Clinical trial NCT02654132
Conditions: Multiple Myeloma
Sponsor: Bristol-Myers Squibb
Start date: 2016-03-18; Completion date: 2021-10-21
Enrollment: 117 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if adding Elotuzumab to Pomalidomide and low-dose dexamethasone is a more effective treatment of relapsed and refractory multiple myeloma compared to pomalidomide and low-dose dexamethasone by itself.

Detailed description:

Arms: arm 1: Biological:Elotuzumab (BMS-901608; HuLuc63)

* Solution, Intravenous(IV),10 mg/kg(Cycles 1 and 2 weekly, on Days 1,8,15,22)
* Solution, Intravenous(IV),20 mg/kg(Cycle 3 and Beyond: Day 1)

Drug: Pomalidomide

•Capsules,Oral,4 mg,once daily, on Days 1-21

Other Name: Pomalyst

Drug: Dexamethasone

* Subjects ≤ 75 years old:

  •Tablets, Oral,28 mg, once daily on: Days 1,8,15,22(Cycles 1\&2) Day 1(Cycle 3 and Beyond)

  •Solution, Intravenous(IV), 8 mg, once daily on: Days 1,8,15,22(Cycles 1\&2) Day 1(Cycle 3 and Beyond)

  •Tablets, Oral,40 mg, once daily on: Days 8,15,22(Cycle 3 and Beyond)
* Subjects \> 75 years old:

  •Tablets, Oral,8 mg, once daily on: Days 1,8,15,22(Cycles 1\&2) Day 1(Cycle 3 and Beyond)

  •Solution, Intravenous(IV), 8 mg, once daily on: Days 1,8,15,22(Cycles 1\&2) Day 1(Cycle 3 and Beyond)

  •Tablets, Oral, 20 mg, once daily on: Days 8,15,22(Cycle 3 and Beyond)

Other Names:

Decadron,Dexamethasone ,Intensol,Dexpak,Taperpak arm 2: Drug: Pomalidomide

• Capsules, Oral, 4 mg, once daily, on Days 1-21 Other Name: Pomalyst

Drug: Dexamethasone

Subjects ≤ 75 years old:

• Tablets, Oral, 40 mg, weekly on Days 1, 8, 15 and 22

Subjects \> 75 years old:

• Tablets, Oral, 20 mg, weekly on Days 1, 8, 15 and 22,

Other Names:

* Decadron
* Dexamethasone Intensol
* Dexpak
* Taperpak
Interventions: intervention 1: Elotuzumab intervention 2: Pomalidomide intervention 3: Dexamethasone
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_000.pdf: 
Page:
1
Protocol Number:
CA204125
IND Number:
100, 043
Ex-US
Non-IND
EUDRACT Number
2014-003282-19
Date:
02-Sep-2015
Revised Date:
11-Nov-2015
Clinical Protocol CA204125
An Open Label, Randomized Phase 2 Trial of Pomalidomide/Dexamethasone With or Without 
Elotuzumab in relapsed and refractory Multiple Myeloma.
Revised Protocol Number: 01
Incorporates Amendment: 02
Study Director/Central Medical Monitor
Suresh Shelat, MD, PhD
Bristol Myers Squibb Company
 
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 
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within your organization or to your independent ethics committee(s). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless 
expressly authorized in writing by BMS. Any supplemental information (eg, amendments) 
that may be added to this document is also confidential and proprietary to BMS and must 
be kept in confidence in the same manner as the contents of this document. Any person 
who receives this document without due authorization from BMS is requested to return it 
to BMS or promptly destroy it. All other rights reserved. References to BMS in this 
protocol may apply to partners to which BMS has transferred obligations, eg, a Contract 
Research Organization (CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a 
copy of this revised protocol to all study personnel under your supervision, and archive the 
previous versions.
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 01
11-Nov-2015
Incorporates Amendment 02
Amendment 02 
11-Nov-2015
Remove the Circulating Multiple Myeloma Cells (CMMC) assay and 
to replace with Gene Expression Profiling
Clarify wording of pomalidomide risk management program and 
Pomalidomide Pregnancy Risk Prevention Plan throughout
Minor formatting and typographical revisions
Original 
Protocol
02-Sep-2015
Not applicable
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SYNOPSIS
Clinical Protocol CA204125
Protocol Title:  An Open Label, Randomized Phase 2 Trial of Pomalidomide/Dexamethasone With or Without 
Elotuzumab in relapsed and refractory Multiple Myeloma
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s): 
See Study Schema for details
Control Arm
Pomalidomide: 4 mg PO QD Days 1-21 of each 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
Elotuzumab Arm
Elotuzumab: 

Cycle 1 - 2: 10 mg/kg IV Days 1, 8, 15 and 22 of each cycle

Cycle 3 and beyond: 20mg/kg IV Day 1 of each cycle
Pomalidomide: 4 mg PO QD Days 1-21 of each 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
A cycle is defined as 28 days. Treatment with study drug continues until disease progression, unacceptable toxicity 
(adverse event related to study drug), or subject meets other criteria for discontinuation of study drug outlined in 
Section 3.5.
Study Phase:  2
 
 
 
Primary Objective:

To compare progression free survival (PFS) between treatment arms
Secondary Objectives:

To compare objective response rate between treatment arms

To compare overall survival between treatment arms
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Study Design:
This is a phase 2 multicenter, open-label, randomized study designed to evaluate the clinical benefit of the 
investigational combination therapy of elotuzumab, pomalidomide, and dexamethasone (E-Pd; the elotuzumab arm) 
when compared to pomalidomide and dexamethasone (Pd; the control arm) in subjects with relapsed and refractory 
multiple myeloma (rrMM). 
 
 
 
 
 
 
 
 
 
 
 
1)
Number of lines of prior therapy (2-3 vs. 4) (Appendix 1 for definition of Line of Therapy)
2)
ISS stage at study entry (I-II vs. III) (Appendix 7 for ISS Staging System).
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Study Schema
Follow- Up
Follow-up 
every
4 weeks for
tumor 
response
until PD; 
then
survival
follow-up 
every
12 weeks or 
more 
frequently
Elotuzumab:  20 mg/kg IV Day 1 of each cycle
Pomalidomide:  4 mg PO daily (Days 1-21) of 
each cycle 
Dexamethasone (weeks with Elotuzumab
dosing): 

28 mg PO + 8 mg IV on day of elotuzumab 
dosing (subjects 75 years) 

8 mg PO + 8mg IV on day of elotuzumab 
dosing (subjects > 75 years) 
Dexamethasone (weeks without Elotuzumab
dosing): 

40 mg PO per week (subjects 75 years old) 

20 mg PO per week (subjects > 75 years old)
See Section 4.5.1.2
Pomalidomide:   4 mg PO daily (Days 1-21) of 
each cycle. 
Dexamethasone: 

40 mg PO per day (Days 1, 8, 15, 22) of each 
cycle (subjects 75 years old)

20 mg PO per day (Days 1, 8, 15, 22) of each 
cycle (subjects > 75 years old)
Cycle 3 and beyond
114 Subjects
(1:1)
Pomalidomide:  4 mg PO daily 
(Days 1-21) of each cycle. 
Dexamethasone: 

40 mg PO per day (Days 1, 8, 
15, 22) of each cycle (subjects 
75 years old)

20 mg PO per day (Days 1, 8, 
15, 22) of each cycle (subjects 
> 75 years old)
Elotuzumab:   10 mg/kg IV (Days 
1, 8, 15, 22) of each cycle 
Pomalidomide:  4 mg PO daily 
(Days 1-21) of each cycle. 
Dexamethasone: 

28 mg PO + 8 mg IV on days
of elotuzumab dosing (subjects 
75 years old)

8 mg PO + 8mg IV on days of 
elotuzumab dosing (subjects 
> 75 years old)
See Section 4.5.1.2
R
A
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Cycle 1 and 2
Control Arm
Elotuzumab
Arm
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Study Population: 
Subjects who are diagnosed with relapsed and refractory multiple myeloma defined as:
1)
Must have received 2 prior lines of therapy (See Appendix 1) which must have included at least 2 consecutive 
cycles of lenalidomide and a proteosome inhibitor alone or in combination.
2)
Documented refractory or relapsed and refractory (R/R) multiple myeloma
3)
Refractory (progressed on or within 60 days of treatment) to their last treatment.
4)
Subjects must have failed treatment with a proteosome inhibitor and lenalidomide in one of the following ways.
a)
“Refractory” to proteosome inhibitor and lenalidomide, and to their last treatment.
b)
“Relapsed and refractory”= patients had achieved at least a partial response to previous treatment with 
proteosome inhibitor or lenalidomide, or both, but progressed within 6 months, and were refractory to their 
last treatment
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational 
[Medicinal] Products (Non-IP/Non-IMP) as listed:
Study Drug for CA204125
Medication
Potency
IP/Non-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 modified IMWG criteria (Appendix 6) will be evaluated 
during the trial for all randomized subjects. The primary endpoint of PFS will be based on the investigator’s 
assessment
Statistical Considerations: 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Endpoints:  
Primary Endpoint:
PFS will be defined as the time, in months, from randomization to the date of the first documented tumor 
progression or death due to any cause. Clinical deterioration will not be considered progression. A subject who 
neither progresses nor dies will be censored on the date of their last tumor assessment. A subject who does not have 
any post-baseline tumor assessments and who has not died will be censored on the date at which they were 
randomized.
Secondary Endpoint:
1)
Objective response rate is defined as the proportion of randomized subjects who achieve a best response of 
partial response (PR) or better using the criteria in Appendix 6 as per investigator’s assessment.
2)
Overall survival is defined as the time from randomization to the date of death from any cause. If a subject has 
not died, their survival time will be censored at the date of last contact (“last known alive date”). A subject will 
be censored at the date of randomization if they were randomized but had no follow-up.
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2 Research Hypothesis ......................................................................................... 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objectives .................................................................................. 
1.3.2 Secondary Objectives ............................................................................... 
 
 
 
 
 
 
 
 
2 ETHICAL CONSIDERATIONS ............................................................................... 
2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
 
 
......................................................................................... 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
3.3.2 Exclusion Criteria .................................................................................... 
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3.3.3 Women of Childbearing Potential ........................................................... 
3.4 Concomitant Treatments ................................................................................... 
3.4.1 Required ................................................................................................... 
3.4.2 Permitted at Investigator’s Discretion ..................................................... 
3.4.3 Prohibited and/or Restricted Treatments................................................. 
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 .............................................................................................. 
4.2 Non-Investigational Product ............................................................................. 
4.2.1 Pomalidomide .......................................................................................... 
4.2.2 Dexamethasone ........................................................................................ 
4.3 Storage and Dispensing..................................................................................... 
 
 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Treatment with Study Drugs .................................................................... 
4.5.1.1 Pomalidomide ................................................................................. 
4.5.1.2 Dexamethasone ............................................................................... 
4.5.1.3 Elotuzumab ..................................................................................... 
4.5.1.4 Elotuzumab Premedication Regimen in Subjects Without a Prior 
Infusion Reaction .................................................................................. 
4.5.1.5 Elotuzumab Premedication Regimen in Subjects With a Prior 
Infusion Reaction .................................................................................. 
4.5.2 Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions
..................................................................................................................... 
4.5.2.1 Grade 1 Infusion Reaction .............................................................. 
4.5.2.2 Grade  2 Infusion Reaction ........................................................... 
4.5.2.3 Grade 4 Infusion Reaction .............................................................. 
4.5.3 Dose Delay, Interruption, or Discontinuation, All Subjects .................... 
4.5.3.1 Elotuzumab ..................................................................................... 
4.5.3.2 Dexamethasone ............................................................................... 
4.5.3.3 Pomalidomide ................................................................................. 
4.5.4 Recommended Dose Reduction ................................................................ 
4.5.4.1 Elotuzumab ..................................................................................... 
4.5.4.2 Dexamethasone ............................................................................... 
4.5.4.3 Pomalidomide ................................................................................. 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction and Return of Study Drug ............................................................. 
4.8.1 Destruction of Study Drug ....................................................................... 
4.9 Return of Study Drug ........................................................................................ 
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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 Period ......................................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Imaging Assessment 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 .................................. 
5.5 Pharmacokinetic Assessments .......................................................................... 
5.5.1 Anti-Drug Antibody (ADA)Assessments .................................................. 
5.5.2 Pharmacogenomic/Pharmacogenetic 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 ..................................................................... 
8 STATISTICAL CONSIDERATIONS....................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s) ................................................................................ 
8.3.1.1 Primary definition of PFS ............................................................... 
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8.3.1.2 Secondary Definition of PFS: ......................................................... 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.3.2.1 Objective response rate................................................................... 
8.3.2.2 Overall survival .............................................................................. 
 
 
 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.2.1 Primary Efficacy Analysis: PFS ..................................................... 
8.4.2.2 Secondary Efficacy Analysis ........................................................... 
8.4.3 Safety Analyses......................................................................................... 
8.4.4 Pharmacokinetic Analyses ....................................................................... 
8.4.5 Biomarker Analyses ................................................................................. 
8.4.6 Outcomes Research Analyses .................................................................. 
8.4.6.1 Analysis of PRO Data ..................................................................... 
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 PERFORMANCE STATUS SCALES ................................................. 
APPENDIX 3 M. D. ANDERSON SYMPTOM INVENTORY - MULTIPLE 
MYELOMA (MDASI - MM) ................................................................................. 
APPENDIX 4 EUROPEAN QUALITY OF LIFE - 5 DIMENSIONS (EQ-5D) ......... 
APPENDIX 5 PREPARATION AND ADMINISTRATION OF ELOTUZUMAB ... 
APPENDIX 6 DEFINITIONS OF RESPONSE AND PROGRESSION CRITERIA 
(MODIFIED FROM IMWG) ................................................................................. 
APPENDIX 7 THE INTERNATIONAL STAGING SYSTEM (ISS) FOR MULTIPLE 
MYELOMA ............................................................................................................ 
APPENDIX 8 POMALIDOMIDE PREGNANCY RISK PREVENTION PLAN ...... 
 
