical Measurements
X 
X 
X 
X
Weight only prior to dosing
Vital Signs
X 
X 
X 
X
Vital signs (body temperature, seated blood pressure, heart rate and 
respiratory rate) will be obtained before the BMS-936558 infusion, after 
the BMS-936558 infusion, before the BMS-663513, and after the 
BMS-663513 infusion. 
Subjects must be observed for 30 minutes after the BMS-663513 infusion 
before discharge. If any vital sign is abnormal at the final check, the subject 
must be observed further for a period of time, as clinically indicated.
The start and stop time of the study drug infusion should be documented. If 
thereare any new or worsening clinically significant changes since the last 
examination, report changes on the appropriate non-serious or serious 
adverse event page.
See Section 4.5.9for treatment of infusion reaction.
Non-Serious Adverse Events
X 
X 
X 
X
Non-serious AEs will be collected starting with the first dose of study 
medication and through 100 days after discontinuation of dosing.
Serious Adverse Events
X 
X 
X 
X
All SAEs must be collected starting at the time a subject signs informed 
consent and through 100 days after discontinuation of dosing. SAEs should 
be approved in TAO within 5business days of entry
Revised Protocol No.: 06
Date: 22-Mar-2017
93
1.0
Approved
930152107
1.0
v
622

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-5:
Retreatment Procedural Outline (CA186107)
Procedure
Cycles 1-6
Notes
D 1a
(-2 days)
D 15
(2 days)
D 29
(2 days)
D 43
(2 days)
D 49-56
Chest Radiograph
As clinically indicated.
Oxygen Saturation Levels
X 
X 
X 
X
Collected pulse oximetry at rest prior to dosing.
Laboratory Tests
X 
X 
X 
X
On study labs (including pregnancy testing) to be done on site/local. 
Within 72 hrs prior to dosing
Chemistry (excluding LFTs)
X 
X 
X 
X
For all visits includes assessments for sodium, potassium, chloride, total 
serum calcium, magnesium, carbon dioxide, phosphorus, BUN, creatinine, 
glucose, total protein, albumin, amylase, lipase, CRP, ferritin, and LDH.
CBC with differential & platelets
X 
X 
X 
X
Should also be collected at each timepoint where samples for 
immunophenotyping are collected as listed in Table 5.7-1
LFT assessments
Weekly during treatment with urelumab 
and for 8 weeks following last urelumab 
dose then Days 1, D15, D29 and D43 of 
each subsequent cycle
Includes AST, ALT, total bilirubin, alkaline phosphatase and GGT.
LFTs will be monitored weekly duringtreatment with urelumab and for 
8weeks following the last dose of urelumab 
TFT
X
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.
Urinalysis
X 
X 
X 
X
Urine to be checked for protein, glucose, blood, leukocyte esterase, specific 
gravity and pH. Microscopic examination of sediment if blood, protein, or 
leukocyte esterase positive on dipstick.
Pregnancy Serum or Urine Test for 
WOCBP
X 
X 
X 
X
Urine or Serum within 24 hours prior to treatment, the minimum sensitivity 
of the pregnancy test must be 25 IU/L or equivalents of HCG. If pregnancy 
test is positive, subject must not receive study drug. Pregnancy test must be 
performed at a minimum of every 4 weeks in the event of dosing delays.
Revised Protocol No.: 06
Date: 22-Mar-2017
94
623
1.0
Approved
930152107
1.0
v

Clinical Protocol
CA186107
BMS-663513
urelumab
Table5.1-5:
Retreatment Procedural Outline (CA186107)
Procedure
Cycles 1-6
Notes
D 1a
(-2 days)
D 15
(2 days)
D 29
(2 days)
D 43
(2 days)
D 49-56
Sample Collection
Pharmacokinetic (PK) Assessments
See Table 5.5.1-3
Immunogenicity Assessments 
See Table 5.5.1-3
Biomarker Assessments
See Table 5.7-3
Efficacy Assessments
Diagnostic Imaging
X
By methods used at baseline.  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
As clinically indicated
Bone Scan
X
As clinically indicated 
PET Scan
X
Required to confirm a CR for subjects with B-cell NHL
Bone marrow aspirate and biopsy
X
Required to confirm CR in subjects with B-cell NHL with bone marrow 
disease at screening
Clinical Drug Supplies
BMS-936558 Administration
X 
X 
X 
X
BMS-663513 Administration 
(Cohort 1, 2, C)
X
X
Cohort 1,2, C 
To start administration no sooner than 30 minutes after completion of the 
BMS-936558 infusion.
Abbreviations: D=Day
a Day 1 of each cycle except where noted
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Table5.1-6:
Retreatment Follow-up Procedural Outline (CA186107)
Procedure
Clinical/Safety Follow-up
Survival
/Long-Term 
Follow-up
Notes
1
30 daysa
(7 days)
2
60 days
(7 days)
3
100 days
(7 days)
every 
12weeks
(2 weeks)
Safety Assessments
Physical Examination (PE)
X
X
X
Vital Signs
X
X
X
Includes body temperature, seated blood pressure, heart 
rate and respiratory rate. Blood pressure, heart rate and 
respiratory rate should be measured after the subject 
has been seated quietly for at least 5 minutes.
Performance Status
X
X
X
ECOG score (Appendix 4)
Monitor for non-Serious Adverse 
Events
X
X
X
Non-serious AEs will be collected starting with the first 
dose of study medication and through 100 days after 
discontinuation of dosing.
Monitor for Serious Adverse Events
X
X
X
All SAEs must be collected starting at the time a 
subject signs informed consent and through 100days 
after discontinuation of dosing. SAEs should be 
approved in TAO within 5business days of entry
Laboratory Tests
Chemistry (excluding LFTs)
X
X
X
Includes assessments for sodium, potassium, chloride, 
total serum calcium, magnesium, carbon dioxide, 
phosphorus, BUN, creatinine, glucose, total protein, 
albumin, amylase, lipase, CRP, ferritin, and LDH.
