Conditions: Multiple Myeloma
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 170
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and effectiveness of several combination therapies for Multiple Myeloma. Upon entry into the study, patients will be randomized (assigned by chance) to receive either:

Group 1: nivolumab, pomalidomide and dexamethasone OR Group 2: pomalidomide and dexamethasone OR Group 3: nivolumab, elotuzumab, pomalidomide and dexamethasone.

Enrollment is closed for all groups.

Detailed description:

Arms:
arm 1: Nivolumab, Pomalidomide and Dexamethasone

Enrollment is closed for this arm arm 2: Pomalidomide and Dexamethasone

Enrollment is closed for this arm arm 3: Nivolumab, Elotuzumab, Pomalidomide and Dexamethasone

Enrollment is closed for this arm

Interventions: intervention 1: Nivolumab intervention 2: Elotuzumab intervention 3: Pomalidomide intervention 4: Dexamethasone
Intervention descriptions: intervention 1: Specified dose on specified days, IV (intravenous) intervention 2: Specified dose on specified days, IV intervention 3: Specified dose on specified days, PO (by mouth) intervention 4: Specified dose on specified days, PO

Protocol document:
Prot_SAP_000.pdf: 
Official Title of Study: 
An Open-Label, Randomized Phase 3 Trial of Combinations of Nivolumab, Pomalidomide and 
Dexamethasone in Relapsed and Refractory Multiple Myeloma  
 
(CheckMate 602: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 602) 
 
PROTOCOL(S) CA209-602 
 
NCT Number: NCT02726581 
  
Document Date (Date in which document was last revised): November 12, 2018 


Page:
1
Protocol Number:
CA209602
IND Number:
128,931
Ex-US
Non-IND
EUDRACT Number
2015-005699-21
Date:
06-Jan-2016
Revised Date:
12-Nov-2018
CLINICAL PROTOCOL CA209602
An Open-Label, Randomized Phase 3 Trial of Combinations of Nivolumab, Pomalidomide and 
Dexamethasone in Relapsed and Refractory Multiple Myeloma
(CheckMate 602: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 602)
Revised Protocol Number: 03
Medical Monitor
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Lawrenceville NJ 08648
Telephone (office): 
Fax: 
24-hr Emergency Telephone Number
USA:
International: 
Bristol-Myers Squibb Research and Development
Route 206 & Province Line Road
Lawrenceville, NJ 08543
Avenue de Finlande 4
B-1420 Braine-l’Alleud, Belgium
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, 
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2
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a 
copy of this revised protocol to all study personnel under your supervision, and archive the 
previous versions.
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Revised Protocol No.: 03
Date: 12-Nov-2018
3
DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 03
12-Nov-2018
Major changes:

Enrollment into the study was stopped as of 23-August-2018, due to 
the results of the futility analysis performed on 12-April-2018.

All efficacy assessments will be based on the investigator evaluation
rather than Independent Review Committee (IRC). 

Bone marrow aspirate collection time-points and samples are reduced; 

 

Update of Appendix 3 Definitions of Response and Progression 
criteria, Appendix 5 Nivolumab Management Algorithm and 
Appendix 6 Pomalidomide Pregnancy Risk Prevention Plan.
Revised 
Protocol 02
22-May-2018
Major changes: 

Incorporates changes required by the FDA per the partial clinical hold 
based on safety concerns from pembrolizumab studies, as well as 
study design and objective changes to reflect endpoints adequacy in 
light of these safety concerns.

Revision of efficacy assessments (Appendix III) to align with the 
current International Myeloma Working Group (IMWG) guidance.
Revised 
Protocol 01
27-Dec-2016
Incorporates changes from Amendment 03
Amendment 
03
27-Dec-2016
Incorporates Investigator Brochure updates, Data Monitoring Committee 
and Investigator Meeting feedback, 
 and allowance for 
BMS-provided pomalidomide
Administrative 
Letter 03
14-Sep-2016  
 to add clarity to eligibility criteria regarding prior 
lines of therapy
Administrative 
Letter 02
30-Mar-2016
In response to Schulman IRB to bring sperm donation language into 
consistency
Administrative 
Letter 01
14-Mar-2016
Original 
Protocol
06-Jan-2016
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OVERALL RATIONALE FOR THE REVISED PROTOCOL 03
As of 23-August-2018, enrollment into the CA209602 study was permanently closed due to 
insufficient benefit observed based on the interim futility analysis of progression free survival 
(PFS). Subjects randomized to the nivolumab+pomalidomide (NPd) or nivolumab+elotuzumab 
+pomalidomide (NEPd) arms may continue treatment based on investigator’s judgement of 
continued clinical benefit. The study will close after all enrolled subjects complete safety follow-
up (i.e., 100 days after the last subject has discontinued study treatment). To align with this change,
study assessments have been modified: all efficacy assessments will now be based on investigator 
evaluation rather than by an independent review committee (IRC), bone marrow aspirate collection 
time-points and samples are reduce
 
 as of Revised Protocol 03.
Additional changes include update of the Nivolumab Management Algorithms (Appendix 5) and 
Pomalidomide Pregnancy Risk Prevention Plan (Appendix 6) and a minor modification of 
Appendix 3: Definitions of Response and Progression Criteria.
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & 
Title
Description of Change
Brief Rationale
Synopsis, 
Objectives, Study 
Assessments, 
Statistical 
Considerations
All efficacy assessments will be based on 
investigator evaluation rather than by 
IRC.
An independent review committee (IRC) 
had been set up to review efficacy data. 
However, after enrollment was 
discontinued, the Sponsor decided to 
discontinue efficacy assessment by IRC
All efficacy objectives and endpoints are 
now based on investigator assessment.
Synopsis, Study 
Design Statistical 
Considerations
Section 1.7 Overall 
Benefit Risk 
Assessment
Section 3.1 Study 
Design and Duration
Text has been modified and/or new text 
added to describe end of enrollment into 
the study. 
As of 23-August-2018, enrollment into 
the CA209602 study was permanently 
closed due to insufficient benefit 
observed based on the interim futility 
analysis of progression free survival 
(PFS). Subjects randomized to the NPd or 
NEPd arms may continue treatment based 
on investigator’s judgement of continued 
clinical benefit.
Section 3.5 
Discontinuation of 
Subjects following 
any Treatment with 
Study Drug. 
Corrected missing end of treatment 
criteria
Deleted in error in Revised Protocol 02. 
Section 4.5.4.4.3 
Nivolumab Dose 
Discontinuation
As of 23-August-2018, subjects may be 
discontinued at the investigator’s 
discretion based on safety results from the 
interim analysis and subject’s derived 
clinical benefit.
Subjects already enrolled in the study and 
randomized to the NPd or NEPd arms 
may continue treatment based on 
investigator’s judgement of continued 
clinical benefit.
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SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & 
Title
Description of Change
Brief Rationale

Section 5.1 Flow 
Chart/Time and 
Events Schedule: 
All Time and Event 
Tables in Section 
5.1 

Section 5.4.2,  
Laboratory 
Assessments for 
Myeloma and 
Table 5.4.2-1 Bone 
Marrow Aspirate 
Samples
Collection time points and samples 
obtained for bone marrow aspirate have 
been modified based on results of the 
futility analyses for PFS. 
Modification of study assessments, based 
on the close in enrollment for this study. 

Section 5.1 Flow 
Chart/Time and 
Events Schedule: 
All Time and Event 
Tables in Section 
5.1

 
 
 
 
 
 
 
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SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03
Section Number & 
Title
Description of Change
Brief Rationale

Section 7 Data 
Monitoring 
Committee and 
Other External 
Committees
Text added to address change from 
Independent Review Committee to 
investigator evaluation for efficacy 
assessments. 
An independent review committee (IRC) 
had been set up to review blinded 
efficacy data. However, after enrollment 
was discontinued, the Sponsor decided to 
discontinue efficacy assessment by IRC.

Section 8, Statistical 
Considerations.
Section has been revised to align with all 
study changes previously described.
Alignment of protocol to 1) end of 
enrollment and 2) use of investigator 
assessments for all efficacy 
objectives/endpoints, replacing IRC.

Appendix 3
Definitions of Response and progression 
criteria: minor adjustment to apply to 
study population The standard IMWG 
response criteria have been limited to the 
eligible patient population in the study.
Alignment with study population

Appendix 5
Hepatic Adverse Event Management 
Algorithm: Footnote stating I-O therapy 
may be delayed rather than discontinued 
if AST/ALT ≤ 8 x ULN or T.bili ≤ 5 x 
ULN has been removed.
Updated to align with nivolumab program 
standard.

Appendix 6
Pomalidomide Pregnancy Risk 
Prevention Plan
Updated Version
Throughout the 
protocol
Editorial or formatting changes that do not impact protocol content.
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SYNOPSIS
Clinical Protocol CA209602
Protocol Title: An Open-Label, Randomized Phase 3 Trial of Combinations of Nivolumab, Pomalidomide and 
Dexamethasone in Relapsed and Refractory Multiple Myeloma
(CheckMate 602: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 602)
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): See Study Schema for details
Control Arm (Pd: Arm B):
Pomalidomide: 4 mg PO QD Days 1-21 of each 28-day cycle
Dexamethasone: 

Subjects years old: 40 mg PO Days (1, 8, 15, and 22) of each cycle

Subjects > 75 years old: 20 mg PO Days (1, 8, 15, and 22) of each cycle
Investigational Arm (N-Pd: Arm A):
Nivolumab:

Cycles 1 through 4: 240 mg IV Days 1, 15 of each 28-day cycle

Cycles 5 and beyond: 480 mg IV Day 1 of each 28-day cycle
Pomalidomide: 4 mg PO QD Days 1-21 of each 28-day cycle
Dexamethasone: 

Subjects years old: 40 mg PO Days (1, 8, 15, and 22) of each cycle

Subjects > 75 years old: 20 mg PO Days (1, 8, 15, and 22) of each cycle
Exploratory Arm (NE-Pd: Arm C):  Enrollment closed per Revised Protocol 02
Nivolumab:

Cycles 1 through 4: 240 mg IV Days 1, 15 of each 28-day cycle

Cycles 5 and beyond: 480 mg IV Day 1 of each 28-day cycle
Elotuzumab: 

Cycles 1 - 2: 10 mg/kg IV Days 1, 8, 15, and 22 of each 28-day cycle

Cycle 3 and 4: 10mg/kg IV Day 1 and 15 of each 28-day cycle

Cycles 5 and beyond: 20 mg/kg IV Day 1 of each 28-day cycle
Pomalidomide: 4 mg PO QD Days 1-21 of each 28-day cycle
Dexamethasone: Days 1, 8, 15, and 22 of each cycle

Subjects 75 years old: weeks with elotuzumab dosing: 28 mg PO + 8 mg IV and 40 mg PO on non-elotuzumab 
dosing weeks

Subjects > 75 years old: weeks with elotuzumab dosing: 8 mg PO + 8 mg IV and 20 mg PO on non-elotuzumab 
dosing weeks
Revised Protocol No.: 03
Date: 12-Nov-2018
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A cycle is defined as 28 days. Treatment with study drug continues until disease progression, unacceptable toxicity, 
or subject meets other criteria for discontinuation of study drug outlined in Section 3.5.
Study Phase: 3
Research Hypothesis:. The addition of nivolumab to pomalidomide and dexamethasone will increase the clinical 
benefit represented by increased progression free survival (PFS) and higher response rate compared to pomalidomide 
and dexamethasone in subjects with relapsed and/or refractory multiple myeloma.
Objectives: 
Primary Objectives
The primary objective is to compare progression free survival (PFS) between N-Pd and Pd arms, by investigator.
Secondary Objectives

To estimate overall survival (OS) within N-Pd and Pd arms 

To assess the time to objective response (TTR) within N-Pd and Pd arms by investigator

To assess the duration of objective response (DOR) within N-Pd and Pd arms by investigator

To compare ORR between N-Pd and Pd arms, by investigator.
Exploratory Objectives

To evaluate efficacy of NE-Pd in subjects with relapsed and/or refractory multiple Myeloma within NE-Pd arm
through the assessment of ORR and PFS

To evaluate efficacy of NE-Pd in subjects who crossed over from the control arm (Pd) to the exploratory arm 
(NE-Pd) through the assessment of ORR and PFS

To assess safety and tolerability
Study Design: 
This is a phase 3 multicenter, randomized, open label study designed to evaluate the clinical benefit and safety of the 
combination therapy of Nivolumab, pomalidomide, and dexamethasone (N-Pd the investigational arm-armA), when 
compared to pomalidomide and dexamethasone (Pd; the control arm-arm B) in subjects with relapsed and/or refractory 
multiple myeloma (rrMM). Revised Protocol 01 included an exploratory third arm evaluating the clinical benefit and 
the safety of the combination therapy of elotuzumab, nivolumab, pomalidomide and dexamethasone (NE-Pd, the 
exploratory arm-arm C) in the same patient population. Additionally, subjects randomized to the Pd arm were allowed 
to cross over to this exploratory NE-Pd arm at the time of progression. Cross over was stopped as of 1 September 
2017. Enrollment in the NE-Pd exploratory arm was stopped as of Protocol version 02 All subjects already randomized 
to the NE-Pd arm, or who crossed over from the Pd to the NE-Pd arm will continue on study as long as they have 
clinical benefit and do not meet the study discontinuation criteria.
Revised Protocol No.: 03
Date: 12-Nov-2018
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Initially, the study was designed to enroll approximately 417 subjects for a total of 348 subjects to be randomized
(assuming 20% screen failure rate) to N-Pd and Pd in a 1:1 ratio. Randomization was performed with the following 
stratification factors: a) number of lines of prior therapy (2 vs 3+); AND b) ISS stage (1-2 vs 3).
Subjects were to continue treatment as long as the subject has clinical benefit from the treatment and does not meet 
criteria for treatment discontinuation.
As of 23-August-2018, the further enrollment of CA209602 study was permanently closed due to the insufficient 
benefit observed based on the interim futility analysis of PFS. A total of 170 subjects were randomized into the study: 
75 to NPd, 71 to Pd and 24 to NE-Pd arms. Subjects randomized to the NPd or NEPd arms may continue  treatment 
based on investigator’s  judgement  of continued clinical benefit. Study will be closed after all subjects complete safety 
follow-up (i.e., 100 days after the last subject has discontinued study treatment). 
The study design schematic is presented below:
Study Population: Subjects who are diagnosed with refractory or relapsed multiple myeloma defined as:
1.
Must have received 2 prior lines of therapy which must have included an immune modulatory drug (IMiD) 
and a proteasome inhibitor (PI) alone or in combination. Subject must have received at least 2 consecutive 
cycles of an IMiD and at least 2 consecutive cycles of a PI. The dose of the prior IMiD (eg, lenalidomide) to 
which the subject has relapsed or been refractory must be the induction dose and NOT a maintenance dose 
(Note: adjusted induction dose for intolerance reasons or for renal impairment is accepted).
2.
Documented refractory or relapsed and refractory (R/R) multiple myeloma
3.
Refractory (lack of response or progressed on or within 60 days of the last dose of treatment) to their last line 
of treatment. Lack of response is defined as not having achieved at least PR.i
4.
Subjects must have failed treatment with a proteasome inhibitor and an IMID in one of the following ways:
a.
“Refractory” = Refractory (lack or response or progressed on treatment or within 60 days of the last 
dose of treatment, regardless of the achievement of initial response) to a proteasome inhibitor and 
an IMiD. Lack of response is defined as not having achieved at least PR.i
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b.
“Relapsed and refractory”= patients had achieved at least a partial response to previous treatment 
with proteasome inhibitor or IMiD or both but then progressed after 60 days of the last dose of 
treatment.
5.
Have measurable disease
6.
Meet all eligibility criteria in Section 3.3
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational [Medicinal] 
Products (Non-IP/Non-IMP) as listed:
Study Drug for CA209602
Medication
Potency
IP/Non-IP
Nivolumab
100 mg (10 mg/mL)
IP
Elotuzumab
400mg/vial
IP
Pomalidomide Capsules
1 mg, 2 mg, 3 mg and 4 mg
Non-IP
Dexamethasone Tablets
2 mg and 4 mg & various strengths
Non-IP
Dexamethasone Solution
4 mg/mL, 8 mg/mL & various 
strengths
Non-IP
Study Assessments: Tumor response assessment by IMWG criteria will be evaluated during the trial for all 
randomized subjects. The primary endpoint PFS will be based on the investigator.
Statistical Considerations:
Sample Size: 
In Revised Protocol 02, the planned sample size for this study was revised to approximately 348 randomized subjects 
randomized at a 1:1 ratio to N-Pd vs Pd. The sample size of the study accounts for the primary efficacy endpoint of 
PFS. PFS will be evaluated for treatment effect at the overall alpha level of 0.05 (two-sided) with 90% power with 
two interim analyses, with the first one for early futility and the second for efficacy.
The study requires at least 262 PFS events to ensure that a two-sided 5% type I error sequential test procedure with 
two interim analyses will have 90% power to detect a hazard ratio (HR) of 0.667, corresponding to a median PFS of 
6 vs 4 months for the N-Pd and Pd arms, respectively.
On 23-August-2018, the Sponsor (BMS) decided to permanently discontinue enrollment based on insufficient clinical 
benefit observed at an interim futility analysis for PFS. A total of 170 subjects have been randomized in the study.
Endpoints:
Primary Endpoints:
The primary objective in the study will be measured by the primary endpoint PFS by investigator within the N-Pd and 
Pd arms.
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Secondary Endpoints:
The secondary objectives in the study will be measured by

OS

ORR 

TTR 

DOR
Analyses:
PFS Analysis Timepoints

At the time of PFS analyses, as assessed by investigator, the distribution of PFS in N-Pd group will be compared 
with the Pd arm via a two-sided, log-rank test stratified by prior lines of therapy and ISS stage at study entry. The 
hazard ratio (HR) and the corresponding 100x(1-adjusted alpha)% confidence interval (CI) will be estimated in a 
stratified Cox proportional hazards model using treatment as a single covariate. 

PFS curves, PFS medians with two-sided 95% CIs, and PFS rates at at select milestone with 95% CIs will be 
estimated using Kaplan-Meier methodology.
Analysis of OS

At the time of PFS analyses, OS will be summarized by the Kaplan-Meier product limit method within each arm. 
Median values along with two-sided 95% CIs based on the log log transformation, will be calculated. Additional 
details of OS analysis will be included in the SAP
Analysis of ORR by investigator

Investigator-determined ORR analyses will be conducted using a two sided Cochran Mantel Haenszel (CMH) 
test stratified by prior lines of therapy and ISS stage at study entry to compare N-Pd to Pd arm. Associated odds 
ratios and 95% CIs will be calculated. Additionally, ORRs and corresponding 95% exact CIs will be calculated 
using the Clopper Pearson method for N-Pd and Pd arms
Analysis of DOR and TTR