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INTRODUCTION AND STUDY RATIONALE
 
 
 
 
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1.3
Objectives(s)
1.3.1
Primary Objectives

To compare progression free survival (PFS) between treatment arms.
1.3.2
Secondary Objectives

To compare objective response rate between treatment arms

To compare overall survival between treatment arms 
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2
ETHICAL CONSIDERATIONS
2.1
Good Clinical Practice
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by the 
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.
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. 
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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:
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. 
Allow time necessary for subject or subject's legally acceptable representative to inquire about 
the details of the study.
Obtain an informed consent signed and personally dated by the subject or the subject's legally 
acceptable representative and by the person who conducted the informed consent discussion. 
Obtain the IRB/IEC’s written approval/favorable opinion of the written informed consent form 
and any other information to be provided to the subjects, prior to the beginning of the study, and 
after any revisions are completed for new information.
If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject.
Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the subject's 
willingness to continue participation in the study. This communication should be documented. 
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. 
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
 
 
 
A cycle is defined as 28 days.
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Table 3.1-1:
Study Design Schematic
114 Subjects
(1:1)
R
A
N
D
O
M
I
Z
A
T
I
O
N
Control Arm
Elotuzumab
Arm
Pomalidomide:  4 mg PO daily 
(Days 1-21) of each cycle. 
Dexamethasone: 

40 mg PO per day (Days 1, 8, 
15, 22) of each cycle (subjects ≤ 
75 years old)

20 mg PO per day (Days 1, 8, 
15, 22) of each cycle (subjects > 
75 years old)
Elotuzumab:   10 mg/kg IV (Days 1, 
8, 15, 22) of each cycle 
Pomalidomide:  4 mg PO daily (Days 
1-21) of each cycle. 
Dexamethasone: 

28 mg PO + 8 mg IV on days of 
elotuzumab dosing (subjects ≤ 75 
years old) 

8 mg PO + 8mg IV on days of 
elotuzumab dosing (subjects > 75 
years old) 
See Section 4.5.1.2
Cycle 1 and 2
Follow- Up
Follow-up 
every
4 weeks for
tumor response
until PD; 
then
survival
follow-up
every
12 weeks
or more 
frequently
Elotuzumab:  20 mg/kg IV Day 1 of each cycle.
Pomalidomide:  4 mg PO daily (Days 1-21) of 
each cycle. 
Dexamethasone (weeks with Elotuzumab 
dosing): 

28 mg PO + 8 mg IV on days of elotuzumab 
dosing (subjects ≤ 75 years) 

8 mg PO + 8mg IV on days of elotuzumab 
dosing (subjects > 75 years) 
Dexamethasone (weeks without Elotuzumab 
dosing): 

40 mg PO per week for subjects 75 years old. 

20 mg PO per week for subjects > 75 years old. 
See Section 4.5.1.2
Pomalidomide:   4 mg PO daily (Days 1-21) of 
each cycle. 
Dexamethasone: 

40 mg PO per day (Days 1, 8, 15, 22) of each 
cycle (subjects ≤ 75 years old)

20 mg PO per day (Days 1, 8, 15, 22) of each 
cycle (subjects > 75 years old)
Cycle 3 and beyond
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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 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 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.
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 (See Appendix 1) which must have 
included at least 2 consecutive cycles of lenalidomide and a proteosome inhibitor alone 
or in combination.
b) Documented refractory or relapsed and refractory (R/R) multiple myeloma
c) Refractory (progressed on or within 60 days of treatment) to their last treatment.
d) Subjects must have failed treatment with a proteosome inhibitor and lenalidomide in one 
of the following ways41.
i)
“Refractory” to proteosome inhibitor and lenalidomide, and to their last treatment.
ii) “Relapsed and refractory”= patients had achieved at least a partial response to 
previous treatment with proteosome inhibitor or lenalidomide, or both, but progressed 
within 6 months, and were refractory to their last treatment.
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e) Measurable disease at screening, based on central lab results, 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.
3) Age and Reproductive Status
a) Males and Females at least 18 years or legal age of consent per local regulations.
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 24 hours prior to the start of study 
drug. See Section 3.3.3 for the definition of WOCBP.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for 4 weeks 
before the start of treatment with study drugs, for the duration of treatment with study 
drugs, and for a total of 120 days post-treatment completion.
e) Males who are sexually active with WOCBP must always use a latex or synthetic 
condom during any sexual contact with females of reproductive potential, even if they 
have undergone a successful vasectomy. They must also agree to follow instructions for 
method(s) of contraception for 4 weeks before the start of treatment with study drugs, for 
the duration of treatment with study drugs, and for a total of 180 days post-treatment 
completion.
f)
Male patients must not donate sperm, for up to 180 days post treatment completion.
g) 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.
h) All Subjects must not donate blood for 90 days post treatment completion.
i)
All subjects must be willing and able to comply with the local pomalidomide risk 
management program or the Pomalidomide Pregnancy Risk Prevention Plan.
j)
All subjects must agree not 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.
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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), amyloidosis, Waldenstrom’s macroglobulinemia, 
or POEMS syndrome (plasma cell dyscrasia with poly neuropathy, organomegaly, 
endocrinopathy, monoclonal protein, and skin changes) 
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) 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, hypertension, arrhythmia, or myocardial infarction in the past 
12 months.
b) Active infection that requires parenteral anti-infective treatment > 14 days
c) Unable to tolerate thromboembolic prophylaxis while on the study
d) Hypersensitivity reaction to prior IMiD (thalidomide or lenalidomide) 
e) Grade 2 peripheral neuropathy (per NCI CTCAE v3.0)
f)
Known active hepatitis A, B, or C
g) Known HIV infection
h) Gastrointestinal disease that may significantly alter the absorption of pomalidomide
i)
Prior or concurrent malignancy, except for the following:
i)
Adequately treated basal cell or squamous cell skin cancer.
ii) Any cancer (other than in-situ) 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.
b) Prior participation in an elotuzumab clinical trial regardless of treatment assignment.
c) Use of any anti-myeloma drug therapy, within 14 days of the initiation of study drug 
treatment or use of any experimental drug therapy or plasmapheresis within 28 days (or 5
half-lives) whichever is longer of the initiation of study drug treatment (includes 
dexamethasone). Bisphosphonate use permitted.
d) Treatment with melphalan or monoclonal antibodies within 6 weeks of the first dose of 
study drug
e) Prior autologous stem cell transplant within 12 weeks of the first dose of study drug.
f)
Prior allogeneic stem cell transplant except subjects who have completed the stem cell 
transplant > 12 months prior to first dose of study drug, have no history of graft versus 
host disease, and are not on topical or systemic immunosuppressive therapy
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g) Treatment with corticosteroids within 3 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).
h) 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.
4) Physical and Laboratory Test Findings
a) Corrected serum calcium 11.5 mg/dl (see equation in Section 5.4.2) within 2 weeks of 
randomization
(despite appropriate measures
such a short course of steroids, 
bisphosphonates, hydration, calcitonin).
b) Absolute neutrophil count < 1 x 10⁹/L (1000/uL). No growth factors allowed within 1 
week of first dose of study drug. No pegylated growth factors within 3 weeks of 
randomization.
c) Platelets < 75 x 109/L (75,000/uL) (< 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 randomization and must be no more than 14 days prior to randomization. No 
transfusions are allowed within 72 hours prior to qualifying laboratory value.
d) Hemoglobin < 80 g/L (8g/dL). Qualifying laboratory value must occur at most recent 
measurement prior to randomization and must be no more than 14 days prior to 
randomization. No transfusions are allowed within 72 hours prior to qualifying laboratory 
value
e) Creatinine clearance < 45 ml/min according to the Cockroft-Gault formula.
1) Female CrCl = (140 - age in years) x body weight in kg x 0.85
2) 72 x serum creatinine in mg/dl
3) Male CrCl = (140 - age in years) x body weight in kg x 1.00
4) 72 x serum creatinine in mg/dl
Qualifying serum creatinine value must occur at most recent measurement prior to randomization
and must be no more than 14 days prior to randomization.
f)
Total bilirubin 2 x ULN
i)
Subjects with known Gilbert’s syndrome must NOT have a total bilirubin 3 x ULN 
and must have a direct bilirubin within the institutional limit of normal
g) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 3 x ULN
5) Other Exclusion Criteria
a) Known hypersensitivity or intolerance to lenalidomide, dexamethasone, or any excipients 
in elotuzumab, formulation or recombinant protein.
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b) Sexually active fertile men not using 2 forms of effective birth control if their partners are 
WOCBP. 
c) Prisoners or subjects who are involuntarily incarcerated.
d) 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), as defined by the local pomalidomide risk 
management program or the Pomalidomide Pregnancy Risk Prevention Plan, must also include 
all females who are menstruating, amenorrheic from previous medical treatments, under 50 years 
of age, and/or perimenopausal, and do not qualify for the category “females not of reproductive 
potential”.
Females not of reproductive potential, as defined by the local pomalidomide risk management 
program or the Pomalidomide Pregnancy Risk Prevention Plan, include females who have been 
in natural menopause for at least 24 consecutive months, or who have had a hysterectomy and/or 
bilateral oophorectomy.
Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their 
judgment in checking serum FSH levels. If the serum FSH level is > 40 mIU/ml at any time 
during the washout period, the woman can be considered postmenopausal:

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
3.4
Concomitant Treatments
3.4.1
Required
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 4.5.1.4 and 4.5.1.5) prior to each dose of 
elotuzumab.
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3.4.2
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

anti-emetics

bisphosphonates
Per the ASCO 2007 Clinical Practice Guidelines42, 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).
3.4.3
Prohibited and/or Restricted Treatments
Any systemic, anti-myeloma therapy other than pomalidomide, dexamethasone, and elotuzumab 
are prohibited while on study therapy. Concomitant steroids, other than weekly dexamethasone 
Section 4.5.1 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,43, 44. 
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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.
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 patient 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 patient 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 (Appendix 6), 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.
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:

Withdrawal of informed consent (subject’s decision to withdraw for any reason)

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.

Pregnancy (Subjects must discontinue elotuzumab and pomalidomide).

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.

Progressive Disease (Appendix 6)

Subjects who receive any non-protocol specified systemic anti-myeloma therapy before 
documented progression will be discontinued from all study treatment (including 
pomalidomide/dexamethasone); however, tumor assessments will continue at 4 week 
intervals until documented progression.

Subjects experiencing a Grade 4 infusion reaction must discontinue elotuzumab. Subjects 
may continue pomalidomide and dexamethasone treatment. Refer to Section 4.5.2.3.

Subjects experiencing angioedema, Grade 4 rash, exfoliative or bullous rash, 
Stevens-Johnson syndrome, or toxic epidermal necrolysis related to pomalidomide must 
discontinue pomalidomide. Subjects in the elotuzumab arm may continue elotuzumab and 
dexamethasone.