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Table5.1-6:
Retreatment Follow-up Procedural Outline (CA186107)
Procedure
Clinical/Safety Follow-up
Survival
/Long-Term 
Follow-up
Notes
1
30 daysa
(7 days)
2
60 days
(7 days)
3
100 days
(7 days)
every 
12weeks
(2 weeks)
CBC with differential & platelets
X
X
X
Should also be collected at each timepoint where 
samples for immunophenotyping are collected as listed 
in Table 5.7-1
LFT assessment
Weekly for 8 weeks following last 
urelumab ( if applicable) and at 30 Day, 60 
Day, 100 Day follow-up
LFTs will be monitored weekly for 8weeks following 
the last dose of urelumab. Includes AST, ALT, total 
bilirubin, alkaline phosphatase and GGT
TFT
X
X
X
To include TSH with reflex testing (free T3 and free 
T4). 
Urinalysis
X
X
X
Urine to be checked for protein, glucose, blood, 
leukocyte esterase, specific gravity and pH. 
Microscopic examination of sediment if blood, protein, 
or leukocyte esterase positive on dipstick.
Pregnancy Serum or Urine Test 
For WOCBP
X
X
X
The minimum sensitivity of the pregnancy test must be 
25 IU/L or equivalents of HCG.
SampleCollection
Pharmacokinetic (PK) Assessments
X
X
X
See Table 5.5.1-3
Immunogenicity (ADA) 
Assessments
X
X
X
See Table 5.5.1-3
Efficacy Assessments
Diagnostic Imaging
X
X
By method used at baseline. 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.
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urelumab
Table5.1-6:
Retreatment Follow-up Procedural Outline (CA186107)
Procedure
Clinical/Safety Follow-up
Survival
/Long-Term 
Follow-up
Notes
1
30 daysa
(7 days)
2
60 days
(7 days)
3
100 days
(7 days)
every 
12weeks
(2 weeks)
Subjects who discontinue the clinical/safetyfollow-up 
phase of the trial with ongoing SD, PR, or CR will 
continue to have tumor imaging completed every 
12weeks for the first year following the Clinical/Safety
Follow-up period and then as per standard of care 
(minimum of every 6 months) until disease progression 
or withdrawal of consent 
Survival Status
Assessment Subject Survival Status
X
Subject status will be assessed by either a clinic visit or 
telephone contact every 12 weeks (2weeks) for up to 
3 years following the first dose of study drug. The 
nature and start dates of any new therapies during this 
period will be recorded.
a Follow-up visits at Days 30, 60 and 100 (7 days) should occur after the last dose or coinciding with the date of discontinuation 7 days if date of discontinuation 
is greater than 30 days after the last dose to monitor for adverse events.
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5.1.1
Retesting During Screening Period
Retesting of laboratory parameters and/or other assessments within any single Screening or 
Lead-in Period will be permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (ie, the most current result prior to Randomization) 
and is the value by which study inclusionwill be assessed, as it represents the subject’s most 
current, clinical state.
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 haveavailable a well-calibrated scale for 
recording body weight, a 12-lead ECG machine, a pulse oximeter for measuring oxygen saturation, 
and a calibrated sphygmomanometer and thermometer for vital signs assessments. A current and 
fully-stocked advanced cardiac life support (ACLS) 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 (-70°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. The site 
will source marketed product from a single commercial lot.
BMS will provide a BMS-approved protocol and any amendments or administrative letters 
(ifrequired), and investigator brochures for urelumab and nivolumab. Case report forms 
(electronic or hard copy) will be provided by BMS as well as a copy of NCI CTCAE 
v4.0.Instructions for local laboratory data entry will be provided. The Central Laboratory will 
provide labels and tubes for the collection of blood samples for PK/biomarker and for genotyping 
analysis and tissue samples. 
5.3
Safety Assessments
Adverse events will be assessed continuously during the study and for 100 days after the last 
treatment. Adverse events will be coded using the most current version of MedDRA and reviewed 
for potential significance and importance. Adverse events will be gradedaccording to the NCI 
CTCAE v4.0. Subjects should be followed until all treatment related adverse events have 
recovered to baseline or are deemed irreversible by the investigator.
At baseline, a medical history will be obtained to capture relevant underlying conditions. Baseline 
signs and symptoms are those that are assessed within 2 weeks prior to subject registration. The 
baseline physical examination should include weight, height, heart rate, blood pressure, 
temperature,and ECOG status and should be performed within 28 days of treatment arm 
assignment. 
 
 
.
Subjects will be considered evaluable for safety if they have received any dose of either study 
drug. Toxicity assessments will be continuous during the Treatment period and the Clinical/Safety
Follow-up periods.
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Body weight and performance status should be assessed at each on-study visit. Vital signs will be 
obtained before the nivolumab infusion, after the nivolumab infusion, before the urelumab 
infusion, and after the urelumab infusion. Subjects must be observed for 30 minutes after the 
urelumab infusion before discharge. If any vital sign is abnormal at the final check, the subject 
must be observed further for a period of time, as clinically indicated. The start and stop time of the 
study drug infusion should be documented. Any new or worsening clinically significant changes 
must be reported on the appropriate non-serious or serious adverse event page.
5.3.1
Hepatotoxicity Assessment
Hepatotoxicity will be monitored using weekly liver function tests (LFTs) including AST, ALT, 
alkaline phosphatase, total bilirubin, and GGT during the 6 cycleswhere subjects are receiving 
combined treatment with urelumab and nivolumab (Table5.1-2), and also weekly for the first 
8weeks following the last dose with urelumab. Following this period ofweekly assessments, LFTs 
will alsobe monitored at all 3 clinical/safety follow-up visits (Table5.1-3). A management 
algorithm for the monitoring and management of hepatotoxicity is included in Appendix 3.
5.3.2
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.
5.3.3
Laboratory Test Assessments
A local laboratory will perform the analyses and will provide reference ranges for these tests. 
Results of clinical laboratory tests performed on Day -1 or Day -2 must be available prior to dosing.
The following clinical laboratory tests will be performed:
Hematology
CBC with differential and platelets
Serum Chemistry
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Total bilirubin
Alkaline phosphatase
Lactate dehydrogenase (LDH)
Gamma-glutamyl transferase (GGT)
Creatinine
Blood Urea Nitrogen (BUN)
Glucose(Fasting at screen visit)
Ferritin
Amylase
Lipase
Total Protein
Albumin
Sodium
Potassium
Chloride
Carbon dioxide
Calcium
Phosphorus
C-reactive protein (CRP)
Magnesium
Uric Acid
Urinalysis
Protein
Glucose
Blood
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Leukocyte esterase
Specific gravity
pH
Microscopic examination of the sediment if blood, protein or leukocytes esterase are positive 
on the dipstick
Serology
Serum for hepatitis C antibody, hepatitis C viral load, hepatitis B surface antigen, Hepatitis A 
IgM, HIV-1, -2 antibody, HPV status (screening only); HIV-1, -2 antibody at sites where 
mandated at screening only
Other Analyses
Protime(PT)/Prothrombin Time (PTT)
Thyroid Function Tests: Free T4, Free T3 and TSH
Pregnancytest (WOCBP only: screening, during dosing at predose and at a minimum of every 
4 weeks, as well as Day 30, 60 and 100 follow-up visits).