DOR and TTR will be computed for subjects who achieve sCR, CR, VGPR, or PR as assessed by investigator
according to modified IMWG criteria. Median values of DOR, along with two-sided 95% CI, will be calculated 
using KM product-limit method. Summary statistics of TTR will be provided. More detailed analysis of DOR 
and TTR will be described in the statistical analysis plan (SAP).
Details on the testing procedure will be described in SAP.
Safety Analysis
The safety analysis will be performed in all treated subjects. Descriptive statistics of safety will be presented using 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 by treatment 
group. Adverse Events (AE), drug-related AEs, Serious Adverse Events (SAE) and drug-related SAEs will be 
tabulated using worst grade per NCI CTCAE v.4.0 criteria by system organ class and preferred term. On-study lab 
parameters including hematology, chemistry, liver function and renal function will be summarized using worst grade 
per NCI CTCAE v.4.0 criteria.
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REFERENCES
i Rajkumar SV1, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform reporting of clinical 
trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011 May 5;117(18):4691-5. doi: 
10.1182/blood-2010-10-299487
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
OVERALL RATIONALE FOR THE REVISED PROTOCOL 03 ............................. 
SUMMARY OF KEY CHANGES OF REVISED PROTOCOL 03............................ 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1 INTRODUCTION AND STUDY RATIONALE ..................................................... 
1.1 Multiple Myeloma ............................................................................................ 
1.2 Current Treatment Regimens and Unmet Medical Need .................................. 
1.3 Study Rationale ................................................................................................. 
1.3.1 Rationale for Nivolumab Development in Multiple Myeloma ................. 
1.3.1.1 Rationale for Nivolumab dose and frequency ................................. 
1.3.1.2 Rationale for Nivolumab 30 Minute Infusion ................................. 
1.3.2 Rationale for Elotuzumab Development in Multiple Myeloma ................ 
1.3.2.1 Rationale for Elotuzumab dose and frequency ............................... 
1.3.2.2 Elotuzumab Infusion Rate ............................................................... 
1.3.3 Rationale for Pomalidomide in Multiple Myeloma ................................. 
1.3.4 Rationale for combining Nivolumab and Pomalidomide in Multiple 
Myeloma ...................................................................................................... 
1.3.5 Rationale for combining Elotuzumab and Pomalidomide in Multiple 
Myeloma ...................................................................................................... 
1.3.6 Rationale for combining Elotuzumab and Nivolumab in Multiple 
Myeloma ...................................................................................................... 
1.4 Research Hypothesis ......................................................................................... 
1.5 Objectives(s) ..................................................................................................... 
1.5.1 Primary Objectives .................................................................................. 
1.5.2 Secondary Objectives ............................................................................... 
1.5.3 Exploratory Objectives ............................................................................ 
1.6 Product Development Background ................................................................... 
1.6.1 Clinical Summary..................................................................................... 
1.6.1.1 Summary of Nivolumab Clinical Pharmacokinetics ....................... 
1.6.1.2 Summary of Relevant Clinical Data ............................................... 
1.7 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 ............................................................................... 
3.2 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
4
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3.4 Concomitant Treatments ................................................................................... 
3.4.1 Prohibited and/or Restricted Treatments................................................. 
3.4.2 Required Treatment ................................................................................. 
3.4.3 Permitted at Investigator’s Discretion ..................................................... 
3.4.4 Surgery and Radiation ............................................................................. 
3.5 Discontinuation of Subjects following any Treatment with Study Drug .......... 
3.6 Post Study Drug Study Follow up .................................................................... 
3.6.1 Withdrawal of Consent ............................................................................ 
3.6.2 Lost to Follow-Up .................................................................................... 
4 STUDY DRUG .......................................................................................................... 
4.1 Investigational Product ..................................................................................... 
4.1.1 Elotuzumab .............................................................................................. 
4.1.2 Nivolumab ................................................................................................ 
4.2 Non-Investigational Product ............................................................................. 
4.2.1 Pomalidomide .......................................................................................... 
4.2.2 Dexamethasone ........................................................................................ 
4.3 Storage and Dispensing..................................................................................... 
4.4 Method of Assigning Subject Identification ..................................................... 
4.4.1 Subject Identification ............................................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Treatment with Study Drugs .................................................................... 
4.5.1.1 Arm A (N-Pd; Investigational arm) ................................................ 
4.5.1.2 Arm B (Pd; Control arm) ................................................................ 
4.5.1.3 Arm C (NE-Pd; Exploratory arm) .................................................. 
4.5.2 Management of Infusion Reactions .......................................................... 
4.5.2.1 Guidelines for Elotuzumab Infusion in Subjects with Infusion 
Reactions ............................................................................................... 
4.5.3 Management Algorithms for Immune Related Adverse Events ................ 
4.5.4 Dose Delay, Interruption, or Discontinuation, All Subjects .................... 
4.5.4.1 Elotuzumab ..................................................................................... 
4.5.4.2 Dexamethasone ............................................................................... 
4.5.4.3 Pomalidomide ................................................................................. 
4.5.4.4 Nivolumab ....................................................................................... 
4.5.5 Recommended Dose Reduction ................................................................ 
4.5.5.1 Nivolumab and Elotuzumab ............................................................ 
4.5.5.2 Dexamethasone ............................................................................... 
4.5.5.3 Pomalidomide ................................................................................. 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
4.10 Retained Samples for Bioavailability / Bioequivalence ................................. 
5 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening or Lead-in Period ....................................... 
5.2 Study Materials ................................................................................................. 
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5.3 Safety Assessments ........................................................................................... 
5.3.1 Assessments for the Study ........................................................................ 
5.3.2 Vital Signs, Physical Measurements, and Physical Examination ............ 
5.3.3 Performance Status .................................................................................. 
5.3.4 Cardiac Assessments ................................................................................ 
5.3.5 Laboratory Assessments for Safety .......................................................... 
5.4 Efficacy Assessments ........................................................................................ 
5.4.1 Primary Efficacy Assessment ................................................................... 
5.4.2 Laboratory Assessments for Myeloma ..................................................... 
5.4.3 Imaging Assessments for Myeloma .......................................................... 
5.4.3.1 Skeletal Survey ................................................................................ 
5.4.3.2 Assessment of Extramedullary Plasmacytoma................................ 
5.4.4 Definitions of Response and Progression Criteria .................................. 
5.8 Other Assessments ............................................................................................ 
5.9 Results of Central 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 ............................................................................. 
7 DATA MONITORING COMMITTEE AND OTHER EXTERNAL COMMITTEES
................................................................................................................................. 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint..................................................................................... 
8.3.1.1 Progression Free Survival .............................................................. 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.3.3 Exploratory Endpoint(s) .......................................................................... 
8.4 Analyses ............................................................................................................ 
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8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Methods for Primary Endpoints ...................................................... 
8.4.2.2 Methods for Secondary Endpoints .................................................. 
8.4.2.3 Methods for Exploratory Endpoints................................................ 
8.4.3 Safety 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 DEFINITION OF LINES OF THERAPY ............................................ 
APPENDIX 2 ECOG PERFORMANCE STATUS ..................................................... 
APPENDIX 3 DEFINITIONS OF RESPONSE AND PROGRESSION CRITERIA . 
APPENDIX 4 THE INTERNATIONAL STAGING SYSTEM (ISS) FOR MULTIPLE 
MYELOMA ............................................................................................................ 
APPENDIX 5 NIVOLUMAB MANAGEMENT ALGORITHMS ............................. 
APPENDIX 6 POMALIDOMIDE PREGNANCY RISK PREVENTION PLAN ...... 
APPENDIX 7 REVISED PROTOCOL SUMMARY OF CHANGE HISTORY ........ 
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1
INTRODUCTION AND STUDY RATIONALE
1.1
Multiple Myeloma 
Among hematologic malignancies, multiple myeloma (MM) is the second most prevalent blood 
cancer after non-Hodgkin lymphoma, representing 10% of hematologic malignancies. In the 
United States there are an estimated 26,850 new cases and 11,240 deaths predicted for 20151. The 
incidence of MM in Europe is 4.5 to 6.0/100,000/year and the mortality is 4.1/100,000/year1. The 
incidence of MM increases with advancing age and the median age of diagnosis in the US is 
70 years1 and in Europe between 65 and 70 years1.
MM is a germinal center-derived tumor with mainly a post-switch B-cell phenotype characterized 
by extensive gene hypermutation in a pattern suggesting antigen selection. It is the most frequent 
primary neoplasm of the bone marrow. Pathologically, it stems from an expansion of a single clone 
of abnormal terminally differentiated B cells (plasma cells) that produce a monoclonal 
immunoglobulin (M-protein) and replace the normal bone marrow, leading to hypofunctioning of 
the bone marrow, osteolytic bone lesions, hypercalcemia, and renal disease2.
1.2
Current Treatment Regimens and Unmet Medical Need
Currently approved treatments commonly used for patients with relapsed / refractory MM include 
proteasome inhibitor (PI) based therapies (eg, bortezomib, carfilzomib), immune modulatory drug 
(IMiD) based therapies (thalidomide, lenalidomide, or pomalidomide) and histone deacetylase 
inhibitors.3,4 More recently an oral proteasome inhibitor (ixazomib) as well as new drug classes, 
elotuzumab (anti-SLAMF7 monoclonal antibody) and daratumumab (anti-CD38 monoclonal 
antibody) have also been approved for treatment of rrMM. There is no cure and current therapies 
can only slow disease progression, prolong survival, and minimize symptoms. While recent 
advances in the use of high-dose chemotherapy, targeted therapeutics, and stem cell transplantation 
have improved overall and event-free survival, the majority of patients with myeloma will relapse 
and disease progression is expected for all but a small percentage.5 Multiple myeloma is associated 
with morbidity and mortality, thus reflecting a significant unmet medical need.
1.3
Study Rationale
1.3.1
Rationale for Nivolumab Development in Multiple Myeloma 
Multiple myeloma (MM) is characterized by immune suppression in the bone marrow (BM) 
microenvironment which supports immune evasion and a growth advantage for malignant plasma 
cells. The nature of this suppression involves many cell types that have been implicated in 
inhibiting immune responses to control myeloma cell growth. In part, PD-L1 has been shown to 
play a role in mediating inhibition of both adaptive and innate immunity in the bone marrow milieu 
of MM patients. As PD-L1 is over-expressed on MM cells and other cells in the BM 
microenvironment from MM patients, its receptor PD-1 is also found over-expressed on both 
CD8+ T and some NK cell subsets. Therefore PD-L1 mediated suppression of PD1+ T and NK 
cells is one potential mechanism in place to confer immune escape.
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PD-L1 in MM
1) PD-L1 on myeloma cells:
While PD-L1 is seldom found on normal plasma cells, myeloma cells frequently express PD-L1 
and this expression is further enhanced when cultured with bone marrow stromal cells 
(BMSCs).6,7,8 Limited data to date also suggests that PD-L1 expression on myeloma cells may be 
increased with disease burden, stage and at time of relapse suggesting a possible mechanism for 
immune escape from current therapies.9
Figure 1.3.1-1:
PD-L1 expression in myeloma cells.
a., b: PD-L1 expression is increased on BM myeloma cells in MM patients
c: PD-L1 expression on BM plasma cells may be increased with disease stage
d: increase in PD-L1 on BM plasma cells associated with progression (within individual patients).6,9
2) PD-L1 on immune cells in MM:
PD-L1 can also mediate suppression of immune effector function through its expression on other 
cells in the BM of MM patients. PD-L1 is found to be over-expressed on both MDSCs 
(myeloid-derived suppressor cells) and pDCs (plasmacytoid dendritic cells) in the BM of MM 
patients and this expression has been shown to drive suppression of both CD8+ T and NK and cell 
responses in vitro.8,10
PD-1 in MM
PD-1 plays a role in maintaining T cell homeostasis and its expression on T cells is generally 
associated with an antigen-activated or an exhausted phenotype. Increased frequency of PD-1 + 
T cell subsets have been reported in many tumor types including MM.8,11 Increased frequency of 
PD1+ NK cells have also been observed in the BM of MM patients.8,12 Therefore expression of 
PD-1 on cytolytic immune cells such as CD8+ T and NK cells (Figure 1.3.1-2) represents a 
possible mechanism of how PD-L1-expressing tumor cells and suppressive immune cells can 
inhibit effector cell function conferring immune escape and growth of myeloma cells.12
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Figure 1.3.1-2:
Increased frequency of PD-1 expression in BM effector cells.8
Effects of PD-1 and/or PD-L1 blockade in enhancing immune cell function and killing of 
myeloma cells.
The PD-1/PD-L1 axis imposes an inhibitory mechanism to reduce effector cell function and killing 
of myeloma cells. This state of inhibition is mediated in part through tumor cell PD-L1 suppression 
of effector cells. Blocking antibodies targeting PD-1 or PD-L1 (or both) can directly enhance 
effector cell function and killing of myeloma cells in vitro (Figure 1.3.1-3). Additionally, 
PD-1/PD-L1-blocking antibodies can inhibit suppressive mechanisms in vitro mediated by 
PD-L1+ MDSCs and pDCs, and overcome bone marrow stromal cell (BMSC)-induced growth of 
myeloma cells.8
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Figure 1.3.1-3:
PD-1/PD-L1 blockade enhances immune effector cell-mediated anti-
myeloma responses in samples from BM of MM patients. Labeled 
target CD138+ MM cells cultured with autologous T or NK cells +/-
aPD1, a-PD-L1 or the combination8
Nivolumab is a fully human, IgG4 (κ) isotype mAb that binds PD-1 on activated immune cells and 
disrupts engagement of the receptor with 
its 
ligands PD-L1(B7-H1/CD274) and 
PD-L2(B7-DC/CD273), thereby abrogating inhibitory signals and augmenting the host antitumor 
response. 
Nivolumab has demonstrated clinical activity as monotherapy in subjects with a variety of 
malignancies including lung, melanoma, renal cell carcinoma and in lymphomas, responses have 
been reported for diffuse large B-cell lymphoma, follicular lymphoma, head and neck cancer, and 
Hodgkin’s lymphoma.
Approximately 8,000 subjects have received nivolumab monotherapy in single- or multiple-dose 
Phase 1/2/3 studies or studies with nivolumab in combination with other therapeutics (ipilimumab, 
cytotoxic chemotherapy, anti angiogenics, and targeted therapies). The safety profile is generally 
consistent across completed and ongoing clinical trials, with no maximum tolerated dose (MTD) 
reached at any monotherapy dose tested up to 10 mg/kg. There was no pattern in the incidence, 
severity, or causality of AEs to nivolumab dose level. The safety profile of nivolumab combination 
therapy varies with the agent combined with nivolumab, but is generally consistent with the safety 
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profiles observed with either agent alone and, in some cases, the frequency of AEs may be greater 
than that observed with either agent alone. For nivolumab monotherapy and combination therapy, 
most high-grade events were manageable with use of corticosteroids and/or hormone replacement 
therapy.
Nivolumab is indicated for the treatment of patients with unresectable or metastatic melanoma as 
both a single agent and in combination with ipilimumab. Nivolumab is also approved for non-small 
cell lung cancer following failure on or after platinum based therapy, as well as for advanced renal 
cell carcinoma following treatment with an anti-angiogenic therapy. Opdivo(nivolumab) is 
approved for use in multiple countries including the United States (US Dec 2014), the European 
Union (EU June 2015) and Japan (Jul 2015). 
1.3.1.1
Rationale for Nivolumab dose and frequency
The nivolumab dose of 240 mg every 2 weeks (Q2W) was selected based on clinical data and 
modeling and simulation approaches using population PK (PPK) and exposure-response analyses 
of data from studies in multiple tumor types (melanoma, non-small-cell lung cancer [NSCLC], and 
renal cell carcinoma [RCC]) where body weight normalized dosing (mg/kg) has been used.
PPK analyses have shown that the PK of nivolumab is linear with proportional exposure over a 
dose range of 0.1 to 10 mg/kg, and no differences in PK across ethnicities and tumor types were 
observed. Nivolumab clearance and volume of distribution were found to increase as the body 
weight increases, but less than the proportional with increasing weight, indicating that mg/kg 
dosing represents an over-adjustment for the effect of body weight on nivolumab PK. The PPK 
model previously developed using data from NSCLC subjects has recently been updated, using 
data from 1544 subjects from 7 studies investigating nivolumab in the treatment of melanoma, 
NSCLC, and RCC. In this dataset, the median (minimum - maximum) weight was 77 kg 
(35 kg - 160 kg) and thus, an approximately equivalent dose of 3 mg/kg for an 80 kg subject, 
nivolumab 240 mg Q2W was selected for future studies. To predict relevant summary exposures 
of nivolumab 240 mg Q2W, the PPK model was used to simulate nivolumab 3 mg/kg Q2W and 
240 mg Q2W. In the simulations, the simulated patient populations consisted of 1000 subjects per 
treatment arm randomly sampled from aforementioned pooled database of cancer subjects. 
Because no differences in PK were noted across ethnicities and tumor types, these simulated 
melanoma and NSCLC data will be applicable to subjects with other tumor types. The simulated 
measure of exposure of interest, time-averaged concentrations (Cavgss) for 240 mg Q2W are 
predicted to be similar for all subjects in reference to 80 kg subjects receiving 3 mg/kg Q2W.
Nivolumab is safe and well tolerated up to 10 mg/kg Q2W dose level. Adverse events have been 
broadly consistent across tumor types following monotherapy and have not demonstrated clear 
dose-response or exposure-response relationships. Additionally, the simulated median and 95th 
prediction interval of nivolumab summary exposures across body weight range (35 - 160 kg) are 
predicted to be maintained below the corresponding observed highest exposure experienced in 
nivolumab ie, 95th percentile following nivolumab 10 mg/kg Q2W from clinical study CA209003. 
Thus, while subjects in the lower body weight ranges would have greater exposures than 80 kg 
subjects, the exposures are predicted to be within the range of observed exposures at doses (up to 
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10 mg/kg Q2W) used in the nivolumab clinical program, and are not considered to put subjects at 
increased risk. For subjects with greater body weights, the simulated ranges of exposures are also 
not expected to affect efficacy, because the exposures predicted following administration of a 
240 mg Q2W are on the flat part of the exposure-response curves for previously investigated 
tumors, melanoma and NSCLC. Given the similarity of nivolumab PK across tumor types and the 
similar exposures predicted following administration of 240 mg flat dose compared to 3 mg/kg, it 
is expected that the safety and efficacy profile of 240 mg nivolumab will be similar to that of 
3 mg/kg nivolumab. Thus nivolumab 240 mg every 2 weeks over 30 minutes for the first 4 months 
will be used this study.
At 4 months after initiation of treatment, subjects will be switched from nivolumab 240 mg every 
2 weeks to nivolumab 480 mg every 4 weeks (Q4W), which provides a more convenient dosing 
regimen for subjects. Based on PK modeling and simulations, administration of nivolumab 480 mg 
Q4W will be started after steady state is achieved with 240 mg Q2W and is predicted to provide 
Cavgss similar to 240 mg Q2W. While 480 mg Q4W is predicted to provide greater (approximately 
20%) maximum steady state concentrations and lower (approximately 10%) steady state trough 
concentrations, these exposures are predicted to be within the exposure ranges observed at doses 
up to 10 mg/kg Q2W used in the nivolumab clinical program, and are not considered to put subjects 
at increased risk. Similar to the nivolumab 240 mg Q2W dosing regimen, the exposures predicted 
following administration of nivolumab 480 mg Q4W, are on the flat part of the exposure-response 
curves for previously investigated tumors, melanoma and NSCLC, and are not predicted to affect 
efficacy. Based on these data, nivolumab 480 mg Q4W is expected to have similar efficacy and 
safety profiles to nivolumab 240 mg Q2W.
1.3.1.2
Rationale for Nivolumab 30 Minute Infusion
Long infusion times place a burden on subjects and treatment centers. Establishing that nivolumab 
can be safely administered using shorter infusion times of 30 minutes duration in subjects will 
diminish the burden provided no change in safety profile. Previous clinical studies show that 
nivolumab has been administered safely over 60 minutes at doses ranging up to 10 mg/kg over 
long treatment duration. In Study CA209010, (a Phase 2, randomized, double blinded, 
dose-ranging study of nivolumab in subjects with advanced/metastatic clear cell RCC) a dose 
association was observed for infusion site reactions and hypersensitivity reactions (1.7% at 
0.3 mg/kg, 3.7% at 2 mg/kg and 18.5% at 10 mg/kg). All the events were grade 1-2 and were 
manageable. An infusion duration of 30 minutes for 240 mg and 480 flat doses of nivolumab 
(~ 60% of the dose provided at 10 mg/kg) are not expected to present safety concerns compared 
to the prior experience at 10 mg/kg nivolumab dose infused over a 60 minute duration.
1.3.2
Rationale for Elotuzumab Development in Multiple Myeloma 
Elotuzumab (BMS-901608, HuLuc63) is a first-in-class, immunostimulatory, humanized 
immunoglobulin G1 (IgG1) monoclonal antibody (mAb) targeted against Signaling Lymphocyte 
Activation Molecule Family 7 (SLAMF7, also called CS1), a glycoprotein highly expressed on 
myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on natural 
killer (NK) cells and at lower levels on other immune cell subsets. SLAMF7 has not been detected 
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on hematopoietic stem cells, nor on other normal solid organ tissues. Elotuzumab binding to 
SLAMF7 directly activates NK cells, but not myeloma cells.13,14 Elotuzumab bound to myeloma 
cells via SLAMF7 further activates NK cells via Fc receptors, thereby enabling selective killing 
of myeloma cells with minimal effects on normal tissue.15
Elotuzumab demonstrates a dual mechanism that includes: 1) direct NK cell activation and 2) NK 
cell-mediated Antigen Dependent Cellular Cytotoxicity (ADCC).
In a Phase 2 trial of elotuzumab combined with lenalidomide and dexamethasone for 
relapsed/refractory myeloma subjects, the objective response rate was 84% and median PFS was 
29 months.16
Risks associated with elotuzumab in early phase studies appear to be limited primarily to infusion 
reactions. These infusion reactions are mitigated with the use of a standard regimen of histamine 
blocking agents, acetaminophen and corticosteroids. Investigator-determined infusion reactions 
were reported in 11% of subjects in the phase 2 trial.
Phase 3 Trial of Elotuzumab in relapsed/refractory MM
The study CA204004 is an ongoing Phase 3, randomized, open-label trial investigating the 
combination of elotuzumab with lenalidomide/low-dose dexamethasone (E-Ld) versus 
lenalidomide/low-dose dexamethasone alone (Ld) in subjects with previously treated relapsed or 
refractory multiple myeloma. The primary objectives of this study were to compare the ORR and 
PFS of E-Ld versus Ld. In total, 646 subjects were randomized and 635 were treated. At the time
of the interim analysis data cut-off, 179 (elotuzumab group, 35%; control group 21%) were still 
on-treatment. The median follow up was 24.5 months and in the elotuzumab group, subjects
received a median of 19 (range, 1 to 42) treatment cycles over a median of 17 months versus 
14 (range, 1 to 40) over 12 months in the control group.
Hazard ratio for progression-free survival was 0.70 (95% confidence interval, 0.57 to 0.85; 
P=0.0004). 1-year progression-free survival rate in the elotuzumab group was 68%, versus 57% in 
the control group; 2-year rate was 41% versus 27%. Median progression-free survival in the 
elotuzumab group was 19.4 months versus 14.9 months in the control group. Overall response rate 
in the elotuzumab group was 79% versus 66% in the control group (P=0.0002).
In the 635 treated subjects, adverse events of any grade occurred in 99% of patients. In the 
elotuzumab group, 34% of the patients experienced grade 3 to 4 neutropenia versus 44% in the 
control group; 77% versus 49% of patients had grade 3 to 4 lymphopenia, respectively. The most 
common non-hematologic toxicities (> 30% of patients) included infections, fatigue, pyrexia, 
diarrhea, constipation, and cough. The most common grade 3 to 4 non-hematologic toxicities were 
fatigue and pneumonia. In the elotuzumab group, infections were reported for 81% of patients 
versus 74% in the control group. When adjusted for the longer drug exposure in the elotuzumab 
group, infection rates were equal in both groups (incidence rate per 100 patient years, 197).
Consequently, despite the higher rate of lymphopenia observed in the elotuzumab group, there 
were no apparent untoward clinical manifestations.
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In the elotuzumab group, study drug toxicity was the primary cause of death in 5 (2%) patients 
versus 6 (2%) in the control group.
Thirty-five (6%) patients had a second primary malignancy: 22 (7%) in the elotuzumab group and 
13 (4%) in the control group. The incidence rates of second hematologic malignancies were 
identical in the elotuzumab and control groups (2% in each group); rates of second solid tumors 
were 3% versus 2%, respectively, and rates of non-melanoma skin cancers were 3.1% versus 1.5%, 
respectively. When adjusted for exposure to study therapy, the incidence rates of second primary 
malignancies per 100 patient-years were similar at 3.5 versus 2.8, respectively. 
Thirty-three (10%) patients receiving elotuzumab had an infusion reaction, including pyrexia, 
chills, and hypertension. Infusion reactions were mostly grade 1 to 2; 1% were grade 3 reactions 
and none were grade 4 to 5. Most infusion reactions occurred in the first 2 cycles of study therapy 
(range cycle 1, day 1 to cycle 11, day 281); five patients had an infusion reaction after cycle 2. 
Infusion of elotuzumab was interrupted in 15 (5%) patients owing to an infusion reaction, for a 
median duration of 15 minutes. Infusion reactions resolved in all patients; however, 2 (1%) patients 
discontinued due to an infusion reaction.
Elotuzumab may be detected in the serum protein electrophoresis (SPEP) and serum 
immunofixation assays of myeloma patients and could interfere with correct response 
classification. A small peak in the early gamma region on SPEP that is IgGƙ on serum 
immunofixation may potentially be attributed to elotuzumab, particularly in patients whose 
endogenous myeloma protein is IgA, IgM, IgD, or lambda light chain restricted. This interference 
can impact the determination of complete response and possibly relapse from complete response 
in patients with IgG kappa myeloma protein.
Elotuzumab was approved in combination with lenalidomide and dexamethasone for the treatment 
of patients with multiple myeloma who have received one to three prior therapies (FDA, 
November-2015) and in MM patients who have received at least one prior therapy (EMA, 2016).
A description and status of all studies are presented in the Investigator Brochure.17
1.3.2.1
Rationale for Elotuzumab dose and frequency
The dose of 10 mg/kg on D1, 8, 15 & 22 of Cycles 1 and 2 then on D1 & 15 during Cycles 3 and 4, 
used in this protocol, is the FDA approved dose and regimen of elotuzumab in combination with 
lenalidomide and dexamethasone.
Clinical Phase I and IIa studies suggests that the trough serum concentrations of elotuzumab in 
subjects treated with 10 and 20 mg/kg doses are above the target levels ie, 70 g/ml, which is 
predicted based on preclinical models. Following elotuzumab dosing of 10 and 20 mg/kg in 
combination with lenalidomide/dex, the observed steady-state Cmin values consistently remained 
above 70 g/mL, the minimum efficacious trough concentrations18. Elotuzumab dosing also 
resulted in > 95% saturation of SLAMF7 on bone marrow plasma cells at doses 10 mg/kg (Figure 
1.3.2.1-1).
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Figure 1.3.2.1-1:
Saturation of SLAMF7 Target on Bone Marrow Myeloma Samples 
from Subjects Treated in a Phase 2 Study of Elotuzumab and 
Lenalidomide/ Dexamethasone (HuLuc63 1703)
Beginning at Cycle 5, elotuzumab will be administered at 20 mg/kg once every 4 weeks. Increasing 
elotuzumab dose and decreasing the administration of elotuzumab frequency to every 4 weeks will 
continue to provide Cmin,ss above 70 ug/ml, and will be more convenient for patients on long 
term therapy and therefore require fewer scheduled clinic visits. With 20 mg/kg Q4W, the 
simulated Cave,ss is 301 ug/ml, which is similar to the 10mg/kg dosing regimen with Cave,ss 
value of 297 ug/ml. In addition, with the estimated Cmin,ss (geometric mean) is 141 ug/ml, and it 
remains above 70 ug/ml, which is the minimum trough concentration at which maximum efficacy 
was seen in preclinical studies and is sufficient to maintain saturation of SLAMF7 by elotuzumab. 
Further, with the 20 mg/kg Q4W dosing, the Cmax,ss (geometric mean) is estimated as 556 ug/ml, 
which is higher than the Cmax,ss of 401 ug/ml at the 10 mg/kg dose. However, in the PPK analysis 
of elotuzumab combination with len/dex, there was no relationship between elotuzumab exposure 
and Grade 3+ AEs hazard ratio. The point estimate indicated no increase in hazard ratio with 
increasing exposure over the range of exposures observed with a 10 mg/kg dosing regimen. This 
exposure-safety analysis indicates that increasing exposure may have limited impact on the safety 
for subjects.
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Figure 1.3.2.1-2:
Model of Elotuzumab Serum Concentration - 10 mg/kg of Study 004 
and 20 mg/kg every 4 Weeks Starting Cycle 5
1.3.2.2
Elotuzumab Infusion Rate
The maximum infusion rate of 2 ml/min was initially explored in the phase 1 and 2 elotuzumab 
clinical trials. However, the infusion of elotuzumab at a faster rate was explored in 2 completed 
trials (HuLuc63-1703, CA204009) and 1 ongoing trial (CA204112). In the phase 2 portion of the 
HuLuc63-1703 trial, 31 subjects had the infusion rate escalated up to 5 mL/min 
(approximately 1 hour infusion). Of the total 3412 elotuzumab infusions administered, 
1127 (33%) infusions were given at 5 mL/min. Nearly all the subject tolerated the faster infusion 
rate of elotuzumab without a reaction except 1 subject with a grade 1 event of nausea considered 
an infusion reaction by the investigator.
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In the CA204009 trial, subjects in the E-Bd arm who did not have any infusion reaction in the first 
4 cycles could have their infusion rate escalated to 5 ml/min. No infusion reactions were reported 
among the 41% of subjects and 19% of infusions administered at the faster rate of 5 ml/min.
In the CA204112 study, the infusion rate was escalated to 5mL/min starting C1D15. As of 
13 Oct 2015, 70 subjects were treated with a median of 6 cycles (1 - 13). A total of 2 subjects (3%) 
experienced infusion reactions (pyrexia, grade 1, and infusion related reaction, grade 2). No grade 
3 - 4 infusion reaction was reported. Of the total of 1113 elotuzumab infusions, 968 infusions were 
given at 5mL/min with no reported infusion reactions. The 2 infusion reactions observed were 
reported at the infusion rate of 2mL/min.
The 5 ml/min infusion rate for elotuzumab will be utilized in this trial based on its safety across 
several prior studies.
1.3.3
Rationale for Pomalidomide in Multiple Myeloma 
Pomalidomide, a derivative of thalidomide with immunomodulatory properties, is approved as a 
treatment option for subjects with relapsed or refractory multiple myeloma who have received at 
least two prior therapies including lenalidomide and bortezomib and who have demonstrated 
disease progression on or within 60 days of completion of the last therapy.
Phase 3 Trial of Pomalidomide in Third Line
The phase 3 study (MM-003/NIMBUS® trial) evaluated the combination of pomalidomide with 
low-dose dexamethasone vs high-dose dexamethasone in refractory or relapsed and refractory MM 
subjects. A total of 302 patients were randomly assigned to receive pomalidomide plus low-dose 
dexamethasone and 153 high-dose dexamethasone. 
Pomalidomide was dosed at 4 mg orally on Days 1-21 of each 28 day cycle and dexamethasone 
was given at a low dose of 40 mg/day on days 1, 8, 15, and 22, orally or at a high dose of 40 mg/day
on days 1–4, 9–12, and 17–20, orally. Treatment continued until disease progression or 
unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS).
Efficacy data from this phase 3 study shows that median PFS with pomalidomide plus low-dose 
dexamethasone was 4.0 months (95% CI 3.6–4.7) versus 1.9 months (1.9–2.2) with high-dose 
dexamethasone (HR 0.48 [95% CI 0.39–0.60]; p<0.0001) favoring the pomalidomide plus low 
dose dexamethasone arm. The median overall survival was also significantly longer in the 
pomalidomide plus low-dose dexamethasone group than in the high dose dexamethasone group 
(12.7 months [95% CI 10.4–15.5] vs 8.1 months [6.9–10.8]; HR 0.74 [0.56–0.97]; p=0.0285). 
Overall response rate after a median follow-up of 10.0 months was documented in 31% of 
302 patients in the pomalidomide plus low-dose dexamethasone group versus 10% of 153 in the 
high-dose dexamethasone group (odds ratio [OR] 4.22 [2.35–7.58]; p<0.0001). 
Regarding safety, the most common grade 3–4 hematological adverse events in the pomalidomide 
plus low dose dexamethasone and high-dose dexamethasone groups were neutropenia (48% vs 
16% respectively), anaemia (33% vs 37%), and thrombocytopenia (22% vs 26%). Grade 3–4 
non-hematological adverse events in the pomalidomide plus low-dose dexamethasone and 
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high-dose dexamethasone groups included pneumonia (13% vs 8%), bone pain (7% vs 5%), and 
fatigue (5% vs 6%). 
The dose of pomalidomide in this study will be 4 mg orally on Days 1-21 of each 28 day cycle in 
combination with low dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally for patients 
75 years old, and 20 mg/day on days 1, 8, 15, and 22, orally for patients >75 years old) which is 
the approved dose and schedule for treatment of this population.
1.3.4
Rationale for combining Nivolumab and Pomalidomide in Multiple 
Myeloma 
The exact mechanism(s) needed to sensitize BM T cells from MM patients to PD-1 blockade is 
unknown but in part may require a reversal of T cell senescence that has been observed in MM19.
In fact, one report presents data supporting the capacity of low concentrations of lenalidomide to 
improve several of the T cell abnormalities of immunosenescence, suggesting it may be a 
beneficial therapy for restoration of T cell-dependent immunity, especially in the elderly which is 
the target demographic for most patients with MM. However, this observation has not been 
validated with T cells from the phenotypes ascribed above to MM patients.19 Therefore, in addition 
to the MoAs described for PD-1/PD-L1 blockade and IMiDs in restoring immune surveillance, 
perhaps IMiDs may also contribute to the reversal of T cell senescence and may at least partially 
sensitize these compromised T cells to PD-1 blockade.
Due to the overlap in rationale for blocking PD-1 versus blocking PD-L1, most of the pre-clinical 
data supports that both approaches generate similar results with regards to enhancing 
T and NK cell function and enhancing the killing of myeloma cells. However, there are some 
subtle yet distinct differences between these two approaches (Figure 1.3.4-1). Blocking PD-1 
inhibits both PD-1: PD-L1 and PD-1: PD-L2 interactions. Antibodies directed toward PD-L1 
would block interactions with PD-1 but would not impair PD-L2 interactions with PD-1.
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Figure 1.3.4-1:
Interactions of B7 ligand family members to CD28 receptor family 
members
Figure 1.3.4-2 summarizes the current understanding of the potential mechanisms for combining 
an IMiD with a PD-1 (or PD-L1) blocking antibody and how these effects would shift the balance 
to restoring immune surveillance in MM.
Figure 1.3.4-2:
Interactions of B7 ligand family members to CD28 receptor family 
members
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Figure 1.3.4-2: Proposed model representing the combination effects of IMiDs and blocking 
antibodies to the PD-1/PD-L1 axis.
Phase 2 Trial of PD-1 Inhibitor with Pomalidomide in 3rd Line Myeloma
An ongoing phase 2 study single arm is evaluating the safety and efficacy of a similar PD-1 
inhibitor (pembrolizumab) in combination with pomalidomide and low dose dexamethasone in 
relapsed/refractory multiple myeloma patients.
Of the first 24 patients, 75% had prior autologous transplantation and 96% were refractory to last 
therapy. All patients had received both IMiDs and Proteosome inhibitors; 75% were double 
refractory to both IMiDs and Proteosome inhibitors and additional 21% were refractory to 
lenalidomide alone. Patients had received a median of 3 lines of prior therapy (range: 1-6). The 
median time from MM diagnosis to study entry was 4 years (range: 1.2-15).
Preliminary safety and efficacy data for the first 24 subjects demonstrated no infusion-related 
reactions. Hematologic toxicities (grade 3) were neutropenia (29%), lymphopenia (17%) and 
thrombocytopenia (8%). Non-hematologic adverse events included (Grade 2; 3): 
fatigue (n=12; 1), constipation (n=10; 0), dyspnea (n=9; 2), itching (n=6; 0), muscle spasms (n=6; 
0), infection (n=4; 3), hyperglycemia (n=5; 0), edema (n= 4; 0), fever (n=3; 0), palpitation (n=2; 
1), rash (n=3; 1) and hypotension (n=3; 0). Events of clinical significance, autoimmune mediated, 
included hypothyroidism (n=2), transaminitis (n=2), and pneumonitis (n=1). Four patients had 
pomalidomide dose reductions due to rash, neutropenia, palpitations and fatigue. Two patients 
died; one after cycle 1 (progressive disease) and one during cycle 2 (sepsis). Objective responses 
(modified IMWG criteria) were observed in 11 of 22 evaluable patients (50%) including: near 
complete response (n=3), very good partial response (n=2), partial response (n=6); additionally, 
3 patients had minimal response, 6 had stable disease and 2 progressed. At a median follow up of 
16 weeks; 17 of 22 patients continued on the study. 
Phase 1 Trial of PD-1 Inhibitor with Lenalidomide in Myeloma
Another ongoing phase 1 study combining the PD1 inhibitor pembrolizumab with lenalidomide 
and dexamethasone in patients with relapsed/refractory multiple myeloma has demonstrated a 
tolerable safety profile of the PD1 inhibitor and IMiD combination. Among the first 17 evaluable 
subjects, sixteen (94%) experienced at least 1 adverse event (AE) of any grade related to study 
treatment and 10 (58%) experienced grade 3/4 treatment-related AEs. No death or treatment 
discontinuation for toxicity has been observed. The most frequent treatment-related AEs were: 
thrombocytopenia (47%), neutropenia (41%), fatigue (29%), and anemia, hyperglycemia, and 
muscle spasms (23% each). No DLTs were observed in the 10-mg lenalidomide cohort. In the 
25-mg lenalidomide cohort, 3 patients (3/13) experienced a dose-limiting toxicity (DLT): 
neutropenia (grade 3 and grade 4), infectious pneumonia (grade 3), and tumor lysis syndrome 
(grade 3) with hyperuricemia (grade 4). All patients recovered from the DLTs without treatment 
discontinuation. Based upon these data the MTD/MAD was defined as pembrolizumab 200 mg 
fixed dose in combination with lenalidomide 25 mg and low-dose dexamethasone 40 mg. The 
preliminary efficacy was also promising in this study with 76% ORR reported so far.
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1.3.5
Rationale for combining Elotuzumab and Pomalidomide in Multiple 
Myeloma 
Combining elotuzumab with lenalidomide, a thalidomide analog with immunomodulatory
properties, is well tolerated and was proven to result a statistically and clinically meaningful 
improvement over lenalidomide/dexamethasone alone in a phase 3 trial. 
Pomalidomide, in the same class as lenalidomide, is approved as a treatment option for subjects
with relapsed or refractory multiple myeloma who have received at least two prior therapies
including lenalidomide and bortezomib and have demonstrated disease progression on or within
60 days of completion of the last therapy.
In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of
hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of
lenalidomide-resistant multiple myeloma cell lines and synergized with dexamethasone in both
lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis.
Pomalidomide enhanced T cell- and natural killer (NK) cell-mediated immunity and inhibited
production of pro-inflammatory cytokines (eg, TNF-and IL-6) by monocytes20.
Since pomalidomide may enhance the activity of NK cells, which are central to the main biological 
activity of elotuzumab, combining both drugs is likely to enhance elotuzumab- mediated 
antibody-dependent cell-mediated cytotoxicity (ADCC) towards primary myeloma cells in a 
similar way to that observed with lenalidomide.
Figure 1.3.5-1 illustrates results from pre-clinical data (Robbins et al, unpublished) showing the 
combination of elotuzumab with pomalidomide +/- dexamethasone (SCID-ICR mice with OPM2 
xenograft) is similar to the combination of elotuzumab and lenalidomide that has been previously 
reported21. 
Therefore, 
in 
pre-clinical 
models 
of 
MM, 
the 
combination 
of 
elotuzumab/pomalidomide enhances the killing of SLAMF7+ myeloma cells in vivo greater than 
either agent alone. Additionally, low doses of dexamethasone do not appear to impair NK function 
in this model and adds to the anti-myeloma activity of the combination in this model.
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Figure 1.3.5-1:
Elotuzumab Synergizes with Pomalidomide to Kill SLAMF7+ Human 
MM Cells in vivo
1.3.6
Rationale for combining Elotuzumab and Nivolumab in Multiple 
Myeloma 
It has been previously shown in pre-clinical models that elotuzumab activity towards MM cells 
can be improved by agents that enhance NK cell activity, either through agonizing activating 
molecules or blocking inhibitory molecules on the surface of NK cells22. Consistent with this 
rationale, PD-1 expression has been shown on both T cells and NK cells in bone marrow samples 
from MM patients, therefore blocking the PD-1/PD-L1 axis may also contribute to increased 
elotuzumab activity towards killing myeloma cells. Figure 1.3.6-1 shows that in pre-clinical in 
vivo models, the combination of elotuzumab and a murine surrogate antibody of nivolumab 
demonstrates enhanced reduction of tumors in mice.23 These results were generated in a 
completely immune competent syngeneic mouse tumor model therefore the net anti-tumor activity 
observed can be mediated by both innate (NK) and adaptive (T cell) immunity. 
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Figure 1.3.6-1:
Elotuzumab Synergizes with a PD-1 blocking antibody to Kill 
SLAMF7+ Tumor Cells in vivo
1.4
Research Hypothesis 
The addition of nivolumab to pomalidomide and dexamethasone will increase the clinical benefit 
represented by increased progression free survival (PFS) and higher response rate compared to 
pomalidomide and dexamethasone in subjects with relapsed and/or refractory multiple myeloma.
1.5
Objectives(s)
1.5.1
Primary Objectives
The primary objective is to compare progression free survival (PFS) between N-Pd and Pd arms, 
by investigator.
1.5.2
Secondary Objectives

To estimate overall survival (OS) within N-Pd and Pd arms 

To assess the time to objective response (TTR) within N-Pd and Pd arms by investigator.