Subjects experiencing a 56 day delay in all study drugs (pomalidomide, dexamethasone, and 
elotuzumab) due to an adverse event(s) related to study treatment must be discontinued from 
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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. Delays greater than 28 days must be 
discussed with the medical monitor.
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event. In most cases, the study drug will be permanently discontinued in 
an appropriate manner. If the investigator determines a possible favorable benefit/risk ratio that 
warrants continuation of study drug, a discussion between the investigator and the BMS Medical 
Monitor/designee must occur.
All subjects who discontinue study drug should comply with protocol specified follow-up 
procedures as outlined in Table 5.1-3. The only exception to this requirement is when a subject 
withdraws consent for all study procedures or loses the ability to consent freely (ie, is imprisoned 
or involuntarily incarcerated for the treatment of either a psychiatric 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 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 contact.
3.6.1
Withdrawal of Consent
Subjects should be encouraged to continue participation in the trial until the laboratory definition 
of disease progression is met (Appendix 6). Subjects who discontinue study therapy before 
progression (eg, due to toxicity) should be encouraged to allow the necessary laboratory 
results (eg, M-protein data, sFLC data. radiologic data, calcium results) to be collected 
until disease progression criteria are fulfilled, even if the subject is on subsequent therapy 
(see Section 8.3.1). Central laboratory assessments are preferred; however assessments may also 
be completed locally. Local lab data can be obtained by the subjects’ local health care provider 
or the site staff. Site staff will enter local lab data into the CRF/database. Withdrawal of consent 
should be minimized because:
1. The subject in this trial who discontinues study therapy before progression will most likely 
be followed by a healthcare provider locally or at the site via routine standard of care 
assessments (ie, monthly M-protein data, calcium, etc) and
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2. In most cases, this protocol would not require any additional samples beyond those 
considered standard of care.
If there is uncertainty about the disease progression criteria, investigators are encouraged to 
contact the BMS Medical Monitor/study director prior to:
1. starting a subject on another myeloma regimen or 
2. performing the end of treatment visit for progression
Subjects who request to discontinue study drug will remain in the study and must continue 
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:
1. Study medication but subject is willing to continue to perform visits for PFS follow-up. 
2. Study medication and study visits for PFS but agrees to provide the results of future 
myeloma assessments from another site/local site.
3. Study treatments and results from another site/local sites, but agrees to be contacted for 
overall survival follow-up.
4. Study treatments and results from another site/local sites, and does not agree to be contacted 
for overall survival follow-up.
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, obituary listings, and databases, in order to obtain updated contact information. 
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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
All protocol-specified investigational and non-investigational products are considered study drug
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Table 4-1:
Study Drugs for CA204125 
Product Description / 
Class and Dosage Form
Potency
IMP/Non-IMP
Blinded or Open 
Label
Packaging / 
Appearance
Storage Conditions
(per label)
Elotuzumab Powder for 
Solution for Infusion
400 mg/vial
IMP
Open Label
20 mL Vial/ Sterile, 
white to off-white, 
preservative-free, 
lyophilized cake
Store at 2C - 8C
Dexamethasone Tablets
2 mg and 4 mg & 
various strengths
Non-IMP
NA
Various packing 
configurations
Refer to label on 
container or package 
insert / summary of 
product characteristics
Dexamethasone Solution
4 mg/mL, 8 mg/mL & 
various strengths
Non-IMP
NA
Various packing 
configurations
Refer to label on 
container or package 
insert / summary of 
product characteristics
Pomalidomide Capsules
1 mg, 2 mg, 3 mg and 4 
mg
Non-IMP
Open label
Various packing 
configurations
Refer to label on 
container or package 
insert 
Dexamethasone tablets and solution for IV infusion may be obtained by the investigating site’s standard prescribing procedures. 
Pomalidomide (Pomalyst®
) may be supplied by BMS centrally or through site standard prescribing procedure.
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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 product is: 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 
Appendix 5. The dose of elotuzumab to be administered to a subject will be calculated by 
multiplying the subject’s weight (kg) by 10 mg/kg in Cycles 1 and 2 (20 mg/kg for Cycle 3 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 Appendix 5. 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.
4.2
Non-Investigational Product
Other medications used in the study as support or escape medication for preventative, diagnostic, 
or therapeutic reasons, as components of the standard of care for a given diagnosis, are 
considered 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 (Section 4.5.1.4) or thromboprophylaxis 
(Section 3.4.1).
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 120 days 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 180 days) 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 
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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. Subjects who have the potential of pregnancy must be 
instructed about contraception and undergo the scheduled pregnancy tests. 
All study participants must be registered into the local, mandatory pomalidomide risk 
management program or follow the Pomalidomide Pregnancy Risk Prevention Plan, and be 
willing and able to comply with all requirements.
Please see the US package insert/SmPC for additional information for prescribing to female 
subjects and male subjects about this restricted distribution program.
Subjects should not break, chew or open the capsules. Pomalidomide should be taken without 
food (at least 2 hours before or 2 hours after a meal). Only enough pomalidomide for one cycle 
of therapy will be supplied to the patient each cycle in accordance with the local pomalidomide 
risk management program or the Pomalidomide Pregnancy Risk Prevention Plan.
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 NIMP for this study and will 
not be provided by the sponsor. It will be obtained by the investigating sites standard prescribing 
procedures except where it may be supplied by BMS due to country availability and specific 
regulatory requirements. Marketed product will be utilized for this study and should be stored in 
accordance with the package insert or summary of product characteristics (SmPC). See Table 
4.5.1.5-1 for dexamethasone dose reduction information if infusion reaction is observed.
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the 
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, do not dispense the study drug and 
contact BMS immediately.
The investigator (or assigned designee, ie, study pharmacist) will dispense the proper number of 
each strength tablet to the subject to satisfy dosing requirements until the subject’s next visit. The 
subject must be instructed to return all unused study medications in the provided packaging at 
each subsequent visit.
Procedures for proper handling and disposal of anticancer drugs should be considered.
Study drug not supplied by BMS will be stored in accordance with the package insert.
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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).
Procedures for proper handling and disposal of anticancer drugs should be considered
 
 
 
 
 
 
 
  
 
 
 
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4.5.2
Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions
4.5.2.1
Grade 1 Infusion Reaction
For Grade 1 elotuzumab infusion-related reactions, by definition, do not require intervention. 
However, increased monitoring is recommended.
4.5.2.2
Grade 2 Infusion Reaction
Infusion reactions during the elotuzumab infusion: For a Grade 2 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. Subjects with a Grade 4 
elotuzumab infusion reaction, see Section 4.5.2.3.
For Grade 2 or 3 infusion reactions, 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 starting at a rate per 
investigator’s discretion, and increasing up to a rate per investigator’s discretion, up to a 
maximum of 5 mL/minute. 
Subjects who experience an infusion reaction require vital signs to be monitored every 
30 minutes for 2 hours after the end of the elotuzumab infusion. 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 4.5.1.5-1.
Infusion reactions after the completion of elotuzumab infusion: Should a Grade 2 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 a maximum of 5 mL/minute on that day. If no Grade 2
infusion reaction occurs, the next infusion may be increased in a stepwise fashion starting at a 
rate per investigators’ discretion, and up to a maximum of 5 mL/minute. If tolerated, all 
subsequent infusions may start at a rate per investigator’s discretion, up to a maximum rate of 
5 ml/minute.
Contact the Medical Monitor with any questions regarding elotuzumab infusion rate escalation. 
4.5.2.3
Grade 4 Infusion Reaction
Acute symptoms should be managed as described in Section 4.5.2.2. Elotuzumab must be 
permanently discontinued. Subjects may continue with pomalidomide and dexamethasone per 
protocol.
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4.5.3
Dose Delay, Interruption, or Discontinuation, All Subjects
If the dose of one drug in the regimen (ie, pomalidomide, dexamethasone, or elotuzumab) is 
delayed, interrupted, or discontinued, the treatment with the other drugs may continue as 
scheduled. However, if dexamethasone is delayed or discontinued discuss ongoing elotuzumab 
administration with the medical monitor. Also see Section 3.5 for delays in study drugs.
Each cycle is 28 days. While dose delays 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 (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. For example, a subject on pomalidomide and dexamethasone may continue on 
study therapy even if dexamethasone must be discontinued for an adverse event. Likewise, a 
subject on the elotuzumab arm may continue on study therapy if elotuzumab must be 
discontinued for an adverse event or other reason. Subjects are considered still on study therapy 
even if they continue solely on pomalidomide or dexamethasone.
Please consult the BMS Medical Monitor or any questions regarding dose interruption or study 
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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
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.
4.5.4.1
Elotuzumab
No dose reduction is allowed for elotuzumab.
4.5.4.2
Dexamethasone
Dexamethasone dose reductions for toxicity must be performed as clinically indicated. 
Recommended management is described in Table 4.5.4.2-1 and Table 4.5.4.2-2 Deviations to the 
recommended dose reductions are allowed based on the clinical judgment of the investigator.
Table 4.5.4.2-1:
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.
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Table 4.5.4.2-1:
Dexamethasone Dose Reductions
CTCAE 
Category
Adverse Event
Treatment Adjustment
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 4.5.4.2-
1 and Table 4.5.4.2-2.
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. 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.
Table 4.5.4.2-2:
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
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4.5.4.3
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 
4.5.4.3-1 and Table 4.5.4.3-2 is based on pomalidomide prescribing information, which contains 
additional guidance on pomalidomide dosing 43 44.
Table 4.5.4.3-1:
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 4.5.4.3-2:
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.
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%.43,44
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Starting at Cycle 1, all treated subjects will be assessed for drug compliance of all treatments 
administered during the course of the study. Treatment compliance will be monitored by drug 
accountability and recorded in the subject’s medical record. 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.
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4.8
Destruction and Return of Study Drug
4.8.1
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as 
partially used study drug containers, vials and syringes may be destroyed on site. 
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible BMS Study Monitor unless study drug containers must be immediately destroyed as 
required for safety, or to meet local regulations (eg, cytotoxics or biologics). 
On-site destruction is allowed provided the following minimal standards are met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste 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 BMS Study Monitor will make 
arrangements for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused 
and/or partially used study drug that was supplied by BMS must be returned to BMS. The return 
of study drug will be arranged by the responsible BMS Study Monitor. 
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept. 
4.10
Retained Samples for Bioavailability / Bioequivalence
Not applicable.
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5.1.1
Retesting During Screening Period
Retesting of laboratory parameters and/or other assessments within the Screening period will be 
permitted (in addition to any parameters that require a confirmatory value).
Any new result will override the previous result (ie, the most current result prior to starting study 
drug) 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 3.0

Elotuzumab Investigator Brochure

Pomalidomide (Pomalyst) Package Insert

Site Manual for operation of IVRS

Subject Dosing Diary

Subject Quality of Life Questionnaires 

Serious Adverse Event (SAE) Case Report Form (CRF) pages

Pregnancy Surveillance Forms
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 submitted to BMS at least once per cycle. In addition, all 
safety lab results that lead to dose delay or discontinuation must be submitted to BMS.
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
Imaging Assessment for the Study
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the Study Investigator as per 
standard medical/clinical judgment.
5.3.2
Vital Signs, Physical Measurements, and Physical Examination
Vital signs (body temperature, seated blood pressure and heart rate) will be recorded as outlined 
in Table 5.1-1, Table 5.1-2 and Table 5.1-3. Blood pressure and heart rate should be measured 
after the subject has been seated quietly for at least 5 minutes prior to dosing. Subjects in the 
control arm will have vital signs measured once at each visit. Subjects randomized to the 
elotuzumab arm will have additional vital signs as follows: 

Prior to pre-medication administration

Prior to the start of the elotuzumab infusion

Thirty minutes after the start of infusion

At the end of the infusion

For Cycles 1 and 2: Thirty minutes and 120 minutes post completion of the elotuzumab 
infusion.