Clinical laboratories will be assessed (seeTable5.1-1, Table5.1-2, Table5.1-3, Table5.1-4, 
Table5.1-5, and Table5.1-6).
Sites should collect these samples between -28 to -1 days from registration to ensure that results 
required for eligibility purposes are verified prior to registration. Pregnancy testing must be 
performed at screening, within 24 hours prior to each administration of study drug andat a 
minimum of every 4 weeks in the event of dosing delays. In addition pregnancy testing should be 
performed at Day 30, 60 and 100 follow-up visits. CBC plus differential and serum chemistry 
panel should be drawn within 72hours prior to each subsequentscheduled cycle. On-study 
laboratory tests will be performed on site/locally. Laboratory tests may be obtained more 
frequently if indicated. Additional laboratory tests should be performed as per standard of care.
Laboratory toxicities (eg, suspected druginduced liver enzyme elevations) will be monitored 
during the Clinical/SafetyFollow-up period via on site/local labs until all study drug related 
toxicities resolve, return to baseline, or are deemed irreversible.
5.4
Efficacy Assessments
Disease assessment with computed tomography (CT) and/or magnetic resonance imaging (MRI) 
as appropriate will be performed at baseline and every 8 weeks until confirmed disease 
progression, at the completion of follow-up, or until subjects withdraw from the study. For subjects 
with B-cell NHL positron emission tomography (PET) will be performed at baseline and in order 
to confirm a complete response. Disease assessments at other timepoints may be performed if the 
investigator is concerned about tumor progression. Assessment oftumor response will be reported 
by the investigator for appropriate populations of subjects as defined by RECIST v1.174(see 
Appendix 1) for subjects with solid tumors and IWG (see Appendix 2) for subjects with B-cell 
NHL. For subjects with marrow involvement at screening, a bone marrow biopsy and aspirate will 
be required to confirm a CR.At the sponsor’s discretion, scans and measurements may be collected 
centrally to be reviewed by independent radiologists using IWG, RECIST v1.1, or other criteria at 
a later date, or at any time during the study.
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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 timepoint tumor assessments will be reported on the CRF based on 
investigators’ assessment using RECIST or IWG criteria. Please refer to Appendix 1 for specifics 
of RECIST v1.1 and Appendix 2 for specifics of the IWG criteria to be utilized in this study.
 
 
 
 
 
 
 
s.
 
 
 
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Table 5.5.1-1:
Pharmacokinetic Sampling Schedule (Dose Escalation )
Study Day
Event
Time 
(relative to 
Nivolumab dosing)
Urelumab
Nivolumab
PK 
Sample
ADA 
Sample
PK 
Sample
ADA 
Sample
C1D1
0 h (pre-dose)a
00:00
X
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
4 h
04:00
X
X
6 h
06:00
X
X
C1D8
168 h
168:00
X
X
C1D15
0 h (pre-dose)
00:00
X
X
C1D29
0 h (pre-dose)
00:00
X 
X 
X 
X
C1D36
168 h
168:00
X
X
C1D43
0 h (pre-dose)
00:00
X
X
C2D1
0 h (pre-dose)
00:00
X 
X 
X 
X
C2D29
0 h (pre-dose)
00:00
X
X
C3D1
0 h (pre-dose)
00:00
X 
X 
X 
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
C3D8
168 h
168:00
X
X
C3D15
0 h (pre-dose)
00:00
X
X
C3D29
0 h (pre-dose)
00:00
X 
X 
X 
X
C3D36
168 h
168:00
X
X
C3D43
0 h (pre-dose)
00:00
X
X
C4D1
0 h (pre-dose)
00:00
X 
X 
X 
X
C5D1
0 h (pre-dose)
00:00
X 
X 
X 
X
C6D1
0 h (pre-dose)
00:00
X 
X 
X 
X
30 Day 
Follow-Up
X 
X 
X 
X
60 Day 
Follow-Upc
X 
X 
X 
X
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Table 5.5.1-1:
Pharmacokinetic Sampling Schedule (Dose Escalation )
Study Day
Event
Time 
(relative to 
Nivolumab dosing)
Urelumab
Nivolumab
PK 
Sample
ADA 
Sample
PK 
Sample
ADA 
Sample
100 Day 
Follow-Upc
X 
X 
X
X
a All subsequent urelumab predose samples can be collected at same time as the nivolumab predose sample
b EOI: End of infusion. This sample should be taken immediately prior to stopping the infusion (preferably within 
2minutes prior to the end of infusion). If the end of infusion is delayed to beyond the normal infusion duration of 
1 hour, the collection of this sample should be delayed accordingly. Urelumab predose samples can be collected at 
same time as the nivolumab predose sample.
c If a subject permanently discontinues study drug treatment during the sampling period, they will move to sampling 
at the follow-up visits. 
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Table 5.5.1-2:
Pharmacokinetic Sampling Schedule (First 6 Subjects in 
Stage 1 Expansion)
Study Day
Event
Time 
(relative to 
Nivolumab dosing)
Urelumab
Nivolumab
PK 
Sample
ADA 
Sample
PK 
Sample
ADA 
Sample
C1D1
0 h (pre-dose)a
00:00
X 
X 
X 
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
4 h
04:00
X
X
6 h
06:00
X
X
C1D8
168 h
168:00
X
X
C1D15
0 h (pre-dose)
00:00
X
X
C1D29
0 h (pre-dose)
00:00
X 
X 
X 
X
C2D1
0 h (pre-dose)
00:00
X 
X 
X 
X
C3D1
0 h (pre-dose)
00:00
X
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
C3D8
168 h
168:00
X
C3D15
0 h (pre-dose)
00:00
X
C3D29
0 h (pre-dose)
00:00
X
C4D1
0 h (pre-dose)
00:00
X 
X 
X 
X
C6D1
0 h (pre-dose)
00:00
X 
X 
X 
X
60 Day 
Follow-Upc
X 
X 
X 
X
100 Day 
Follow-Upc
X 
X 
X 
X
a All subsequent urelumab predose samples can be collected at same time as the nivolumab predose sample
b EOI: End of infusion. This sample should be taken immediately prior to stopping the infusion (preferably within 
2minutes prior to the end of infusion). If the end of infusion is delayed to beyond the normal infusion duration of 
1 hour, the collection of this sample should be delayedaccordingly. Urelumab predose samples can be collected at 
same time as the nivolumab predose sample.
c If a subject permanently discontinues study drug treatment during the sampling period, theywill move to sampling 
at the follow-up visits.