To assess the duration of objective response (DOR) within N-Pd and Pd arms by investigator.

The compare objective response rate (ORR) between N-Pd and Pd arms, by investigator.
1.5.3
Exploratory Objectives

To evaluate efficacy of NE-Pd in subjects with relapsed and/or refractory multiple Myeloma 
within NE-Pd arm through the assessment of ORR and PFS

To evaluate efficacy of NE-Pd in subjects who crossed-over from the control arm (Pd) to the 
exploratory arm (NE-Pd) through the assessment of ORR and PFS

To assess safety and tolerability
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1.6
Product Development Background
1.6.1
Clinical Summary
1.6.1.1
Summary of Nivolumab Clinical Pharmacokinetics
The pharmacokinetics (PK) of nivolumab were studied in subjects over a dose range of 0.1 to 
10 mg/kg administered as a single dose or as multiple doses of nivolumab every 2 or 3 weeks. The 
geometric mean (% CV%) clearance (CL) was 9.5 mL/h (49.7%), geometric mean volume of 
distribution at steady state (Vss) was 8.0 L (30.4%), and geometric mean elimination half-life 
(t1/2) was 26.7 days (101%). Steady-state concentrations of nivolumab were reached by 12 weeks 
when administered at 3 mg/kg Q2W, and systemic accumulation was approximately 3-fold. The 
exposure to nivolumab increased dose proportionally over the dose range of 0.1 to 10 mg/kg 
administered every 2 weeks. The clearance of nivolumab increased with increasing body weight. 
The PPK analysis suggested that the following factors had no clinically important effect on the CL 
of nivolumab: age (29 to 87 years), gender, race, baseline LDH, PD-L1. A PPK analysis suggested 
no difference in CL of nivolumab based on age, gender, race, tumor type, baseline tumor size, and 
hepatic impairment.
Although ECOG status, baseline glomerular filtration rate (GFR), albumin and body weight had 
an effect on nivolumab CL, the effect was not clinically meaningful. Additionally, PPK and 
exposure response analyses have been performed to support use of 240 mg Q2W dosing in addition 
to the 3 mg/kg Q2W regimen. Using the PPK model, exposure of nivolumab at 240 mg flat dose 
was identical to a dose of 3 mg/kg for subjects weighing 80 kg, which was the approximate median 
body weight in nivolumab clinical trials (see Section 1.3.1.1).
Full details on the clinical pharmacology aspects of nivolumab can be found in the Investigator 
Brochure.
1.6.1.2
Summary of Relevant Clinical Data
Nivolumab Phase 1 Monotherapy Results in hematological malignancies including Myeloma
Preliminary safety data from an ongoing Phase 1 study for patients with a variety of hematologic 
malignancies (CA209039) suggested that the safety for these malignancies seems similar to that 
for solid tumors. As of 02-May-2015, data were available for 105 patients, including 27 subjects 
with MM, treated with Nivolumab monotherapy. Treatment with nivolumab in patients with 
hematological malignancies has been well tolerated and toxicities have been generally 
manageable. There was 1 DLT (Dose Limiting Toxicity) at the 1 mg/kg dose level in a patient 
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with multiple myeloma who experienced Grade 3 pneumonia and Grade 3 pneumonitis. There was 
1 DLT at the 3 mg/kg dose level in a patient with small lymphocytic lymphoma who experienced 
Grade 3 hypereosinophilia and Grade 3 diplopia. The MTD was not reached.
Adverse events were reported in 104 of 105 (99%) patients and Grade 3 events in 64 (61%) 
patients. Related AEs were reported in 72 (68.6%) patients. Those that occurred in more than 5% 
of patients included: fatigue (16.2%), rash (10.5%), pneumonitis (9.5%), pruritus (9.5%), diarrhea 
(8.6%), pyrexia (8.6%), decreased appetite (7.6%), thrombocytopenia (6.7%), leukopenia (5.7%), 
lymphopenia (5.7%), hypocalcaemia (5.7%) and lipase increased (5.7%). Related Grade 3 events 
were reported in 23 (21.9%) patients; the most common of which was leukopenia that occurred in 
4 (3.8%) patients. twenty five (23.8%) patients discontinued therapy due to AEs, 15 of which were 
related to study therapy. A total of 37 (35.2%) patients died: 28 due to disease, 8 due to other 
causes, and 1 due to drug toxicity. Drug-related pneumonitis was observed in 10 patients (9.5%): 
Seven patients had Grade 1 or 2 pneumonitis; 2 had Grade 3; one patient had Grade 4.
Preliminary efficacy results in 27 relapsed/refractory multiple myeloma patients have 
demonstrated stable disease among 63% of patients with the remainder progression on single agent 
nivolumab.
1.7
Overall Risk/Benefit Assessment
Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma, 
representing 10% of hematologic malignancies. While recent advances in the use of high-dose 
chemotherapy, targeted therapeutics, and stem cell transplantation have improved overall and 
event-free survival, the majority of patients with myeloma will relapse and disease progression is 
expected for all but a small percentage24. The subjects treated in this trial will receive an 
anti-myeloma regimen of pomalidomide + dexamethasone which demonstrated improvements in 
PFS, overall survival, and overall response in patients with refractory or relapsed and refractory 
multiple myeloma,
including patients with disease refractory to both bortezomib and 
lenalidomide25.
Pomalidomide has gained U.S. FDA and EMA approval in this population of MM patients at a 
dose of 4 mg, which is the dose being used in this trial. Pomalidomide is an analogue of 
thalidomide, which is known to cause severe life-threatening human birth defects. Because of this 
potential toxicity and to avoid fetal exposure, pomalidomide is only available under a special 
restricted distribution program Pomalyst REMS. Subjects must follow the local commercial 
Pomalidomide Pregnancy Risk Prevention Plan.  For those countries where local Pomalidomide 
Pregnancy Prevention Program does not exist, subjects must follow the Pomalidomide Global 
Pregnancy Prevention Plan for clinical trials (Appendix 6). All investigators and subjects must 
fully comply with and participate in the pregnancy prevention program in order to participate in 
this trial.
Nivolumab is approved in multiple solid tumor indications based on its favorable benefit/risk 
assessment. In hematological malignancies including multiple myeloma, nivolumab monotherapy 
was generally well tolerated and toxicity profile was similar to that observed in solid tumors. 
Nivolumab has the potential for clinically relevant unique AEs potentially caused by an 
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inflammatory mechanism. These include pulmonary toxicity, hepatotoxicity, diarrhea/colitis, 
endocrinopathies, and nephrotoxicity. To date, these unique AEs have been manageable with 
frequent monitoring, prompt diagnosis, and initiation of corticosteroids, dose interruption, and 
adequate supportive care. The management algorithms of the immune related AEs are included in 
Appendix 5.
Emerging preliminary data on safety and efficacy of the PD1 inhibitor pembrolizumab in 
combination with IMiDs (pomalidomide and lenalidomide) in relapsed/refractory multiple 
myeloma patients have demonstrated a clinical benefit and was well tolerated. Being a PD1 
inhibitor, nivolumab is expected to have an acceptable tolerance profile in combination with 
pomalidomide similar to that of pembrolizumab. 
Elotuzumab has proven activity in relapsed/refractory multiple myeloma patients in combination 
with IMiDs. The addition of elotuzumab to lenalidomide and low dose dexamethasone has 
significantly prolonged the PFS compared to lenalidomide and low dose dexamethasone.
Elotuzumab as monotherapy or in combination with immunomodulatory agents such as
thalidomide or lenalidomide is well tolerated. Safety data from the ongoing randomized phase 3 
study of lenalidomide and dexamethasone with or without elotuzumab in patients with relapsed or 
refractory multiple myeloma (Eloquent 2) has shown that elotuzumab was well tolerated in 
combination with lenalidomide/dexamethasone, with minimal incremental toxicity and no new 
safety signals. The safety profile of elotuzumab was consistent across IMiD combination studies 
(thalidomide and lenalidomide). Key elotuzumab adverse events have been infusion related 
events26. These have all been managed by medications and resolved in less than 24 hours. The 
frequency and intensity of infusion related adverse events has been mitigated with premedications, 
including corticosteroids, histamine-1 and -2 antagonists, and acetaminophen. Guidelines for the 
management of infusion reactions are also provided in this protocol.
Since lenalidomide and pomalidomide are in the same class of drugs, and have a similar safety and 
pharmacokinetic profile, elotuzumab is expected to elicit a similar safety profile in combination 
with pomalidomide as it did in the lenalidomide - elotuzumab and thalidomide -elotuzumab 
combinations.
Because nivolumab and elotuzumab have non-overlapping toxicity profiles, the combination of 
both drugs with pomalidomide and dexamethasone is not expected to increase toxicities.
Based on the above assessment, the potential benefit of combining nivolumab and elotuzumab 
with pomalidomide and dexamethasone appears to outweigh the potential risk. The overall 
risk/benefit assessment supports the evaluation of these combinations in this setting.
It is possible that unforeseen or unanticipated adverse events may occur. In order to minimize the 
overall risks to participating subjects, the protocol has inclusion-exclusion criteria appropriate to 
the population, and specific follow-up safety assessments. Adverse events and serious adverse 
events will be reviewed on an ongoing basis by the Medical Monitor and the Sponsor’s 
pharmacovigilance group to look for trends and safety concerns. Additionally, to ensure subjects’ 
safety, an independent Data Monitoring Committee (DMC) will also be established to monitor the 
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safety of subjects treated with the combination regimens regularly and identify any early safety 
signal.
Recent safety concerns of increased risk of mortality and severe adverse events have been reported 
from two studies with pembrolizumab, an anti-PD-1 monoclonal antibody not approved for 
treatment of multiple myeloma, in combination with IMiD (lenalidomide and pomalidomide) and 
dexamethasone (https://www.fda.gov/Drugs/DrugSafety/ucm574305.htm). In light of these safety 
concerns, on 1 September 2017 the FDA requested that CA209602 be placed on partial clinical 
hold. As a consequence, as of 1-September-2017, enrollment in this study was stopped, as well as 
the cross-over of subjects randomized to the Pd control arm into the exploratory NE-Pd arm. 
Subjects on treatment as of 1-September-2017 who were deriving clinical benefit can continue 
treatment and must be monitored as per protocol requirements. As of Revised Protocol 02, the 
exploratory NE-Pd arm is removed from the study design, and enrollment in the study is focused 
on the investigational (N-Pd) and control (Pd) arms. 
At FDA request, an interim PFS futility analysis based on the 12- April- 2018 database lock was 
performed to compare PFS between NPd and Pd arms. Based on the results of this futility analysis, 
on 23-August-2018 Bristol-Myers Squibb (BMS) has decided to permanently discontinue 
enrollment into the study due to insufficient evidence. The number of deaths that have occurred in 
the Arm NEPd (50%) were higher compared to those in the Arm NPd (29%) and Arm Pd (23%). 
Three additional subjects in Arm Pd who crossed over to Arm NE-Pd have died due to disease 
progression, resulting in a total of 19 (27%) deaths in Arm Pd. 
Among all treated subjects, the rates of serious adverse events [SAE] were higher in patients in  
Arm N-Pd (58%) and Arm NE-Pd (63%) compared to patients in Arm Pd (50%).
Deaths were mostly due to disease progression. Non-progression related causes of death are 
variable, with no distinct pattern or unifying mechanism. One death due to study drug toxicity was 
observed on the NPd arm due to pneumonitis complicated by pneumocystis infection.
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).
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.
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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 which will include all elements required by ICH, GCP and applicable regulatory 
requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
1) Provide a copy of the consent form 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
3) Allow time necessary for subject or subject's legally acceptable representative to inquire about 
the details of the study
4) 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
5) Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects, prior to the beginning of the study, 
and after any revisions are completed for new information
6) If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject
7) 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, 
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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 must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
Subjects unable to give their written consent (eg, stroke or subjects with severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to refuse 
participation in, or to be withdrawn from, the clinical study at any time should be considered by 
the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
3
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a phase 3 multicenter, randomized, open label study designed to evaluate the clinical benefit 
and safety of the combination therapy of Nivolumab, pomalidomide, and dexamethasone (N-Pd 
the investigational arm A), when compared to pomalidomide and dexamethasone (Pd; the control 
arm B) in subjects with relapsed and/or refractory multiple myeloma (rrMM). 
Up to Revised Protocol 01, the study design included an exploratory third arm evaluating the 
clinical benefit and the safety of the combination therapy of elotuzumab, nivolumab, 
pomalidomide and dexamethasone (NE-Pd, the exploratory arm-[arm C]) in the same patient 
population. Additionally, subjects randomized to the Pd arm were allowed to cross over to this 
exploratory NE-Pd arm at the time of progression. Cross over was stopped as of 1 September 2017. 
Enrollment in the NE-Pd exploratory arm was stopped as of Revised Protocol 02. All subjects 
already randomized to the NE-Pd arm, or who crossed over from the Pd to the NE-Pd arm will 
continue on study as long as they have clinical benefit and do not meet the study discontinuation 
criteria. 
Initially, the study was designed to enroll approximately 417 subjects for a total of 348 subjects to 
be randomized (assuming 20% screen failure rate) to N-Pd and Pd arms in a 1:1 ratio. 
Randomization was performed with the following stratification factors: a) number of lines of prior 
therapy (2 vs 3+); AND b) ISS stage (1-2 vs 3).
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Subjects were to continue treatment as long as the subject has clinical benefit from the treatment 
and does not meet criteria for treatment discontinuation.
As of 23-August-2018, any additional enrollment of CA209602 study was permanently closed due 
to the insufficient benefit observed based on the interim futility analysis of PFS. A total of 170 
subjects were randomized into the study: 75 to NPd, 71 to Pd and 24 to NE-Pd arms. Subjects 
randomized to the NPd or NEPd arms may continue treatment based on investigator’s judgement 
of continued clinical benefit. Study will be closed after all subjects complete safety follow-up (i.e., 
100 days after the last subject has discontinued study treatment).
The study design schematic is presented in Figure 3.1-1.
Figure 3.1-1:
Study Design Schematic
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit will be 
eligible to receive BMS supplied study drug. Study drug will be provided via an extension of the 
study, a rollover study requiring approval by responsible health authority and ethics committee or 
through another mechanism at the discretion of BMS. BMS reserves the right to terminate access 
to BMS supplied study drug if any of the following occur: a) the marketing application is rejected 
by responsible health authority; b) the study is terminated due to safety concerns; c) the subject 
can obtain medication from a government sponsored or private health program; or d) therapeutic 
alternatives become available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
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3.3.1
Inclusion Criteria
1. Signed Written Informed Consent
a) Subject is, in the investigator’s opinion, willing and able to comply with the protocol 
requirements
b) Subject has given voluntary written informed consent before performance of any 
study-related procedure not part of normal medical care, with the understanding that 
consent may be withdrawn by the subject at any time without prejudice to their future 
medical care
2. Target Population
a) Must have received 2 prior lines of therapy which must have included an immune 
modulatory drug (IMiD) and a proteasome inhibitor (PI) alone or in combination. Subject 
must have received at least 2 consecutive cycles of an IMiD and at least 2 consecutive 
cycles of a PI. The dose of the prior IMiD (eg lenalidomide) to which the subject has 
relapsed or been refractory must be the induction dose and NOT a maintenance dose (Note: 
adjusted induction dose for intolerance reasons or for renal impairment is accepted). 
b) Documented refractory or relapsed and refractory (R/R) multiple myeloma
c) Refractory (lack of response or progressed on or within 60 days of the last dose of
treatment) to their last line of treatment. Lack of response is defined as not having achieved 
at least PR. (Rajkumar et al., Blood 2011)27
d) Subjects must have failed treatment with a proteasome inhibitor and an IMiD (alone or in 
combination) in one of the following ways27
i)
“Refractory” = Refractory (lack of response or progressed on treatment or within 60 
days of the last dose of treatment, regardless of the achievement of initial response) to 
a proteasome inhibitor and an IMiD (alone or in combination). Lack of response is 
defined as not having achieved at least PR. (Rajkumar et al., Blood 2011)27
ii) “Relapsed and refractory”= Relapsed and refractory (achieve at least a partial response)
to previous treatment with proteasome inhibitor or IMiD (alone or in combination) but 
then progressed after 60 days of the last dose of treatment.
e) Measurable disease at screening, based on central lab results within 28 days of 
randomization, defined as one or more of the following:
i)
Serum IgG, IgA, or IgM M-protein 0.5 g/dL (5 g/L)
ii) Urine M-Protein 200 mg (0.2 g) excreted in a 24-hour collection sample
iii) Involved serum free light chain (sFLC) 100 mg/L (10 mg/dL) provided the FLC ratio 
is abnormal
f)
Eastern Cooperative Oncology Group (ECOG) performance status 2 (Appendix 2)
g) Subject Re-enrollment: This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, subject has not been randomized / has 
not been treated). If re-enrolled, the subject must be re-consented
3. Age and Reproductive Status
a) Males and Females at least 18 years or legal age of consent per local regulations
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b) Women of childbearing potential (WOCBP) must have two negative serum or urine 
pregnancy tests (minimum sensitivity 25 mIU/mL or equivalent units of HCG). One 
10-14 days prior to start of the study drug and one within 24 hours prior to the start of study 
drug
i)
WOCBP must agree to follow instructions for method(s) of contraception from the time 
of enrollment for the duration of treatment with study drug plus 5 half-lives of study 
drug plus 30 days (duration of ovulatory cycle) for a total of 23 weeks (except the Pd
arm- where only 4 weeks is required) post treatment completion
ii) Men who are sexually active with WOCBP must agree to follow instructions for 
method(s) of contraception for the duration of treatment with study drug plus 
5 half-lives of study drug plus 90 days (duration of sperm turnover) for a total of 31 
weeks (except the Pd arm -where only 4 weeks is required) post-treatment completion
c) Women must not be breastfeeding
d) Male patients must not donate sperm, for up to 7 months (4 weeks only for Pd arm) post 
treatment completion
e) Azoospermic males and WOCBP who are not heterosexually active are exempt from 
contraceptive requirements. However they must still undergo pregnancy testing as
described in this section
f)
All subjects must not donate blood for 90 days post treatment completion
g) All subjects must be willing and able to comply with Pomalyst® REMS program, where 
applicable
h) All subjects must agree not to share study medication
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 
in the informed consent document.
3.3.2
Exclusion Criteria
1. Target Disease Exceptions
a) Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of 
plasma cell dyscrasia
b) Subjects with monoclonal gammopathy of undetermined significance (MGUS), 
smoldering multiple myeloma (SMM), primary amyloidosis (without active multiple 
myeloma), Waldenstrom’s macroglobulinemia, or POEMS syndrome (plasma cell 
dyscrasia with poly neuropathy, organomegaly, endocrinopathy, monoclonal protein, and 
skin changes)
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c) Subjects with active plasma cell leukemia (defined as either 20% of peripheral blood white 
blood cell count comprised of plasma/CD138+ cells or an absolute plasma cell count of 
2 x 109/L)
2. Medical History and Concurrent Diseases
a) Women who are of childbearing potential not complying to the above described 
contraceptive measures or are breastfeeding, and sexually active fertile men whose partners 
are WOCBP if they are not complying to the above described contraceptive measures
b) Any uncontrolled or severe cardiovascular or pulmonary disease determined by the 
investigator, including:
i)
NYHA functional classification III or IV, congestive heart failure, unstable or poorly 
controlled angina, uncontrolled hypertension, serious arrhythmia, or myocardial 
infarction in the past 12 months
ii) Subjects with interstitial lung disease that is symptomatic or may interfere with the 
detection or management of suspected drug-related pulmonary toxicity
c) Active systemic infection 
d) Subjects with an active, known or suspected autoimmune disease. Subjects with type I 
diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders 
(such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not 
expected to recur in the absence of an external trigger are permitted to enroll
e) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg 
daily prednisone equivalent) or other immunosuppressive medications within 14 days of 
initiation of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses 
> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune 
disease
f)
Unable to tolerate thromboembolic prophylaxis while on the study
g) Serious hypersensitivity reaction (as per investigator assessment) to prior IMiD
(thalidomide or lenalidomide)
h) Grade 2 peripheral neuropathy (per NCI CTCAE v4.0)
i)
Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic 
infection
j)
Known history of positive test for human immunodeficiency virus (HIV) or known 
acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed 
at sites where mandated by local regulation
k) Gastrointestinal disease that may significantly alter the absorption of pomalidomide
l)
Prior or concurrent invasive malignancy, except for the following:
i)
Adequately treated basal cell or squamous cell skin cancer
ii) Adequately treated in-situ cancer
iii) Any cancer (other than those noted above) from which the subject has been disease free 
for > 3 years prior to study entry
3. Prior Therapy or Surgery
a) Prior treatment with pomalidomide or nivolumab (or any PD-1 or PD-L1 inhibitor).
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b) Use of any anti-myeloma drug therapy, within 14 days of the initiation of study drug 
treatment. Bisphosphonate use permitted if initiated prior to first dose of study medication
c) All prior drug-related AEs should have resolved or returned to baseline for the subject to 
be eligible
d) Prior autologous stem cell transplant within 12 weeks of the first dose of study drug
e) Prior allogeneic stem cell transplant or graft versus host disease (GVHD) within 12 months 
of the first dose of study drug, or subjects on topical or systemic immunosuppressive 
therapy for GVHD
f)
Treatment with corticosteroids within 2 weeks of the first dose of study drug, except for 
the equivalent of 10 mg prednisone per day or corticosteroids with minimal to no 
systemic absorption (ie, topical or inhaled steroids) or for short course (4 days) of 40 mg 
dexamethasone or equivalent for emergency use (baseline M proteins must be drawn after 
this short course and prior to randomization). Adrenal replacement steroid doses > 10 mg 
daily prednisone equivalent, are permitted in the absence of active autoimmune disease
g) Major cardiac surgery within 8 weeks prior to the first dose of study drug; all other major 
surgery within 4 weeks prior to the first dose of study drug. (Kyphoplasty is not considered 
major surgery); subjects should have been fully recovered from any surgical related 
toxicities
h) Treatment with plasmapheresis within 4 weeks prior to randomization.
i)
Subjects who have received a live / attenuated vaccine within 30 days of first treatment.
4. Physical and Laboratory Test Findings
Screening Laboratory evaluations within the following parameters:
a) Absolute neutrophil count (ANC) < 1,000 cells/µL (1.0 x 109/L) (Growth factors cannot 
be used within 1 week of first drug administration. No pegylated growth factors within 
3 weeks of first drug administration)
b) Platelet count < 75,000 cells/µL (75 x 109/L) (< 30 x 109/L if 50% of bone marrow 
nucleated cells were plasma cells). Qualifying laboratory value must occur at most recent 
measurement prior to study entry. No transfusions are allowed within 72 hours prior to 
qualifying laboratory value
c) Hemoglobin < 8 g/dl (No transfusions are allowed within 72 hours prior to qualifying
laboratory value) 
d) Total Bilirubin > 1.5 X upper limit of normal (ULN) (except subjects with Gilbert 
Syndrome, who can have total bilirubin up to 3.0 X ULN)
e) AST (SGOT) and ALT (SGPT) > 3.0x ULN
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f)
Renal function: Estimated creatinine clearance by Cockcroft-Gault formula < 30 mL/min

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
g) Corrected serum calcium 11.5 mg/dl within 2 weeks of initiation of study drug (despite 
appropriate measures such a short course of steroids, bisphosphonates, hydration, 
calcitonin)
5. Allergies and Adverse Drug Reaction
a) History of allergy or hypersensitivity to study drug components
b) History of severe hypersensitivity reaction to any monoclonal antibody
6. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific 
circumstances a person who has been imprisoned may be included or permitted to continue 
as a subject. Strict conditions apply and Bristol-Myers Squibb approval is required
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 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 years in the absence of other biological or physiological causes. In addition, 
females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 
40 mIU/mL to confirm menopause.
*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 
judgement in checking serum FSH levels. 

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
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Other parenteral products may require washout periods as long as 6 months. If the serum FSH level 
is > 40 mIU/ml at any time during the washout period, the woman can be considered 
postmenopausal.
3.4
Concomitant Treatments
3.4.1
Prohibited and/or Restricted Treatments
Any systemic, anti-myeloma therapy other than the study drugs is prohibited while on study 
therapy. Concomitant steroids, other than weekly dexamethasone or steroids allowed (as defined 
in eligibility criteria) are prohibited unless used to treat an adverse event. Guidelines for selection 
and use of other concomitant medications should be derived from the pomalidomide and 
dexamethasone prescribing information. 
Avoid co-administration of pomalidomide with strong inhibitors of CYP1A2 unless medically 
necessary. Co-administration of pomalidomide with drugs that are strong inhibitors of CYP1A2 
(eg, ciprofloxacin, enoxacin and fluvoxamine) and CYP3A4/5 (eg, ketoconazole) or P-gp could 
increase pomalidomide exposure and should be avoided, unless medically necessary,28, 29. The 
FDA DDI database link is the following: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio
nsLabeling/ucm093664.htm
Other than study medications, administration of any therapeutic or diagnostic investigational agent 
(for any indication) is prohibited while on study therapy without prior Sponsor approval.
Immunosuppressive agents are prohibited (unless utilized to treat drug-related adverse events).
Any live / attenuated vaccine (eg varicella, zoster, yellow fever, rotavirus, oral polio and measles, 
mumps, rubella (MMR)) is prohibited during treatment and until 100 days post last dose.
3.4.2
Required Treatment
Subjects must receive thrombo-embolic prophylaxis, per institutional guidelines or PI discretion. 
Examples of commonly used thrombo-embolic prophylaxis medications include aspirin, low 
molecular weight heparin, and vitamin K antagonists.
Subjects must receive pre-medications (Sections 4.5.1.3.6 and 4.5.1.3.7) prior to each dose of 
elotuzumab.
3.4.3
Permitted at Investigator’s Discretion
IV corticosteroids, diphenhydramine, or hydroxyzine, acetaminophen/ paracetamol, H2 inhibitors 
(ie, cimetidine), leukotriene inhibitors (montelukast sodium) for the management of infusion 
reactions. Additional supportive measures should be provided as indicated including:

oxygen inhalation

epinephrine

bronchodilators

oral antiviral and antimicrobial prophylaxis
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
anti-emetics

bisphosphonates
Subjects are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses > 10 mg 
daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for 
prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-
type hypersensitivity reaction caused by a contact allergen) is permitted
Per the ASCO 2007 Clinical Practice Guidelines30, bisphosphonate therapy should be administered 
for a period of 2 years. At 2 years, the investigator should seriously consider discontinuing 
bisphosphonates in subjects with at least stable disease, although further use is at the discretion of 
the investigator.
Routine clinical practice for monitoring and prevention of osteonecrosis of the jaw 
(ie, comprehensive dental exam, treating active oral infections, eliminating sites of high risks for 
oral infection, excellent oral hygiene and avoiding invasive dental procedures while on treatment) 
must be followed.

Erythropoietin (EPO) or erythropoiesis stimulating agents (prior and ongoing use according to 
the package insert and institutional guidelines)

Red blood cell or platelet transfusion

Prophylactic administration of G-CSF for neutropenic subjects or therapeutic use in subjects 
with serious neutropenic complications (such as tissue infection, sepsis syndrome or fungal 
infection) may be considered at the investigator's discretion, consistent with American Society 
of Clinical Oncology guidelines (American Society of Clinical Oncology 2006).
3.4.4
Surgery and Radiation
Use of radiotherapy or surgical intervention must be recorded on the appropriate Case Report 
Form.
Localized radiation therapy to a site of pre-existing disease may be permitted while on study. 
Following approval by the medical monitor, the subject may continue with protocol therapy 
without interruption during the course of palliative radiation therapy if the investigator believes 
that the risk of excessive bone marrow suppression or other toxicity is acceptable, and it is in the 
best interest of the subject to do so.
If the subject develops a definite increase in the size of existing bone lesions or soft tissue 
plasmacytomas that meets the criteria for disease progression (see Appendix 3) treatment must be 
discontinued for progressive disease regardless of whether radiation therapy is initiated 
(Section 3.5).
Kyphoplasty, vertebroplasty, or emergency orthopedic surgery is permitted.
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3.5
Discontinuation of Subjects following any Treatment with Study Drug 
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:

Subject’s request to stop study treatment

Progressive Disease according to IMWG criteria

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 involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness

Subjects who receive any non-protocol specified systemic anti-myeloma therapy before 
documented progression will be discontinued from all study treatment (including 
pomalidomide and dexamethasone); however, tumor assessments will continue at 4 week 
intervals until documented progression.

Subjects experiencing a Grade 4 infusion reaction related to elotuzumab must discontinue 
elotuzumab only. Subjects may continue nivolumab, pomalidomide and dexamethasone 
treatment. Refer to Section 4.5.4.