For Cycle 3 and beyond: 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 2 hours after the end of the elotuzumab infusion.
Height will be recorded at screening. Weight will be measured at study visits as indicated in 
Table 5.1-1, Table 5.1-2 and Table 5.1-3
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 and Table 
5.1-3 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 
A MUGA scan or 2-dimensional echocardiogram and electrocardiogram (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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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
Platelets
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
Total Protein
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
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
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5.4
Efficacy Assessments
Efficacy endpoints will be based on analysis of serum and urine electrophoresis (SPEP and 
UPEP), sFLC (for those with sFLC disease only), 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 and Table 5.1-3. 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 5.4.2-1. 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
Response criteria in Appendix 632,33 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 disease progression based on Appendix 6, irrespective of dose delays or 
treatment cycle. If subject does not have documented disease progression as defined in 
Appendix 6 at the time of study drug discontinuation, then tumor assessments must 
continue to be performed according to the same schedule described above until disease 
progression even if a subsequent anti-myeloma treatment is initiated prior to disease 
progression. 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 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), 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 disease progression or withdrawal 
of consent, even if the subject is discontinued from study therapy and has started new myeloma 
therapy. Confirmation of PR is required on 2 consecutive assessments for Serum, Urine and 
sFLC.
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1) Serum: SPEP for M protein quantification, total serum protein, serum immunofixation, and 
quantitative immunoglobulin assay.
a.
Serum Immunofixation 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. All other serum tests will be followed at each tumor assessment.
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 considered oligosecretory must have sFLC 
assessed at each cycle until until progression.
b. Serum must be collected at screening and time of serum and urine IFE negativity to 
confirm CR and be sent to the central lab for sFLC analysis. This measurement is 
required to assess for sCR
3) Urine: 24-hour urine collection for M protein quantification, urinary light chains, and 
immunofixation. 24-hour urine must be collected with each cycle for all subjects.
a.
Urine Immunofixation is required at baseline and to confirm CR, regardless of whether 
measurable M-protein was present at baseline.
b. All other urine tests will be followed at each tumor assessment. 
4) Bone marrow aspiration/biopsy:
Table 5.4.2-1:
Bone Marrow Samples
Sample
Local Laboratory
Central Laboratory
Aspirate
1) Samples required at the following times 
to evaluate percentage plasma cells:
a) Screening (within 35 days of 
randomization) 
b) When subject is immunofixation 
negative in both serum and urine 
(second bone marrow sample not 
required for confirmation) 
i) In addition, evaluate flow cytometry 
to assess plasma cell clonality 
(ie, lambda and kappa IHC or flow 
cytometry to assess light chain 
restriction.
c) At time of suspected disease 
progression, if needed 
(see Section 5.4.4) to assess PD in 
subjects whose myeloma become 
nonsecretory.
Evaluation of percentage of plasma cells 
should be performed locally per 
a) Screening (within 35 days of randomization
i) Genetic assessments (FISH) should be 
performed by the central laboratory on a 
fresh bone marrow sample. However, if a 
new bone marrow sample collection is not 
feasible 
and 
if 
this 
assessment 
was 
performed locally within the 35 days of 
randomization, the local results must be 
entered into the eCRF.
Contact BMS 
medical monitor in these cases.
b) Aspirate 
samples are required for 
biomarker assessments (section 5.6.1).
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Table 5.4.2-1:
Bone Marrow Samples
Sample
Local Laboratory
Central Laboratory
institution standard practice; 
Plasma cell percentage and light chain 
restriction assessments are required. If 
not available, IHC can be performed on 
bone marrow core biopsy.
Biopsy
Not required by protocol unless an aspirate 
sample (at any time point above) is not 
available due to a dry tap or due to 
laboratory preferences of the local 
pathologist
5) Serum Corrected Calcium: Serum corrected calcium should be collected with each cycle 
for all subjects until 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
progression), whether or not present at baseline, and at the time of CR/sCR assessment.
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.
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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 6 for definitions of response and progression. All criteria are derived from 
IMWG46,47,48, except for minor (minimal) response, which is derived from EBMT. All response 
categories require 2 consecutive assessments made before initiation of any new therapy.
5.5
Pharmacokinetic Assessments
Blood samples for pharmacokinetic (PK) assessment will be drawn according to the PK 
sampling schedule provided in Table 5.5.1-1. Development of anti-drug antibodies (ADA) will 
be evaluated in all subjects receiving elotuzumab at specified time points as noted in Table 5.5.1-
1. Blood samples for the analysis of serum concentrations of elotuzumab should be drawn from 
the arm not used for infusion of study drug. Detailed instructions for the collection, processing, 
handling, labeling, storage, and shipment of PK and ADA samples will be provided in the central 
laboratory manual.
It is important to record the actual time of sample collection, even if this deviates from the 
protocol specified time.
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5.5.1
Anti-Drug Antibody (ADA)Assessments 
Development of Anti-Drug elotuzumab Antibodies (ADA) will be evaluated in subjects 
receiving elotuzumab at specified time points as noted in Table 5.5.1-1.
Table 5.5.1-1:
PK and ADA Sampling Schedule
Cycle Number
Study 
Day
Time (Event)
PK Collectiona
ADA Collectiona
1
1
0 H (pre-dose)
X
X
2 hours post-end of infusion
X
8
0 H (pre-dose)
X
2 hours post-end of infusion
X
15
0 H (pre-dose)
X
22
0 H (pre-dose)
X
2 hours post-end of infusion
X
2
1
0 H (pre-dose)
X
X
2 hours post-end of infusion
X
22
0 H (pre-dose)
X
2 hours post-end of infusion
X
3
1
0 H (pre-dose)
X
X
2 hours post-end of infusion
X
4
1
0 H (pre-dose)
X
X
5
1
0 H (pre-dose)
X
X
6
1
0 H (pre-dose)
X
X
7
1
0 H (pre-dose)
X
X
2 hours post-end of infusion
X
Every 3rd Cycle 
after Cycle 7 (ie 
Cycle 10, 13...etc)
1
0 H (pre-dose)
X
X
End of Study / Discontinuationb
X
X
30-Day Follow-Upb
X
X
60 Day Follow-Upb
X
X
a Subjects who miss a PK and ADA collection, because elotuzumab was not given, should collect PK and ADA 
samples on the day (predose) that elotuzumab is restarted (noting the actual time of collection and dosing), and 
then continue following the schedule in Table 5.5.1-1
b If elotuzumab is discontinued, but the subject remains on study drug(s), PK and ADA samples will be collected 
at: the day of the last elotuzumab dose, 30 days after the last elotuzumab dose and 60 days after the last 
elotuzumab dose
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5.5.2
Pharmacogenomic/Pharmacogenetic Assessments
Genetic assessment (FISH) of myeloma cells will be performed by a central laboratory on the 
fresh bone marrow, during the screening period. If a fresh aspirate is not available, but local 
genetic assessment has been performed since completing the last regimen, but prior to entering 
this study, these results must be entered into the CRF/eCRF. This assessment is considered to be 
standard of care for myeloma. Contact BMS medical monitor in these cases. Assessment may 
include but not be limited to FISH analyses in Section 5.6. In addition, potential biomarkers of 
resistance or sensitivity to pomalidomide or elotuzumab may be explored in these tumor 
samples.
5.6.1
Bone Marrow Aspirate Samples:
Bone marrow aspirates for Biomarker Assessments will be evaluated at a Central Lab:
1) Cytometry of:
a) Plasma cell (PC) subsets:  Evaluation of, but not limited to SLAMF7 (target of 
elotuzumab) and PD-L1 on enumerated CD138+/CD38+ PCs. PC subsets will be further 
subdivided into normal and aberrant (malignant) based on differential expression of 
CD19 and CD56. 
b) Lymphoid and myeloid subsets:  will be enumerated and evaluated for expression of but 
not limited to SLAMF7 and PD-1. In addition to the absolute lymphocyte count, 
enumeration and percentage of cell subsets will be determined by multiparameter 
cytometry to assess major NK cells subsets, naïve and memory T cell subsets, Treg cells, 
Th17 cells, MDSCs, and pDCs.
2) Gene expression: CD138 magnetic separation and enrichment of CD138+ (plasma cells) and 
CD138-negative (which includes lymphocytes) cells and RNAseq of PCs and lymphocytes in 
the bone marrow microenvironment. 
3) Protein analysis (marrow): Following separation of CD138+ and CD138- cell cellular 
fractions from the bone marrow aspirate (see “Gene expression analysis”), the soluble 
(non-cellular) fraction will be assessed for proteins, including but not limited to soluble 
SLAMF7 (sSLAMF7) and potentially immune regulators such as cytokines/chemokines.
4) Fluorescence in-situ hybridization (FISH): bone marrow aspirates obtained at screening will 
be used to identify prognostic cytogenetic markers that may include but are not limited to: 
t(4 ;14), t(14 ;16), t(11 ;14), t(6;14), t(14;20), 1q gains/amp, del(17p), del(1p), and del(13). 
FISH analysis will be limited to bone marrow aspirates obtained at screening (mandated) and 
at EOT (if available). 
5) Molecular minimum residual disease (MRD) assessment by Adaptive® ClonoSIGHT assay.
6) Cytometry MRD: using a portion of the bone marrow sample collected at time of CR/sCR.
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5.6.2
Peripheral Blood Samples: 
Peripheral Blood samples for Biomarker Assessments will be evaluated at a Central Lab:
1) Lymphoid and myeloid subsets: (same population as with marrow).
2) Molecular (MRD) whole blood assessment by AdaptiveClonoSIGHT assay.
3) Protein analysis (serum): Assessment of soluble proteins in circulation that include but are 
not limited to sSLAMF7 and potentially immune regulators such as cytokines/chemokines.
4) Fc-γR polymorphisms: for genotyping of Fc receptor genes (minimally CD16a and CD32a) 
and other host genes that may be related to regulators of immune response and anti-tumor 
activity.
5) Gene Expression Profiling: gene expression levels and changes (along with gene networks or 
pathways) to better understand the complex nature of the immune response.
5.7
Outcomes Research Assessments
5.7.1
Patient-reported Outcomes (PRO) Assessments
To assess the impact of treatment on patient-reported outcomes, two questionnaires will be used:
1) M.D. Anderson Symptom Inventory Multiple Myeloma module MDASI-MM (Appendix 4), 
which measures symptoms.
2) EuroQol Group’s EQ-5D (Appendix 5), which measures utilities, and is a preference-based 
measure of health status.
Questionnaires will be administered to all subjects per the schedule in Table 5.1-1, Table 5.1-2
and Table 5.1-3. 
All questionnaires will be administered at (1) baseline (prior to randomization); (2) on Day 1 of 
each 4 week treatment cycle; (3) at the end of treatment or study withdrawal; (4) at each survival 
follow-up at the post treatment phase of the study via telephone. Traditional telephone 
communication between research staff and patient, or automated interactive voice response 
(IVR) system may reduce the burden of missing data in monitoring patient reported outcomes 
while they are away from the clinical sites. EQ-5D has been validated in paper, telephone 
interview, as well as IVR formats. Telephone interview scripts in local languages, detailed 
training and instructions will be provided to field staff administering the questionnaire.
Subjects should fill out the questionnaire prior to any study-related procedures, treatment or 
clinical assessment in order to prevent these variables from influencing PRO results. PRO 
instruments are provided as part of the CRF. Questionnaires will be provided in the subject’s 
preferred language.
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M. D. Anderson Symptom Inventory (MDASI) is reliable, valid instrument that was designed 
for ease of administration and that asks patients to rate 13 symptoms (“core” items) and 
6 symptom-related interference items that are common across cancer types and treatments. The 
multiple myeloma module of the MDASI (MDASI-MM) is a site-specific module that augments 
the 19 core MDASI symptom and interference items with additional items identified as unique to 
multiple myeloma. Along with the core MDASI’s 13 symptom items and 6 interference items, 
the MDASI-MM also assesses 7 multiple myeloma-specific symptom items: bone aches, muscle 
weakness, sore mouth/throat, rash, difficulty concentrating, constipation, and diarrhea.
EuroQol Group’s EQ-5D:
Because oncology therapies may positively or negatively affect a patient’s quality of life, a 
common methodological approach is used to quantify this effect by “quality adjusting” survival 
in comparative treatment arms. The result, quality adjusted life years (QALYs), is a measure of 
both the length and quality of life and is used as a measure of benefit in cost-utility analysis. 
Unfortunately, general PRO instruments such as the EORTC QLQ C30 are not designed to 
measure subject preferences (or utilities) in a way that is suitable for calculating QALYs. 
Therefore, a separate validated instrument, in this case the EuroQol EQ 5D, will be used to 
quantify utilities to calculate QALYs for cost utility analyses.
The EQ 5D is a 5-item questionnaire and a “thermometer” visual analogue scale ranging from 
0 (worst imaginable health state) to 100 (best imaginable health state) that will be administered 
at the same intervals as the other PRO instruments, including at the Screening Visit to assess the 
comparability of the groups at study initiation. The time referent is “today” for this instrument.
Enhancing Compliance
It is necessary to implement specific measures to ensure optimal compliance in PRO data 
collection. Both staff and patients will be provided with the necessary training and resources for 
optimal data collection at the appropriate times. Collaboration between the study coordinator, the 
data center responsible for the day to day administration of the study and the individual 
investigators can lead to organizational improvements. More specific measures will be targeted 
at the patient, the physician and the data manager or the research nurse, though there is 
considerable overlap.
Missing Data
If a questionnaire is missing during the acceptable time delay, a reason should be recorded 
(eg, refusal, nurse forgot, etc.), and the patient should be contacted by telephone and mail with 
the questionnaire and a reply paid envelope. An acceptable time delay or “window” during 
which the questionnaire must be completed is 1 week during treatment, at EOT, and the first 
two visits post treatment, to ensure evaluation of short-term toxicity and response. During 
follow up for EQ-5D, a wider window (3 weeks) would be acceptable after the first two 
post-treatment visits.
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5.7.2
Healthcare Resource Utilization
During the study, healthcare resource utilization (HRU) data associated with medical encounters 
related to disease or treatments or both will be collected for all subjects. Specifically, HRU is 
evaluated based on the number of medical care encounters such as hospital admissions and their 
duration, outpatient visits, diagnostic tests and procedures, and concomitant medications. HRU 
data will be collected from all sites. The medical resource utilization data will be utilized to 
conduct economic analyses.
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 
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.)
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)
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
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. 
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)
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6.1.1
Serious Adverse Event Collection and Reporting
Sections 5.6.1 and 5.6.2 in the Investigator Brochure (IB) represent the Reference Safety 
Information to determine expectedness of serious adverse events for expedited reporting. 
Following the subject’s written consent to participate in the study, all SAEs, whether related or 
not related to study drug, must be collected, including those thought to be associated with 
protocol-specified procedures. All SAEs must be collected that occur during the screening period 
and within 60 days of discontinuation of dosing or within 30 days of the last visit for screen
failures. The investigator must report any SAE that occurs after these time periods and that is 
believed to be related to study drug or protocol-specified procedure. 
An SAE report must be completed for any event where doubt exists regarding its seriousness. 
If the investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship must be specified in the narrative section of the SAE Report Form.
SAEs, whether related or not related to study drug, and pregnancies must be reported to BMS 
(or designee) within 24 hours of awareness of the event. SAEs must be recorded on the SAE 
Report Form; pregnancies on a Pregnancy Surveillance Form (electronic or paper forms). The 
preferred method for SAE data reporting collection is through the eCRF. The paper 
SAE/pregnancy surveillance forms are only intended as a back-up option when the eCRF system 
is not functioning. In this case, the paper forms are to be transmitted via email or confirmed 
facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Facsimile Number:  Refer to Contact Information list.
For studies capturing SAEs through electronic data capture (EDC), electronic submission is the 
required method for reporting. In the event the electronic system is unavailable for transmission, 
paper forms must be used and submitted immediately. When paper forms are used, the original 
paper forms are to remain on site.
SAE Telephone Contact (required for SAE and pregnancy reporting): Refer to Contact 
Information list.
If only limited information is initially available, follow-up reports are required. (Note: Follow-up 
SAE reports must include the same investigator term(s) initially reported.) 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, the SAE report must be updated and submitted within 24 hours to BMS 
(or designee) using the same procedure used for transmitting the initial SAE report.
All SAEs must be followed to resolution or stabilization.
6.2
Nonserious Adverse Events
A nonserious adverse event is an AE not classified as serious.
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6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug. Nonserious 
AE information should also be collected from the start of a placebo lead-in period or other 
observational period intended to establish a baseline status for the subjects. 
Nonserious AEs should be followed to resolution or stabilization, or reported as SAEs if they 
become serious (see Section 6.1.1). Follow-up is also required for nonserious AEs that cause 
interruption or discontinuation of study drug and for those present at the end of study treatment 
as appropriate. All identified nonserious AEs must be recorded and described on the nonserious 
AE page of the CRF (paper or electronic). 
Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported/identified during the course of the study.
6.3
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the nonserious AE CRF 
page or SAE Report Form (paper or electronic) as appropriate:

Any laboratory test result that is clinically significant or meets the definition of an SAE 

Any laboratory test result abnormality that required the subject to have study drug 
discontinued or interrupted

Any laboratory test result abnormality that required the subject to receive specific corrective 
therapy.
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia versus low hemoglobin value).
6.4
Pregnancy
If, following initiation of the 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 (90 days) plus one ovulatory cycle (30 days) for a total of 120 days, or plus one 
spermatogenesis cycle (90 days) for a total of 180 days after product administration, the 
investigator must immediately notify the BMS Medical Monitor/designee of this event and 
complete and forward a Pregnancy Surveillance Form to BMS Designee within 24 hours of 
awareness of the event and in accordance with SAE reporting procedures described in Section 
6.1.1.
In most cases, the study drug will be permanently discontinued in an appropriate manner 
(eg, dose tapering if necessary for subject safety).
In the rare event that the benefit of continuing study drug is thought to outweigh the risk, after 
consultation with BMS, the pregnant subject may continue study drug after a thorough 
discussion of benefits and risk with the subject 
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Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy (eg, x-ray studies). Other appropriate pregnancy 
follow-up procedures should be considered if indicated.
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.
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).
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.
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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.
7
DATA MONITORING COMMITTEE 
Not applicable.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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8.3
Endpoints
8.3.1
Primary Endpoint(s)
8.3.1.1
Primary definition of PFS
PFS will be defined as the time, in months, from randomization to the date of the first 
documented tumor progression or death due to any cause. Clinical deterioration will not be 
considered progression. A subject who neither progresses nor dies will be censored on the date of 
their last tumor assessment. A subject who does not have any post-baseline tumor assessments 
and who has not died will be censored on the date at which they were randomized.
8.3.1.2
Secondary Definition of PFS: 
PFS will be analyzed after censoring patients who either received subsequent therapy or had two 
or more missing tumor assessments prior to their disease progression or death. In this secondary 
definition, PFS will also be measured as the time in months from randomization to the date of the 
first documented tumor progression or death due to any cause, provided death does not occur 
more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical 
deterioration will not be considered progression.
The following censoring rules will be applied for this definition of PFS:

Subjects who receive secondary anti-myeloma therapy prior to documented progression will 
be censored on the date of the last adequate tumor assessment prior to the initiation of the 
new therapy.

Subjects who have an event (documented progression or death) > 10 weeks (2 assessment 
visits) after the last prior tumor assessment will be censored at the last adequate prior 
assessment.

Subjects who neither receive subsequent therapy prior to progression nor have a progression 
event will be censored at their last adequate tumor assessment.
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8.3.2
Secondary Endpoint(s)
8.3.2.1
Objective response rate
Objective response rate is defined as the proportion of randomized subjects who achieve a best 
response of partial response (PR) or better using the criteria in Appendix 6. 
8.3.2.2
Overall survival
Overall survival is defined as the time from randomization to the date of death from any cause. If 
a subject has not died, their survival time will be censored at the date of last contact (“last known 
alive date”). A subject will be censored at the date of randomization if they were randomized but 
had no follow-up. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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8.4.2.2
Secondary Efficacy Analysis
Objective response rate is a secondary objective. A two-sided 
= 0.2 level 
Cochran-Mantel-Haenszel (CMH) test, stratified using the same factors as in PFS, will be used to 
compare the response rate between the treatment arms. The response rate, along with its exact 
two-sided 80% CI, will be computed within each treatment arm. A two-sided, 80% CI for 
difference of response rate between the treatment arms will also be computed. In addition, the 
two-sided 95% CI will also be computed.
Overall survival is another secondary objective. It will be compared between arms using a 
stratified group sequential log-rank test procedure with a two-sided, =0.2 level. The 
stratification factors will be the same as those used for the analyses of PFS and tumor response. 
The OS function for each randomized arm will be estimated using the Kaplan-Meier 
product-limit method. Median and two-sided, confidence intervals for median OS will be 
computed by randomized arm. 
8.4.3
Safety Analyses
Safety analyses will be conducted on all treated population. Adverse events and laboratory 
parameters will be summarized using CTCAE version 3.0. Summary tables will be presented on 
safety parameters for each treatment arm. Limited safety analysis will be presented on all treated 
subjects in the lead in phase of the study.
8.4.4
Pharmacokinetic Analyses
Summary statistics will be calculated for elotuzumab concentrations and summarized by 
scheduled sample collection time. This data will be combined with concentration data from other 
studies to conduct a population pharmacokinetic (PPK) analysis. Results of PPK will be reported 
separately. Anti-drug antibodies will also be assessed.
 
 
 
 
 
 
 
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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 to include investigational product and 
the following non-investigational product(s) pomalidomide and dexamethasone. 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
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
amount transferred to another area/site for dispensing or storage

non-study disposition (eg, lost, wasted) 

amount destroyed at study site, if applicable

amount returned to BMS

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 paper or electronic SAE form and Pregnancy Surveillance form, respectively. Spaces may be 
left blank only in those circumstances permitted by study-specific CRF completion guidelines 
provided by BMS. 
The confidentiality of records that could identify subjects must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, including any paper or electronic SAE/pregnancy CRFs, must be promptly 
reviewed, signed, and dated by the investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form .For electronic CRFs, review 
and approval/signature is completed electronically through the BMS 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:

Subject recruitment (eg, among the top quartile of enrollers)

Involvement in trial design

Other criteria (as determined by the study team)
The data collected during this study are confidential and proprietary to BMS. Any publications 
or abstracts arising from this study 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
Term
Definition
Complete Abstinence
If one form of contraception is required, Complete 
Abstinence is defined as complete avoidance of heterosexual 
intercourse and is an acceptable form of contraception for all 
study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly 
effective contraception must be discussed in the event that 
the subject chooses to forego complete abstinence.
If two forms of contraception is required, Complete 
abstinence is defined as complete avoidance of heterosexual 
intercourse and is an acceptable form of contraception for all 
study drugs. Subjects who choose complete abstinence are 
not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. 
Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject 
chooses to forego complete abstinence.
Expanded definition Complete abstinence as defined as 
complete avoidance of heterosexual intercourse is an 
acceptable form of contraception for all study drugs. This 
also means that abstinence is the preferred and usual lifestyle 
of the patient. This does not mean periodic abstinence 
(eg, calendar, ovulation, symptothermal, profession of 
abstinence for entry into a clinical trial, post-ovulation 
methods) and withdrawal, which are not acceptable methods 
of contraception. Subjects who choose complete abstinence 
are not required to use a second method of contraception, but 
female subjects must continue to have pregnancy tests. 
Acceptable alternate methods of highly effective 
contraception must be discussed in the event that the subject 
chooses to forego complete abstinence
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11
LIST OF ABBREVIATIONS
Term
Definition
ADA
Anti-Drug Antibodies
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
EORTC
European Organization for Research and Treatment of Cancer
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
HRQoL
Health Related Quality of Life
HRT
Hormone replacement therapy
ICH
International Council on Harmonization
IF
Immunofixation
IHC
Immunohistochemistry
IL-2
Interleukin 2
IMiDs
Immune Modulatory Drugs
IMWG
International Myeloma Working Group
IRB/IEC
Institutional Review Board/Independent Ethics Committee
IV
Intravenous
ITT
Intent-to-treat
NK
Natural Killer
NKT
Natural Killer T-Cells
Ld
Lenalidomide (low-dose) dexamethasone
LD
Lenalidomide (high-dose) dexamethasone
LdE
Lenalidomide, (low-dose) dexamethasone, elotuzumab
LPFV
Last patient first visit
MDASI-MM
MD Anderson Symptom Inventory Multiple Myeloma Module
MGUS
Monoclonal Gammopathy of Undetermined Significance
MM
Multiple Myeloma
MR
Minor (Minimal) Response
MRD
Minimal Residual Disease
MRI
Magnetic Resonance Imaging
MTD
Maximum tolerated dose
NK
Natural Killer 
NKT
Natural Killer T-cell
ORR
Objective Response Rate
OS
Overall Survival
PBMC
Peripheral blood mononuclear cells
Pd
Pomalidomide (low dose) dexamethsone
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Term
Definition
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
sSLAMF7
soluble SLAMF7
SMM
Smoldering Multiple Myeloma
WOCBP
Women of childbearing potential
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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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SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
AN OPEN LABEL, RANDOMIZED PHASE 2 TRIAL OF 
POMALIDOMIDE/DEXAMTHASONE WITH OR WITHOUT ELOTUZUMAB IN 
RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Protocol CA204-125
FINAL
V 1.1
2.0
930102782
3.0
v


Official Title of Study: 
AN OPEN LABEL, RANDOMIZED PHASE 2 TRIAL OF 
POMALIDOMIDE/DEXAMTHASONE WITH OR WITHOUT ELOTUZUMAB IN 
RELAPSED AND REFRACTORY MULTIPLE MYELOMA 
 
NCT Number: NCT02654132 
 
Document Date (Date in which document was last revised): 01-May-2018  


Statistical Analysis Plan
CA204-125
BMS-901608
elotuzumab
TABLE OF CONTENTS
STATISTICAL ANALYSIS PLAN................................................................................................1 
TABLE OF CONTENTS.................................................................................................................2 
LIST OF TABLES...........................................................................................................................6 
1 
BACKGROUND AND RATIONALE.........................................................................7 
2 
STUDY DESCRIPTION..............................................................................................8 
2.1 
Study Design.................................................................................................................8 
2.2 
Treatment Assignment................................................................................................10 
2.3 
Blinding and Unblinding ............................................................................................10 
2.4 
Protocol Amendments ................................................................................................10 
2.5 
Independent Data Monitoring Committee and Other External Committees ..............10 
2.6 
Interim Analysis..........................................................................................................10 
3 
OBJECTIVES.............................................................................................................11 
3.1 
Primary .......................................................................................................................11 
3.2 
Secondary ...................................................................................................................11 
 
 
4 
ENDPOINTS..............................................................................................................11 
4.1 
Endpoint Definitions...................................................................................................11 
4.1.1 
Progression-Free Survival..........................................................................................11 
4.1.1.1 
Definition of an Adequate Tumor Assessment............................................................11 
4.1.1.2 
Date of Progression or Censoring When Different Components of a Per Time 
Point Tumor Assessment Conducted at Different Times ............................................12 
4.1.1.3 
Primary Definition of Progression-Free Survival (PFS) ...........................................12 
4.1.1.4 
Secondary Definition of Progression-Free Survival ..................................................12 
4.1.2 
Objective Response Rate (ORR) .................................................................................13 
4.1.3 
Overall Survival..........................................................................................................13 
4.1.4 
Time to Tumor Response ............................................................................................13 
4.1.5 
Duration of Response .................................................................................................13 
4.2 
Pharmacokinetic Endpoints ........................................................................................13 
4.3 
Immunogenicity Endpoints.........................................................................................13 
4.4 
Safety Endpoints.........................................................................................................13 
 
 
5.1 
Progression-Free Survival ..........................................................................................14 
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5.2 
Objective Response Rate............................................................................................14 
5.3 
Overall Survival..........................................................................................................14 
6 
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS 
FOR ANALYSES.......................................................................................................14 
6.1 
Study Periods..............................................................................................................14 
6.2 
Treatment Regimens...................................................................................................15 
 
 
7 
STATISTICAL ANALYSES.....................................................................................16 
7.1 
General Methods.........................................................................................................16 
7.2 
Study Conduct ............................................................................................................17 
7.2.1 
Accrual Patterns.........................................................................................................17 
7.2.2 
Protocol Violations.....................................................................................................17 
 