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Table 5.5.1-3: 
Pharmacokinetic Sampling Schedule (After 6 subject in Stage 1 
Expansion, all subjects in Stage 2 Expansion and Retreatment)
Study Day
Event
Time
(relative to 
Nivolumab dosing)
Urelumab
Nivolumab
PK 
Sample
ADA 
Sample
PK 
Sample
ADA 
Sample
C1D1
0 h (pre-dose)a
00:00
X
X 
X 
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
C1D29
0 h (pre-dose)
00:00
X
X 
X 
X
C2D1
0 h (pre-dose)
00:00
X
X 
X 
X
C3D1
0 h (pre-dose)
00:00
X
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
C4D1
0 h (pre-dose)
00:00
X
X 
X 
X
C6D1
0 h (pre-dose)
00:00
X
X 
X 
X
60 Day 
Follow-Upc
X
X 
X 
X
100 Day 
Follow-Upc
X
X 
X 
X
a All subsequent urelumab predose samples can be collected at same time as the nivolumab predose sample.
b EOI: End of infusion. This sample should be taken immediately prior to stopping the infusion (preferably within 
2minutes prior to the end of infusion). If the end of infusion is delayed to beyond the normal infusion duration of 
1 hour, the collection of this sample should be delayed accordingly. Urelumab predose samples can be collected at 
same time as the nivolumab predose sample.
c If a subject permanently discontinues study drug treatment during the sampling period, they will move to sampling 
at the follow-up visits.
Revised Protocol No.: 06
Date: 22-Mar-2017
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CA186107
BMS-663513
urelumab
Table 5.5.1-4:
Pharmacokinetic Sampling Schedule (Subjects with Melanoma PD-
L1 negative)
Study Day
Event
Time
(relative to 
Nivolumab dosing)
Urelumab
Nivolumab
PK 
Sample
ADA 
Sample
PK 
Sample
ADA 
Sample
C1D1
0 h (pre-dose)a
00:00
X
X 
X
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
C1D29
0 h (pre-dose)
00:00
X
X 
X
X
C2D1
0 h (pre-dose)
00:00
X
X 
X
X
C3D1
0 h (pre-dose)
00:00
X
X
1 h (EOI 
nivolumab)b
01:00
X
2 h (EOI 
urelumab)b
02:00
X
C4D1
0 h (pre-dose)
00:00
X
X 
X
X
C6D1
0 h (pre-dose)
00:00
X
X 
X
X
60 Day 
Follow-Upc
X
X 
X
X
100 Day 
Follow-Upc
X
X 
X
X
a All subsequent urelumab predose samples can be collected at same time as the nivolumab predose sample.
b EOI: End of infusion. This sample should be taken immediately prior to stopping the infusion (preferably within 
2minutes prior to the end of infusion). If the end of infusion is delayed to beyond the normal infusion duration of 
1 hour, the collection of this sample should be delayed accordingly. Urelumab predose samples can be collected at 
same time as the nivolumab predose sample.
c If a subject permanently discontinues study drug treatment during the sampling period, they will move to sampling 
at the follow-up visits.
Revised Protocol No.: 06
Date: 22-Mar-2017
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6
ADVERSE EVENTS
An Adverse Event(AE)is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation subject administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess all 
adverse events (AE). The casual relationship can be one of the following:
Related: There is a reasonable causal relationship betweenstudy 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.
Adverse events can be spontaneously reported or elicited during open-ended questioning, 
examination, or evaluation of a subject. (In order to prevent reporting bias, subjects should not be 
questioned regarding the specific occurrence of one or more AEs.)
6.1
Serious Adverse Events
A Serious Adverse Event (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 (seeNOTE
below)
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results in persistent or significant disability/incapacity
is a congenital anomaly/birth defect 
is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg,medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above). Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization). Potential drug induced liver injury (DILI) is also considered an important 
medical event. (See Section 6.6for 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 induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (SeeSection6.1.1
for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy (eg, death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be report) should be reported as 
SAE (see Section 6.1.1for reporting details).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies: 
a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event)
elective surgery, planned prior to signing consent
admissions as per protocol for a planned medical/surgical procedure
routine health assessment requiring admission for baseline/trending of health status 
(eg,routine colonoscopy)
medical/surgical admission other than remedying ill health state and planned prior to entry 
into the study. Appropriate documentation is requiredin 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, 
care-giver respite, family circumstances, administrative)
admission for administration of anticancer therapy in the absence of any other SAEs.
6.1.1
Serious Adverse Event Collection and Reporting
The Investigator Brochures (IB) represent the Reference Safety Information to determine 
expectedness of serious adverse events 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 
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must be collected that occur during the screening period and within 100 days of discontinuation of 
dosing. If applicable, SAEs must be collected that relate to any later protocol-specified procedure 
(eg, a follow-up skin biopsy). 
The investigator should report any SAE occurring after these time periods that is believed to be 
related to study drug or protocol-specified procedure. 
An SAE report should 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 should 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 
(ordesignee) within 24 hours. 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 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. The paper forms should be used and submitted immediately, only 
in the event the electronic system is unavailable for transmission. When paper forms are used, the 
original paper forms are to remain on site.
SAE Telephone Contact(required for SAE and pregnancy reporting): See Contact Information 
list.
If only limited information is initially available, follow-up reports are required. (Note:Follow-up 
SAE reports should 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, a follow-up SAE report should be sent within 24 hours to BMS (ordesignee) 
using the same procedure used for transmitting the initial SAE report.
All SAEs should be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. 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 AEsthat cause 
interruption or discontinuation of study drug and for those that are 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). 