Subjects experiencing angioedema, Grade 4 rash, exfoliative or bullous rash, Stevens Johnson 
syndrome, or toxic epidermal necrolysis must discontinue pomalidomide and nivolumab. 
Subjects may continue on elotuzumab and dexamethasone.

Subjects experiencing a 56 day delay in all study drugs (nivolumab, pomalidomide, 
dexamethasone, and elotuzumab) due to an adverse event(s) related to study treatment must be 
discontinued from study drug. Subjects experiencing delays unrelated to study therapy, for 
example due to radiation therapy, may delay study treatment up to 84 days. Further delays may 
be allowed after discussion with the BMS Medical Monitor.

Subjects experiencing a Grade 3 or 4 infusion reaction related to nivolumab must discontinue 
nivolumab only. Subjects may continue elotuzumab, pomalidomide and dexamethasone 
treatment. Refer to Section 4.5.4 for additional reasons to discontinue nivolumab dosing 
permanently.
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event and treatment with the IMPs would immediately be stopped. In 
most cases, the study drug will be permanently discontinued in an appropriate manner. Please call 
the BMS Medical Monitor within 24 hours of awareness of the pregnancy. If the investigator 
determines a possible favorable benefit/risk ratio that warrants continuation of study drug
(ie, allowing restart of study drug if patient chose to terminate the pregnancy), a discussion 
between the investigator and the BMS Medical Monitor/designee must occur so permission can 
be granted.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Section 5. The only exception to this requirement is when a subject 
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
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ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF) page.
3.6
Post Study Drug Study Follow up
PFS and OS are key endpoints of the study. Post treatment study follow-up is essential to 
preserving subject safety and the integrity of the study. Subjects who discontinue study treatment 
prior to progression must continue to be followed for collection of protocol-defined PFS. Subjects 
who discontinue study therapy must also continue to be followed for overall survival data until 
death or the conclusion of the study.
BMS may request that survival data be collected on all treated/randomized subjects outside of the 
protocol defined window, Table 5.1-3. At the time of this request, each subject will be contacted 
to determine their survival status unless the subject has withdrawn consent for all contacts or is 
lost to follow-up. 
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 
should be documented in the subject’s medical records. If it is determined that the subject has died, 
the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study has 
been included in the subject’s informed consent, then the investigator may use a Sponsor-retained 
third-party representative to assist site staff with obtaining subject’s contact information or other 
public vital status data necessary to complete the follow-up portion of the study. The site staff and 
representative will consult publicly available sources, such as public health registries and 
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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:
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Table 4.-1:
Study Drugs for CA209602
Product Description / 
Class and Dosage 
Form
Potency
IP/Non-IP
Blinded or Open 
Label
Packaging / 
Appearance
Storage Conditions
(per label)
Nivolumab
(BMS-936558-01) 
Solution for Injectiona
100 mg (10 mg/mL)
IP
Open label
10 mL Vial/ Clear to 
opalescent colorless to 
pale yellow liquid. May 
contain particles
2 to 8C. Protect from 
light and freezing
Elotuzumab Powder for 
Solution for Infusion
400 mg/vial
IP
Open label
20 mL Vial/ Sterile, 
white to off-white, 
preservative-free, 
lyophilized cake
Store at 2C - 8C.
Dexamethasone 
Tabletsb
2 mg and 4 mg & 
various strengths
Non-IP
Open label
Various packing 
configurations
Refer to label on 
container or package 
insert / summary of 
product characteristics
Dexamethasone 
Solutionb
4 mg/mL, 8 mg/mL & 
various strengths
Non-IP
Open label
Various packing 
configurations
Refer to label on 
container or package 
insert / summary of 
product characteristics
Pomalidomide 
Capsulesb
1 mg, 2 mg, 3 mg and 
4 mg
Non-IP
Open label
Various packing 
configurations
Refer to label on 
container or package 
insert 
a May be labeled as either “BMS-936558-01” or “Nivolumab.”
b Pomalidomide capsules, dexamethasone tablets and solution for IV infusion will be obtained by the investigating site’s standard prescribing procedures.  They 
may be supplied by BMS according to country availability and specific regulatory requirements.
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4.1
Investigational Product
An investigational product, also known as investigational medicinal product in some regions, is 
defined a pharmaceutical form of an active substance or placebo being tested or used as a reference 
in a clinical study, including products already with a marketing authorization but used or 
assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form.
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the investigator to ensure that investigational product is only dispensed to 
study subjects. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations.
In this protocol, investigational products are: nivolumab solution for IV infusion and elotuzumab 
powder for solution for infusion.
4.1.1
Elotuzumab
Before administration the drug product should be stored and prepared as per the instructions in 
pharmacy manual or elotuzumab investigator brochure. The dose of elotuzumab to be administered 
to a subject will be calculated by multiplying the subject’s weight (kg) by 10 mg/kg (Cycles 1 
through 4) and by 20 mg/kg (Cycles 5 and beyond). The subject’s predose weight on Day 1 of 
each cycle will be used to calculate the dose for each cycle. Each dose should be infused as per
instructions in the elotuzumab investigator brochure. The infusion start and stop time will be 
recorded in the CRF. If the infusion is stopped mid-session for any reason, the stop/start time must 
be recorded together with an explanation.
4.1.2
Nivolumab
Nivolumab will be administered at a dose of 240 mg as an intravenous infusion over 30 minutes 
every 2 weeks (Days 1 and 15 of each 28 day cycle) during Cycles 1 through 4. Starting Cycle 5 
and beyond, nivolumab will be administered at a dose of 480 mg as an intravenous infusion over 
30 minutes every 4 weeks (Day 1 of each 28 day cycle). Please refer to the nivolumab investigator 
brochure and/or pharmacy manual for guidelines on drug preparation and administration. Flush 
the intravenous line at the end of infusion 
4.2
Non-Investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as 
non-investigational products.
In this protocol, non-investigational product(s) are: Pomalidomide (Pomalyst) capsules 1 mg, 
2 mg, 3 mg, and 4 mg, dexamethasone tablets and concentrate for solution for IV infusion, or 
products used for Elotuzumab premedication (Sections
4.5.1.3.6 and 4.5.1.3.7) or 
thromboprophylaxis (Section 3.4.2). 
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4.2.1
Pomalidomide
Pomalidomide is an analogue of thalidomide. Thalidomide is a known human teratogen that causes 
severe life-threatening human birth defects. If pomalidomide is taken during pregnancy, it may 
cause birth defects or death to an unborn baby. Females must not get pregnant: (1) for at least 
4 weeks before starting pomalidomide, (2) while taking pomalidomide, (3) during any 
interruptions in pomalidomide treatment and (4) for at least 4 weeks after their last dose of 
pomalidomide. Furthermore, subjects taking pomalidomide should refrain from donating blood 
(until at least 90 days) or sperm (until at least 4 weeks) after last dose of pomalidomide. 
Because of this potential toxicity and to avoid fetal exposure to pomalidomide, pomalidomide is 
only available under a special restricted distribution program. Each risk management program is 
country or region specific. Under these programs, only prescribers and pharmacists registered with 
the program can prescribe and dispense the product. In addition, pomalidomide must only be 
dispensed to subjects who are registered and meet all the conditions of the local pomalidomide 
risk management program or meet all the conditions of the Pomalidomide Pregnancy Risk 
Prevention Plan (Appendix 6). Subjects who have the potential of pregnancy must be instructed 
about contraception and undergo the scheduled pregnancy tests. 
Subjects should not break, chew or open the capsules. Pomalidomide should be taken in 
accordance with local label.
WOCBP must have negative pregnancy testing and use contraception methods before initiating 
pomalidomide.
The trade name of pomalidomide may vary in other countries. In such cases, refer to country trade 
name.
4.2.2
Dexamethasone
Dexamethasone tablets and solution for IV infusion is considered Non-IP/Non-IMP for this study. 
Marketed product will be utilized for this study and should be stored in accordance with the 
package insert or summary of product characteristics (SmPC).
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be dispensed 
and contact BMS immediately.
Procedures for proper handling and disposal of anticancer drugs should be considered.
Study drug not supplied by BMS need to be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required to ensure drug is accurately administered. This includes 
documentation of drug storage, administration and, as applicable, storage temperatures, 
reconstitution, and use of required processes (eg, required diluents, administration sets).
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Infusion-related supplies (eg, IV bags, in-line filters, 0.9% NaCl solution, pump) will not be 
supplied by the sponsor and should be purchased locally if permitted by local regulations.
Please refer to the current version of the IB and/or pharmacy manual for complete storage, 
handling, dispensing, and infusion information for nivolumab and elotuzumab.
Nivolumab vials must be stored at a temperature of 2°to 8°C and should be protected from light 
and freezing. Elotuzumab vials must be stored at a temperature of 2° to 8°C. 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 prepared drug storage and use time of nivolumab and elotuzumab under room 
temperature/light and refrigeration, please refer to the nivolumab and elotuzumab IB section for 
“Recommended Storage and Use Conditions” and/or pharmacy manual. 
4.4
Method of Assigning Subject Identification
4.4.1
Subject Identification
Subjects will be identified and informed consent obtained. Subjects must be enrolled into the study 
by the interactive web response system (IWRS) to obtain the subject number. The following 
information is required for subject enrollment:

Date of Birth

Site number

Date that informed consent was obtained
Once it has been determined that a subject is eligible for randomization, the site will enter into the 
IWRS to obtain the treatment assignment. Subjects will be randomized to pomalidomide + 
dexamethasone + nivolumab (N-Pd investigational arm) or pomalidomide + dexamethasone 
(Pd Control arm) in a 1:1 ratio. The randomization will be carried out via permuted blocks within 
each stratum and stratified by the following factors:
a) number of lines of prior therapy (2 vs 3+)
b) ISS stage (1-2 vs. 3)
Additional details will be included in the IWRS manual including instructions for subjects at the 
time of cross-over to NE-Pd. 
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4.5
Selection and Timing of Dose for Each Subject
4.5.1
Treatment with Study Drugs
4.5.1.1
Arm A (N-Pd; Investigational arm) 
Table 4.5.1.1-1:
Arm A (N-Pd; Investigational arm)
Cycle (28 days)
Cycles 1 - 4 
Cycles 5 and Beyond
Day
1
8
15
22
28
1
8
15
22
28
Pomalidomide
Day 1-21
Day 1-21
Dexamethasone
X
X
X
X
X
X
X
X
Nivolumaba
X
X
X
a Nivolumab dose is 240 mg during Cycles 1 - 4 then 480 mg during Cycles 5 and beyond
4.5.1.1.1
Pomalidomide
Administered orally at the dose of 4 mg daily on Days 1 - 21 of each 28 day cycle. Pomalidomide 
should be taken in accordance with local label. 
Subjects should be instructed that if a dose of pomalidomide has been missed and it has been less 
than 12 hours since the subject’s regular dosing time, to take pomalidomide as soon as the subject 
remembers. If it has been more than 12 hours, the dose must be skipped. Subjects should not take 
2 doses at the same time.
4.5.1.1.2
Dexamethasone
Table 4.5.1.1-2:
Dexamethasone Dosing, All Cycles
Age
Day
1
8
15
22
75 years old
Dexamethasone
(mg)
40 mg PO 
40 mg PO
40 mg PO
40 mg PO
> 75 years old 
Dexamethasone
(mg)
20 mg PO
20 mg PO
20 mg PO
20 mg PO
At the investigator’s discretion, the oral dexamethasone may be given as a split dose over 
2 consecutive days each week.
4.5.1.1.3
Nivolumab
Nivolumab will be administered at a dose of 240 mg as an intravenous infusion over 30 minutes 
every 2 weeks (Days 1 and 15 of each 28 day cycle) during Cycles 1 through 4. Starting Cycle 5 
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and beyond, nivolumab will be administered at a dose of 480 mg as an intravenous infusion over 
30 minutes every 4 weeks (Day 1 of each 28 day cycle).
Subjects may be dosed no less than 12 days from the previous dose. There are no premedications 
recommended for nivolumab on the first cycle. 
Nivolumab can be delayed within a 3 day window of Day 1 and Day 15, during cycles 1 through 4, 
as long as the 12 day interval between 2 nivolumab doses is respected. During cycles 5 and beyond, 
nivolumab can be delayed within a week. For subjects being dosed in the nivolumab 480 mg Q4W 
part of the study, for the first dose, it may be dosed no less than 12 days from the previous dose 
and for subsequent doses it should be dosed no less than 21 days from the previous dose. 
Nivolumab can be delayed within a 7 day window of Day 1 as long as the 12 day and 21 day 
intervals for the first 480 mg dose and subsequent 480 mg doses, respectively, between 2 
nivolumab doses is respected. Doses that fall outside the allowed window should be skipped.
Subjects should be carefully monitored for infusion reactions during nivolumab administration. If 
an acute infusion reaction is noted, subjects should be managed according to Section 4.5.2.1.4.
There will be no dose escalations or reductions of nivolumab allowed. Doses of nivolumab may 
be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.
4.5.1.2
Arm B (Pd; Control arm) 
Table 4.5.1.2-1:
Arm B (Pd; Control arm)
Cycle (28 days)
All Cycles 
Day
1
8
15
22
28
Pomalidomide
Day 1-21
Dexamethasone
X
X
X
X
4.5.1.2.1
Pomalidomide
Administered orally at the dose of 4 mg daily on Days 1 - 21 of each 28 day cycle. Pomalidomide 
should be taken in accordance with local label. 
Subjects should be instructed that if a dose of pomalidomide has been missed and it has been less 
than 12 hours since the subject’s regular dosing time, to take pomalidomide as soon as the subject 
remembers. If it has been more than 12 hours, the dose must be skipped. Subjects should not take 
2 doses at the same time
4.5.1.2.2
Dexamethasone
Table 4.5.1.2-2:
Dexamethasone Dosing, All Cycles
Age
Day
1
8
15
22
75 years old
Dexamethasone
40 mg PO 
40 mg PO
40 mg PO
40 mg PO
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Table 4.5.1.2-2:
Dexamethasone Dosing, All Cycles
Age
Day
1
8
15
22
(mg)
> 75 years old 
Dexamethasone
(mg)
20 mg PO
20 mg PO
20 mg PO
20 mg PO
At the investigator’s discretion, the oral dexamethasone may be given as a split dose over 2 
consecutive days each week.
4.5.1.3
Arm C (NE-Pd; Exploratory arm) 
Table 4.5.1.3-1:
Treatment Schedule
Cycle (28 days)
Cycles 1 & 2
Cycles 3 & 4
Cycles 5 and Beyond
Day
1
8
15
22
28
1
8
15
22
28
1
8
15
22
28
Pomalidomide
Day 1-21
Day 1-21
Day 1-21
Dexamethasone
X
X
X
X
X
X
X
X
X
X
X
X
Nivolumaba
X
X
X
X
X
Elotuzumabb
X
X
X
X
X
X
X 
a Nivolumab dose is 240 mg during Cycles 1 - 4 then 480 mg during Cycles 5 and beyond
b Elotuzumab dose is 10 mg/kg during Cycles 1 - 4 then 20 mg/kg during Cycles 5 and beyond
4.5.1.3.1
Pomalidomide
Administered orally at the dose of 4 mg daily on Days 1 - 21 of each 28 day cycle. Pomalidomide 
should be taken in accordance with local label. 
Subjects should be instructed that if a dose of pomalidomide has been missed and it has been less 
than 12 hours since the subject’s regular dosing time, to take pomalidomide as soon as the subject 
remembers. If it has been more than 12 hours, the dose must be skipped. Subjects should not take 
2 doses at the same time.
4.5.1.3.2
Dexamethasone
Table 4.5.1.3-2:
Dexamethasone Dosing, All Subjects Receiving Elotuzumab
Age
Day
1
8
15
22
Cycles 1 and 2
75 years old
Dexamethasone
(mg)
28 mg PO +
8 mg IV
28 mg PO +
8 mg IV
28 mg PO +
8 mg IV
28 mg PO +
8 mg IV
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Table 4.5.1.3-2:
Dexamethasone Dosing, All Subjects Receiving Elotuzumab
Age
Day
1
8
15
22
> 75 years old
Dexamethasone
(mg)
8 mg PO +
8 mg IV
8 mg PO +
8 mg IV
8 mg PO +
8 mg IV
8 mg PO +
8 mg IV
Cycle 3 and 4
75 years old
Dexamethasone
(mg)
28 mg PO +
8 mg IV
40 mg PO
28 mg PO +
8 mg IV
40 mg PO
> 75 years old
Dexamethasone
(mg)
8 mg PO +
8 mg IV
20 mg PO
8 mg PO +
8 mg IV
20 mg PO
Cycle 5 and Beyond
75 years old
Dexamethasone
(mg)
28 mg PO +
8 mg IV
40 mg PO
40 mg PO
40 mg PO
> 75 years old
Dexamethasone
(mg)
8 mg PO +
8 mg IV
20 mg PO
20 mg PO
20 mg PO
At the investigator’s discretion, the oral dexamethasone may be given as a split dose over 
2 consecutive days each week.
On days of elotuzumab infusion dexamethasone will be administered as a split dose of:

28 mg PO, for subjects 75 years old or 8 mg PO for subjects > 75 years old (between 
3 - 24 hours before the start of elotuzumab infusion) (At the discretion of the investigator, the 
oral dexamethasone component may be given as a split dose 12 - 24 and 3 hours prior to 
elotuzumab), AND

8 mg IV (on the day of elotuzumab infusion at least 45 minutes before the start of infusion)
If elotuzumab dosing is skipped or discontinued, dexamethasone will be administered orally as in 
days without elotuzumab.
4.5.1.3.3
Nivolumab
Nivolumab will be administered at a dose of 240 mg as an intravenous infusion over 30 minutes 
every 2 weeks (Days 1 and 15 of each 28 day cycle) during Cycles 1 through 4. Starting Cycle 5 
and beyond, nivolumab will be administered at a dose of 480 mg as an intravenous infusion over 
30 minutes every 4 weeks (Day 1 of each 28 day cycle)
Nivolumab should be administered before elotuzumab.
Subjects may be dosed no less than 12 days from the previous dose. There are no premedications 
recommended for nivolumab on the first cycle. 
Nivolumab can be delayed within a 3 day window of Day 1 and Day 15, during cycles 1 through 
4, as long as the 12 day interval between 2 nivolumab doses is respected. During cycles 5 and 
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beyond, nivolumab can be delayed within a week. Doses that fall outside the allowed window 
should be skipped.
Subjects should be carefully monitored for infusion reactions during nivolumab administration. If 
an acute infusion reaction is noted, subjects should be managed according to Section 4.5.2.1.4.
There will be no dose escalations or reductions of nivolumab allowed. Doses of nivolumab may 
be interrupted, delayed, or discontinued depending on how well the subject tolerates the treatment.
4.5.1.3.4
Elotuzumab
Elotuzumab will be administered at a dose of 10 mg/kg as an intravenous infusion weekly (Days 1, 
8, 15 and 22 of each 28 day cycle) during Cycles 1 and 2 then every 2 weeks (Days 1 and 15 of 
each 28 day cycle) during Cycles 3 and 4. Starting Cycle 5 and beyond, Elotuzumab will be 
administered at a dose of 20 mg/kg as an intravenous infusion every 4 weeks (Day 1 of each 28 day 
cycle).
Nivolumab should be administered first over 30 min followed by elotuzumab. The elotuzumab 
premedications can be administered before nivolumab infusion. There is no specific time interval 
needed between nivolumab and elotuzumab infusions. 
In Cycles 1 to 2, elotuzumab doses that fall outside of the pre-specified window of -1to3 days 
must be skipped.
Beginning with Cycle 3 and beyond, elotuzumab dosing may be delayed for up to 1 week. If unable 
to administer within 1 week, then the dose should be skipped and resumption of the elotuzumab 
continues per the protocol defined schedule.
Table 4.5.1.3-3:
Elotuzumab Dosing, All Subjects Receiving Elotuzumab
Cycles 1 and 2
DAY
1
8
15
22
Elotuzumab (IV)
10 mg/kg
10 mg/kg
10 mg/kg
10 mg/kg
Cycle 3 and 4
Elotuzumab (IV)
10 mg/kg
10 mg/kg
Cycle 5 and Beyond
Elotuzumab (IV)
20 mg/kg
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4.5.1.3.5
Elotuzumab infusion rate
During the first cycle, the elotuzumab infusion rate will be increased gradually to a maximum of 
5 mL/min as presented in Table 4.5.1.3-4.
Table 4.5.1.3-4:
Elotuzumab Infusion Rate
Infusion Rate
Duration of infusion
Volume delivered
Volume remaining
Cycle 1 Dose 1
Approximate Total Duration: 2hrs 50min
262 mL
0.5 mL/min
30 min
15 mL
247 mLa
1 mL/min
30 min
30 mL
217 mL
2 mL/min
110 min
217 mL
0 mL
Cycle 1 Dose 2
Approximate Total Duration: 1hrs 13min
262 mL
3 mL/min
30 min
90 mL
172 mL
4 mL/min
43 min
172 mL
0 mL
Cycle 1 Dose 3 and 4
Approximate Total Duration: 53min
262 mL
5 mL/min
53 min
262 mL
0 mL
Cycle 2 +
Approximate Total Duration: 53min
262 mL
5 mL/min
53 min
262 mL
0 mL
a Volume for 80 kg subject. Total volume varies according to the subject weight.
Please note that infusion rate increase to the next higher level only if no infusion reactions encountered.
4.5.1.3.6
Elotuzumab Premedication Regimen in Subjects Without a Prior Infusion 
Reaction
Consult the Medical Monitor for further guidance regarding alternative premedications for subjects 
allergic or intolerant to any premedication or to determine if locally used equivalent medications 
are acceptable.
On weeks of elotuzumab infusion, the dexamethasone dose will be split into a PO and IV 
administration which will also serve as premedication for elotuzumab.
Intravenous and PO dexamethasone doses are calculated to provide a total dose that is 
bioequivalent to an oral dose of 40 mg (subjects who are 75 years old) or 20 mg (in subjects who 
are > 75 years old). (Dexamethasone 8 mg IV is approximately bioequivalent to 11 mg PO).
In addition, the following must also be administered 45 to 90 minutes before initiating the 
elotuzumab:

H1 blocker: diphenhydramine (25 - 50 mg po or IV) or equivalent

H2 blocker: ranitidine (50 mg IV) or equivalent (eg, 150 mg po)

Acetaminophen (650 - 1000 mg po).
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4.5.1.3.7
Elotuzumab Premedication Regimen in Subjects With a Prior Infusion 
Reaction
To be re-treated with elotuzumab, subjects with a prior infusion reaction must receive H1, 
H2 blockers and acetaminophen at maximum doses specified (ie, 50 mg diphenhydramine, 50 mg 
ranitidine (or equivalent), and 650-1000 mg acetaminophen) 45 to 90 minutes before initiating the 
elotuzumab (premedications can be administered prior to nivolumab infusion in NE-Pd arm).
To prevent imbalance in dexamethasone exposure between the arms of the study, doses of 
intravenous dexamethasone above 10 mg require a decrease in the PO dexamethasone. 
Recommended dexamethasone dosing is summarized in Table 4.5.1.3-5.
Decisions to use more aggressive premedication schemes in subjects with prior Grade 1 infusion 
reactions or only one prior Grade 2 infusion reaction must be approved by the Medical Monitor.
Table 4.5.1.3-5:
Corticosteroid Premedication
For Subjects 75 years old
For Subjects >75 years old
Prior Infusion 
Reaction
Corticosteroid Premedicationa Before 
Elotuzumab
None or
Only Grade 1 
infusion reactionb
28 mg po dexamethasone (3 - 24 hrs 
before elotuzumab)
AND
8 mg IV dexamethasone at least 45 min 
before elotuzumab 
8 mg po dexamethasone (3 - 24 hrs before 
elotuzumab) 
AND
8 mg IV dexamethasone at least 45 min before 
elotuzumab 
Prior Grade 2 
infusion reactionc
28 mg po dexamethasone (3 - 24 hrs 
before elotuzumab) 
AND
10 mg IV dexamethasone at least 45 min 
before elotuzumab 
8 mg po dexamethasone (3 - 24 hrs before 
elotuzumab) 
AND
10 mg IV dexamethasone at least 45 min 
before elotuzumab 
Prior Grade 3 or 
recurrent Grade 2 
infusion reaction
8 mg oral dexamethasone (12 - 24 hrs 
before elotuzumab) 
AND
8 mg oral dexamethasone (at least 3 hrs 
before elotuzumab, on the same day as 
the infusion) 
AND
18 mg IV dexamethasone at least 45 min 
before elotuzumab
2 mg oral dexamethasone (12 - 24 hrs before 
elotuzumab) 
AND
2 mg oral dexamethasone (at least 3 hrs before 
elotuzumab, on the same day as the infusion) 
AND
12 mg IV dexamethasone at least 45 min 
before elotuzumab
For prior infusion reactions, use maximum doses H1, H2 blockers and acetaminophen 
a At the discretion of the investigator, the oral dexamethasone component may be given as a split dose 12-24 and 
3 hours before elotuzumab.
b Subjects with prior Grade 1 infusion reaction may be premedicated as per Grade 2 infusion reactions.
c Subjects with prior Grade 2 infusion reaction may be premedicated as per Grade 3 infusion reactions.
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If a subject with a prior Grade 2 to 3 infusion reaction also requires dose reduction of 
dexamethasone, the dexamethasone dose on the days of elotuzumab infusion should be no less 
than 8 mg IV (on the day of elotuzumab infusion at least 45 minutes before elotuzumab).
Subjects with Grade 4 infusion reaction, see Section 4.5.2.1.3.
4.5.2
Management of Infusion Reactions
4.5.2.1
Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions
4.5.2.1.1
Grade 1 Infusion Reaction
For Grade 1 elotuzumab infusion-related reactions, by definition, do not require intervention. 
However, increased monitoring is recommended.
4.5.2.1.2
Grade 2 or 3 Infusion Reaction
Infusion reactions during the elotuzumab infusion: For a Grade 2 or 3 elotuzumab 
infusion-related reaction, the infusion must be interrupted. The subject should be treated as 
clinically indicated with one or more of the following medications or interventions: antiemetics, 
antihistamines, analgesics, corticosteroids, leukotriene inhibitors, oxygen inhalation, epinephrine, 
bronchodilators, or other supportive measures as indicated.
Once the elotuzumab infusion-related reaction has resolved to Grade 1, the infusion can be 
restarted at 0.5 mL/minute. If symptoms do not recur after 30 minutes, the infusion rate may be 
increased in a stepwise fashion (0.5 mL/minute every 30 minutes or per investigator’s discretion) 
to the rate at which the infusion reaction occurred. If no recurrence of the infusion reaction, the 
escalation regimen according to the table above can be resumed.
Subjects who experience an infusion reaction require vital signs to be monitored every 30 minutes 
for 1 or 2 hours after the end of the elotuzumab infusion (or as clinically indicated per 
investigator’s discretion). If the elotuzumab infusion reaction recurs, the infusion must be stopped 
and not restarted on that day. Appropriate therapy should be administered to address the subject’s 
signs and symptoms. The infusion can be reattempted at the next protocol defined infusion time 
point at the investigator’s discretion with additional premedication as described in Table 4.5.1.3-
5.
Infusion reactions after the completion of elotuzumab infusion: Should a Grade 2 or 3 infusion 
reaction occur following completion of an elotuzumab infusion, the subject should be treated as 
above.
Elotuzumab infusions on subsequent weeks after a prior Grade 2 or 3 infusion reaction: 
Subjects with a prior Grade 2 or 3 infusion reaction during Cycle 1 should have the subsequent 
infusion started at 0.5 mL/min. The infusion rate may be escalated in a stepwise fashion 
(0.5 mL/minute every 30 minutes) to the rate at which the infusion reaction occurred. If no 
Grade 2 infusion reaction occurs, the escalation regimen may be resumed and the next infusion 
may be initiated as planned per the regimen.
Contact the Medical Monitor with any questions regarding elotuzumab infusion rate escalation.
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4.5.2.1.3
Grade 4 Infusion Reaction
Acute symptoms should be managed as described in Section 4.5.2.1.2. Elotuzumab must be 
permanently discontinued. Subjects may continue with nivolumab, pomalidomide and 
dexamethasone per protocol.
4.5.2.1.4
Treatment of Nivolumab-Related Infusion Reactions
Since nivolumab contains only human immunoglobulin protein sequences, it is unlikely to be 
immunogenic and induce infusion or hypersensitivity reactions. However, if such a reaction were 
to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, arthalgias, 
hypotension, hypertension, bronchospasm, or other allergic-like reactions. All Grade 3 or 
4 infusion reactions should be reported within 24 hours to the study medical monitor and reported 
as an SAE if it meets the criteria. Infusion reactions should be graded according to NCI CTCAE 
(Version 4.0) guidelines.
Treatment recommendations are provided below and may be modified based on local treatment 
standards and guidelines, as appropriate:
For Grade 1 symptoms: (mild reaction; infusion interruption not indicated; intervention not 
indicated):

Remain at bedside and monitor subject until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg at least 30 minutes before 
additional nivolumab administrations.
For Grade 2 symptoms: (moderate reaction required therapy or infusion interruption but responds 
promptly to symptomatic treatment (eg, antihistamines, non-steroidal anti-inflammatory drugs, 
narcotics, corticosteroids, bronchodilators, IV fluids); prophylactic medications indicated for 
24 hours):

Stop the nivolumab infusion, begin an IV infusion of normal saline, and treat the subject with 
diphenhydramine 50 mg IV (or equivalent) and/or acetaminophen/paracetamol 325 to 
1000 mg; remain at bedside and monitor subject until resolution of symptoms. Corticosteroid 
and/or bronchodilator therapy may also be administered as appropriate. If the infusion is 
interrupted, then restart the infusion at 50% of the original infusion rate when symptoms 
resolve; if no further complications ensue after 30 minutes, the rate may be increased to 100% 
of the original infusion rate. Monitor subject closely. If symptoms recur, then no further 
nivolumab will be administered at that visit.