 
7.3.1 
Subject Disposition.....................................................................................................18 
7.3.2 
Demographic and Subject Characteristics.................................................................18 
7.3.3 
Disease Characteristics at Baseline...........................................................................18 
7.3.4 
Prior Anti-Myeloma Therapy .....................................................................................19 
7.3.5 
General Medical History............................................................................................20 
7.3.6 
Baseline Safety Laboratory Tests ...............................................................................20 
7.4 
Extent of Exposure .....................................................................................................20 
7.4.1 
Study Therapy.............................................................................................................20 
7.4.1.1 
Duration of Study Therapy .........................................................................................21 
7.4.2 
Dose Modifications.....................................................................................................21 
7.4.2.1 
Elotuzumab Dose Reduction.......................................................................................21 
7.4.2.2 
Elotuzumab Dose Delay .............................................................................................21 
7.4.2.3 
Elotuzumab Dose Omission........................................................................................21 
7.4.2.4 
Elotuzumab Dose Interruption ...................................................................................22 
7.4.2.5 
Elotuzumab IV Rate Reduction...................................................................................22 
7.4.2.6 
Pomalidomide Dose Reduction...................................................................................22 
7.4.2.7 
Pomalidomide Dose Interruption ...............................................................................23 
7.4.2.8 
Dexamethasone (IV) and Oral....................................................................................23 
7.4.2.9 
Cumulative Dose, Dose Intensity, and Relative Dose Intensity..................................24 
7.4.3 
Premedication Other than Dexamethasone for Hypersensitivity Reactions ..............26 
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7.4.4 
Concomitant Medication ............................................................................................26 
7.4.5 
Discontinuation of Study Therapy ..............................................................................26 
7.4.6 
Subsequent Anti-Myeloma Therapy............................................................................27 
7.5 
Efficacy.......................................................................................................................27 
7.5.1 
Primary Analysis of Progression-Free Survival.........................................................28 
7.5.1.1 
Supportive Analyses of Progression-Free Survival....................................................28 
7.5.1.2 
Subset Analyses of Progression-Free Survival...........................................................29 
7.5.2 
Analysis of Objective Response ..................................................................................30 
7.5.2.1 
Subset Analyses of Objective Response......................................................................31 
7.5.2.2 
Time to Tumor Response and Duration of Response..................................................31 
7.5.3 
Analysis of Overall Survival.......................................................................................31 
7.5.4 
Currentness of PFS and OS Data...............................................................................31 
7.5.5 
Efficacy Assessments ..................................................................................................31 
7.6 
Safety..........................................................................................................................32 
7.6.1 
Adverse Events............................................................................................................32 
7.6.2 
Serious Adverse Events and Adverse Event Leading to Discontinuation...................33 
7.6.3 
Adverse Events of Special Interest..............................................................................33 
7.6.3.1 
Infusion Reaction........................................................................................................33 
7.6.3.2 
Opportunistic Infections .............................................................................................34 
7.6.3.3 
Second Primary Malignancies....................................................................................34 
7.6.4 
Safety in subgroups.....................................................................................................34 
7.6.5 
Deaths.........................................................................................................................35 
7.6.6 
Clinical Laboratory Evaluations................................................................................35 
7.6.7 
Echocardiogram, MUGA Scan and Electrocardiograms...........................................36 
7.6.8 
Vital Signs, Physical Measurements...........................................................................36 
7.7 
Pharmacokinetic Analysis ..........................................................................................36 
7.8 
Anti Drug Antibody Analysis.....................................................................................36 
7.9 
Pharmacogenomic Analysis........................................................................................37 
7.10 
Health Related Quality of Life ...................................................................................38 
7.11 
Healthcare Resource Utilization Data ........................................................................39 
8 
CONVENTIONS........................................................................................................39 
8.1 
Baseline Definition.....................................................................................................39 
8.2 
Age Definition ............................................................................................................39 
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LIST OF TABLES
  
 
 
 
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2.3
Blinding and Unblinding
Not applicable. 
2.4
Protocol Amendments
Not applicable.
2.5
Independent Data Monitoring Committee and Other External 
Committees
Not applicable.
 
 
 
 
 
 
 
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3
OBJECTIVES
3.1
Primary
The primary objective of this study is to compare progression free survival (PFS) between 
treatment arms.
3.2
Secondary
The secondary objectives are:

To compare objective response rate between treatment arms

To compare overall survival between treatment arms
4
ENDPOINTS
4.1
Endpoint Definitions
4.1.1
Progression-Free Survival
4.1.1.1
Definition of an Adequate Tumor Assessment
In the analysis of PFS, subjects who do not progress are censored. A non-progressing subject can 
be censored on the date of a tumor assessment only if there is sufficient information to rule out 
progression. An “adequate” tumor assessment visit for ruling out progression will require the 
following information:

Serum monoclonal paraprotein results, if measurable at baseline by central lab, and

Urine monoclonal paraprotein results, if measurable at baseline by central lab.
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Serum free light chain results, if measurable at baseline by central lab. This is only relevant for
subjects who do not have measurable serum and urine monoclonal paraprotein results.
4.1.1.2
Date of Progression or Censoring When Different Components of a Per 
Time Point Tumor Assessment Conducted at Different Times
As different tumor measurements may be conducted on different days, for instance, the blood draw 
for serum M-protein may be on a different date than 24-hour urine, the investigators were 
instructed to report the earliest date of the measurements associated with that time point for 
progression. In contrast, if tumor measurements are done on different dates and the subject is being 
censored, instructions were to report the latest date of the measurements associated with that time 
point.
4.1.1.3
Primary Definition of Progression-Free Survival (PFS)
PFS will be primarily analyzed applying an intent-to-treat (ITT) definition that utilizes all of the 
data on each randomly assigned subject at the time of the PFS analysis. PFS will be defined as the 
time from randomization to the date of the first documented tumor progression or death due to any 
cause. Clinical deterioration will not be considered progression. A subject who neither progresses 
nor dies will be censored on the date of their last adequate tumor assessment. A subject who does 
not have any post-baseline tumor assessments and who has not died will be censored on the date 
of randomization. 
4.1.1.4
Secondary Definition of Progression-Free Survival 
PFS will also be analyzed after censoring patients who either received subsequent therapy or had 
two or more missing tumor assessments prior to their disease progression or death. In this 
secondary definition, PFS will be measured as the time in months from randomization to the date 
of the first documented tumor progression or death due to any cause, provided death does not occur 
more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical 
deterioration will not be considered progression.
The following censoring rules will be applied for this definition of PFS:

Subjects who receive subsequent anti-myeloma therapy prior to documented progression will
be censored on the date of the last adequate tumor assessment prior to the initiation of the new
therapy.

Subjects who have an event (documented progression or death) > 10 weeks (2 assessment
visits) after the last prior adequate tumor assessment will be censored at the last prior
assessment.

Subjects who neither receive subsequent therapy prior to progression nor have a progression
event (including death) will be censored at their last adequate tumor assessment.

In addition, subjects who do not have any post-baseline adequate tumor assessments and who
do not die within 10 weeks of randomization will be censored on the date of randomization.
In all cases, if there are no adequate assessments for censoring then the patient is censored on the 
randomization date.
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4.1.2
Objective Response Rate (ORR)
The best overall response is determined as the best assessment based on all on-study efficacy data 
for the subject. 
Objective response rate is defined as the proportion of randomized subjects who achieve a best 
response of stringent complete response (sCR), complete response (CR), very good partial 
response (VGPR) or partial response (PR) using the modified IMWG criteria as per investigator’s 
assessment.
4.1.3
Overall Survival
Overall survival is defined as the time from randomization to the date of death from any cause. If 
a subject has not died, their survival time will be censored at the date of last contact (“last known 
alive date”). Subject will be censored on the date of randomization if they were randomized but 
had no follow-up.
4.1.4
Time to Tumor Response
Time to response is defined as the time, in months, from randomization to the first objective 
documentation of PR or better. Time to response is restricted to the randomized subjects who 
achieved a best response of PR or better.
4.1.5
Duration of Response 
Duration of response will be restricted to the randomized subjects with objective response of PR 
or better. It is measured from the time, in months, that the criteria for objective response are first 
met until the date of a progression event (according to the primary definition of PFS). A subject 
with objective response who does not have a progression event will be censored at the same time 
they were censored under the primary definition of PFS.
4.2
Pharmacokinetic Endpoints 
The serum concentrations of elotuzumab at each time point (of the sampling schedule) will be 
summarized. The Cmin (minimum drug concentration observed) by study day will be summarized.
4.3
Immunogenicity Endpoints 
Anti-drug antibody (ADA) is an immunogenicity endpoint. ADA will be evaluated using a 
validated bridging ligand binding method. For subjects who are found to have anti-elotuzumab 
antibodies, a titer will be reported to enable a qualitative comparison between subjects and within 
subjects at different time points.
4.4
Safety Endpoints
The safety endpoints include serious and non-serious adverse events, laboratory evaluations, 
deaths, and reasons off treatment.
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5.1
Progression-Free Survival
The primary objective of the study is to compare the progression-free survival between the 
treatment arms in all randomized subjects. The number of events and power of this study were 
calculated assuming an exponential distribution for PFS in each arm. 
The study will require at least 71 PFS events (progressions or deaths), for a two-sided experiment-
wise  = 0.2 log-rank test, to show a statistically significant difference in PFS between the 
treatment arms with 85% power when the true hazard ratio of the experimental arm to the control 
arm is 0.57. This is equivalent to demonstrating an improvement in median PFS from 4.0 months 
in the Pd arm9 to a median PFS of 6.8 months in the E-Pd arm.1 A total of 105 subjects are to be
randomized. Assuming approximately 10% of subjects may be lost to follow-up for the primary 
endpoint data, an additional 9 subjects would be randomized in the study. It is estimated that it 
would take approximately 9 months for full accrual of 114 subjects (assuming a fixed accrual rate 
of 13 subjects per month) and another 6 months to obtain the required number of events.
5.2
Objective Response Rate
Objective response rate is a secondary objective for this study. With a sample size of 114 subjects, 
there will be at least 90% power to detect a 23% improvement in response rate, using a two-sided 
0.2 level test, in the E-Pd arm (to 58%) compared with a response rate of 35% in the Pd arm.
5.3
Overall Survival
OS is another secondary objective for this study. The final analysis of OS will be conducted after 
at least 78 deaths have been observed from 114 subjects. This is expected to happen 18 months 
(1.5 years) from the time of the final PFS analysis. With 78 events the study will have 75 % power 
using a two-sided log-rank test at a  = 0.2 level, to show a statistically significant difference when 
the true hazard ratio is 0.64. This is equivalent to demonstrating a 56% improvement in median 
OS, i.e., 19.8 months in the E-Pd arm compared to the median OS in the Pd arm of 12.7 months.9
6
STUDY PERIODS, TREATMENT REGIMENS AND POPULATIONS FOR 
ANALYSES
6.1
Study Periods
There are three periods in this study: screening, on-treatment and post-treatment follow-up.
Screening: Most screening procedures must be done no more than 14 days prior to randomization. 
Some exceptions include efficacy assessments and ECGs, which can be done up to 28 days prior 
to randomization, and bone marrow which can be done up to 35 days prior to randomization. See 
Section 5 of the Protocol for full details of study procedures and timings. For analyses purposes 
1
Meletios A. Dimopoulos, Martha Q Lacy, et al. Pomalidomide in Combination with Low-Dose 
Dexamethasone: Demonstrates a Significant Progression Free Survival and Overall Survival Advantage, in 
Relapsed/Refractory MM: A Phase 3, Multicenter, Randomized, Open-Label Study Blood (ASH Annual Meeting 
Abstracts), Nov 2012; 120: LBA-6.
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data collected within 60 days of randomization and prior to first dose will fall into the 
screening/baseline period. Site personnel should make every effort to initiate study drug treatment 
within three days after randomization.
On-Treatment Period: The on-treatment period has two phases: the first two cycles and Cycle 3 
and beyond. All cycles are 28 days in duration. The first two cycles are characterized by weekly 
visits, safety assessments, and, in the experimental arm, elotuzumab infusions, while Cycle 3 and 
beyond are characterized by monthly visit, safety assessments and, in the experimental arm, 
elotuzumab infusions. Subjects should have myeloma urine and serum laboratory assessments 
every four weeks while on treatment until they progress and should have imaging for 
extramedullary plasmacytomas, as clinically indicated, and at the time of CR/sCR assessment. The 
timing of the tumor assessments will be independent of dosing. Study treatment ends when the 
subject progresses, experiences unacceptable toxicity, or withdraws consent.
Follow-up Period: Subjects who discontinue study therapy prior to progression must continue to 
undergo tumor assessments on the same schedule used in the on-treatment period, regardless of 
whether they are receiving new anti-myeloma therapy. The only exception to this is if the subject 
withdraws consent for all study procedures or loses the ability to consent freely.
Follow-up for survival and subsequent myeloma therapy after a subject progresses will be 
conducted every 12 weeks, or more frequently, until the subject dies or the study ends.
6.2
Treatment Regimens
Subjects will be randomized to one of two treatment arms, E-Pd or Pd. Subjects will receive these 
treatments in 28-day cycles until disease progression, unacceptable toxicity or withdrawal of 
consent.
On Arm A (E-Pd) subjects receive:

Elotuzumab: 10mg/kg intravenous (IV) on Days 1, 8, 15 and 22 of the cycle, during Cycles 1
and 2 and 20mg/kg intravenous (IV) on Day 1 of the cycle in subsequent cycles (Cycle 3 and
beyond).

Pomalidomide: 4mg orally (PO) daily (Days 1-21) of each cycle.

Dexamethasone: Administered on Days 1, 8, 15 and 22 of cycle. 28mg PO for subjects  75
years old (or 8mg PO for subjects > 75 years old) + 8mg IV whenever given prior to
elotuzumab; 40mg PO for subjects  75 years old (or 20 mg PO for subjects > 75 years old)
on weeks on which no elotuzumab is given.
On Arm B (Pd) subjects receive:

Pomalidomide: 4mg orally (PO) daily (Days 1-21) of each cycle.