All nonserious adverse events (not only those deemed to be treatment-related) should be collected 
continuously during the treatment period and for a minimum of 100 days following the last dose 
of study treatment.
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities that 
are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (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).
6.4
Pregnancy
If, following initiation of the investigational product, it is subsequently discovered that a study 
subject is pregnant or may have been pregnant at the time of study exposure, including during at 
least 5 half lives after product administration, the investigator must immediately notify the 
BMSMedical Monitor/designee of this event and complete and forward a Pregnancy Surveillance 
Form to BMS Designee within 24 hours 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).
In the rare event that the benefit of continuing study drug is thought to outweigh the risk, after 
consultation with BMS, the pregnant subject may continue study drug after a thorough discussion 
of benefits and risk with the subject.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
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The investigator must immediately notify the BMS Medical Monitor (or designee) of this event 
and complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours 
and in accordance with SAE reporting procedures described in Section 6.1.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 6.1.1for reporting details).
6.6
Potential Drug Induced Liver Injury (DILI)
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).
Potential drug induced liver injury
 is defined as: 
1) Aminotransferase (ALT or AST) elevation > 3 times upper limit of normal (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 AT elevation and hyperbilirubinemia, 
including, but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drug(s) known to be hepatotoxic.
6.7
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, 
electrocardiograms, x-ray filming, any other potenti
al safety assessments required or not required 
by the protocol should also be recorded as a nonserious or serious AE, as appropriate, and reported 
accordingly.
6.7.1
Treatment Algorithms for Drug-related Adverse Events
Treatment algorithms for the management of potential drug-related adverse events are located in 
Appendix 3. 
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6.7.2
Rapid Notification of Other Adverse Events of Interest
In addition to serious adverse events, overdose, and pregnancy, the following adverse events will 
also be reported on an expedited basis to the BMS Medical Monitor or Study Director by phone 
or e-mail:
Adverse events that potentially meet DLT criteria; see section 4.5.2
Any potential Hy’s Law case (> 3 x ULN of either ALT/AST with concurrent >2 x ULN of 
Total Bilirubin and no alternate etiology)
Grade 2 study-drug related adverse events (including neurologic toxicity)
Grade 2 diarrhea/colitis
Grade 3 motor neurologic toxicityregardless of causality
7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
8.1.1
Dose Escalation
In dose escalation, the sample size at each dose cannot be determined exactly, as it depends on the 
number of observed toxicities. Between 3 and 12 subjects approximately are expected to be treated 
during dose escalation in each dose level. 
8.1.2
Cohort Expansion
8.1.2.1
Stage 1
During Stage 1 of cohort expansion,approximately 20subjects in each tumor type will be treated 
atthe MTD/HADdose level and schedule. A sample size of approximately 20 subjects in each 
tumor type in Stage 1is intended to provide a better picture of the safety of each regimen. For 
example, if a low grade adverse event were observed in 3or fewer patients, the 90% 1-sided upper 
confidence interval would be 30%. In addition, it allows for a futility assessment. In general, if the 
true response rate is 20%, 30%, 40%, or 50%, the probability of seeing 4or more responses in the 
20patients is 58.9%, 89.3%, 98.4%, and 99.9%, respectively. If the true response rate is 30%, the 
likelihood of seeing less than 4/20responses is 10.7% (false negative rate). Conversely, if the true 
response rate is 10%, the likelihood of seeing 4or more responses is 13.3% (false positive rate).
8.1.2.2
Stage 2: 
During Stage 2 of cohort expansion, up to approximately 20 additional subjects will be treated in 
each tumor type. This will allow for further establishment of the safety profile of the combination 
and a preliminary assessment of efficacy. The total of approximately 40subjects (20from Stage1 
Expansion and 20 from Stage 2) is designed to provide higher precision around estimates of safety 
and preliminary efficacy. If in a cohort of 40 subjects 7, 10, or 15responses are observed, then the 
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lower limit of the one-sided 90% exact binomial CI for the ORR is 10%, 16%, and 27% 
respectively. These calculations are made using the Clopper-Pearson method for exact confidence 
intervals. If the true ORR in a tumor type is 50%, then with 40 subjects in a tumor type, thereis 
96% chance of observing at least 15 responses, and 87% chance of observing at least 17responses, 
and there is 8%chance of observing 15 or fewer responses (false negative rate).
An additional 50 treatment naïve PD-L1 negative melanoma subjects will be treated at MTD/HAD 
to further evaluate if there is an efficacy signal in this population.   Additional subjects may be 
enrolled and treated so as to accrue a minimum of 50 evaluable subjects with at least 2 on treatment 
scans.  These 50 PD-L1 negative melanoma patients will be combined for analysis with 
approximately 18 PD-L1 negative melanoma patients from Cohort 2 fora total of 68 PD-L1 
negative melanoma patients.  Assuming an ORR of approximately 56%, a minimum of 38/68 
responders would provide a 95% Clopper-Pearson confidence interval with a lower limit above 
42%.
8.2
Populations for Analyses
All Enrolled Data set: subjects who signed informed consent and registered in the study.
All Treated Data set: all subjects who received at least one dose of either study drug.
Response-Evaluable Data Set: all treated subjects who receive either study drug, have a 
baseline tumor assessment with measurable disease, and one of the following:
at least one evaluable on-treatment tumor assessmentprior to subsequent therapy,
clinical progressionprior to subsequent therapy, or 
death, if death occurs within 100 days after last dose.
Urelumab Pharmacokinetic Data Set: all subjects who receive at least one dose of urelumab 
and have adequate serum concentration data for urelumab PK.
Nivolumab Pharmacokinetic Data Set: all subjects who receive at least one dose of nivolumab 
and have adequateserum concentration data for nivolumab PK.
Urelumab Immunogenicity Data Set: all subjects who receive at least one dose of urelumab 
with baseline and at least one post-baseline urelumab ADAassessment available.
Nivolumab Immunogenicity Data Set: all subjects who receive at least one dose of nivolumab 
with baseline and at least one post-baseline nivolumab ADA assessment available. 
Biomarker Data Set: all treated subjects who have evaluable biomarker data available.
8.3
Endpoint Definitions
Safety is the primary endpoint in this Phase 1/2 study. All subjects who receive at least one dose 
of urelumab or nivolumab will be evaluated for safety as measured by the occurrence of adverse 
events, serious adverse events, deaths and laboratory abnormalities, assessedduring treatment and 
for 100 days in follow-up.