For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg 
should be administered at least 30 minutes before nivolumab infusions. If necessary, 
corticosteroids (up to 25 mg of SoluCortef or equivalent) may be used.
For Grade 3 or 4 symptoms: (severe reaction, Grade 3: prolonged [ie, not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following 
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initial improvement; hospitalization indicated for other clinical sequelae (eg, renal impairment, 
pulmonary infiltrates). Grade 4: Life-threatening; pressor or ventilatory support indicated):

Immediately discontinue infusion of nivolumab. Begin an IV infusion of normal saline and 
treat the subject as follows: Recommend bronchodilators, epinephrine 0.2 to 1 mg of a 1:1000 
solution for subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution injected 
slowly for IV administration, and/or diphenhydramine 50 mg IV with methylprednisolone 
100 mg IV (or equivalent), as needed. Subject should be monitored until the Investigator is 
comfortable that the symptoms will not recur, nivolumab will be permanently discontinued. 
Investigators should follow their institutional guidelines for the treatment of anaphylaxis. 
Remain at bedside and monitor subject until recovery of the symptoms.
In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine or corticosteroids).
4.5.3
Management Algorithms for Immune Related Adverse Events
Immuno-oncology (I-O) agents are associated with AEs that can differ in severity and duration 
than AEs caused by other therapeutic classes. Nivolumab is considered an immuno-oncology agent 
in this protocol. Early recognition and management of AEs 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 AEs:

Gastrointestinal

Renal

Pulmonary

Hepatic

Endocrinopathy

Skin

Neurological
The above algorithms are found in Appendix 5 and in the nivolumab Investigator Brochure.
4.5.4
Dose Delay, Interruption, or Discontinuation, All Subjects
If the dose of one drug in the regimen (ie, pomalidomide, dexamethasone, nivolumab or 
elotuzumab) is interrupted, or discontinued, the treatment with the other drugs may continue as 
scheduled. However, if dexamethasone is interrupted or discontinued discuss ongoing elotuzumab 
administration with the medical monitor (applicable for NE-Pd arm only).
Each cycle is 28 days. While dose delays (within the allowed window determined below for 
nivolumab and elotuzumab) or interruptions are permitted, the start of each cycle cannot be 
delayed and is fixed (ie, anchored) relative to Cycle 1 Day 1. Adjustments to the Cycle 1 Day 1 
anchored schedule should not be performed. Should the start of a cycle be delayed, it is expected 
the following cycle begin as anchored to Cycle 1 Day 1. For example, if a subject is unable to start 
Cycle (X) until 3 days after the anchored start date, all assessments should be recorded on Cycle 
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(X) Day 3. The following cycle should begin on Day 1 (not Day 3) of Cycle (X+1). Missed doses 
should be skipped, not delayed, if not given within the allowed window.
Subjects may continue on study therapy even if components of the study therapy must be 
discontinued.
Please consult the BMS Medical Monitor or any questions regarding dose interruption or study
therapy discontinuation.
4.5.4.1
Elotuzumab
In Cycles 1 to 2, elotuzumab doses that fall outside of the pre-specified window of -1to3 days 
must be skipped.
Beginning with Cycle 3 and beyond, elotuzumab dosing may be delayed for up to 1 week. If unable 
to administer within 1 week, then the dose should be skipped and resumption of the elotuzumab 
continues per the protocol defined schedule.
Subjects experiencing a Grade 4 infusion reaction related to elotuzumab must permanently 
discontinue elotuzumab.
4.5.4.2
Dexamethasone
Dexamethasone interruption should be performed as clinically indicated at the discretion of the 
investigator.
For subjects receiving elotuzumab, the weekly dexamethasone that coincides with or is temporally 
closest to the next elotuzumab dosing must be administered as part of the premedication for 
elotuzumab per the guidance in Section 4.5.1.3.2.
4.5.4.3
Pomalidomide
Pomalidomide interruption should be performed as clinically indicated at the discretion of the 
investigator.
Subjects should be instructed that if a dose of pomalidomide has been missed and it has been less 
than 12 hours since the subject’s regular dosing time, to take pomalidomide as soon as the subject 
remembers. If it has been more than 12 hours, the dose must be skipped. Subjects should not take 
2 doses at the same time.
4.5.4.4
Nivolumab
For subjects being dosed in the nivolumab 240 mg Q2W part of the study, they may be dosed no 
less than 12 days from the previous dose. Nivolumab can be delayed within a 3 day window of 
Day 1 and Day 15 as long as the 12 day interval between 2 nivolumab 240 mg doses is respected. 
Doses that fall outside the allowed window should be skipped.
For subjects being dosed in the nivolumab 480 mg Q4W part of the study, for the first dose, it may 
be dosed no less than 12 days from the previous dose and for subsequent doses it should be dosed 
no less than 21 days from the previous dose. Nivolumab can be delayed within a 7 day window of 
Day 1 as long as the 12 day and 21 day intervals for the first 480 mg dose and subsequent 480 mg 
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doses, respectively, between 2 nivolumab doses is respected. Doses that fall outside the allowed 
window should be skipped.
A pattern of immune-related AEs (IMAEs) has been defined in subjects treated with nivolumab, 
for which management algorithms have been developed. Appendix 5 includes these 
comprehensive algorithms for supportive care, by system organ and by severity (See Section 
4.5.3).
4.5.4.4.1
Dose Delay/Interruption Criteria for Nivolumab
Nivolumab administration should be delayed for the following:

Grade 2 non-skin, drug-related AE, with the exception of fatigue

Grade 2 drug-related creatinine, AST, ALT and/or Total Bilirubin abnormalities

Grade 3 skin, drug-related AE

Grade 3 drug-related laboratory abnormality, with the following exceptions: 

Grade 3 lymphopenia or asymptomatic amylase or lipase does not require dose delay

Grade 3 AST, ALT, Total Bilirubin will require dose discontinuation (see Section
4.5.4.4.3)

Any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of
the investigator, warrants delaying the dose of study medication.
Participants who require delay of nivolumab should be re-evaluated weekly or more frequently if 
clinically indicated and resume nivolumab dosing when re-treatment criteria are met.
Additional criteria for nivolumab dose delay/interruption are included in the nivolumab IMAE 
management algorithm in Appendix 5. 
4.5.4.4.2
Criteria to Resume Treatment with Nivolumab 
Subjects may resume treatment with nivolumab when the drug-related AE(s) resolve(s) to 
Grade 1 or baseline, 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.

For participants with Grade 2 AST, ALT and/or Total Bilirubin abnormalities, dosing may 
resume when laboratory values return to baseline and management with corticosteroids, if 
needed, is complete.

Drug-related pulmonary toxicity, diarrhea or colitis must have resolved to baseline before 
treatment is resumed. Participants with persistent Grade 1 pneumonitis after completion of a 
steroid taper over at least 1 month may be eligible for retreatment if discussed with and 
approved by BMS Medical Monitor (or designee).
Participants with drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement may resume treatment after consultation with the BMS Medical Monitor (or 
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designee). Adrenal insufficiency requires discontinuation regardless of control with hormone 
replacement.
Dose delay/interruption of nivolumab which results in treatment interruption of > 8 weeks require 
treatment discontinuation, with exceptions as noted in Section 4.5.4.4.3. There will be no dose 
reductions for nivolumab.
4.5.4.4.3
Nivolumab Dose Discontinuation
Nivolumab treatment should be permanently discontinued for the following:

Any Grade 2 drug-related uveitis, eye pain or blurred vision that does not respond to topical 
therapy and does not improve to Grade 1 severity within the re-treatment period OR requires 
systemic treatment 

Any Grade 3 non-skin, drug-related AE lasting > 7 days or recurs, with the following 
exceptions for laboratory abnormalities, drug-related uveitis, pneumonitis, bronchospasm, 
neurologic toxicity, hypersensitivity reactions, infusion reactions, and endocrinopathies:

Grade 3 drug-related uveitis, pneumonitis, bronchospasm, neurologic toxicity, 
myocarditis, hypersensitivity reaction, or infusion reaction of any duration requires 
discontinuation

Grade 3 drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement do not require discontinuation. Adrenal insufficiency requires 
discontinuation regardless of control with hormone replacement.

Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation 
except:
Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding requires 
discontinuation
Grade 3 drug-related AST, ALT or Total Bilirubin requires discontinuation*
Concurrent AST or ALT > 3 x ULN and total bilirubin > 2x ULN
* In most cases of Grade 3 AST or ALT elevation, study treatment will be permanently 
discontinued. If the investigator determines a possible favorable benefit/risk ratio that warrants 
continuation of study treatment, a discussion between the investigator and the BMS Medical 
Monitor/designee must occur.

Any Grade 4 drug-related adverse event or laboratory abnormality (including but not limited 
to creatinine, AST, ALT, or Total Bilirubin), except for the following events which do not 
require discontinuation:

Grade 4 neutropenia 7 days

Grade 4 lymphopenia or leukopenia or asymptomatic amylase or lipase

Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 72 hours 
of their onset

Grade 4 drug-related endocrinopathy adverse events, such as, hyper- or hypothyroidism, 
or glucose intolerance, which resolve or are adequately controlled with physiologic 
hormone replacement (corticosteroids, thyroid hormones) or glucose-controlling agents, 
respectively, may not require discontinuation after discussion with and approval from the 
BMS Medical Monitor.
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
Any event that leads to delay in dosing lasting > 8 weeks from the previous dose requires 
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 treatment in a subject with a dosing delay lasting > 8 
weeks from the previous dose, the BMS medical monitor must be consulted. Tumor 
assessments should continue as per protocol even if dosing is delayed/interrupted. Periodic 
study visits to assess safety and laboratory studies should also continue as clinically 
indicated during such dosing delays/interruption.

Dosing delays lasting > 8 weeks from the previous dose that occur for non-drug-related 
reasons may be allowed if approved by the BMS medical monitor. Prior to re-initiating 
treatment in a subject with a dosing delay lasting > 8 weeks, the BMS medical monitor 
must be consulted. Tumor assessments should continue as per protocol even if dosing is 
delayed/interrupted. Periodic study visits to assess safety and laboratory studies should 
also continue as clinically indicated during such dosing delays/interruption.

Any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of 
the Investigator, presents a substantial clinical risk to the subject with continued nivolumab 
dosing.

At investigator’s discretion, based on the safety results from the interim analysis and subject’s 
derived clinical benefit (as of 23-Aug-2018).
Additional criteria for nivolumab dose discontinuation are included in the nivolumab IMAE 
management algorithm in Appendix 5.
4.5.5
Recommended Dose Reduction
The criteria presented in this section for dose modification of dexamethasone and pomalidomide 
are meant as general guidelines. They are based on current US standards of clinical practice. Local 
standards may differ and may be followed. Dose modification may occur in the setting of lower 
grade toxicity if the investigator, in consultation with the Medical Monitor/Sponsor, believes that 
it is in the interest of subject safety.
4.5.5.1
Nivolumab and Elotuzumab
No dose reductions are allowed for nivolumab or elotuzumab.
4.5.5.2
Dexamethasone
Dexamethasone dose reductions for toxicity must be performed as clinically indicated. 
Recommended management is described in Table 4.5.5.2-1 and Table 4.5.5.2-2. Deviations to the 
recommended dose reductions are allowed based on the clinical judgment of the investigator.
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Table 4.5.5.2-1:
Dexamethasone Dose Reductions
CTCAE 
Category
Adverse Event
Treatment Adjustment
Gastrointestinal
Dyspepsia, gastric or duodenal 
ulcer, gastritis
Grade 1 - 2 
(requiring medical management)
Treat with a proton pump inhibitor.
If symptoms persist despite above measures, decrease by 
1 dose level.
Grade 3 
(requiring hospitalization or 
surgery)
Hold dexamethasone until symptoms are adequately 
controlled. Reduce by 1 dose level and resume along with 
concurrent therapy with a proton pump inhibitor.
If symptoms persist despite above measures, reduce to dose 
level -3 (dose withheld).
Acute pancreatitis
Reduce to dose level -3 (dose withheld).
Cardiovascular
Edema
Grade 3 (limiting function and 
unresponsive to therapy or 
anasarca)
Use diuretics as needed, and decrease dexamethasone by 
1 dose level. If edema persists despite above measures, 
decrease by another dose level.
Neurology
Confusion or Mood alteration 
Grade 2 (interfering with 
function interfering with 
activities of daily living)
Hold dexamethasone until symptoms resolve.
Decrease by 1 dose level and resume.
If symptoms persist despite above measures, decrease by 
another dose level.
Musculoskeletal
Muscle weakness 
Grade 2 (symptomatic and 
interfering with function 
interfering with activities of 
daily living)
Hold dose until muscle weakness is Grade 1.
Decrease dexamethasone by 1 dose level and resume.
If weakness persists despite above measures, decrease by 
another dose level.
Metabolic
Hyperglycemia
Grade 3 or higher
Treat with insulin or oral hypoglycemics as needed. If 
uncontrolled despite above measures, decrease by 1 dose 
level until glucose levels are satisfactory.
Constitutional
Insomnia Grade 2
Decrease by 1 dose level and resume.
Dose reduction for persistent Grade 2 or Grade 3 AEs believed to be related to dexamethasone 
and not listed above are permitted. Dose reductions should follow the guidance in Table 4.5.5.2-1
and Table 4.5.5.2-2.
For subjects receiving elotuzumab, regardless of dexamethasone dose reduction, at least 8 mg of 
the weekly dexamethasone dose must be administered IV as part of the premedication for 
elotuzumab with the remainder of the weekly dexamethasone dose administered orally as 
described in Section 4.5.1.3.2. Contact the Medical Monitor to discuss dexamethasone IV 
premedication for subjects in the investigational arm who reach dose level -3 and must discontinue 
dexamethasone due to dose limiting toxicity.
On days without elotuzumab, no IV dexamethasone should be administered.
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Table 4.5.5.2-2:
Dexamethasone Dose Levels
Dose Level
Reducing Dexamethasone on 
Weeks with Elotuzumab
Reducing Dexamethasone on 
Weeks Without Elotuzumab
PO
IV
PO
IV
0
75 years old - 28 mg
8 mg
75 years old - 40 mg
N/A
> 75 years old - 8 mg
> 75 years old - 20 mg
-1
75 years old - 12 mg
8 mg
75 years old - 20 mg
N/A
> 75 years old - 2 mg
> 75 years old - 12 mg
-2
75 years old - 0 mg
8 mg
75 years old - 12 mg
N/A
> 75 years old - 0 mg
> 75 years old - 8 mg
-3
75 years old - 0 mg
Contact 
Medical 
Monitor
75 years old - 0 mg
N/A
> 75 years old - 0 mg
> 75 years old - 0 mg
4.5.5.3
Pomalidomide
Below are the recommended dose adjustments for the management of thrombocytopenia and 
neutropenia judged by the investigator to be related to pomalidomide. Information in Table 4.5.5.3-
1 and Table 4.5.5.3-2 is based on pomalidomide prescribing information, which contains 
additional guidance on pomalidomide dosing 28,29. Investigators should follow the guidelines in 
the prescribing information for pomalidomide. Some clinically relevant events and their 
management are presented below.
Table 4.5.5.3-1:
Treating Thrombocytopenia Related to Pomalidomide
When Platelet Count:
Recommended Course:

Fall to < 25,000 per mm3

Interrupt 
pomalidomide 
treatment, 
follow 
Complete Blood Count weekly.

Return to > 50,000 per mm3

Resume pomalidomide at 3 mg daily

For each subsequent drop < 25,000 mm3

Interrupt pomalidomide treatment

Return to 50,000 mm3

Resume pomalidomide at 1 mg less than previous 
dose
Table 4.5.5.3-2:
Treating Neutropenia Related to Pomalidomide
When Neutrophil Count:
Recommended Course:

Fall to < 500 per mm3 or febrile neutropenia (fever 
38.5oC and ANC < 1,000 mm3)

Interrupt 
pomalidomide 
treatment, 
follow 
Complete Blood Count weekly.

ANC returns to 1000 per mm3

Resume pomalidomide at 3 mg daily

For each subsequent drop < 500 mm3

Interrupt pomalidomide treatment

Return to 1000 mm3

Resume pomalidomide at 1 mg less than previous 
dose
ANC, absolute neutrophil count. In case of neutropenia, consider the use of growth factors in subject management.
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If necessary to co-administer strong inhibitors of CYP1A2 in the presence of strong inhibitors of 
CYP3A4 and P-glycoprotein, consider reducing pomalidomide dose by 50%.28,29
4.6
Blinding/Unblinding
Not applicable
4.7
Treatment Compliance
Treatment compliance will be monitored by drug accountability and recorded in the subject’s 
medical record and CRF. For those medications taken at home (PO dexamethasone and 
pomalidomide), subjects will be provided with a medication diary in which to record study drug 
doses and will be instructed to bring this diary and study drug containers to clinic visits.
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 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 disposal vendor 
must be documented

Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
Revised Protocol No.: 03
Date: 12-Nov-2018
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1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused and/or 
partially used study drug that was supplied by BMS must be returned to BMS. The return of study 
drug will be arranged by the responsible Study Monitor. 
4.10
Retained Samples for Bioavailability / Bioequivalence
Not applicable. 
Revised Protocol No.: 03
Date: 12-Nov-2018
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4.0
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Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
5
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (CA209602) - All Subjects
Procedure
Screening
Visit
Use of Central (CL) or 
Local (LL) Lab
Notes
Eligibility Assessments
Informed Consent 
X
Prior to any screening procedures (note:  any procedure/lab done before ICF 
signed would be acceptable if part of standard of care)
Inclusion/Exclusion Criteria 
X 
Within 14 days of randomization
Medical History 
X
Includes date and ISS Stage at initial diagnosis of MM (Within 28 days of 
randomization) 
International Staging System (ISS) 
stage at study entry31
X
Appendix 4
Safety Assessments
Physical Examination 
X 
Full physical examination, including weight, within 14 days of 
randomization - Section 5.3.2
Vital Signs
X 
Temperature, BP, HR within 14 days of randomization - Section 5.3.2
Performance Status (ECOG) 
X 
Evaluate prior to dosing (Appendix 2) within 14 days of randomization 
Serious Adverse Events Assessment 
X 
Collected from the time of informed consent
Second Primary Malignancy
X
Collected from the time of informed consent - Section 6.7
Concomitant Medications 
X 
Within 14 days of randomization
ECG 
X 
LL
Within 28 days of randomization - Section 5.3.4
Laboratory Assessments
CBC, Differential, Platelets 
X 
LL
Within 14 days of randomization - Section 5.3.5
Hepatitis B surface antigen 
(HBV sAg), and hepatitis C antibody 
X
LL
Within 28 days of randomization - Section 5.3.5
Revised Protocol No.: 03
Date: 12-Nov-2018
73
4.0
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930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-1:
Screening Procedural Outline (CA209602) - All Subjects
Procedure
Screening
Visit
Use of Central (CL) or 
Local (LL) Lab
Notes
(HCV Ab) or HCV ribonucleic acid 
(RNA)
Serum Chemistry
X 
LL
Within 14 days of randomization - Section 5.3.5
Thyroid stimulating hormone (TSH) 
(reflex to free T3/total T3, free T4 for 
abnormal TSH result)
X
LL
Within 28 days of randomization - Section 5.3.5
Creatinine Clearance Assessment 
X 
LL
By Cockcroft-Gault within 14 days of randomization (Section 3.3.2 for 
calculation)
Pregnancy Test 
X 
LL
For WOCBP only, 2 pregnancy tests, one 10 - 14 days prior to start of 
study drug and one within 24 hours prior to start of study drug. Urine tests 
must have a sensitivity of 25 mIU/mL
Serum 2-microglobulin 
X
CL
Within 28 days of randomization. Central lab analysis for stratification
Serum Albumin
X
CL
Within 28 days of randomization. Central lab analysis for stratification
Efficacy Assessments
 
Myeloma Urine and Serum Lab tests 
(SPEP/UPEP/sFLC)
X
CL
Section 5.4.2
Within 28 days of randomization; Central Laboratory analysis; 
Results must be available prior to first dose of study drug
Revised Protocol No.: 03
Date: 12-Nov-2018
74
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930097316
4.0
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Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-1:
Screening Procedural Outline (CA209602) - All Subjects
Procedure
Screening
Visit
Use of Central (CL) or 
Local (LL) Lab
Notes
Bone Marrow Aspirate
X
LL
Section 5.4.2
Bone Marrow aspirate is mandatory.
Bone marrow biopsy is optional. Bone marrow biopsy is required if an 
aspirate sample (at any required time point) is not available due to a dry tap.
Plasma cell percentage is required and should be performed locally per 
institution standard practice, within 35 days of randomization.
X
CL
Section 5.4.2  and Table 5.4.2-1
Bone Marrow aspirate is mandatory. 
Collections are required at screening, VGPR, and every 6 Cycles thereafter
until PD. In subjects with confirmed PD, collection is optional upon PD 
confirmation.
Corrected Calcium
X
LL
Section 5.4.2; Within 14 days of randomization; 
Results must be available prior to first dose of study drug.
Skeletal Survey 
X
LL
Section.5.4.3.1
Within 28 days of randomization
CT or MRI assessment for 
extramedullary soft tissue 
plasmacytoma 
X
LL
Section 5.4.3.2
Within 28 days of randomization, if subject had a previous extramedullary 
or bone plasmacytoma
Clinical Drug Supplies
Randomize
X
First dose of study drug must occur within 5 days of randomization.
Revised Protocol No.: 03
Date: 12-Nov-2018
75
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4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-2:
Procedural Outline (CA209602) Procedures Cycles 1 & 2 - All Subjects
Procedure
Local 
Lab (LL)
or
Central 
Lab (CL)
Day 
1
Day 
8*
Day 
15
Day 
22*
Rest 
Days
23-28
Notes
(within 72 hours prior to dosing)
* Day 8 & 22 pertain to the NE-Pd arm only
Safety Assessments
Targeted Physical 
Examination
X
Section 5.3.2
Perform prior to dosing, include weight
Vital Signs
X
X
X
X
Section 5.3.2 Temperature, BP, HR. Additional vital signs needed for 
Cycle 1 for NE-Pd arm as described in section 5.3.2
Performance Status 
(ECOG)
X
If performed and recorded at screening, to be done on C2D1 only. 
(Appendix 2)
Serious Adverse 
Events Assessment
X
X
X
X
Evaluate prior to dosing
Adverse Events 
Assessment
X
X
X
X
Evaluate prior to dosing
Concomitant 
Medications
X
X
X
X
Evaluate prior to dosing
Second Primary 
Malignancy
X
Section 6.7
Laboratory Tests for 
Safety
*DAY 8 & 22 only pertain to the NE-Pd arm
CBC & Differential
LL
X
X
X
X
Section 5.3.5
Can be drawn up to 3 days prior to dosing 
Serum Chemistry
LL
X
Section 5.3.5
If performed and recorded at screening, to be done on C2D1 only. 
Can be drawn up to 3 days prior to dosing.
Revised Protocol No.: 03
Date: 12-Nov-2018
76
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-2:
Procedural Outline (CA209602) Procedures Cycles 1 & 2 - All Subjects
Procedure
Local 
Lab (LL)
or
Central 
Lab (CL)
Day 
1
Day 
8*
Day 
15
Day 
22*
Rest 
Days
23-28
Notes
(within 72 hours prior to dosing)
* Day 8 & 22 pertain to the NE-Pd arm only
Thyroid function test
LL
X*
TSH (reflex to free T3/Total T3 and free T4 if abnormal result) to be 
performed every *2 cycles (7 days) from first dose regardless of 
dosing schedule (at screening, C2D1, C4D1, C6D1....etc).
Pregnancy Test
LL
X
X
X
X
Section 5.3.5
For WOCBP only. Urine tests must have a sensitivity of at least 
25 mIU/mL. Weekly test within 24 hours of study medication 
Efficacy Assessments
Myeloma Urine and 
Serum Lab tests 
(SPEP/UPEP/sFLC)
CL
Every 4 weeks from date of 
first dose of study therapy 
until confirmed disease 
progression, regardless of 
whether subject is on study 
therapy or subsequent therapy.
Section 5.4.2
Day 1 of each cycle (including Cycle 1) until confirmed disease 
progression, even if subject is on subsequent therapy.
24- hour urine sample can be collected within 7 days of visit, and 
must be obtained in all subjects
Bone marrow aspirate 
LL
See note
Section 5.4.2
Bone Marrow aspirate is mandatory.
Bone marrow biopsy is optional. Bone marrow biopsy is required if an 
aspirate sample (at any required time point) is not available due to a dry 
tap.
Collections are required at screening, ≥VGPR, and every 6 Cycles 
thereafter until PD. In subjects with confirmed PD, collection is optional
upon PD confirmation.
Evaluation of percentage of plasma cells and clonality is required and 
should be performed locally per institution standard practice.
CL
See note 
Section 5.4.2 and Table 5.4.2-1
Collections are required at screening, ≥VGPR, and every 6 Cycles 
thereafter until PD. In subjects with confirmed PD, collection is optional
upon PD confirmation.
Revised Protocol No.: 03
Date: 12-Nov-2018
77
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-2:
Procedural Outline (CA209602) Procedures Cycles 1 & 2 - All Subjects
Procedure
Local 
Lab (LL)
or
Central 
Lab (CL)
Day 
1
Day 
8*
Day 
15
Day 
22*
Rest 
Days
23-28
Notes
(within 72 hours prior to dosing)
* Day 8 & 22 pertain to the NE-Pd arm only
Corrected Calcium 
LL
Every 4 weeks from date of 
first dose of study therapy 
until confirmed disease 
progression, regardless of 
whether subject is on study 
therapy or subsequent therapy.
Serum calcium and albumin from peripheral blood at D1 of each cycle 
until confirmed disease progression, even if subject is on subsequent 
therapy
Skeletal Survey
LL
If clinically indicated
See Section 5.4.3.1
CT/MRI Assessment 
of Extramedullary Soft 
Tissue plasmacytoma 
LL
As clinically indicated 
Section 5.4.3.2 (in subjects with baseline plasmacytoma, imaging 
follow-up should be done regularly per investigator’s discretion). 
Imaging confirmation of disappearance of plasmacytoma is required at
time of CR/sCR if it was not confirmed before.
Response Assessment
(Per IMWG)
Every 4 weeks from date of 
first dose of study drug until 
confirmed progression
regardless of whether on study 
therapy or subsequent therapy. 
Section 5.4.1
Response assessments (PRand PD require confirmation (2 
consecutive assessment)s (Appendix 3).
Revised Protocol No.: 03
Date: 12-Nov-2018
78
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-2:
Procedural Outline (CA209602) Procedures Cycles 1 & 2 - All Subjects
Procedure
Local 
Lab (LL)
or
Central 
Lab (CL)
Day 
1
Day 
8*
Day 
15
Day 
22*
Rest 
Days
23-28
Notes
(within 72 hours prior to dosing)
* Day 8 & 22 pertain to the NE-Pd arm only
Dosing
*DAY 8 & 22 only pertain to the NE-Pd arm
Premedication for 
Elotuzumab
(Elotuzumab Arm 
Subjects Only)
X
X
X
X
Sections 4.5.1; Nivolumab is infused before elotuzumab in the NE-Pd 
arm. Elotuzumab premedications can be administered before nivolumab 
infusion.
Elotuzumab Infusion
X
X
X
X
Section 4.5.1.3 for Elotuzumab window; Nivolumab is infused first on 
the NE-Pd arm
Nivolumab Infusion
X
X
Section 4.5.1. Nivolumab is infused first on the NE-Pd arm
Pomalidomide 
Administration
Day 1 - 21 of cycle
Dispense pomalidomide on Day 1 of each cycle per the local risk 
management program or the Pomalidomide Pregnancy Risk Prevention 
Plan (Appendix 6).
Dexamethasone 
Administration
X
X
X
X
Dexamethasone dosing per Section 4.5.1.
Revised Protocol No.: 03
Date: 12-Nov-2018
79
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930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-2:
Procedural Outline (CA209602) Procedures Cycles 1 & 2 - All Subjects
Procedure
Local 
Lab (LL)
or
Central 
Lab (CL)
Day 
1
Day 
8*
Day 
15
Day 
22*
Rest 
Days
23-28
Notes
(within 72 hours prior to dosing)
* Day 8 & 22 pertain to the NE-Pd arm only
Revised Protocol No.: 03
Date: 12-Nov-2018
80
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-3:
Procedural Outline (CA209602) Cycles 3 and 4 
Procedure
Local Lab (LL)
or
Central Lab (CL)
Day 1
Day 8
Day 15
Day 22
Rest Days
23-28
Notes
(within 72 hours prior to dosing)
Safety Assessments
Targeted Physical Examination
X
Section 5.3.2
Perform prior to dosing, include weight 
Vital Signs
X
X
Section 5.3.2
Performance Status (ECOG)
X
Appendix 2
Evaluate prior to dosing
Serious Adverse Events Assessment
X
X
Evaluate prior to dosing
*NSAEs and SAEs must be collected up 
to 100 days after study drug 
discontinuation. SAEs related to any later 
protocol-specified procedure must be 
collected.
Adverse Events Assessment
X
X
Evaluate prior to dosing
*NSAEs and SAEs must be collected up 
to 100 days after study drug 
discontinuation. SAEs related to any later 
protocol-specified procedure must be 
collected.
Second Primary Malignancy
X
Section 6.7
30 and 100 day assessments may be 
performed 1 week.
Follow-up: Assess every 12 weeks
(2 weeks), or more frequently.
Concomitant Medications
X
Evaluate prior to dosing
Laboratory Assessments
CBC & Differential
LL
X
Section 5.3.5
Can be drawn up to 3 days prior to dosing
Revised Protocol No.: 03
Date: 12-Nov-2018
81
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-3:
Procedural Outline (CA209602) Cycles 3 and 4 
Procedure
Local Lab (LL)
or
Central Lab (CL)
Day 1
Day 8
Day 15
Day 22
Rest Days
23-28
Notes
(within 72 hours prior to dosing)
Serum Chemistry
LL
X
Section 5.3.5
Can be drawn up to 3 days prior to dosing
Thyroid function test
LL
X*
TSH (reflex to free T3/Total T3 and free 
T4 if abnormal result) to be performed 
every *2 cycles (7 days) from first dose 
regardless of dosing schedule.
Pregnancy Test
LL
X
Sections 5.3.5 & 6.4
For WOCBP only.
Tests must occur within 24 hours prior to 
dosing. If irregular menstrual cycles the 
pregnancy test should occur on Days 1 
and 15 of each cycle.
Urine tests must have a sensitivity of at 
least 25 mIU/mL
*WOCBP must have a pregnancy test 
30 and 100 days post end of treatment
Efficacy Assessments
Myeloma Urine and Serum Lab 
tests
(SPEP/UPEP/sFLC)
CL
Every 4 weeks from date of the first dose of study 
drug therapy until confirmed disease 
progression, regardless of whether subject is on 
study therapy or subsequent therapy.
See Section 5.4.2
Day 1 of each cycle until confirmed 
disease progression, even if subject is on 
subsequent therapy.
24-hour urine sample can be collected 
within 7 days of visit, and must be 
obtained in all subjects 
Corrected Calcium 
LL
Every 4 weeks from date of the first dose of study 
drug therapy until confirmed disease 
progression, regardless of whether subject is on 
study therapy or subsequent therapy.
Serum calcium and albumin from 
peripheral blood at D1 of each cycle until 
confirmed disease progression, even if 
subject is on subsequent therapy.
Revised Protocol No.: 03
Date: 12-Nov-2018
82
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-3:
Procedural Outline (CA209602) Cycles 3 and 4 
Procedure
Local Lab (LL)
or
Central Lab (CL)
Day 1
Day 8
Day 15
Day 22
Rest Days
23-28
Notes
(within 72 hours prior to dosing)
Bone Marrow Aspirate 
CL
See Note
Section 5.4.2  and Table 5.4.2-1
Bone Marrow aspirate is mandatory. 
Collections are required at screening,
≥VGPR, and every 6 Cycles thereafter
until PD. In subjects with confirmed PD, 
collection is optional upon PD 
confirmation.
Bone Marrow Aspirate
LL
See Note
Section 5.4.2
Bone Marrow aspirate is mandatory. Bone 
marrow biopsy is optional. Bone marrow 
biopsy is required if an aspirate sample (at 
any required time point) is not available 
due to a dry tap.
Collections are required at screening, 
≥VGPR, and every 6 Cycles thereafter 
until PD. In subjects with confirmed PD, 
collection is optional upon PD 
confirmation.
Evaluation of percentage of plasma cells 
and clonality is required and should be 
performed locally per institution standard 
practice.
Skeletal Survey
LL
If clinically indicated.
Section 5.4.3.1
CT/MRI Assessment of 
Extramedullary Soft Tissue 
plasmacytoma 
LL
As clinically indicated
Section 5.4.3.2 (in subjects with baseline 
plasmacytoma, imaging follow-up should 
be done regularly per investigator’s 
discretion). Imaging confirmation of 
Revised Protocol No.: 03
Date: 12-Nov-2018
83
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-3:
Procedural Outline (CA209602) Cycles 3 and 4 
Procedure
Local Lab (LL)
or
Central Lab (CL)
Day 1
Day 8
Day 15
Day 22
Rest Days
23-28
Notes
(within 72 hours prior to dosing)
disappearance of plasmacytoma is 
required at time of CR/sCR if it was not 
confirmed before
Response Assessment Per IMWG
Every 4 weeks from date of first dose of study drug 
until confirmed progression regardless of 
whether on study therapy or subsequent therapy.
Section 5.4.1
Response assessments (PR) and PD 
require confirmation (2-consecutive 
assessments) (Appendix 3).
Dosing
Premedication for Elotuzumab
(Elotuzumab Arm Subjects Only)
X
X
Sections 4.5.1, Nivolumab is infused first 
on the NE-Pd arm
Elotuzumab Infusion
X
X
Section 4.5.5.1 for Elotuzumab window, 
Nivolumab is infused before elotuzumab 
in the NE-Pd arm. Elotuzumab 
premedications can be administered 
before nivolumab.
Nivolumab Infusion
X
X
Section 4.5.1, Nivolumab is infused first 
on the NE-Pd arm
Revised Protocol No.: 03
Date: 12-Nov-2018
84
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930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-3:
Procedural Outline (CA209602) Cycles 3 and 4 
Procedure
Local Lab (LL)
or
Central Lab (CL)
Day 1
Day 8
Day 15
Day 22
Rest Days
23-28
Notes
(within 72 hours prior to dosing)
Pomalidomide Administration
Day 1 - 21 of Cycle
Dispense pomalidomide on Day 1 of each 
cycle per the local risk management 
program or the Pomalidomide Pregnancy 
Risk Prevention Plan (Appendix 6).
Dexamethasone Administration
X
X
X
X
Dexamethasone dosing per 
Section 4.5.1.2
Revised Protocol No.: 03
Date: 12-Nov-2018
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4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Safety Assessments
Targeted Physical 
Examination
X
X
Section 5.3.2
Perform prior to dosing, include 
weight 
Vital Signs
X
X
Section 5.3.2
Performance Status 
(ECOG)
X
X
Appendix 2
Evaluate prior to dosing
Serious Adverse 
Events Assessment
X
X
X*
Evaluate prior to dosing
*NSAEs and SAEs must be collected 
up to 100 days after study drug 
discontinuation. SAEs related to any 
later protocol-specified procedure 
must be collected.
Adverse Events 
Assessment
X
X
X*
Evaluate prior to dosing
*NSAEs and SAEs must be collected 
up to 100 days after study drug 
discontinuation. SAEs related to any 
later protocol-specified procedure 
must be collected.
Revised Protocol No.: 03
Date: 12-Nov-2018
86
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Second Primary 
Malignancy
X
X
X
X
Section 6.7
30 and 100 day assessments may be 
performed 1 week.
Follow-up: Assess every 12 weeks (
2 weeks), or more frequently. 
Concomitant 
Medications
X
X
X
Evaluate prior to dosing
Subsequent Myeloma 
Therapy
X
X
X
30 and 100 day assessments may be 
performed 1 week, 
Follow-up: Assess every 12 weeks (
2 weeks), or more frequently.
Laboratory 
Assessments
CBC & Differential
LL
X
X
X
Section 5.3.5
Can be drawn up to 3 days prior to 
dosing 
Serum Chemistry
LL
X
X
X
Section 5.3.5
Can be drawn up to 3 days prior to 
dosing
Revised Protocol No.: 03
Date: 12-Nov-2018
87
4.0
Approved
930097316
4.0
v
Approved
1.0
v