Dexamethasone: 40mg PO for subjects  75 years old (or 20 mg PO for subjects > 75 years
old) on Days 1, 8, 15 and 22 of each cycle.
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All enrolled subjects: All subjects who gave signed informed consent and who were entered in the 
IVRS.
Randomized subjects: All enrolled subjects who were randomized. 
Treated subjects: This population includes all randomized subjects who received at least one dose 
of study medication (pomalidomide, dexamethasone or elotuzumab).
PK evaluable subjects: All treated subjects with at least one elotuzumab serum concentration data.
The analysis of baseline characteristics, efficacy and subject-reported outcomes will be carried out 
on the Randomized subjects population, with subjects grouped according to the treatment arm to 
which they were randomized. The analysis of extent of exposure and safety will be based on the 
Treated subjects population, with subjects grouped according to the treatment received, where 
treatment received is defined as the treatment arm to which they were randomized, unless they 
received the wrong treatment throughout the study.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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7.2
Study Conduct
7.2.1
Accrual Patterns
Tables summarizing accrual by center, country, region (North America, Europe, Japan, and 
Australia) overall and by treatment group will be generated (see Appendix 3 for a list of countries 
in each region). Subject accrual will also be summarized by the randomization stratification factors 
per IVRS (number of lines of prior therapy (2-3 vs. > 4) and ISS Staging at study entry (I-II vs. 
III)), overall and by treatment group. In addition, this summary will also be presented based on the 
stratification information obtained from the baseline CRF pages. A cross tabulation of IVRS vs. 
Baseline stratification factors will also be summarized.
7.2.2
Protocol Violations
A relevant protocol deviation is defined as a deviation from the protocol which is programmed in 
the database and which could potentially affect the interpretability of the study results. 
The number and percentage of subjects with any relevant protocol deviation and each specific
deviation will be presented overall and by treatment group.
The following eligibility deviations are considered relevant in this study and will be summarized 
for all treated subjects: 
1) Number of prior systemic anti-myeloma therapy is < 2
2) Non-measurable disease. This occurs when none of the following three conditions are met:

Serum IgG, IgA, or IgM M-protein 0.5g/dL

M-protein  200mg in 24-hour urine

Involved serum free light chain (sFLC)  100 mg/dL provided the FLC ratio is abnormal
3) Ineligible for this study due to failure to meet criteria for refractory or relapsed and refractory
MM. This occurs when:

Subjects did not progress (on or within 60 days of treatment) to their last treatment (not
refractory).

Subjects did not fail treatment with a proteosome inhibitor and lenalidomide. This occurs 
when none of these take place:
i)
“Refractory” to proteosome inhibitor and lenalidomide, and to their last treatment.
ii) “Relapsed and refractory” = patients had achieved at least a partial response to previous
treatment with proteosome inhibitor or lenalidomide, or both, but progressed within 6
months, and were refractory to their last treatment.
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Also, the following on-treatment deviations are considered relevant in this study and will be 
summarized for all treated subjects:
4) Non-protocol specified systemic anti-myeloma therapy prior to discontinuation of study
therapy
5) Received non-assigned treatment regimen throughout the study
6) No baseline efficacy assessment. This occurs when there are no tumor assessments at all
(laboratory assessments) on or prior to first day of dosing.
7) Subjects continuing to receive study therapy after 10 weeks of documented progression per
investigator (as progression needs to be confirmed).
If assessments based on the central laboratory is unavailable, but the local laboratory results are 
available, then those will be used for evaluating deviations 2 and 6.
A by subject listing of relevant protocol deviations will be provided.
 
 
 
 
 
 
 
. 
7.3.2
Demographic and Subject Characteristics
Demographic and baseline characteristics will be summarized, overall and by treatment group. 
The following parameters will be summarized; age at the time of informed consent (years), age 
category at time of informed consent (< 65 years,  65 years), and (< 75 years, ≥75 years), gender 
(Male, Female), race (White, Black/African American, American Indian/Alaska Native, Asian, 
Native Hawaiian/Other Pacific Islander, Other), ethnicity – for US subjects only (Hispanic/Latino, 
Not Hispanic/Latino), weight (kg), and ECOG performance status (0, 1, 2).
An accompanying by-subject listing of demographic and subject characteristics will be presented. 
7.3.3
Disease Characteristics at Baseline
Baseline disease characteristics will be summarized, overall and by treatment group. The following 
parameters will be presented to summarize baseline disease:

Serum M-protein (g/L)
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Urine M-protein (g/24 hours)

Serum free light chain (g/L)

Myeloma type (IgG, IgA, IgM, Light chain disease)

Number of lytic bone lesions (0, 1-3, >3)

Myeloma risk category

High risk: ISS stage II or III and t(4;14) or del(17p) abnormality

Low risk: ISS stage I or II and absence of t(4;14), del(17p) and 1q21 abnormalities
and age < 55 years

Standard risk: any subjects not meeting the definition of high or low risk.

Not Evaluable: Subjects with missing data preventing their classification in the 
other 3 categories

Individual FISH abnormalities (del 17p, t(14; 16), t(4; 14), del(1q), and del(1p))

β2 microglobulin (mg/L) (<3.5, ≥3.5-5.5, ≥5.5)

Albumin (g/L) (<3.5, ≥3.5)

LDH (<300 IU/L, ≥300 IU/L)

Soft tissue plasmacytomas (Yes, No)

Refractory Status to prior lines of therapy:
- Refractory to lenalidomide
- Relapsed and refractory to lenalidomide
- Refractory to proteasome inhibitor (PI)
- Relapsed and refractory to proteasome inhibitor (PI)
- Refractory to both PI and lenalidomide
- Relapsed and refractory to both PI and lenalidomide

ISS Stage (I, II, III) at enrollment and at diagnosis

Time from disease diagnosis to randomization (months)
An accompanying by-subject listing of disease characteristics at baseline will be presented. All 
reports will be presented in standard international (SI) units and summaries in US units will also 
be available.
7.3.4
Prior Anti-Myeloma Therapy
Prior systemic anti-myeloma therapy (which will be identified from the eCRF page “Prior Therapy 
for Multiple Myeloma”) will be categorized using the WHO drug dictionary and will be 
summarized overall and by treatment group. The latest version of the drug dictionary at the time 
of the analysis will be used. The number and percentage of subjects with any prior systemic 
anti-myeloma therapy, the number and percentage of subjects who have received exactly 2, 3, and  
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≥4 prior lines of therapy, and the number of subjects receiving each therapy (generic term) will be 
presented.
A summary of the number and percentage of subjects receiving prior stem cell transplantation and
prior radiotherapy will be presented overall and by treatment group. 
A summary of the number and percentage of subjects receiving prior surgery related to cancer and 
each type of surgery (Kyphoplasty, Orthopedic surgery, Debulking surgery or Other) will be 
presented overall and by treatment group. 
A by-subject listing containing relevant information on prior radiotherapy, prior surgery and prior 
systemic anti-myeloma therapy will be provided.
7.3.5
General Medical History
The number and percentage of subjects with any relevant medical history and by body system will 
be presented, overall and by treatment group. 
By subject listings of medical history will be provided. A by subject listing of pregnancy test data 
will also be provided.
7.3.6
Baseline Safety Laboratory Tests
Baseline safety laboratory evaluations will be the last available samples taken on or before 
Cycle 1, Day 1 and within 60 days of randomization. 
Baseline safety laboratory values (both SI and US units) will be presented by CTC severity grade, 
by treatment group. Separate tables will be generated for hematology (hemoglobin, WBC, ANC 
[neutrophils plus bands], ALC [absolute lymphocyte count] and platelets [neutrophils plus bands]), 
liver function (ALT, AST, alkaline phosphatase, albumin and total bilirubin) and renal 
function/electrolytes (sodium, potassium, bicarbonate, calcium, glucose, and creatinine, creatinine 
clearance < 60ml/min, ≥ 60ml/min). Sodium, potassium, calcium, and random glucose will be 
presented separately, based on their high and low values.
CTC grades will be derived as part of the analysis data set programming using version 3.0.
7.4
Extent of Exposure
7.4.1
Study Therapy
Pomalidomide, oral dexamethasone and IV dexamethasone are given at fixed doses and are not 
adjusted for body surface area or weight. The elotuzumab dose, in contrast, is adjusted for weight. 
Throughout this SAP, a subject’s elotuzumab dose level at a particular time point will refer to the 
actual dose, in mg/kg, rather than their planned dose. A subject’s actual elotuzumab dose level will 
be computed by dividing their total dose delivered, in mg, as recorded on the Record of Study 
Medication - Elotuzumab eCRF page, by their latest pre-dose weight, in kg, on Day 1 of that cycle. 
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7.4.1.1
Duration of Study Therapy
The number of cycles of treatment received by subjects will be summarized (using n, mean, STD, 
median, min, max, q1 and q3) by treatment group. A summary of the number of subjects taking 
each drug in each cycle will also be presented by treatment group. 
The duration of each treatment (elotuzumab, dexamethasone [oral and IV combined] and 
pomalidomide), in months, will be calculated as:
(date of last dose of the drug - date of first dose of the drug + 1) / 30.4375
Duration of each of the study treatments will be summarized by treatment group.
7.4.2
Dose Modifications
7.4.2.1
Elotuzumab Dose Reduction
Reduction of elotuzumab dosing is not permitted as per the protocol. 
7.4.2.2
Elotuzumab Dose Delay
A delay for elotuzumab will be computed based on records from the dosing CRF page. A delay in 
elotuzumab dosing will be defined as the number of days from the start date of the previous 
infusion to the start date of the current infusion being > 8 days and ≤10 days (if in cycles 1, 2 or 
cycle 3) or > 29 days and ≤ 35 days (from cycle 3 - onwards).
For courses with a delay of elotuzumab infusion, the time of delay in infusion will be summarized 
in the categories: 2-3 days, 4-7 days. 
The number and percentage of subjects with any dose delay, with 1, 2, 3, or  4 reported delays 
will be summarized. For subjects with a delay, their reason for delay (from the dose modification 
page of the CRF) will be summarized in the groups: “hematologic toxicity”, “non-hematologic 
toxicity”, “AE”, “dosing error” and “other”. For subjects without an available reason for delay, the 
category “unknown” will be used. 
7.4.2.3
Elotuzumab Dose Omission
An omission for elotuzumab will be calculated based on records from the dosing CRF page. If the 
interval between the two dosing dates for elotuzumab is > 10 days (in cycles 1, 2 or cycle 3) or > 
35 days (from cycle 3 onwards), the dose will be considered to have been omitted.
For courses with an omission of elotuzumab infusion, the time between the previous and current 
infusion will be summarized in the categories: < 11 - 14, 15 - 21, 22-35, > 35 days.
The number and percentage of subjects with a dose omission, and with 1, 2, 3, or  4 omissions 
will be summarized. For subjects with an omission, their reason for omission (from the dose 
modification page of the CRF) will be summarized in the groups: “hematologic toxicity”, “non-
hematologic toxicity”, “AE”, “dosing error” and “other”. For subjects without an available reason 
for omission, the category “unknown” will be used. 
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A by-subject listing for dose delay and omission will be presented for all treated subjects. This 
listing will include all reported delays or omission per CRF, regardless of whether the subject had 
a computed delay or omission based on the actual dosing dates.
7.4.2.4
Elotuzumab Dose Interruption
The number and percentage of subjects with any interruption in their elotuzumab infusion, with 1, 
2, 3, or  4 interruptions, with an interruption due to “infusion reaction”, “infusion administration 
issues” and “other” will be presented. In addition, duration of interruptions (in minutes) will be 
summarized via descriptive statistics. 
A subject listing will be generated for elotuzumab IV interruptions. This listing will include reason 
for interruption, whether the interruption was resumed, and duration of the interruption.
7.4.2.5
Elotuzumab IV Rate Reduction
The number and percentage of subjects with any elotuzumab IV rate reduction, with 1, 2, 3, or ≥ 
4 rate reductions, and with rate reductions due to “infusion reaction,” “infusion administration 
issues,” and “other” will be presented. 
A by-subject listing will be generated for elotuzumab IV rate reductions
7.4.2.6
Pomalidomide Dose Reduction
Reduction of Pomalidomide will be computed based on the actual dose received. In any study day 
(excluding, cycle 1, day 1), the drug will have a calculated reduction compared to the previous 
day, if the actual level of the administered dose is below the actual level of the administered dose 
in the previous instance. The information for this analysis will be derived programmatically, using 
the total daily dose on the “Record of Study Medication - pomalidomide” eCRF page. 
The daily dose levels are defined as follows:

Dose level 0 or full dose (4mg)

Dose level -1 (3mg)

Dose level -2 (2mg)

Dose level -3 (1mg)
The number and percentage of subjects with a dose reduction, and the lowest dose level achieved 
per subject (-1, -2, -3), will be presented by treatment group. 
The reason for dose reduction as reported by the investigator will be tabulated for all instances 
with a calculated reduction based on the dose modification for Pomalidomide page. A category 
“unknown” will be defined for all calculated reductions with no reason reported by the 
investigator. 
A by-subject listing of dose reductions will be generated. This will include all reported reductions 
per investigator, regardless of whether it met the requirements for a calculated reduction.
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7.4.2.7
Pomalidomide Dose Interruption 
In any cycle, the Pomalidomide dose will be considered as interrupted if there is a gap of two or 
more days between two dosing dates within that cycle where the patient did not receive the study 
drug. This will be calculated based on the information from the dose modification CRF for 
Pomalidomide.
The number and percentage of subjects with dose interruption, with 1, 2, 3, or  4 reported 
interruptions will be presented. For subjects with a computed interruption, their reason for 
interruption will be summarized from the dose modification CRF. For subjects without an 
available reason for interruption, the category “unknown” will be used.
7.4.2.8
Dexamethasone (IV) and Oral
Doses of Dexamethasone IV and oral will be categorized according to the following dose-levels
Table 7.4.2.8-1:
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
For IV dexamethasone the following summaries will be provided:

The number of subjects with any dose delay, with 1, 2, 3, or  4 reported delays, and with a
reason for delay of “hematologic toxicity”, “non-hematologic toxicity”, “AE”, “dosing error”
and “other”.

The number of subjects with any reported dose omission, with 1, 2, 3, or  4 reported
omissions, and with a reported reason for omission of “hematologic toxicity”, “non-
hematologic toxicity”, “AE”, “dosing error” and “other”.