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8.3.1
Primary Endpoint(s)
The primary objective (to assess the safety and tolerability of urelumab given in combination with 
nivolumab and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) 
of the combination) will be measured by the following primary endpoints. 
a) Incidence of adverse events: all non-serious adverse events will be collected from Day1 
until 100 days after the subject’s last dose of study drug or until they discontinuethe study 
as per Section 3.5. All serious adverse events must be collected from the date of the 
subject’s written consent until 100 days after discontinuation of dosing or until they 
discontinue the study as per Section 3.5.
b) Incidence of clinical laboratory test abnormalities including hematology and serum 
chemistry, and thyroid panel abnormalities, assessed at specified time points as designated 
in the Time and Events Section (5.1).
Assessments will be based on adverse event reports and the results of vital sign measurements, 
electrocardiograms (ECGs), physical examinations, imaging studies, and clinical laboratory tests. 
Adverse events will be categorized using the most current version of the Medical Dictionary for 
Regulatory Activities (MedDRA); both AEs and laboratory tests will be graded using 
NCICTCAEv4.0.All subjects who receive study drug therapy will be evaluated for safety as 
measured by the rate of adverse events (AEs), and serious adverse events (SAEs), and will be 
assessed during treatment and for 100 days in follow-up.
8.3.2
Secondary Endpoints
8.3.2.1 
Efficacy Endpoints
The secondary objective of assessing preliminary anti-tumor activity will be based on endpoints 
described below using RECIST v1.1 and investigator assessed response per IWG criteria for 
lymphomas. 
Best overall response (BOR)is the best responsedesignation recorded between the start of the 
study treatment and the date of objectively documented progression based on RECIST v1.1 
(orrelapsed based on IWG) taking into account any requirement for confirmation, or the date of 
subsequent anti-cancer therapy, whichever occurs first in the study. CR or PR determinations 
included in the BOR assessment must be confirmed by a consecutive second (confirmatory) 
evaluation meeting the criteria for response that is performed at least 4 weeks after the criteria for 
response are first met.When SD is believed to be the best response, it must meet a minimum 
SD duration of 49 days. Measurements must have met the SD criteria at least once after 
study entry. The above will be determined based on tumor measurements occurring every 8 weeks 
during the Treatment period (Cycle 1 Day 1 through Cycle 6 Day 56), and at planned timepoints 
during the Clinical/SafetyFollow-up period.
Study level endpoints used to assess this objective are defined as follows: 
Objective response rate (ORR)is defined as the total number of subjects whose BOR is either 
CR or PR divided by the total number of subjects in the population of interest.
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Duration of Response (DOR)computed only for subjects with a BOR of CR or PR is defined as 
the number of days between the date of first response and the subsequent date of objectively 
documented disease progression based on the criteria (RECIST v1.1) or relapse based on IWG, or 
deathdue to any cause, if death occurred within 100 days after last dose, whichever occurs first. 
If death is more than 100 days after last dose, then DOR is censored at the last tumor assessment 
date. For those subjects who remain alive and have not progressed or received subsequent therapy, 
duration of response will be censored onthe date of last tumor assessment. Subjects who receive 
subsequent therapy will be censored at the start of subsequent therapy.
Progression-Free Survival Rate (PFSR)is defined as the probability of a subject remaining 
progression-free and surviving a specific length of time (eg, 24 weeks). The PFS for a given subject 
will be computed based on the number of days between the first dose of study drug and progressive 
disease, relapse,or deathdueto any cause, if death occurred within 100 days after last dose. The
PFSR will be estimated using Kaplan-Meier methods. For those subjects who remain alive and 
have not progressed, PFS will be censored on the date of the last tumor assessment. Subjects who 
did not have any on study tumor assessment and did not diewill be censored on the date of first 
dose of study medication.The above will be calculated based on tumor measurements occurring 
every 8 weeks during treatment and at planned timepoints during the Clinical/SafetyFollow-up 
period. 
8.3.2.2
Pharmacokinetics (PK)
Urelumab and nivolumab maximum concentration (Cmax [µg/mL]), end of infusion concentration 
(Ceoinf), time to maximum concentration (Tmax [hr]), trough concentration (Ctrough [µg/mL]), 
area under the curve (AUC[0-T] and AUC[TAU] [µg.hr/mL]) will be evaluated using 
non-compartmental analysis in all study subjects. (Table 5.5.1-1)
8.3.2.3
Immunogenicity 
Occurrence of specific anti-drug antibodies to urelumab and nivolumab will be determined from 
measurements obtained at planned timepoints specified in Table 5.5.1-1).
Endpoints for the study are incidence rates of persistent positive ADA as well as neutralizing 
positive ADA from initiation of each drug treatment up to and including the follow-up period of 
the last study drug dosed.Based on recommendation from BMS Immunogenicity Council, 
Harmonization of Clinical Immunogenicity Reporting by an Initiative of the Therapeutic Protein 
Immunogenicity Focus Group of the American Association Pharmaceutical Scientists, and the 
FDA Guidance for Industry Immunogenicity Assessment for Therapeutic Protein Products, the 
following definitions will be applied:
ADA Status of a Subject:
Baseline ADA Positive Subject: A subject with baseline ADA positive sample 
ADA Positive Subject: A subject with atleast one ADA positive sample relative to baseline at 
any time after initiation of treatment during the defined observation time period. 
ADA Negative Subject: A subject with no ADA positive sample after the initiation of treatment
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Definitions for potential ADA Status of a Sample (Baseline ADA Positive, ADA Positive, or ADA 
Negative), as well as sub-categories of ADA Positive Subject such as Persistent Positive, Only the 
Last Sample Positive, Other Positive and Neutralizing Positive will be provided in the statistical 
analysis plan (SAP).
 
 
 
 
 
 
 
 
8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
Frequency distributions of gender and race will be tabulated. Summary statistics for age, body 
weight, and height will be collected, and Body Mass Index (BMI) will be derived.