Clinical Protocol
CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Thyroid function test
LL
X*
X
X
TSH (reflex to free T3/Total T3 and 
free T4 if abnormal result) to be 
performed every *2 cycles (7 days) 
from first dose regardless of dosing 
schedule.
Pregnancy Test
LL
X
X
X*
Sections 5.3.5 & 6.4
For WOCBP only. 
Tests must occur within 24 hours prior 
to dosing. 
Urine tests must have a sensitivity of 
at least 25 mIU/mL 
*WOCBP must have a pregnancy test 
30 and 100 days post end of treatment
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Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Efficacy Assessments
Myeloma Urine and 
Serum Lab tests
(SPEP/UPEP/sFLC)
CL
Every 4 weeks from date of the first dose of study drug therapy until 
confirmed disease progression, regardless of whether subject is on study 
therapy or subsequent therapy.
See Section 5.4.2
Day 1 of each cycle until confirmed 
disease progression, even if subject is 
on subsequent therapy.
24-hour urine sample can be collected 
within 7 days of visit, and must be 
obtained in all subjects. 
Corrected Calcium 
LL
Every 4 weeks from date of the first dose of study drug therapy until 
confirmed disease progression, regardless of whether subject is on study 
therapy or subsequent therapy.
Serum calcium and albumin from 
peripheral blood at D1 of each cycle 
until confirmed disease progression, 
even if subject is on subsequent 
therapy
Bone Marrow Aspirate 
CL
See note
Section 5.4.2 and Table 5.4.2-1
Bone Marrow aspirate is 
mandatory.
Collections are required at screening, 
≥VGPR, and every 6 Cycles thereafter 
until PD. In subjects with confirmed 
PD, collection is optional upon PD 
confirmation.
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CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Bone Marrow Aspirate
LL
See note
Section 5.4.2  
Bone Marrow aspirate is mandatory. 
Bone marrow biopsy is optional. Bone 
marrow biopsy is required if an 
aspirate sample (at any required time 
point) is not available due to a dry tap.
Collections are required at screening, 
≥VGPR, and every 6 Cycles thereafter 
until PD. In subjects with confirmed 
PD, collection is optional upon PD 
confirmation.
Evaluation of percentage of plasma 
cells and clonality is required and 
should be performed locally per 
institution standard practice.
Skeletal Survey
LL
If clinically indicated.
Section 5.4.3.1
CT/MRI Assessment 
of Extramedullary Soft 
Tissue plasmacytoma 
LL
As clinically indicated 
Section 5.4.3.2 (in subjects with 
baseline plasmacytoma, imaging 
follow-up should be done regularly
per investigator’s discretion). Imaging 
confirmation of disappearance of 
plasmacytoma is required at time of 
CR/sCR if it was not confirmed before
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CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Response Assessment
Per IMWG
Every 4 weeks from date of first dose of study drug until confirmed 
progression regardless of whether on study therapy or subsequent therapy.
Section 5.4.1
Response assessments (PRand PD 
require confirmation (2-consecutive 
assessments) (Appendix 3).
Survival Status
X
X
30 and 100 day visits may be 
performed 1 week, 
Follow-up: Assess every 12 weeks
(2 weeks), or more frequently
Dosing
Premedication for 
Elotuzumab
(Elotuzumab Arm 
Subjects Only)
X
Sections 4.5.1, Nivolumab is infused 
first on the NE-Pd arm
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CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Elotuzumab Infusion
X
Section 4.5.1 for Elotuzumab window, 
Nivolumab is infused before 
Elotuzumab in the 
NE-Pd arm/Elotuzumab 
premedications can be administered
before nivolumab.
Nivolumab Infusion
X
Section 4.5.1 Nivolumab is infused 
first on the NE-Pd arm
Pomalidomide 
Administration
Day 1 - 21 of Cycle
Dispense pomalidomide on Day 1 of 
each cycle per the local risk 
management program or the 
Pomalidomide Pregnancy Risk 
Prevention Plan (Appendix 6).
Dexamethasone 
Administration
X
X
X
X
Dexamethasone dosing per Section
4.5.1
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CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
Revised Protocol No.: 03
Date: 12-Nov-2018
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CA209602
BMS-936558
nivolumab
Table 5.1-4:
Procedural Outline (CA209602) Cycles 5 and Beyond
Procedure
Local 
Lab 
(LL)
or
Central 
Lab 
(CL)
Day 
1
Day 
8
Day 
15
Day 
22
Rest 
Days
23-28
End Of 
Treatment
Follow up 
visits:
Days 30
& 100 
post end 
of 
treatment 
(+/- 7 day 
window
Survival 
Follow-
Up
(+/-14 
day 
window)
Notes
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Date: 12-Nov-2018
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nivolumab
5.1.1
Retesting During Screening or Lead-in Period
Retesting of laboratory parameters and/or other assessments within any single screening will be 
permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (ie, the most current result prior to Randomization) 
and is the value by which study inclusion will be assessed, as it represents the subject’s most 
current, clinical state.
Laboratory parameters and/or assessments that are included in Table 5.1-1, Screening Procedural 
Outline may be repeated in an effort to find all possible well-qualified subjects. Consultation with 
the Medical Monitor may be needed to identify whether repeat testing of any particular parameter 
is clinically relevant.
5.2
Study Materials
The following will be distributed to sites for use in this study:

NCI CTCAE booklets version 4.0

Elotuzumab Investigator Brochure

Nivolumab Investigator Brochure

Pomalidomide (Pomalyst) Package Insert

Site Manual for operation of IWRS

Subject Dosing Diary

Subject Quality of Life Questionnaires 

Serious Adverse Event (SAE) Case Report Form (CRF) pages

Pregnancy Surveillance Forms

Pharmacy Binder

Laboratory manuals for collection and handling of blood samples

Laboratory manual for local lab data entry
5.3
Safety Assessments
Only data for the procedures and assessments specified in this protocol should be submitted to 
BMS. Additional procedures and assessments may be performed as part of standard of care; 
however, the data for these assessments should remain in the subject’s medical record and should 
not be provided to BMS, unless specifically requested from the Sponsor. Safety assessments must 
be done prior to dosing. The local safety labs (complete blood count, chemistry panel) and 
procedures may be collected or performed up to 3 days prior to the visit. For subjects who skip a 
dose, local safety labs results must be collected at least once per cycle. 
All subjects will be assessed for safety. Safety evaluations include assessments of AEs, clinical 
laboratory tests (hematology, chemistry), vital sign measurements, and physical examination with 
assessment of ECOG PS. Investigators are responsible for monitoring the safety of subjects who 
have entered this study and for alerting the Sponsor to any event that seems unusual, even if this 
event may be considered an unanticipated benefit to the subject. The investigator is responsible 
for appropriate medical care of subjects during the study.
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5.3.1
Assessments 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.
5.3.2
Vital Signs, Physical Measurements, and Physical Examination
Vital signs (body temperature, seated blood pressure, heart rate will be recorded as outlined in 
Table 5.1-1, Table 5.1-2, Table 5.1-3, and Table 5.1-4. Blood pressure and heart rate should be 
measured after the subject has been seated quietly for at least 5 minutes prior to dosing. Subjects 
will have vital signs measured once at each visit. Subjects randomized to the NE-Pd arm will have 
additional vital signs during Cycle 1 only, as follows: 

Prior to pre-medication administration

Prior to the start of the elotuzumab infusion

Thirty minutes after the start of elotuzumab infusion

At the end of the elotuzumab infusion

Post infusion vital signs will be measured at 30 minutes.

Subjects who experience a Grade 2 infusion reaction require vital signs to be monitored every 
30 minutes for 1 - 2 hours after the end of the elotuzumab infusion (at the investigator’s 
discretion).
Weight will be measured at study visits as indicated in Table 5.1-1, Table 5.1-2, Table 5.1-3, Table 
5.1-4.
A full physical examination will be performed at the screening visit, whereas a targeted exam will 
occur at Day 1 and during on-treatment up to 3 days prior to dosing and post-treatment visits. A 
targeted physical examination may be performed by a qualified professional guided by the 
examiner’s observations and/or subject complaints on new or changed conditions, symptoms, or 
concerns. Targeted physical exam includes assessment of heart, lung, and abdomen.
5.3.3
Performance Status
Performance assessment will be performed as indicated in Table 5.1-1, Table 5.1-2, Table 5.1-3, 
and Table 5.1-4 using ECOG performance scale and criteria as described in Appendix 2. The 
assessment should be completed prior to any study-related procedures, treatment or clinician 
assessment.
5.3.4
Cardiac Assessments 
ECG will be performed at screening within 28 days of randomization.
5.3.5
Laboratory Assessments for Safety
Laboratory assessments for safety will be performed at local laboratories. Safety laboratory 
assessments are listed in Table 5.3.5-1.
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nivolumab
Table 5.3.5-1:
Safety Laboratory Assessments
Safety Laboratory Assessments
Screening as outlined in Table 5.1-1
Within 14 days of randomization
Study Visits as outlined in
Table 5.1-2 and Table 5.1-3
Serum Hematology
CBC
X
X
Differential (absolute counts: 
neutrophils, lymphocytes, 
monocytes, basophils, 
eosinophils)
X
X
Serum Chemistry
Sodium
X
X
Potassium
X
X
Chloride
X
X
Carbon Dioxide or 
Bicarbonatea
X
X
Albumin
X
X
Alkaline Phosphatase
X
X
ALT (SGPT)
X
X
AST (SGOT)
X
X
Total Bilirubin
X
X
Direct Bilirubinb
X
Lactate Dehydrogenase
X
X
BUN (or Urea)
X
X
Creatinine
X
X
Glucose
X
X
Calcium
X
X
Magnesium
X
X
Pregnancy Test
Urine or Serum Pregnancy
X (2 tests: one 10 - 14 days prior to the start 
of study drug and one within 24 hours prior 
to the start of study drug)
X
Additional Assessments
Hepatitis B surface antigen
(HBV sAg), and hepatitis C 
antibody (HCV Ab) or HCV 
ribonucleic acid (RNA)
Xc
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Table 5.3.5-1:
Safety Laboratory Assessments
Safety Laboratory Assessments
Screening as outlined in Table 5.1-1
Within 14 days of randomization
Study Visits as outlined in
Table 5.1-2 and Table 5.1-3
Thyroid stimulating hormone 
(TSH) (reflex to free T3/Total 
T3, free T4 for abnormal TSH 
result)
Xc
Xd
a To be done in sites where this is a standard part of the chemistry panel. In sites where testing for CO2/HCO3 is not 
standard, the test is optional
b Only required for subjects with Gilbert’s Syndrome. See Section 3.3.2
c Within 28 days of randomization
d TSH (reflex to free T3/Total T3 and free T4 if abnormal result) to be performed every *2 cycles (7 days) from 
first dose regardless of dosing schedule (at screening, C2D1, C4D1, C6D1...etc).
5.4
Efficacy Assessments
Efficacy endpoints will be based on analysis of serum and urine electrophoresis (SPEP and UPEP), 
sFLC (for those with sFLC only disease), corrected calcium (serum calcium and serum albumin), 
imaging and bone marrow assessments, all at predefined intervals as specified in Table 5.1-1, 
Table 5.1-2, Table 5.1-3 and Table 5.1-4. Assessments done at local labs versus central labs are 
indicated in Table 5.1-1, Table 5.1-2, Table 5.1-3, and Table 5.1-4. Assessments for SPEP, UPEP 
and sFLC will be based on central lab results, whereas assessments of bone marrow, bone lesions, 
extramedullary plasmacytomas, and corrected calcium will be based on local analysis at the site.
5.4.1
Primary Efficacy Assessment
IMWG Response criteria in Appendix 3 will be used for the efficacy analysis. For the purposes of 
this study, all subjects’ tumor assessments by myeloma laboratory tests (SPEP M protein and 
UPEP M protein quantification, corrected calcium (calcium and albumin), and serum free light 
chain) should be re-evaluated per the protocol-stated frequency relative to the date of first dose of 
study drug until confirmed disease progression based on Appendix 3, irrespective of dose delays 
or treatment cycle. If subject does not have documented disease progression as defined in 
Appendix 3 at the time of study drug discontinuation, then disease assessments must continue 
to be performed according to the same schedule described above until confirmed disease 
progression even if a subsequent anti-myeloma treatment is initiated prior to disease 
progression confirmation. Subjects will be followed every 12 weeks, or more frequently, after 
disease progression for survival, subsequent myeloma therapy, and development of second 
primary malignancy.
All efficacy laboratory assessments (SPEP, UPEP, serum/urine immunofixation, and sFLC) 
should be done through the central laboratory, except corrected calcium (serum calcium and serum 
albumin), and bone marrow assessments for plasma cell percentage and light chain restriction 
(clonality by IHC or flow cytometry). All bone marrow aspirate and core biopsy samples for 
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disease assessment should be assessed locally. 
 
For any SPEP, UPEP, or 
sFLC assessment performed locally, in lieu of a central lab assessment, (ie, if the subject cannot 
complete a visit at the study site after treatment discontinuation), M protein absolute quantification 
(eg, g/dL or g/L) or sFLC (eg, mg/L or mg/dL) must be performed. Any laboratory samples 
analyzed locally, including for efficacy, must be entered on the appropriate CRF/eCRF as 
requested by the Sponsor to properly assess efficacy per protocol criteria.
5.4.2
Laboratory Assessments for Myeloma
All laboratory efficacy assessments must be performed until confirmed disease progression or 
withdrawal of consent, even if the subject is discontinued from study therapy and has started new 
myeloma therapy. Confirmation of PR and PD is required on 2 consecutive assessments.
Elotuzumab may be detected in the serum protein electrophoresis (SPEP) and serum 
immunofixation assays of myeloma patients and could interfere with correct response 
classification. A small peak in the early gamma region on SPEP that is IgGƙ on serum 
immunofixation may potentially be attributed to elotuzumab, particularly in patients whose 
endogenous myeloma protein is IgA, IgM, IgD, or lambda light chain restricted. This interference 
can impact the determination of complete response and possibly relapse from complete response 
in patients with IgG kappa myeloma protein. It is likely that nivolumab may also be detected by 
SPEP and immunofixation but this is still under investigation. Serum or peripheral blood samples, 
collected during the study, may be analyzed for the presence of monoclonal antibody interference.
1) Serum: SPEP for M protein quantification, total serum protein, serum immunofixation, and 
quantitative immunoglobulin assay.
a.
Serum Immunofixation (IFE) is required at baseline and to confirm CR regardless of 
whether measurable M-protein was present at baseline.
b. Subjects with measurable disease in SPEP will be assessed for response based on SPEP 
and not by the serum FLC assay.
c.
Subjects with measurable disease in both SPEP and UPEP will be assessed for response 
based on these two tests and not by the serum FLC assay.
d. Subjects with FLC only disease (i.e. serum and urine IFE negative) should be monitored 
by sFLC only; SPEP, UPEP and IFE are required only to code CR in those subjects
e.
Subjects with measurable disease by sFLC only, but with non-measurable serum M-
protein, will be monitored by sFLC assay for response. However, their SPEP should also 
be monitored for progression. 
2) Serum free light chain (sFLC): 
a.
Subjects without measurable serum M-protein (ie, < 0.5 g/dL (5 g/L)) or urine M-protein 
(ie, < 200 mg (0.2 g) per 24 hours) and with measurable involved sFLC are considered 
oligosecretory and must have sFLC assessed at each cycle until confirmed progression.
Please note that SPEP and UPEP should still be followed in those patients.
b. In subjects with measurable disease in serum &/or urine,  sFLC must be assessed a time 
of serum and urine IFE negativity to assess for sCR
3) Urine: 24-hour urine collection for M protein quantification and immunofixation. 24-hour 
urine must be collected with each cycle for all subjects.
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a.
Urine Immunofixation (IFE) is required at baseline and to confirm CR, regardless of 
whether measurable M-protein was present at baseline.
b. Subjects with measurable disease in UPEP will be assessed for response based on UPEP 
and not by the serum FLC assay.
c.
Subjects with measurable disease in both SPEP and UPEP will be assessed for response 
based on these two tests and not by the serum FLC assay
d. Subjects with FLC only disease (i.e. serum and urine IFE negative)  should be monitored 
by sFLC only; SPEP, UPEP and IFE are required only to code CR in those subjects
e.
Subjects with measurable disease by sFLC only, but with non-measurable urine M-protein, 
will be monitored by sFLC assay for response. However, their UPEP should also be 
monitored for progression.
4) Bone marrow aspirate:
Bone marrow aspirate samples will be collected at the timepoints described below for the 
 disease assessment 
(% plasma cells and light chain restriction)
. 
Disease assessments for CR/sCR confirmation will be performed at the local lab. These include 
but are not limited to plasma cell percentage and light chain restriction, per IMWG criteria (See 
Appendix 3).
 bone 
marrow aspirate samples should be collected at the following timepoints:

Required collections at: Screening, ≥VGPR, and every 6 cycles thereafter until PD. In 
subjects with confirmed PD, bone marrow aspirate collection is optional.
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BMS-936558
nivolumab
Table 5.4.2-1:
Bone Marrow Aspirate Samples
Collection
Timing
Local Laboratory
Central Laboratory
Required
Screening (within 35 
days of 
randomization)
Plasma Cell Percentage 
(PC %)
FISH (at screening only)


Required
≥VGPR, then every 6 
cycles thereafter until 
PD.
Bone marrow aspirate 
is optional upon 
progression 
confirmation.
PC %,
Light chain restriction
N.B. Only required to 
confirm CR and sCR.


Note: Bone marrow biopsy is not required by protocol unless an aspirate sample (at any time point above) is not 
available due to a dry tap. In cases of dry tap, bone marrow biopsy can only be used for assessment of PC% and 
Kappa/lambda ratio by IHC
5) Serum Corrected Calcium: Serum corrected calcium should be collected with each cycle for 
all subjects until confirmed disease progression. 
Corrected Calcium, mg/dL = (0.8 x [Normal Albumin, g/dL - Subject’s Albumin, g/dL] + Serum 
Ca, mg/dL
5.4.3
Imaging Assessments for Myeloma
5.4.3.1
Skeletal Survey
Skeletal survey, by conventional radiography, for metastatic disease will be performed within 
28 days of randomization in all subjects. Skeletal survey will be performed on study if clinically 
indicated (development of compression fracture does not exclude response). Use of conventional 
or low dose CT scan (ie, of the spine) or MRI bone survey is acceptable. If imaging is performed 
on treatment for assessment of progression, the site must use the same modality of imaging as used 
in screening. The number and location of skeletal lesions and whether they are lytic should be 
recorded on the eCRF. On treatment survey should record whether there is an increase in the
number or size of lytic lesions.
5.4.3.2
Assessment of Extramedullary Plasmacytoma
Computed tomography or MRI should be performed at screening, if clinically indicated or if 
patient had a previous extramedullary or bone plasmacytoma. To minimize unnecessary radiation 
in myeloma subjects where progression is primarily based on serum and urine M-protein, on study 
assessments should only be performed if clinically indicated (ie, pain, concern for disease
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progression), whether or not present at baseline. In subjects with baseline plasmacytoma, imaging 
follow-up should be done regularly per investigator’s discretion. Imaging confirmation of 
disappearance of plasmacytoma is required at time of CR/sCR if it was not confirmed before.
A sum of the products of the longest diameters and longest perpendicular diameter for all 
measurable lesions will be calculated at screening. This sum will be used as the reference for on 
study assessments by which to characterize the objective tumor response.
All tumor measurements must be made in millimeters. All documented measurable and 
non-measurable lesions are to be followed throughout the trial. All assessments to be used for 
tumor response evaluation, including the baseline assessment, must be performed using the same 
method for repeat assessment. CT and MRI scanning are the preferable methods of assessment. 
Conventional CT and MRI should be performed with contiguous cuts of 10 mm or less or with 
cuts of 5 (or 10) mm if spiral CT scanning is used. Imaging-based evaluation is preferred to 
evaluation by clinical examination. Evaluation by chest x-ray is less preferable than CT or MRI, 
and should only be used for well-defined lesions surrounded by aerated lung. Clinical examination 
is only acceptable when lesions are superficial, such as a skin nodule or palpable lymph node. Skin 
lesions must be documented by a photograph with a ruler. Ultrasound is not acceptable for 
documentation of measurable disease.
Duplicate copies of all imaging studies used for tumor response evaluation will be made available 
for review by the Sponsor upon request.
Measurable disease are lesions that can be accurately measured in 2 dimensions and both diameters 
must be 20 mm when evaluated by standard CT scanning or 10 mm when evaluated by spiral 
CT scanning or MRI. The minimum diameter size should be at least twice the slice thickness.
Non-measurable disease are all other lesions (or sites of disease), including those that are too small 
(ie, do not meet above criteria), occur within a previously irradiated area (unless they are 
documented as new lesions since the completion of radiation therapy), bone lesions, 
leptomeningeal disease, ascites, pleural or pericardial effusion (exception for effusions 
documented by cytology as not malignant or present at baseline without progression), lymphangitis 
cutis/pulmonis, abdominal masses that are not pathologically/cytologically confirmed and 
followed by imaging techniques, and cystic lesions.
5.4.4
Definitions of Response and Progression Criteria
See Appendix 3 for definitions of response and progression. All criteria are derived from 
IMWG32,33,34. All response and progression categories require 2 consecutive assessments to 
confirm response and progression before initiation of any new therapy.
NB: Table in Appendix 3 is inclusive of multiple response category definitions; however, the 
protocol/CRF is not reporting on all of these response categories.  
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BMS-936558
nivolumab
Revised Protocol No.: 03
Date: 12-Nov-2018
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5.8
Other Assessments 
Not applicable
5.9
Results of Central Assessments
All efficacy laboratory assessments should be performed by the central laboratory. Investigative 
site staff will receive reports of the results on an ongoing basis for treatment decisions and patient 
management throughout the study. If the investigator chooses to perform any additional serum and 
urine myeloma lab tests locally, the results must be reported in the CRF.
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 
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unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug.
The causal relationship to study drug is determined by a physician and should be used to assess all 
adverse events (AE). The causal relationship can be one of the following:
Related: There is a reasonable causal relationship between study drug administration and 
the AE.
Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.
The term "reasonable causal relationship" means there is evidence to suggest a causal relationship. 
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.)
BMS will be reporting adverse events to regulatory authorities and ethics committees according to 
local applicable laws including European Directive 2001/20/EC and FDA Code of Federal 
Regulations 21 CFR Parts 312 and 320.
6.1
Serious Adverse Events
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 (see NOTE 
below)

results in persistent or significant disability/incapacity

is a congenital anomaly/birth defect

is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [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 6.6 for the definition of potential DILI.)
Suspected transmission of an infectious agent (eg, pathogenic or nonpathogenic) via the study drug 
is an SAE.
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Although pregnancy, overdose, cancer, and potential drug induced liver injury (DILI) are not 
always serious by regulatory definition, these events must be handled as SAEs. (See Section 6.1.1
for reporting pregnancies).
Any component of a study endpoint that is considered related to study therapy (eg, death is an 
endpoint, if death occurred due to anaphylaxis, anaphylaxis must be reported) should be reported 
as SAE (see Section 6.1.1 for reporting details).
NOTE: 
The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status 
(eg, routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (eg, lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)

Admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 of the nivolumab and elotuzumab Investigator Brochure (IB) contains 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 must be collected that occur during the screening 
period and within 100 days of discontinuation of dosing or within 30 days of the last visit for 
screen failures. For subjects randomized and never treated with study drug, SAEs should be 
collected for 30 days from the date of randomization.
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure. 
The investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure. 
An SAE report must be completed for any event where doubt exists regarding its seriousness. 
If the investigator believes that an SAE is not related to study drug, but is potentially related to the 
conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
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SAEs, whether related or not related to study drug, and pregnancies must be reported to BMS 
(or designee) within 24 hours of awareness of the event. SAEs must be recorded on the SAE Report 
Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). The preferred 
method for SAE data reporting collection is through the eCRF. The paper SAE/pregnancy 
surveillance forms are only intended as a back-up option when the eCRF system is not functioning.
In this case, the paper forms are to be transmitted via email or confirmed facsimile (fax) 
transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number: Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. In the event the electronic system is unavailable for transmission, 
paper forms must be used and submitted immediately. When paper forms are used, the original 
paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
A SUSAR (Suspected, Unexpected Serious Adverse Reaction) is a subset of SAEs and will be 
reported to the appropriate regulatory authorities and investigators following local and global 
guidelines and requirements.
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 until 100 days 
from the last dose 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.
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment as 
appropriate. All identified nonserious AEs must be recorded and described on the nonserious AE 
page of the CRF (paper or electronic). 
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Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities that 
are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form electronic) as appropriate. Paper forms are only intended as a back-up 
option when the electronic system is not functioning.