8.4.2 
Efficacy Analyses
Individual best overall response (BOR), duration of response and PFS will be listed using RECIST 
v1.1 and IWG criteria, as appropriate. BOR outcomes will be tabulated by disease type and 
treatment (eg, with a column for each dose/regimen combination). The objective response rate 
(ORR) and PFS rate (eg, at 24 weeks) and corresponding confidence interval will be provided by 
tumor type and treatment. The duration of response and PFS will be estimated by Kaplan-Meier
(K-M) methodologyby disease type, depending on data availability. PFS rates at 24weeks will be 
similarly estimated, based on K-M methodology. ORR, duration of response and PFS analyses 
will include subjects in the cohort expansion phase and subjects in dose escalation matching those 
in cohort expansion by disease type and treatment. Individual changes in the tumor burden over 
time may be presented graphically within a disease type. Landmark overall survival will be 
assessed as part of exploratory efficacy analysis, using Kaplan-Meier plots and the median (as 
measured using Kaplan-Meier Method) for each tumor type.
8.4.3
Safety Analyses
All recorded adverse events will be listed and tabulated by system organ class, preferred term, 
tumortype, and treatmentarm. Vital signs and clinical laboratory test results will be listed and 
summarized by tumor type and treatmentarm. Any significant physical examination findings, and 
clinical laboratory results will be listed. ECG readings will be evaluated by the investigator and 
abnormalities, if present, will be listed.
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8.4.4
Pharmacokinetic Analyses
Summary statistics will be tabulated for the pharmacokinetic parameters by tumor type, dose, 
regimen, study day and time on urelumab PK subjects and nivolumab PK subjects, where data is 
available. This data may also be pooled with other datasets for population PK analysis which will 
be part of a separate report.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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8.4.6
Outcomes Research Analyses
Not applicable.
8.4.7
Other Analyses
A listing will be provided of all available immunogenicity data. Additionally, a listing of 
immunogenicity data from those subjects with at least one positive anti-drug antibody (ADA) at 
any time point will be provided by treatment for each analyte. Finally, the number (%) of subjects 
with the following anti-drug responses will be reported for each analyte if applicable, by dose, and 
overall: Baseline ADA Positive, ADA Positive (Persistent Positive, Only the Last Sample 
Positive), ADA Positive with Neutralizing Positive, and ADA Negative
To examine the potential relationship between immunogenicity and safety, the frequency and type 
of AEs of special interest may be summarized by overall immunogenicity status. Associations 
between trough concentrations of urelumab (ornivolumab) and corresponding ADA assessments 
may also be explored. 
8.5
Interim Analyses
Dataemerging from this study may be needed for timely decisions about adjustments to procedures 
in subsequent parts of the study. Therefore, data may be reviewed prior to the final lock of the 
study database. Additional interim analyses may also be performed for administrative purposes or 
publications. Analyses will only consist of listings, summaries, and graphs of the available data. 
No formal inferences requiring any adjustment to statistical significance level will be performed. 
Efficacy analyses based on interim data may use response evaluable or all treated populations 
depending on the purpose of the analysis. 
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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. 
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, investigatorsmust inform their IRB(s)/IEC(s).
9.1.2
Monitoring
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF pages and/or electronic files may serve as source 
documents.
In addition, the study may be evaluated by 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 onpaper or entered 
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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 (EMRs/EHRs), 
adverseevent tracking/reporting, protocol required assessments, and/or drug accountability 
records).
When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original.
9.1.3
Investigational Site Training
Bristol-Myers Squibb will provide quality investigational staff training prior to study initiation. 
Training topics will include but are not limited to: GCP, AE reporting, study details and procedure, 
electronic CRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS. 
9.2.2
Study Drug Records
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site to include investigational product. 
Records or logs must comply with applicable regulations and guidelines and should include:
amount received and placed in storage area
amount currently in storage area
label identification number or batch number 
amount dispensed to and returned by each subject, including unique subject identifiers
amount transferred to another area/site for dispensing or storage
non-study disposition (eg, lost, wasted) 
amount destroyed at study site, if applicable
amount returned to BMS
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retain samples for bioavailability/bioequivalence, if applicable 
dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form.
BMS will provide forms to facilitate inventory control if the investigational site does not have an 
established system that meets these requirements.
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 
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 electronic data capture 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 a qualified physician who is an investigator or qualified physician 
who is a subinvestigator and who is delegated thistask on the Delegation of Authority Form. For 
electronic CRFs, review and approval/signature is completed electronically through the BMS 
electronic data capture 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 electronic data capture 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 considering the following criteria.
Subject recruitment(eg, among the top quartile of enrollers)
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Involvement in trial design
Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications or 
abstracts arising from this study require approval by BMS prior to publication or presentation and 
must adhere to BMS’s publication requirements as set forth in the approved clinical trial agreement 
(CTA). All draft publications, including abstracts or detailed summaries of any proposed 
presentations, must be submitted to BMS at the earliest practicable time for review, but at any 
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 60days for purposes of 
filing a patent application.
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GLOSSARY OF TERMS
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete Abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Female subjects must continue 
to have pregnancy tests. Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject chooses to 
forego complete abstinence.
If two forms of contraception is required, Complete abstinence is defined 
as complete avoidance of heterosexual intercourse and is an acceptable 
form of contraception for all study drugs. Subjects who choose complete 
abstinence are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. Acceptable 
alternate methods of highly effective contraception must be discussed in 
the event that the subject chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as complete 
avoidance of heterosexual intercourse is an acceptableform of 
contraception for all study drugs. This also means that abstinence is the 
preferred and usual lifestyle of the patient. This does not mean periodic 
abstinence (eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation methods) and 
withdrawal, which are not acceptable methods of contraception. Subjects 
who choose complete abstinence are not required to use a second method 
of contraception, but female subjects must continue to have pregnancy 
tests. Acceptable alternate methods of highly effective contraception must 
be discussed in the event that the subject chooses to forego complete 
abstinence.
Medical Research
Those scientific activities which cannot be reasonably anticipated at the 
time of trial design, for which we would like to collect and/or retain 
samples from study participants. Examples of Medical Research include, 
but are not limited to, new assay development and validation, companion 
diagnostic development, new hypotheses in the interaction of drug and 
the human body, and exploration of emerging science in the 
understanding of disease.
Adverse Reaction
An adverse event that is considered by either the investigator or BMS as 
related to the investigational product
Unexpected Adverse Reaction
An adverse reaction, the nature or severity of which is not consistent with 
the applicable product information (eg, Investigator Brochure for an 
unapproved investigational product)
Serious Adverse Event
Serious adverse event defined as 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, results in persistent or significant 
disability/incapacity, is a congenital anomaly/birth defect, is an important 
medical event (defined as a medical event(s)that may not be immediately 
life threatening or result in death or hospitalization but, based upon 
appropriate medical and scientific judgment, may jeopardize the subject 
or may require intervention [eg, medical, surgical] to prevent one of the 
other serious outcomes listed in the definition above). Examples of such 
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Term
Definition
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). For reporting purposes 
only, BMS also considers the occurrence of pregnancy, overdose 
(regardless of association with an AE), and cancer as important medical 
events.
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LIST OF ABBREVIATIONS
Term
Definition
AE
adverse event
ACLS
advanced cardiac life support
ADA
anti-drug antibodies
AI
accumulation index
AI_AUC
AUC Accumulation Index; ratio of AUC(TAU) at steady state to 
AUC(TAU) after the first dose
AI_Cmax
Cmax Accumulation Index; ratio of Cmax at steady state to Cmax after 
the firstdose
AI_Ctau
Ctau Accumulation Index; ratio of Ctau at steady state to Ctau after the 
first dose
ALK
anaplastic lymphoma kinase
ALP
Alkaline phosphatase
ALT
alanine aminotransferase
AML
Acute myeloid leukemia
ANC
absolute neutrophil count
ASCT
autologous stem cell transplant
AST
aspartate aminotransferase
AT
aminotransaminases
AUC
area under the concentration-time curve
AUC(INF)
area under the concentration-time curve from time zero extrapolated to 
infinite time
AUC(0-T)
area under the concentration-time curve from time zero to the time of 
the last quantifiable concentration
AUC(TAU)
area under the concentration-time curve in one dosing interval
-HCG
beta-human chorionic gonadotrophin
BMI
body mass index
BMS
Bristol-Myers Squibb
BOR
best overall response
BP
blood pressure
BRAF
B-Rapidly Accelerated Fibrosarcoma
BTLA
B-and T-Lymphocyte Attenuator
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Term
Definition
BUN
blood urea nitrogen
C
Celsius
Ca++
calcium
CBC
complete blood count
CFR
Code of Federal Regulations 
CI
confidence interval
CL
Clearance
C1-
chloride
CLcr
creatinine clearance
CLT
total body clearance
cm
centimeter
Cmax, CMAX
maximum observed concentration
Cmin, CMIN
trough observed concentration
CNS
Central nervous system
CR
complete remission (IWG criteria) or complete response (RECIST)
CRC
Colorectal Cancer
Crcl
creatinine clearance
CRF
Case Report Form, paper or electronic
CRP
c-reactive protein
CT
Computed tomography
ctDNA
Circulating tumor DNA
CTLA4
Cytotoxic T Lymphocyte Antigen 4
CTCAE
Common Terminology Criteria for Adverse Events
Ctrough
Trough observed plasma concentration
dL
deciliter
DLBCL
diffuse large B cell lymphoma
DNA
deoxyribonucleic acid
DLT(s)
Dose Limiting Toxicity(ies)
DOR
Duration of Response
ECG
electrocardiogram
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Term
Definition
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
ECOG
Eastern Cooperative Oncology Group
eg
exempli gratia (for example)
EGFR
Epidermal growth factor receptor
ELISA
Enzyme-linked immunosorbent assay
ESR
Expedited Safety Report
FDA
Food and Drug Administration
FPE
formalin-fixed paraffin-embedded
FNA
fine needle aspiration
FSH
follicle stimulating hormone
g
gram
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GFR
glomerular filtration rate
GnRH
gonadotropin releasing hormone
HAD
highest administered dose
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCO3-
bicarbonate
HCC
hepatocellular carcinoma
HIV
Human Immunodeficiency Virus
HLA
Human Leukocyte Antigen
HPV
human papillomavirus
HR
heart rate
HRT
hormone replacement therapy
HSCT
Hematopoietic stem cell transplant
ICD
International Classification of Diseases
ICOS
Inducible T-cell Co-stimulator
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Term
Definition
ie
id est (that is)
IEC
Independent Ethics Committee
IND
Investigational New Drug Exemption
I-O
Immuno-oncology
IRB
Institutional Review Board
IU
International Unit
IV
intravenous
IWG
International Working Group
K+
potassium
kg
kilogram
KIR
Killer-cell Immunoglobulin-like Receptors
K-M
Kaplan-Meier
L
liter
LCM
laser capture microdissection
LDH
lactate dehydrogenase
LFT
Liver Function Test
MDSCs
myeloid derived suppressor cells
MedDRA
Medical Dictionary for Regulatory Activities
MEL
melanoma
mg
milligram
Mg++
magnesium
min
minute
mL
milliliter
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
g
microgram
Na+
sodium
N/A
not applicable
NCI
National Cancer Institute
ng
nanogram
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Term
Definition
NHL
non-Hodgkin’s lymphoma
NK
natural killer
NSCLC
non small cell lung cancer
NSAID
nonsteroidal anti-inflammatory drug
ORR
Overall Response Rate
OS
overall survival
PBMC
peripheral blood mononuclear cells
PD
pharmacodynamics
PD-1
Programmed Death-1
PD-L1
Programmed Death Ligand-1
PE
physical exam
PET
positron-emission tomography
PFS
progression free survival
PFSR
progression-free survival rate
PK
pharmacokinetics
PR
partial remission (IWG) or partial response (RECIST)
PT
prothrombin time
PTT
partial thromboplastin time
QC
quality control
RBC
red blood cell
RCC
renal cell carcinoma
RECIST
Response EvaluationCriteria In Solid Tumors
SAE
serious adverse event
SAP
statistical analysis plan
SCCHN
squamous cell carcinoma of head and neck
SD
standard deviation or stable disease (RECIST)
SHP-1, -2
Src homology region 2 domain-containing phosphatase-1, -2
SNP
single nucleotide polymorphism
SOP
standard operating procedures
TAO
Trial Access Online, the BMS implementation of an EDC capability
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Term
Definition
Tbili
Total bilirubin
T-HALF (t1/2)
Half life
TIA
transient ischemic attack
TIL(s)
tumor infiltrating lymphocyte(s)
Tmax, TMAX
time of maximum observed concentration
TSH
thyroid stimulating hormone
ULN
upper limit of normal
Vss/F (or Vss)
apparent volume of distribution at steady state
WBC
white blood cell
WHO
World Health Organization
WOCBP
women of childbearingpotential
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