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the subject to have study drug discontinued 
or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the study drug , 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 time 
to washout plus one ovulatory cycle (30 days) for a total of 23 weeks, or plus one spermatogenesis 
cycle (90 days) for a total of 31 weeks after product administration (for patients in arms A and C; 
4 week duration needed for arm B), the investigator must immediately notify the BMS Medical 
Monitor/designee of this event and complete and forward a Pregnancy Surveillance Form to BMS 
Designee within 24 hours of awareness of the event and in accordance with SAE reporting 
procedures described in Section 6.1.1. Refer to pomalidomide pregnancy risk prevention plan for 
additional information (Appendix 6). 
In most cases, the study drug will be permanently discontinued in an appropriate manner (eg, dose 
tapering if necessary for subject safety). Please call the BMS Medical Monitor within 24 hours of 
awareness of the pregnancy.
The investigator must immediately notify the BMS (or designee) Medical Monitor of this event 
and complete and forward a Pregnancy Surveillance Form to BMS (or designee) within 24 hours 
of awareness of the event and in accordance with SAE reporting procedures described in 
Section 6.1.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
BMS. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
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6.5
Overdose
An overdose is defined as the accidental or intentional administration of any dose of a product that 
is considered both excessive and medically important. All occurrences of overdose must be 
reported as an SAE (see Section 6.1.1 for reporting details.).
Of note, doses up to 20mg/kg of elotuzumab and doses of up to 10mg/kg of nivolumab have been 
safely administered in prior studies. 
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. AT (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, electrocardiogram, 
x-ray filming, any other potential safety assessment required or not required by protocol should 
also be recorded as a nonserious or serious AE, as appropriate, and reported accordingly.
Second primary malignancies (SPMs) will be collected throughout the study which includes 
assessments during survival follow-up. All SPMs that occur during the screening period and within 
60 days of discontinuation of dosing will be reported as an SAE regardless of relationship to study 
drug. Additionally, any SPM that occurs after this timeframe and considered related to study drug 
will be reported as an SAE. All other SPMs will be collected and reported on a separate CRF page.
Immune-mediated adverse events (IMAEs) are AEs consistent with an immune-mediated
mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection
or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology
which were exacerbated by the induction of autoimmunity. Information supporting the assessment
will be collected on the subject’s case report form.
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7
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
An independent data monitoring committee (DMC) will be established before the first subject is
treated to provide oversight of safety and study conduct. The DMC will review safety and efficacy 
data at periodic intervals.
The first comprehensive safety review will occur after the first 42 treated subjects (ie, the first 
6 subjects in the exploratory arm) have been followed for 1 month
An independent review committee (IRC) had been set up to review blinded responses and 
progression criteria in each subject. However, after enrollment was discontinued, it was decided 
to discontinue efficacy assessment by IRC.
Separate charters will provide further guidance and describe the activities of these committees.
8
STATISTICAL CONSIDERATIONS
8.1
Sample Size Determination
Prior to Revised Protocol 02, the study planned to randomize 406 subjects at a 3:3:1 ratio to N-Pd 
vs Pd vs NE-Pd. Also, subjects randomized to the Pd control arm were allowed to cross-over to 
the exploratory NE-Pd arm upon progression. As of 1 September 2017, cross-over was no longer 
permitted and as of Revised Protocol 02, the exploratory NE-Pd arm was closed to enrollment.
In Revised Protocol 02, the planned sample size for this study was revised to approximately 348 
randomized subjects randomized at a 1:1 ratio to N-Pd vs Pd. The sample size of the study accounts 
for the primary efficacy endpoint of PFS. PFS will be evaluated for treatment effect at the overall 
alpha level of 0.05 (two-sided) with 90% power with two interim analyses, with the first one for 
early futility and the second for efficacy.

The study requires at least 262 PFS events to ensure that a two-sided 5% type I error sequential 
test procedure with two interim analyses will have 90% power to detect a hazard ratio (HR) of 
0.667, corresponding to a median PFS of 6 vs 4 months for the N-Pd and Pd arms, respectively.
East version 6.3 was used for sample size/power computation. 
Table 8.1-1:
Schedule of Analyses
Interim analysis for PFS
Final analysis for PFS
Condition for PFS
Interim 1: at least 131 PFS events (for 
futility only)
Interim 2: at least 184 PFS events (for 
efficacy only)
at least 262 PFS events
Expected timing
Interim 1: 8 months after enrollment is 
reopened
Interim 2: 16 months after enrollment is re-
opened
22 months after enrollment is re-opened
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Table 8.1-1:
Schedule of Analyses
Interim analysis for PFS
Final analysis for PFS
Alpha Level
Interim 1: Futility boundary on HR 1.053
Interim 2: PFS at 0.0148 levela
Final PFS at 0.0456 levela
a Using Lan-DeMets spending function with O’Brien and Fleming type of boundary when exactly 184 PFS events 
are observed at the interim analysis for PFS.
On 23-August-2018, the Sponsor (BMS) decided to permanently discontinue enrollment based on 
insufficient clinical benefit observed at an interim futility analysis for PFS. A total of 170 subjects 
had been randomized in the study.
8.2
Populations for Analyses

All Enrolled subjects: All subjects who signed an informed consent form and were 
registered into the IWRS

All Randomized subjects: All enrolled subjects who were randomized to any treatment 
arm. This is the primary dataset for analyses of study conduct, efficacy parameters, baseline 
characteristics

All Treated subjects: All randomized subjects who received at least one dose of study drug.
This is the primary dataset for safety and exposure analyses.
8.3
Endpoints
8.3.1
Primary Endpoint
The primary objectives in the study will be measured by the primary endpoint of PFS assessed by 
investigator within the N-Pd and Pd arms.
8.3.1.1
Progression Free Survival
PFS is defined as the time from randomization to the date of the first documented tumor 
progression or death due to any cause. PFS will be determined by an investigator, based upon 
laboratory data (eg, SPEP/IFE, UPEP/IFE, bone marrow disease assessment, serum FLC) as 
defined by the IMWG criteria. Subjects who die without a reported prior progression will be 
considered to have progressed on the date of their death. Subjects who did not progress or die will 
be censored on the date of their last efficacy assessment. Subjects who did not have any on study 
efficacy assessments and did not die will be censored on the date they were randomized. Subjects 
who started any subsequent anti-cancer therapy without a prior reported progression will be 
censored at the last efficacy assessment prior to subsequent anti-cancer therapy.
8.3.2
Secondary Endpoint(s)
Overall Survival (OS) 
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OS is defined as the time between the date of randomization and the date of death due to any cause. 
OS will be censored on the last date a subject was known to be alive. 
Objective Response Rate (ORR) 
Objective response rate is defined as the proportion of randomized subjects who achieve a best 
overall response of stringent complete response (sCR), complete response (CR), very good partial 
response (VGPR), or partial response (PR) using the IMWG criteria.
Time to Response (TTR)
Time to Response (TTR) is defined as the time from the date of randomization to the date of the 
first sCR, CR, VGPR, or PR. TTR will be evaluated for responders (BOR is either sCR, CR, 
VGPR, or PR) only.
Duration of Response (DOR)
Duration of Response (DOR) is defined as the time between the date of first response to the date 
of the first objectively documented tumor progression as assessed by independent review 
committee according to modified IMWG criteria or death due to any cause prior to subsequent 
anti-cancer therapy. Subjects who neither progress nor die will be censored on the date of their last 
tumor assessment prior to subsequent anti-cancer therapy. DOR will be evaluated for responders 
(BOR is either sCR, CR, VGPR, or PR) only.
8.3.3
Exploratory Endpoint(s) 
Within the NE-Pd arm, the following endpoints are considered as exploratory endpoints, ORR,
PFS, DOR, and TTR by investigator.
For subjects who crossed-over from the control arm (Pd) to the exploratory arm (NE-Pd), the 
following endpoints are considered as exploratory efficacy endpoints, ORR, PFS, DOR, and TTR 
by investigator.
8.4
Analyses
The main analysis will be performed after the last subject has complete safety follow up (at least 
100 days after study drug discontinuation).
8.4.1
Demographics and Baseline Characteristics
Demographic and baseline characteristics will be summarized for all randomized subjects by 
treatment group, as randomized, using descriptive statistics.
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8.4.2
Efficacy Analyses
8.4.2.1
Methods for Primary Endpoints
PFS Analysis Time points

At the time of PFS analyses, as assessed by investigator, the distribution of PFS in N-Pd group 
will be compared with the Pd via a two-sided, log-rank test stratified by prior lines of therapy 
and ISS stage at study entry. The hazard ratio (HR) and the corresponding 100x(1-adjusted 
alpha)% confidence interval (CI) will be estimated in a stratified Cox proportional hazards 
model using treatment as a single covariate.

PFS curves, PFS medians with two-sided 95% CIs, and PFS rates at select milestone with 95% 
CIs will be estimated using Kaplan-Meier methodology.
8.4.2.2
Methods for Secondary Endpoints
Analysis of OS

At the time of PFS analyses, OS will be summarized by the Kaplan-Meier product-limit 
method within each arm. Median values along with two-sided 95% CIs based on the log-log 
transformation, will be calculated. Additional details of OS analysis will be included in the 
SAP
Analysis of ORR by Investigator

Investigator-determined 
ORR 
analyses 
will 
be 
conducted 
using 
a 
two-sided 
Cochran-Mantel-Haenszel (CMH) test stratified by prior lines of therapy and ISS stage at study 
entry to compare N-Pd to Pd arm. Associated odds ratios and 95% CIs will be calculated. 
Additionally, ORRs and corresponding 95% exact CIs will be calculated using the 
Clopper-Pearson method for N-Pd and Pd arms
Analysis of DOR and TTR

DOR and TTR will be computed for subjects who achieve sCR, CR, VGPR, or PR as assessed 
by investigator according to modified IMWG criteria. Median values of DOR, along with two-
sided 95% CI, will be calculated using KM product-limit method. Summary statistics of TTR 
will be provided. More detailed analysis of DOR and TTR will be described in the SAP
Details on the testing procedure will be described in SAP.
8.4.2.3
Methods for Exploratory Endpoints
Details of following analyses will be included in the SAP.

Analyses of the data for subjects who crossed-over from the control arm (Pd) to the exploratory 
arm (NE-Pd) will be analyzed separately

Analyses of the data in NE-Pd arm are of exploratory nature and may be performed at several 
times prior to completion of the study in order to facilitate program decisions
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8.4.3
Safety Analyses
The safety analysis will be performed in all treated subjects. Descriptive statistics of safety will be 
presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.0 by treatment group. Adverse Events (AE), drug-related AEs, Serious 
Adverse Events (SAE) and drug-related SAEs will be tabulated using worst grade per NCI CTCAE 
v.4.0 criteria by system organ class and preferred term. On-study lab parameters including 
hematology, chemistry, liver function and renal function will be summarized using worst grade 
per NCI CTCAE v.4.0 criteria.
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8.4.7
Other Analyses 
Not applicable
8.5
Interim Analyses
Interim Analysis for PFS Futility 
At FDA’s request on 21-June-2018, a formal PFS interim analysis for futility was conducted in 
August 2018 based on the database lock on 12-April-2018. The investigator assessed progression 
events (NPd and Pd arms) were used in this analysis. Prior to running the futility analysis, a futility 
criteria was defined based on conditional power assuming 85 events (30% information fraction).  
The stopping criteria for futility was that the conditional power under observed trend is strictly 
less than 1%. This would correspond to a HR (NPd vs. Pd) boundary of 0.995 and the 
corresponding conditional power under alternative would be 67.8%, ie if alternative hypothesis is 
true (HR = 0.667), there is still 67.8% chance that the study will be positive at the final analysis. 
Subsequently, after conducting the interim analysis, the decision was made to permanently 
discontinue enrolment based on insufficient clinical benefit observed at an interim futility analysis 
for PFS. All futility analyses were conducted by the unblinded independent statistics vendor. 
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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, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a schedule 
of on-site visits for targeted review of study records. 
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. CRF pages and/or electronic files may serve as the source documents:
such as outcome assessments.
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. 
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9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event 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 for investigational products. Records or 
logs must comply with applicable regulations and guidelines and should include:

amount received and placed in storage area

amount currently in storage area

label identification number or batch number 

amount dispensed to and returned by each subject, including unique subject identifiers

amount transferred to another area/site for dispensing or storage

nonstudy disposition (eg, lost, wasted) 
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
amount destroyed at study site, if applicable

amount returned to BMS

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 
understanding of product safety. CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported or identified during the course of the study.
For sites using the BMS 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 
electronic SAE form and Pregnancy Surveillance form, respectively. If electronic SAE form is not 
available, a paper SAE form can be used. Spaces may be left blank only in those circumstances 
permitted by study-specific CRF completion guidelines provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. For electronic CRFs, review and approval/signature is completed 
electronically through the BMS 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. 
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For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria:

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 must adhere to the publication requirements set forth in the clinical 
trial agreement (CTA) governing [Study site or Investigator] participation in the study. These 
requirements include, but are not limited to, submitting proposed publications to BMS at the 
earliest practicable time prior to submission or presentation and otherwise within the time period 
set forth in the CTA.
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10
GLOSSARY OF TERMS
N/A
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11
LIST OF ABBREVIATIONS
Term
Definition
ADCC
Antibody dependent cell-mediated cytotoxicity
AE
Adverse event
BMS
Bristol-Myers Squibb
CDR
Complementary Determining Regions
°C
Celsius
CI
Confidence Interval
CMH
Cochran-Mantel-Haenszel
CMMC
Circulating Multiple Myeloma Cells
CR
Complete response
CRF
Case Report Form
CrCl
Creatinine Clearance
CS1
CD-2 subset 1
CT
Computerized tomography
CTCAE
Common Terminology Criteria for Adverse Events
DILI
Drug induced liver injury
DLT
Dose-limiting toxicity
DMC
Data monitoring committee
DVT
Deep Vein Thrombosis
EBMT
European Group for Blood and Bone Marrow Transplant
ECG
Electrocardiogram
E-Pd
Elotuzumab Pomalidomide (low dose) dexamethasone
EPO
Erythropoietin
FSH
Follicle-stimulating hormone
GCP
Good Clinical Practice
G-CSF
Granulocyte colony-stimulating factor
HCG
Human Chorionic Gonadotropin
HR
Hazard Ratio
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Term
Definition
HRT
Hormone replacement therapy
ICH
International Council on Harmonization
IF
Immunofixation
IHC
Immunohistochemistry
I-O
Immuno-oncology
IL-2
Interleukin 2
IMiDs
Immune Modulatory Drugs
IMWG
International Myeloma Working Group
IRB/IEC
Institutional Review Board/Independent Ethics Committee
IRC
Independent Review Committee
IV
Intravenous
ITT
Intent-to-treat
NE-Pd
Nivolumab Elotuzumab Pomalidomide dexamethasone
NK
Natural Killer
NKT
Natural Killer T-Cells
N-Pd
Nivolumab pomalidomide dexamethasone
Ld
Lenalidomide (low-dose) dexamethasone
LD
Lenalidomide (high-dose) dexamethasone
LdE
Lenalidomide, (low-dose) dexamethasone, elotuzumab
LPFV
Last patient first visit
MGUS
Monoclonal Gammopathy of Undetermined Significance
MM
Multiple Myeloma
MR
Minor (Minimal) Response
MRI
Magnetic Resonance Imaging
MTD
Maximum tolerated dose
NK
Natural Killer 
NKT
Natural Killer T-cell
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Term
Definition
ORR
Objective Response Rate
OS
Overall Survival
Pd
Pomalidomide (low dose) dexamethsone
PFS
Progression-free survival
PK
Pharmacokinetic
PR
Partial Response
rrMM
relapsed refractory Multiple Myeloma
SAE
Serious adverse event
sCR
Stringent complete response
sMICA
soluble major histocompatibility complex class I chain-related gene A
SLAMF7
Signaling Lymphocyte Activation Molecule family 7
SPM
Second primary malignancy
SMM
Smoldering Multiple Myeloma
WOCBP
Women of childbearing potential
VGPR
Very Good Partial Response
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12
REFERENCES
1
DeVita VT, Lawrence TS, and Rosenberg SA. Cancer: Principles and Practice of Oncology 
9th edition. Chapter 136; pp 1999-1999. Wolters Kluwer/ Lippincott, Williams, and Wilkins 
2011.
2
International Myeloma Foundation. Concise Review of the Disease and Treatment Options 
2008/2009 Edition. Available at: http://myeloma.org/. Accessed 25-May-2010.
3
Pratt, Guy. Histone deacetylase inhibitors in multiple myeloma. The Lancet Oncology , 
Volume 14 , Issue 11 , 1038 - 1039
4
Ludwig H, Beksac M, Bladé J, et al. Current multiple myeloma treatment strategies with novel 
agents: a European perspective. The Oncologist. 2010; 15:6-25.
5
Jemal A, Marray T, Samuels A, Tiwari RC, Ghafoor, A, Thun MJ. Cancer Statistics. CA 
Cancer J Clin 2005;55: 10-50.
6
Liu, Blood, 2007. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and 
increase expression after stimulation with IFN- g and TLR ligands via a MyD88-, TRAF6-, 
and MEK-dependent pathway.
7
Hallett, Biol. Blood Marrow Transplant, 2011. Immunosuppressive Effects of Multiple 
Myeloma Are Overcome by PD-L1 Blockade.
8
Gorgun, Clinical Cancer Research, 2015. Lenalidomide Enhances Immune Checkpoint 
Blockade Induced Immune Response in Multiple Myeloma
9
Tamura, Leukemia, 2012. Marrow stromal cells induce B7-H1 expression on myeloma cells, 
generating aggressive characteristics in multiple myeloma.
10 Ray, Leukemia, 2015. Targeting PD1–PDL1 immune checkpoint in plasmacytoid dendritic 
cell interactions with T cells, natural killer cells and multiple myeloma cells.
11 Rosenblatt, J. Immunotherapy, 2011. PD-1 blockade by CT-011, anti PD-1 antibody, enhances 
ex-vivo T cell responses to autologous dendritic/myeloma fusion vaccine.
12 Benson, Blood, 2010. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple 
myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody
13 Collins SM, Bakan CE, Swartzel GD, et. al. Elotuzumab directly enhances NK cell cytotoxicity 
against myeloma via CS1 ligation: evidence for augmented NK cell function complementing 
ADCC. Cancer Immunol Immunother. 2013 Dec;62(12):1841-9.
14 Guo H, Cruz-Munoz M-E, Wu N, et. al. Immune cell inhibition by SLAMF7 is mediated by 
mechanism requiring Src kinases, CD45 and SHIP-1 defective in multiple myeloma cells. Mol 
Cell Biol. 2015 Jan;35(1):41-51
15 Hsi ED, Steinle R, Balasa B, et. al. CS1, a potential new therapeutic antibody target for the 
treatment of multiple myeloma. Clin Cancer Res. 2008 May 1;14(9):2775-84
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16 Richardson, Paul G et al. Elotuzumab in combination with lenalidomide and dexamethasone 
in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-
label, phase 1b–2 dose-escalation study. The Lancet Haematology , Volume 2 , Issue 12 , e516 
- e527 
17 Elotuzumab IB. Version 11. August 2015.
18 Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in Combination With Lenalidomide and 
Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma.; JCO 2012; 
30(16):1953-1959.
19 Suen, Leukemia, 2015. The failure of immune checkpoint blockade in multiple myeloma with 
PD-1 inhibitors in a phase 1 study.
20 http://www.pomalyst.com/wp-content/uploads/2013/08/prescribing_information.pdf
21 Balasa B1, Yun R, Belmar NA, et. al. Elotuzumab enhances natural killer cell activation and 
myeloma cell killing through interleukin-2 and TNF-α pathways. Cancer Immunol 
Immunother. 2015 Jan;64(1):61-73.
22 Robbins M, Jure-Kunkel M, Dito G, et. al. Effects of IL-21, KIR blockag and CD137 agonism 
on the non-clinical activity of elotuzumab. Blood 2014 124:4717.
23 Bezman NA, Jhatakia A, Kearney Ay, et al. PD-1 blockade enhances elotuzumab efficacy in 
mouse tumor models. Blood Advances  2017; 1:753-65.
24 Jemal A, Marray T, Samuels A, Tiwari RC, Ghafoor, A, Thun MJ. Cancer Statistics. CA
Cancer J Clin 2005;55: 10-50.
25 Richardson PG, Siegel D, Baz R, et al. Phase 1 study of pomalidomide MTD, safety, and 
efficacy in patients with refractory multiple myeloma who have received lenalidomide and 
bortezomib. Blood. 2013;121(11):1961-1967.
26 Elotuzumab IB. Version 11. August 2015
27
Rajkumar SV, Harousseau JL, Durie B, et al. Consensus recommendations for the uniform 
reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. 
Blood. 2011 May 5;117(18):4691-5. doi: 10.1182/blood-2010-10-299487
28 http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/
DrugInteractionsLabeling/ucm093664.htm#potency
29 http://www.pomalyst.com/hcp
30 Kyle RA, Yee GC, Somerfield MR, Flynn PJ, Halabi S, Jagannath S, Orlowski RZ, Roodman 
DG, Twilde P, Anderson K; American Society of Clinical Oncology. American Society of 
Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in 
multiple myeloma. J Clin Oncol. 2007 Jun 10;25(17):2464-72.
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31 Greipp PR, San Miguel JF, Brian GM, Durie JJ, Crowley BB, Blade J, Boccadoro J, Child A, 
Avet-Loiseau H, Kyle RA, Laheuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik 
C, Sonneveld P, Tosi P, Turesson I, Westin J. International Staging System for Multiple 
Myeloma. J Clin Oncology 2005 23:3412-3420.
32 Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International 
uniform response criteria for multiple myeloma. Leukemia 2006; 20: 2220.
33 Anderson KC, Kyle RA, Rajkumar SV, et al. Leukemia 2008; 231-239.
34 San Miguel J, Weisel K, Moreau P, Lacy M et al. Pomalidomide plus low-dose dexamethasone 
versus high-dose dexamethasone alone for patients with relapsed and refractory multiple 
myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 
Oct;14(11):1055-66.
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APPENDIX 1
DEFINITION OF LINES OF THERAPY
Line of Therapy (from International Myeloma Working Group (Rajkumar, 2011)) is defined as 
one or more cycles of a planned treatment program. This may consist of one or more planned 
cycles of single-agent therapy or combination therapy, as well as a sequence of treatments 
administered in a planned manner. For example, a planned treatment approach of induction 
therapy followed by autologous stem cell transplantation, followed by maintenance is considered 
one line of therapy. Each subsequent line of therapy starts when a planned course of therapy is 
modified to include other treatment agents (alone or in combination) as a result of disease 
progression, relapse, or toxicity. A new line of therapy also starts when a planned period of 
observation off therapy is interrupted by a need for additional treatment for the disease.
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APPENDIX 2
ECOG PERFORMANCE STATUS 
These scales are used by doctors and researchers to assess how a patient’s disease progressing, 
assess how the disease affects the dailing living abilitiesof the patient and determine appropriate 
treatment and prognosis. They are included here for health care professionsals to assess.
ECOG PERFORMANCE STATUS
0
Fully active, able to carry on all pre-disease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours
3
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair
5
Dead
Toxicity and Response Criteria of the Eastern Cooperative Oncology Group.
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APPENDIX 3
DEFINITIONS OF RESPONSE AND PROGRESSION CRITERIA
NB: The table below is inclusive of multiple response category definitions; however, the 
protocol/CRF is not reporting on all of these response categories. The standard IMWG 
response criteria have been limited to the eligible patient population in the study.
Table 1:
IMWG criteria for response assessment including criteria for 
minimal residual disease
Response Subcategory
Response criteriaa
IMWG MRD criteria (requires a complete response as defined below)
Sustained MRD-
negative
MRD negativity in the marrow (NGF or NGS, or both) and by imaging as defined 
below, confirmed minimum of 1 year apart. Subsequent evaluations can be used to 
further specify the duration of negativity (eg, MRD-negative at 5 years)b
Flow MRD-negative
Absence of phenotypically aberrant clonal plasma cells by NGF on bone marrow 
aspirates using the EuroFlow standard operation procedure for MRD detection in 
multiple myeloma (or validated equivalent method) with a minimum sensitivity of 1 
in 10⁵ nucleated cells or higher1
Sequencing MRD-
negative
Absence of clonal plasma cells by NGS on bone marrow aspirate in which presence of 
a clone is defined as less than two identical sequencing reads obtained after DNA 
sequencing of bone marrow aspirates using the LymphoSIGHT platform (or validated 
equivalent method) with a minimum sensitivity of 1 in 10⁵ nucleated cells or higher
Imaging-positive MRD-
negative
MRD negativity as defined by NGF or NGS plus disappearance of every area of 
increased tracer uptake found at baseline or a preceding PET/CT or decrease to less 
mediastinal blood pool SUV or decrease to less than that of surrounding normal 
tissuec
Standard IMWG response criteria
Stringent complete
response
Complete response as defined below plus normal FLC ratio and absence of clonal 
cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ 
and λ patients, respectively, after counting ≥100 plasma cells)d
Complete responsee
Negative immunofixation on the serum and urine and disappearance of any soft tissue 
plasmacytomas and < 5% plasma cells in bone marrow aspirates
Very good partial 
responsee
Serum and urine M-protein detectable by immunofixation but not on electrophoresis 
or ≥90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h
Partial response
≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by 
≥90% or to < 200 mg per 24 h;
If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference 
between involved and uninvolved FLC levels is required in place of the M-protein 
criteria;
If serum and urine M-protein are unmeasurable, and serum-free light assay is also 
unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein,
provided baseline bone marrow plasma-cell percentage was ≥30%. In addition to 
these criteria, if present at baseline, a ≥50% reduction in the size (SPD)f of soft tissue 
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Table 1:
IMWG criteria for response assessment including criteria for 
minimal residual disease
plasmacytomas is also required
Minimal response
25% but 49% reduction of serum M-protein and reduction in 24-h urine M-protein 
by 50–89%. In addition to the above listed criteria, if present at baseline, a 50% 
reduction in the size (SPD)f of soft tissue plasmacytomas is also required
Stable disease
Not recommended for use as an indicator of response; stability of disease is best 
described by providing the time-to-progression estimates. Not meeting criteria for
complete response, very good partial response, partial response, minimal response, or 
progressive disease
Progressive diseaseg
Any one or more of the following criteria:
1.
Increase of 25% from lowest confirmed response value in one or more of the 
following criteria:
a)
Serum M-protein (absolute increase must be 0.5 g/dL);
b)
Serum M-protein increase 1 g/dL, if the lowest M component was 5 
g/dL;
c)
Urine M-protein (absolute increase must be 200 mg/24 h);
d)
In patients without measurable serum and urine M-protein levels, the 
difference between involved and uninvolved FLC levels (absolute increase 
must be > 10 mg/dL);
2.
Appearance of a new lesion(s), 50% increase from nadir in SPDf of > 1 lesion, 
or 50% increase in the longest diameter of a previous lesion > 1 cm in short 
axis;
IMWG=International Myeloma Working Group. MRD=minimal residual disease. NGF=next-generation flow. 
NGS=next-generation sequencing. FLC=free light chain. M-protein=myeloma protein. SPD=sum of the products of 
the maximal perpendicular diameters of measured lesions. FCM=flow cytometry. SUVmax=maximum standardised 
uptake value. MFC=multiparameter flow cytometry. 18F-FDG PET=18F -fluorodeoxyglucose PET. 
a All response categories require two consecutive assessments made any time before starting any new 
therapy; for MRD there is no need for two consecutive assessments, but information on MRD after each 
treatment stage is recommended (eg, after induction, high-dose therapy/ASCT, consolidation, maintenance). 
MRD tests should be initiated only at the time of suspected complete response.  All categories of response and 
MRD require no known evidence of progressive or new bone lesions if radiographic studies were performed. 
However, radiographic studies are not required to satisfy these response requirements except for the requirement 
of FDG PET if imaging MRD-negative status is reported. Each category, except for stable disease, will be 
considered unconfirmed until the confirmatory test is performed. The date of the initial test is considered as the 
date of response for evaluation of time dependent outcomes such as duration of response.
b Sustained MRD negativity when reported should also annotate the method used (eg, sustained flow MRD-
negative, sustained sequencing MRD-negative).
c Criteria used by Zamagni and colleagues,2 and expert panel (IMPetUs; Italian Myeloma criteria for PET Use).3, 4
Baseline positive lesions were identified by presence of focal areas of increased uptake within bones, with or 
without any underlying lesion identified by CT and present on at least two consecutive slices. Alternatively, an 
SUVmax=2·5 within osteolytic CT areas >1 cm in size, or SUVmax=1·5 within osteolytic CT areas 1 cm in 
size were considered positive. Imaging should be performed once MRD negativity is determined by MFC or 
NGS.
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d Presence/absence of clonal cells on immunohistochemistry is based upon the //L ratio. An abnormal κ/λ ratio 
by immunohistochemistry requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting 
presence of an abnormal clone is κ/λ of > 4:1 or < 1:2.
e When the only method to measure disease is by serum FLC levels: complete response can be defined as a normal 
FLC ratio of 0·26 to 1·65 in addition to the complete response criteria listed previously. Very good partial 
response in such patients requires a 90% decrease in the difference between involved and uninvolved FLC 
levels
f Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT 
scans where applicable. For patients with only skin involvement, skin lesions should be measured with a ruler. 
Measurement of tumour size will be determined by the SPD
g Positive immunofixation alone in a patient previously classified as achieving a complete response will not be 
considered progression. In the case where a value is felt to be a spurious result per physician discretion (eg, a 
possible laboratory error), that value will not be considered when determining the lowest value.
References
1.
Paiva B, Gutierrez NC, Rosinol L, et al, for the GEM (Grupo Español de MM)/PETHEMA (Programa para el 
Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Groups. High-risk cytogenetics and 
persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response 
after autologous stem cell transplantation in multiple myeloma. Blood 2012; 119: 687–91.
2.
Zamagni E, Nanni C, Mancuso K, et al. PET/CT improves the definition of complete response and allows to 
detect otherwise unidentifi able skeletal progression in multiple myeloma. Clin Cancer Res 2015; 21: 4384–90.
3.
Usmani SZ, Mitchell A, Waheed S, et al. Prognostic implications of serial 18-fl uoro-deoxyglucose emission 
tomography in multiple myeloma treated with total therapy 3. Blood 2013;121: 1819–23.
4.
Nanni C, Zamagni E, Versari A, et al. Image interpretation criteria for FDG PET/CT in multiple myeloma: a 
new proposal from an Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET USe). Eur J Nucl Med 
Mol Imaging 2015; 43: 414–21.
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APPENDIX 4
THE INTERNATIONAL STAGING SYSTEM (ISS) FOR MULTIPLE 
MYELOMA
Stage
Criteria
Median Survival 
(months)
Stage I
Serum 2-microglobulin < 3.5 mg/L (296.2 nmol/L)
Serum albumin 3.5 g/dL
62
Stage II
Not stage I or III
(There are two categories for stage II)
serum β2-microglobulin < 3.5 mg/L (296.2 nmol/L) but serum 
albumin < 3.5 g/dL OR
β2-microglobulin 3.5 to < 5.5 mg/L (296.2 to < 465.5 nmol/L)
irrespective of the serum albumin level
44
Stage III
Serum β2-microglobulin 5.5 mg/L (465.5 nmol/L)
29
Greipp PR, San Miguel JF, Brian GM, Durie JJ, Crowley BB, Blade J, Boccadoro J, Child A, Avet-Loiseau H, Kyle 
RA, Laheuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, 
Westin J. International Staging System for Multiple Myeloma. J Clin Oncology 2005 23:3412-3420.
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APPENDIX 5
NIVOLUMAB MANAGEMENT ALGORITHMS
These general guidelines constitute guidance to the Investigator and may be supplemented by 
discussions with the Medical Monitor representing the Sponsor. The guidance applies to all 
immuno-oncology agents and regimens.
A general principle is that differential diagnoses should be diligently evaluated according to 
standard medical practice. Non-inflammatory etiologies should be considered and appropriately 
treated.
Corticosteroids are a primary therapy for immuno-oncology drug-related adverse events. The 
oral equivalent of the recommended IV doses may be considered for ambulatory patients with 
low-grade toxicity. The lower bioavailability of oral corticosteroids should be taken into account 
when switching to the equivalent dose of oral corticosteroids.
Consultation with a medical or surgical specialist, especially prior to an invasive diagnostic or 
therapeutic procedure, is recommended.
The frequency and severity of the related adverse events covered by these algorithms will depend 
on the immuno-oncology agent or regimen being used.
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APPENDIX 6
POMALIDOMIDE PREGNANCY RISK PREVENTION PLAN
Appendix 6 only applies to participants in certain countries or regions.
All participants must follow either the local pomalidomide risk management program or the 
Pomalidomide Pregnancy Risk Prevention Plan.
1
POMALIDOMIDE PREGNANCY PREVENTION PLAN FOR SUBJECTS IN
CLINICAL TRIALS
The Pregnancy Prevention Plan (PPP) applies to all subjects receiving pomalidomide within a 
clinical trial. The following PPP documents are included: 
1. The Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable 
Birth Control Methods document (Section 2) provides the following information:

Potential risks to the fetus associated with pomalidomide exposure

Definition of Female of Childbearing Potential (FCBP) / female not of childbearing 
potential (FNCBP)

Requirements for counseling of all subjects receiving pomalidomide about pregnancy 
precautions and the potential risks of fetal exposure to pomalidomide

Acceptable birth control methods for both female subjects of childbearing potential and 
male subjects receiving pomalidomide in the study

Pregnancy testing requirements for subjects receiving pomalidomide who are FCBP
2. The Pomalidomide Education and Counseling Guidance Document for each gender (female 
and male (Section 3 and Section 4 respectively) must be completed and signed by a trained 
counselor at the participating clinical center prior to each dispensing of pomalidomide.  A 
copy of this document must be maintained in the subject’s records for each dispense.
3. The Pomalidomide Information Sheet (Section 4) will be given to each subject receiving 
pomalidomide. The subject must read this document prior to starting pomalidomide and each 
time the subject receives a new supply of pomalidomide.
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2
POMALIDOMIDE RISKS OF FETAL EXPOSURE, PREGNANCY TESTING 
GUIDELINES AND ACCEPTABLE BIRTH CONTROL METHODS 
2.1
Risks Associated with Pregnancy
Pomalidomide was teratogenic in both rats and rabbits when administered during the period of 
organogenesis. Pomalidomide is an analogue of thalidomide. Thalidomide is a known human 
teratogen that causes severe life-threatening human birth defects. If pomalidomide is taken 
during pregnancy, it can cause birth defects or death to an unborn baby.
The teratogenic effect of pomalidomide in humans cannot be ruled out. Therefore, a pregnancy 
prevention program must be followed.
2.1.1
Definition of Females of Childbearing Potential (FCBP)
A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a 
hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal 
(amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 
consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
2.1.2
Definition of Females Not of Childbearing Potential
Females who do not meet the above definition of FCBP should be classified as FNCBP.
2.2
Counseling
2.2.1
Females of Childbearing Potential
For a FCBP, pomalidomide is contraindicated unless all of the following are met (ie, all FCBP 
must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide):

She understands the potential teratogenic risk to the unborn child

She understands the need for effective contraception, without interruption, 28 days before 
starting pomalidomide, throughout the entire duration of pomalidomide, during dose 
interruptions and for at least 28 days after the last dose of pomalidomide

She understands and agrees to inform the Investigator if a change or stop of method of 
contraception is needed

She must be capable of complying with effective contraceptive measures

She is informed and understands the potential consequences of pregnancy and the need to 
notify her study doctor immediately if there is a risk of pregnancy

She understands the need to commence pomalidomide as soon as it is dispensed following a 
negative pregnancy test

She understands and accepts the need to undergo pregnancy testing based on the frequency 
outlined in this plan (Section 2.4) and in the Informed Consent

She acknowledges that she understands the hazards pomalidomide can cause to an unborn 
fetus and the necessary precautions associated with the use of pomalidomide.
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The Investigator must ensure that a FCBP:

Complies with the conditions of the pregnancy prevention plan, including confirmation that 
she has an adequate level of understanding

Acknowledges the aforementioned requirements.
2.2.2
Females Not of Childbearing Potential
For a FNCBP, pomalidomide is contraindicated unless all of the following are met (ie, all 
FNCBP must be counseled concerning the following risks and requirements prior to the start of 
pomalidomide):

She acknowledges she understands the hazards pomalidomide can cause to an unborn fetus 
and the necessary precautions associated with the use of pomalidomide.
2.2.3
Males
The effect of pomalidomide on sperm development is not known and has not been studied. The
risk to an unborn baby in females of child bearing potential whose male partner is receiving
pomalidomide is unknown at this time. Therefore, male subjects taking pomalidomide must meet 
the following conditions (ie, all males must be counseled concerning the following risks and 
requirements prior to the start of pomalidomide study therapy):

Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female 
or a FCBP

Understand the need for the use of a condom even if he has had a vasectomy, if engaged in 
sexual activity with a pregnant female or a FCBP l.

Understand the potential teratogenic risk if the subject donates semen or sperm.
2.3
Contraception
2.3.1
Female Subjects of childbearing Potential
Females of childbearing potential enrolled in this protocol must agree to use two reliable forms 
of contraception simultaneously or to practice complete abstinence (True abstinence is 
acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic 
abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal 
are not acceptable methods of contraception.) from heterosexual contact during the following 
time periods related to this study: 1) for at least 28 days before starting pomalidomide; 2) while 
taking pomalidomide; 3) during dose interruptions; and 4) for at least 28 days after the last dose 
of pomalidomide.
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method. If the below contraception methods are not appropriate for 
the FCBP, she must be referred to a qualified provider of contraception methods to determine the 
medically effective contraception method appropriate to the subject. The following are examples 
of highly effective and additional effective methods of contraception:
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
Examples of highly effective methods:
Intrauterine device (IUD)
Hormonal (birth control pills, injections, implants, levonorgestrel-releasing intrauterine
system [IUS], medroxyprogesterone acetate depot injections,
ovulation inhibitory
progesterone-only pills [e.g. desogestrel])
Tubal ligation
Partner’s vasectomy

Examples of additional effective methods:
Male condom
Diaphragm
Cervical Cap
Because of the increased risk of venous thromboembolism in subjects with multiple myeloma 
taking pomalidomide and dexamethasone, combined oral contraceptive pills are not 
recommended. If a subject is currently using combined oral contraception the subject should 
switch to another one of the effective methods listed above. The risk of venous 
thromboembolism continues for 4 to 6 weeks after discontinuing combined oral contraception. 
The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone.
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics 
should be considered particularly in subjects with neutropenia.
2.3.2
Male Subjects
Male subjects must practice complete abstinence (True abstinence is acceptable when this is in 
line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, 
ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods 
of contraception.) or agree to use a condom during sexual contact with a pregnant female or a 
FCBP while taking pomalidomide, during dose interruptions and for at least 28 days after the last 
dose of pomalidomide, even if he has undergone a successful vasectomy.
2.4
Pregnancy testing
Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL must be 
performed for FCBP.
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least 
25 mIU/mL) prior to starting pomalidomide. The first pregnancy test must be performed within 
10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be 
performed within 24 hours prior to the start of pomalidomide. The subject may not receive 
pomalidomide until the study doctor has verified that the results of these pregnancy tests are 
negative.
Females of childbearing potential with regular or no menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every 28 days while 
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taking pomalidomide, at study discontinuation, and at Day 28 following the last dose of 
pomalidomide.
Females of childbearing potential with irregular menstrual cycles must agree to have pregnancy 
tests weekly for the first 28 days of study participation and then every 14 days while taking 
pomalidomide, at study discontinuation, and at Days 14 and 28 following the last dose of 
pomalidomide.
2.5
Pregnancy Precautions for Pomalidomide Use
2.5.1
Before Starting Pomalidomide
2.5.1.1
Female Subjects of Childbearing Potential
Females of childbearing potential must have two negative pregnancy tests (sensitivity of at least 
25 mIU/mL) prior to starting pomalidomide. The first pregnancy test must be performed within 
10 to 14 days prior to the start of pomalidomide and the second pregnancy test must be 
performed within 24 hours prior to the start of pomalidomide. The subject may not receive 
pomalidomide until the study doctor has verified that the results of these pregnancy tests are 
negative.
Females of childbearing potential must use two reliable forms of contraception simultaneously, 
or practice complete abstinence (True abstinence is acceptable when this is in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, 
symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of 
contraception.) from heterosexual contact for at least 28 days before starting pomalidomide.
2.5.1.2
Male Subjects
Male subjects must agree to practice complete abstinence (True abstinence is acceptable when 
this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg 
calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not 
acceptable methods of contraception.) or agree to use a condom during sexual contact with a 
pregnant female or a FCBP while taking pomalidomide, during dose interruptions and for at least 
28 days after the last dose of pomalidomide, even if he has undergone a successful vasectomy.
2.5.2
During and After Study Participation
2.5.2.1
Female Subjects:

Females of childbearing potential with regular or no menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every 28 days 
while taking pomalidomide, at study discontinuation, and at Day 28

following the last dose of pomalidomide.

Females of childbearing potential with irregular menstrual cycles must agree to have 
pregnancy tests weekly for the first 28 days of study participation and then every
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
14 days while taking pomalidomide, at study discontinuation, and at Days 14 and 28 
following the last dose of pomalidomide.

At each visit, the Investigator must confirm with the FCBP that she is continuing to use two 
reliable methods of birth control if not committing to complete abstinence, or confirm 
commitment to complete abstinence.

If a FCBP considers the need to change or to stop a method of contraception, the Investigator 
must be notified immediately.

Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days.

If pregnancy or a positive pregnancy test does occur in a subject, pomalidomide must be 
immediately discontinued.

Pregnancy testing and counseling must be performed if a subject misses her period or if her 
pregnancy test or her menstrual bleeding is abnormal. Pomalidomide must be discontinued 
during this evaluation.

Females must agree to abstain from breastfeeding while taking pomalidomide and for at least 
28 days after the last dose of pomalidomide.
2.5.2.2
Male Subjects:

Must practice complete abstinence (True abstinence is acceptable when this is in line with the 
preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, 
symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of 
contraception.) or use a condom during sexual contact with a pregnant female or a FCBP 
while receiving pomalidomide, during dose interruptions and for at least 28 days after the last 
dose of pomalidomide, even if he has undergone a successful vasectomy.

Must not donate semen or sperm while receiving pomalidomide, during dose interruptions or 
for at least 28 days after the last dose of pomalidomide.

Counseling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days

If pregnancy or a positive pregnancy test does occur in the partner of a male subject while 
taking pomalidomide, the Investigator must be notified immediately.
2.5.3
Additional precautions

Subjects should be instructed to never give pomalidomide to another person.

Subjects should be instructed to return any unused capsules to the study doctor.

Subjects should not donate blood while receiving pomalidomide, during dose interruptions 
and for at least 28 days after the last dose of pomalidomide.

No more than a 28-day pomalidomide supply may be dispensed with each cycle of 
pomalidomide.
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Pomalidomide Education and Counseling Guidance Document
To be completed prior to each dispensing of pomalidomide.
Protocol Number: ___________________________
Subject Name (Print): __________________ 
DOB: _____/_____/_____ (mm/dd/yyyy)

FCBP (Female of childbearing potential): a female who: 1) has achieved menarche
(first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the
surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of
both ovaries) or 3) has not been naturally postmenopausal (amenorrhea following
cancer therapy does not rule out childbearing potential) for at least 24 consecutive
months (ie, has had menses at any time during the preceding 24 consecutive
months)

NOT FCBP
2.6
Female of Childbearing Potential:
1. I have verified and counseled the subject regarding the following:

Potential risk of fetal exposure to pomalidomide: A teratogenic potential of
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during
pregnancy, it may cause birth defects or death to any unborn baby. Females are
advised to avoid pregnancy while taking pomalidomide. Females of childbearing
potential must agree not to become pregnant while taking pomalidomide. 

That the required pregnancy tests performed are negative.

The subject confirmed that she is using TWO reliable methods of birth control at 
the same time, or complete abstinence (True abstinence is acceptable when this is 
in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg
calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal 
are not acceptable methods of contraception.) from heterosexual contact (at least
28 days prior to receiving pomalidomide, while receiving pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide):
One highly effective method and one additional method of birth control must be 
used AT THE SAME TIME. The following are examples of highly effective and 
additional effective methods of contraception:

Examples of highly effective methods:
Intrauterine device (IUD)
Hormonal (birth control pills, injections, implants, levonorgestrel-
releasing intrauterine system [IUS], medroxyprogesterone acetate depot 
injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel])
Tubal ligation
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Partner’s vasectomy

Examples of additional effective methods:
Male condom
Diaphragm
Cervical Cap

The subject confirmed that even if she has amenorrhea she must comply with 
advice on contraception.

Pregnancy tests before, during administration of pomalidomide and at the last 
dose of pomalidomide, even if the subject agrees not to have reproductive 
heterosexual contact.

Frequency of pregnancy tests to be done:

Two pregnancy tests will be performed prior to receiving pomalidomide, one 
within 10 to 14 days, and a second within 24 hours of the start of 
pomalidomide.

Every week during the first 28 days of this study and a pregnancy test every 
28 days while the subject is taking pomalidomide if menstrual cycles are 
regular.

Every week during the first 28 days of this study and a pregnancy test every 
14 days while the subject is taking pomalidomide if menstrual cycles are 
irregular.

If the subject missed a period or has unusual menstrual bleeding.

When the subject is discontinued from the study and at Day 28 after the last 
dose of pomalidomide if menstrual cycles are regular. If menstrual cycles are 
irregular, pregnancy tests will be done at discontinuation from the study and at 
Days 14 and 28 after the last dose of pomalidomide.

The subject confirmed that she will stop taking pomalidomide immediately in the 
event of becoming pregnant and to call her study doctor as soon as possible.

The subject confirmed that she has not and will not breastfeed a baby while taking 
pomalidomide and for at least 28 days after the last dose of pomalidomide.

The subject has not and will never share pomalidomide with anyone else.

The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide.

The subject has not and will not break, chew, or open pomalidomide capsules at 
any point.

The subject confirmed that she will return unused pomalidomide capsules to the 
study doctor.
2. I have provided the Pomalidomide Information Sheet to the subject.
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2.7
Female not of childbearing potential (natural menopause for at least 24 
consecutive months, a hysterectomy, or bilateral oophorectomy):
1. I counseled the female NOT of childbearing potential regarding the following:

Potential risk of fetal exposure to pomalidomide: A teratogenic potential of
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during
pregnancy, it may cause birth defects or death to any unborn baby

The subject has not and will never share pomalidomide with anyone else.

The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide.

The subject has not and will not break, chew, or open pomalidomide capsules at 
any point.

The subject confirmed that she will return unused pomalidomide capsules to the 
study doctor.
2. I have provided the Pomalidomide Information Sheet to the subject.
Do Not Dispense Pomalidomide if:

The subject is pregnant.

No pregnancy tests were conducted for a FCBP.

The subject states she did not use TWO reliable methods of birth control (unless 
practicing complete abstinence from heterosexual contact) at least 28 days prior to 
receiving pomalidomide, while receiving pomalidomide and during dose 
interruptions.

The subject stated that she has or does not want to adhere to pregnancy precautions 
outlined within this PPP.
Counselor Name (Print): ________________________
Counselor Signature: _______________________
Date:_____/_____/____(dd/mmm/yyyy)
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s
records.**
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3
POMALIDOMIDE EDUCATION AND COUNSELING GUIDANCE
DOCUMENT FOR MALE SUBJECTS
To be completed prior to each dispensing of pomalidomide.
Protocol Number: ___________________________
Subject Name (Print): __________________ 
DOB: _____/_____/_____ (mm/dd/yyyy)
1. I have verified and counseled the subject regarding the following:

Potential risk of fetal exposure to pomalidomide: A teratogenic potential of 
pomalidomide in humans cannot be ruled out. If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby.

The subject confirmed that he has practiced complete abstinence (True abstinence 
is acceptable when this is in line with the preferred and usual lifestyle of the 
subject. Periodic abstinence [eg calendar, ovulation, symptothermal or post-
ovulation methods] and withdrawal are not acceptable methods of contraception.) 
or used a condom when engaging in sexual contact (including those who have had 
a vasectomy) with a pregnant female or FCBP, while taking pomalidomide, 
during dose interruptions and for at least 28 days after the last dose of 
pomalidomide.

The subject confirmed that he has not impregnated his female partner while in the 
study.

The subject confirmed that he will notify his study doctor if his female partner 
becomes pregnant and the female partner of a male subject taking pomalidomide 
confirmed that she will call her healthcare provider immediately if she becomes 
pregnant.

The subject has not and will never share pomalidomide with anyone else.

The subject confirmed that he has not donated and will not donate semen or sperm 
while taking pomalidomide or during dose interruptions and that he will not 
donate semen or sperm for at least 28 days after the last dose of pomalidomide.

The subject has not and will not donate blood while taking pomalidomide, during 
dose interruptions and for at least 28 days after the last dose of pomalidomide.

The subject has not and will not break, chew, or open pomalidomide capsules at 
any point.

The subject confirmed that he will return unused pomalidomide capsules to the 
study doctor.
2. I have provide the Pomalidomide Information Sheet to the subject.
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Do Not Dispense Pomalidomide if:

The subject stated that he has or does not want to adhere to pregnancy precautions 
outlined within this PPP.
Counselor Name (Print): _______________________
Counselor Signature: _______________________
Date:_____/_____/____(dd/mmm/yyyy)
**Maintain a copy of the Education and Counseling Guidance Document in the subject’s
records.**
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4
POMALIDOMIDE INFORMATION SHEET 
FOR SUBJECTS ENROLLED IN CLINICAL RESEARCH STUDIES
Please read this Pomalidomide Information Sheet before you start taking pomalidomide and each 
time you get a new supply. This Pomalidomide Information Sheet does not take the place of an 
informed consent to participate in clinical research or talking to your study doctor or healthcare 
provider about your medical condition or your treatment.
What is the most important information I should know about pomalidomide?
1. Pomalidomide may cause birth defects (deformed babies) or death of an unborn baby. 
Pomalidomide is similar to the medicine thalidomide. It is known that thalidomide causes 
life-threatening birth defects. Pomalidomide has not been tested in pregnant women but may 
also cause birth defects. Pomalidomide was found to cause birth defects when tested in 
pregnant rats and rabbits.
If you are a female who is able to become pregnant:

Do not take pomalidomide if you are pregnant or plan to become pregnant

You must practice complete abstinence from sexual contact with a male or use two 
reliable , separate forms of effective birth control at the same time: 
for 28 days before starting pomalidomide
while taking pomalidomide
during breaks (dose interruptions) of pomalidomide
for at least 28 days after the last dose of pomalidomide

You must have pregnancy testing done at the following times:
within 10 to 14 days prior to the first dose of pomalidomide
24 hours prior to the first dose of pomalidomide
weekly for the first 28 days
if you have regular menstrual periods: every 28 days after the first month
if you have irregular menstrual periods: every 14 days after the first month
if you miss your period or have unusual menstrual bleeding
28 days after the last dose of pomalidomide (14 and 28 days after the last dose if 
menstrual periods are irregular)

Stop taking pomalidomide if you become pregnant during treatment
If you suspect you are pregnant at any time during the study, you must stop 
pomalidomide immediately and immediately inform your study doctor. The study 
doctor will report all cases of pregnancy to Celgene Corporation. 

Do not breastfeed while taking pomalidomide and for at least 28 days after the last 
dose of pomalidomide
The study doctor will be able to advise you where to get additional advice on 
contraception.
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If you are a female not able to become pregnant:
In order to ensure that an unborn baby is not exposed to pomalidomide, your study doctor 
will confirm that you are not able to become pregnant.
If you are a male:
The effect of pomalidomide on sperm development is not known and has not been 
studied. The risk to an unborn baby in females whose male partner is receiving 
pomalidomide is unknown at this time.
Male subjects (including those who have had a vasectomy) must practice complete 
abstinence or must use a condom during sexual contact with a pregnant female or a 
female that can become pregnant:

While you are taking pomalidomide

During breaks (dose interruptions) of pomalidomide

For at least 28 days after the last dose of pomalidomide  
Male subjects should not donate sperm or semen while taking pomalidomide, 
during breaks (dose interruptions) and for at least 28 days after the last dose of 
pomalidomide. 
If you suspect that your partner is pregnant any time during the study, you must 
immediately inform your study doctor. The study doctor will report all cases of 
pregnancy to Celgene Corporation. Your partner should call their healthcare 
provider immediately if they become pregnant.
2. All Subjects

Do not share pomalidomide with other people. It must be kept out of the reach of 
children and should never be given to any other person.

Do not donate blood while you take pomalidomide, during breaks (dose interruptions) 
and for at least 28 days after the last dose of pomalidomide.

Do not break, chew, or open pomalidomide capsules at any point.

You will get no more than a 28-day supply of pomalidomide  at one time.

Return unused pomalidomide capsules to your study doctor.
Additional information is provided in the informed consent form and you can ask your study 
doctor for more information.
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APPENDIX 7
REVISED PROTOCOL SUMMARY OF CHANGE HISTORY
Overall Rationale for the Revised Protocol 02, 22-May-2018
Revised Protocol 02 incorporates changes required by the FDA per the partial clinical hold that 
was based on safety concerns from pembrolizumab studies Keynote 183 and 185. Study design 
and objective changes to reflect endpoints adequacy in light of these safety concerns were also 
incorporated. Additional changes include the revision of efficacy assessments in the protocol to 
align with the current International Myeloma Working Group (IMWG) guidance
 
 
Revisions pertain to both present and future subjects.
The revisions of Revised Protocol 02 should be implemented once IRB/IEC/HA approval is 
received.
Summary of key changes of Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Title page
Change in BMS study personnel.
Administrative change
Title page, Synopsis
Elotuzumab has been removed from the 
title of the study. 
Title updated to reflect the removal of 
the exploratory NE-Pd arm. 
Synopsis, Investigational 
Product(s), Dose and Mode 
of Administration, 
Duration of Treatment with 
Investigational Product(s)
Exploratory Arm (NE-Pd: Arm C) is 
closed to enrollment.
To focus enrollment on the 
investigational and control arms, the 
exploratory NE-Pd arm was removed.
Synopsis Objectives
Section 1.5 Objective(s)
Changed objective response rate (ORR) 
from primary to secondary objective.
Promoted overall survival (OS) from 
exploratory objective to secondary 
objective. 
Based on pembrolizumab data, BMS 
deemed ORR as a co-primary 
endpoint for an accelerated approval 
strategy is no longer adequate. 
Progression free survival (PFS) is a 
clinically relevant surrogate endpoint 
for efficacy.
As the gold standard for efficacy, OS 
was upgraded to secondary objectives.
Synopsis, Study Design, 
Study Schema
Section 3.1 Study Design 
and Duration
Figure 3.1-1 Study Design 
Schematic
Exploratory NE-Pd arm is removed 
from study design.
Cross-over was removed.
Sample size and randomization ratio 
were updated to reflect that only N-Pd 
and Pd arm are continuing enrollment.
Study schema was updated.
To focus enrollment on the 
investigational and control arms, the 
exploratory NE-Pd arm was 
removed. 
Cross-over was stopped as of 1 Sept 
2017 per the FDA request.
Synopsis Study Population
Section 3.3.1 Inclusion 
Criteria
Clarified definitions of ‘refractory’ and 
‘relapsed and refractory’ definitions.
To align with IMWG definitions.
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Summary of key changes of Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Synopsis, Statistical 
Considerations 
Section 8 Statistical 
Considerations
Updated Sample Size Determination to 
reflect the change in study design (ie, 
removal of NE-Pd arm). 
Updated Populations for Analyses, 
Endpoints, Efficacy Analyses, and 
Interim Analyses for efficacy to reflect 
the changes in study objectives (ie, 
primary objective changed from co-
primary (ORR and PFS) to PFS only).
Added an Interim analysis for futility 
(ie, 50% of total events within N-Pd and 
Pd arms)
Statistical considerations section was 
updated to reflect the changes in study 
design and study objectives.
Section 1.7 Overall 
Risk/Benefit Assessment
Add information on the safety risk 
concerns from the pembrolizumab studies 
and how they affected this study.
Language was added to inform study 
investigators of the safety risks 
concerns from the pembrolizumab 
studies communicated by the FDA, 
the partial clinical hold placed on the 
study by the FDA in light of these 
concerns, and the stopped cross-over 
from the control Pd arm to the 
exploratory NE-Pd arm that FDA 
required amongst the hold conditions.
Section 3.3.2 Exclusion 
Criteria
Criterion 2 Medical 
History and Concurrent 
Diseases c)
Updated to active systemic infection
Systemic added for clarification
Section 3.3.2 Exclusion 
Criteria 3. Prior Therapy or 
Surgery
New exclusion criteria of plasmapheresis 
within 4 weeks of randomization.
Plasmapheresis may interfere with 
eligibility assessments for measurable
disease and with quantification of 
baseline value for M protein/ sFLC 
necessary for accurate response 
assessment. This exclusion criterion 
was inadvertently omitted in earlier 
protocol version.
New criterion added: subjects who have 
received a live / attenuated vaccine within 
30 days of first treatment are excluded.
Updated exclusion for nivolumab 
protocols.
Section 3.4.1 Prohibited 
and/or Restricted 
Treatments
Any live / attenuated vaccine (eg 
varicella, zoster, yellow fever, rotavirus, 
oral polio and measles, mumps, rubella 
(MMR)) is prohibited during treatment 
and until 100 days post last dose.
Update for nivolumab protocols.
Section 4.5.1.1.1 
Pomalidomide
Removed requirement for pomalidomide
administration at least 2 hours prior to 
nivolumab dosing.
To align with pomalidomide package 
insert.
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Summary of key changes of Revised Protocol 02
Section Number & Title
Description of Change
Brief Rationale
Section 4.5.4.4, Nivolumab 
Updated criteria for dose delays and 
discontinuation for nivolumab.
Alignment with nivolumab program 
standard.
Section 5.1 Flow 
Chart/Time and Events 
Schedule 
Clarified requirements for efficacy 
assessments. 
Included new schedule of bone marrow 
aspirate collection for 
 
 disease assessments.
Aligned more clearly with IMWG 
guidance
Section 5.4 Primary 
Efficacy
Clarified requirements for safety 
assessments
Included new schedule of bone marrow 
aspirate collection for 
 
 disease assessments
Clearer alignment with IMWG 
guidance.
Section 12, References
New references added to support protocol revisions 
Appendix 3
IMWG efficacy assessments updated 
Alignment with current IMWG 
standards.
Appendix 6
Pomalidomide Pregnancy Risk 
Prevention Plan
Added appendix.
Throughout
Minor editorial and formatting changes. 
Revised Protocol No.: 03
Date: 12-Nov-2018
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