The number of subjects with any reduction in the dose of the drug,  and with a reason for the
reduction of “hematologic toxicity”, “non-hematologic toxicity”, “AE”, “dosing error”, and
“other”).
For PO dexamethasone the following summaries will be produced:
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The number of subjects with any dose modification, and with a reason for the modification of
“hematologic toxicity”, “non-hematologic toxicity”, “AE”, “dosing error” and “other”).

The total number of modifications of the drug experienced by a subject, both overall and by
the reason for the modification.
By subject listings of record of study medication for each of IV dexamethasone and PO 
dexamethasone will be provided. 
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7.4.3
Premedication Other than Dexamethasone for Hypersensitivity 
Reactions
A by-subject listing of pre-medication for elotuzumab, other than dexamethasone, will be 
provided. This listing will be generated from the “Pre-medication for elotuzumab” eCRF module 
and pre-medications will be coded using the BMS WHO drug dictionary. 
7.4.4
Concomitant Medication
Concomitant medications are medications, other than study medication or pre-medications for 
elotuzumab recorded on the “Pre-medication for elotuzumab” eCRF page, which are taken by 
subjects any time on-study, no earlier than the first day of study drug and no later than 60 days 
after the last dose of study drug. Concomitant medications will be coded using the BMS WHO 
drug dictionary. If there is clear evidence to suggest that the medication stopped prior to the first 
dose of study medication, the medication will be assumed to be Prior only.
The number and percentage of subjects taking any concomitant medication and each medication 
(Anatomical Therapeutic Chemical [ATC] classification system drug name) will be summarized, 
overall and by treatment group. 
A by subject listing of concomitant medication will be provided. 
7.4.5
Discontinuation of Study Therapy
The number and percentage of subjects who have discontinued all study treatment and reason for 
discontinuation will be summarized by treatment group and overall using the subject status eCRF 
page from end of treatment. This summary, unlike other analyses of exposure, will include all 
randomized subjects and will be grouped by treatment group as randomized. This is done in order 
to give a full accounting of all subjects who are off study treatment, including those who were 
randomized but never treated. 
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In addition, for subjects in the Elotuzumab arm, who discontinued one drug, while continuing at 
least one of the other two study drugs, their reason for treatment discontinuation will be 
summarized based on the dose modification CRF. Subjects will be counted in this summary if 
there is evidence from the dosing CRF that the subject received the combination therapy in at least 
one cycle, followed by additional cycles, where one of the drugs in the combination was 
discontinued. 
7.4.6
Subsequent Anti-Myeloma Therapy
The number and percentage of subjects with any subsequent systemic anti-myeloma therapy, 
reason for first subsequent systemic anti-myeloma therapy regimen (Documented progression of 
disease, Clinical deterioration without documented progression, Maintenance therapy without 
disease progression or clinical deterioration, or Other) and all subsequent systemic anti-myeloma 
therapy agents given categorized using the BMS WHO drug dictionary will be presented by
treatment group.
The number and percentage of subjects with any subsequent surgery, type of first subsequent
surgery (Kyphoplasty, Orthopedic surgery, Debulking surgery or Other) will be presented by
treatment group. 
The number and percentage of subjects with any subsequent radiation therapy will be presented 
by treatment group. 
A by-subject listing of all subsequent surgery, all subsequent radiation therapy, and all subsequent 
systemic anti-myeloma therapy will be provided.
7.5
Efficacy
Efficacy analyses (PFS, ORR and OS) will be conducted on the population of all randomized 
subjects, grouped by arm assigned at randomization, unless otherwise noted. 
Unless stated otherwise, whenever a stratified analysis is specified, the stratifications factors will 
be those used in the randomization (per IVRS), that is:

Number of prior lines of therapy (2-3 vs. > 4)

ISS Staging at study entry (I-II vs. III)
The final analysis of PFS will occur after at least 71 progression events have been observed. This
analyses will serve as the basis for the clinical study report. The final analysis of OS will be 
conducted after at least 78 deaths have been observed.
All p-values reported will be 2-sided. The alpha () level used for the two-sided CI will be same 
as nominal significance level for hypothesis testing ( = 0.2). In addition two-sided 95% CI for 
these endpoints will also be provided. The p-values presented in the clinical study report will be 
rounded to the fourth decimal place. Point estimates and confidence bounds for efficacy variables 
will be rounded to the second decimal place.
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7.5.1
Primary Analysis of Progression-Free Survival
The primary objective of this study is to compare PFS (based on the primary definition) across the 
two randomized arms. A two-sided  = 0.2 log-rank test, stratified by number of lines of prior 
therapy (2-3 vs. > 4) and ISS Staging at study entry (I-II vs. III) will be used to compare the PFS 
of subjects randomized to E-Pd to that of subjects randomized to Pd. 
A stratified Cox proportional hazard model for PFS with treatment arm as single covariate will be 
used to report the hazard ratio of E-Pd to Pd and its corresponding 80% (and 95%) CI. The 
stratification factors will be the same as those used in the randomization.
The PFS function for each treatment arm will be estimated using the KM product limit method 
and will be displayed graphically. Median PFS will be estimated via the KM curve. Two-sided 
95% CI for the median PFS will be computed for each randomized arm by the Brookmeyer and 
Crowley method using the log-log transformation of the survivor function.
The method of Gail and Simon12 will be used to test for a qualitative interaction between treatment
and strata, number of lines of prior therapy (2-3 vs. > 4) and ISS Staging at study entry (I-II vs. 
III). This test will be conducted at the  = 0.10 level and using the HR as estimate for treatment 
effect.
The proportional hazards assumption will be assessed via the following hazard rate model, which 
contains a time dependent covariate:
ɉሺݐǡ ݖሻൌɉ௜ሺݐሻ݁ሺሼ௕భା௕మൈሾ୪୭୥ሺ௧ሻሿሽൈ௓ሻǡ
݅ൌሼͳ െͶሽ
where i = 1 - 4 corresponds to each of the four levels the stratum can take, and Z is the treatment 
indicator, which is equal to 1 for the combination arm and 0 for the control arm. The transformation 
of time is log(t). The null hypothesis, that the proportional hazards assumption is valid, i.e., that 
b2 = 0, will be tested against the alternative hypothesis that b2 0 using a Wald statistic. 
Sensitivity analyses of PFS will also be conducted based on the secondary definition of PFS. These 
analyses will be the same as those specified above in Section 7.5, Primary Analysis of PFS.
7.5.1.1
Supportive Analyses of Progression-Free Survival
The following supportive analyses will be conducted using both the ITT and the secondary 
definitions of PFS. P-values provided for these analyses are descriptive and will be used to evaluate 
the results in context of the primary analyses. 
1) A multivariate Cox regression model will be used in order to estimate the treatment effect after
adjustment for possible imbalances in known or potential prognostic factors. The factors used
in the randomization, which, by definition, will be balanced across arms, will still be included
in the model as stratification factors. However, all additional factors will be incorporated as
covariates. The additional factors, which are all measured at baseline, will include: age (< 75
vs. ≥75), gender (male vs. female), ECOG PS (0-1 vs. 2), prior stem cell transplantation (yes
vs. no), high myeloma risk (yes vs. no) [see Section 7.5.1.2 for details], time from initial
diagnosis,
creatinine 
clearance 
(<60ml/min 
vs.
60ml/min), 
and 
LDH
(< 300IU/L, 300IU/L).
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The level of the covariate normally associated with the worst prognosis will be coded as the 
reference level:

Age: ≥75

Gender: Female

ECOG: 2

Prior stem cell transplantation: Yes

High myeloma risk: Yes

Time from initial diagnosis ( median)

Creatinine clearance: < 60ml/min

LDH (300IU/L)
The p-value associated with treatment and with each of the baseline covariates will be 
presented. The hazard ratio along with the associated 95% CI will also be presented. In
adddtion, an 80% CI will be provided for the treatment effect.
2) PFS using stratification factors as obtained from the baseline CRF pages (instead of IVRS).
The p-value and the hazard ratio associated with treatment will be presented along with the
associated 2-sided 80% and 95% CIs. This analysis will be performed only if there is a
difference of 10% in strata between the IVRS and CRF pages.
3) PFS using an un-stratified log rank test. The p-value and hazard ratio associated with treatment
will be presented along with its associated two-sided 80% and 95% CIs.
4) PFS using an unstratified Cox proportional hazards model, adjusted, using as covariates only
the two stratification factors used in randomization. The p-value and hazard ratio associated
with treatment will be presented along with its associated two-sided 80% and 95% CIs.
5) PFS for subjects with no relevant deviation. These analyses will be conducted only if there are
more than 5% subjects with relevant protocol deviations. The p-value and hazard ratio
associated with treatment will
be presented along with its
associated two-sided
80% and 95% CIs.
A by-subject listing will be presented including treatment arm, PFS duration under the primary 
definition, PFS duration under the secondary definition, whether the subject was censored under 
the primary definition, and if censored,  the reason, and whether the subject was censored under 
the secondary definition, and if censored, the reason.
7.5.1.2
Subset Analyses of Progression-Free Survival
The influence of baseline and demographic characteristics on the treatment effect will be explored 
via exploratory subset analyses for the following factors:

Age (< 75  years, ≥75 years)

Age (< 65 years, ≥65 years)

Race (White, Black, Asian, Other)

Gender (Male, Female)

Baseline 	2 microglobulin (mg/L) (< 3.5, 3.5)
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ISS Stage at study entry (I-II, III)

Baseline LDH (< 300IU/L, 300IU/L)

Baseline creatinine clearance (ml/min) (< 60, 60)

Number of lines of prior therapy (2-3, 4)

Region (North America, Europe, Japan, And Australia)

Baseline ECOG performance status (0-1, 2)

Prior stem cell transplant (Yes, No)

Myeloma risk category (High risk, Low risk and Other)

High risk: ISS stage II or III and t(4;14) or del(17p) abnormality

Low risk: ISS stage I or II and absence of t(4;14), del(17p) and 1q21 abnormalities and
age < 55 years

Standard risk: any subjects not meeting the definition of high or low risk and enough data 
to be classified as standard risk

Individual FISH abnormalities (del 17p, t(14; 16), t(4; 14), del(1q), and del(1p))
The hazard ratio of E-Pd to Pd and the associated 95% CI for each subgroup category will be 
presented in a forest plot. The estimate of each hazard ratio and CI will be generated using an
unstratified Cox proportional hazards model with treatment as the only covariate.
7.5.2
Analysis of Objective Response 
The number and percentage of subjects in each category of best overall response per investigator 
assessment (stringent complete response [sCR], complete response [CR], very good partial 
response [VGPR], partial response [PR], minor response [MR], stable disease [SD],  progressive 
disease [PD], or unable to determine [UD]) will be presented by treatment group. An estimate of 
the response rate and an associated exact two-sided 95% CI (Clopper and Pearson13) will be
computed, by treatment group. 
One of the secondary objectives is to compare the ORR in the two treatment groups using a two-
sided  = 0.2 level Cochran-Mantel-Haenszel (CMH) test stratified by the same factors used in 
the analysis of PFS. An estimate of the treatment odds ratio and corresponding two-sided 80% CI 
will be computed. A two-sided 95% CI will also be computed.
A 2-sided, 80% CI (along with 95% CI) for the difference of ORR between treatment arms will be 
computed for all randomized subjects by the method of DerSimonian and Laird14, using a fixed-
effects model (setting 
2 equal to zero), adjusting for the stratification factors. The weighted
response rate difference and 80% CI (along with 95% CI) can be determined using the following 
formula:
ߠ෠ൌσ
ߠప෡ݓ௜
ସ
௜ୀଵ
σ
ݓ௜
ସ
௜ୀଵ
׽ ܰሺߠǡ ͳȀ ෍ݓ௜ሻ
ସ
௜ୀଵ
where ߠప෡is the response rate difference of the ith stratum and ݓ௜ൌͳȀݒܽݎሺߠ෠௜ሻ.
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7.5.2.1
Subset Analyses of Objective Response
The influence of baseline and demographic characteristics on the treatment effect will be explored 
via exploratory subset analysis. The subsets will be the same as those analyzed for PFS.
The odds ratio and corresponding 95% CI will be presented for each subgroup in a forest plot.
7.5.2.2
Time to Tumor Response and Duration of Response
The analyses of duration of response will be conducted using the same censoring rules as used in 
the primary definition of PFS. The distribution of duration of response will be estimated, by arm, 
using the KM product limit method. The KM estimates will be presented graphically and will 
present number of events, number of subjects involved, medians along with 95% CIs for the 
medians. 
Time to first tumor response which does not involve censoring, will be summarized by treatment 
group, using descriptive statistics. 
No p-values will be provided for those analyses.
A by-subject listing will be presented including treatment arm, duration of response, whether the 
subject was censored for duration of response, and, if so, the reason. 
7.5.3
Analysis of Overall Survival
Overall survival is another secondary objective. It will be compared between arms using a stratified 
log-rank test procedure with a two-sided,  =0.2 level. The stratification factors will be the same
as those used for the analyses of PFS and tumor response. The OS function for each randomized 
arm will be estimated using the Kaplan-Meier product-limit method. Median and two-sided 95% 
confidence intervals for median OS will be computed by randomized arm.
All analyses performed for PFS (detailed in Section 7.5.1) will be repeated for OS. Supportive 
analyses of PFS (detailed in Section 7.5.1.1) as well as the subset analyses (detailed in Section 
7.5.1.2) will also be repeated for OS.
7.5.4
Currentness of PFS and OS Data
Time from last tumor assessment to data cut-off in months will be summarized by treatment arm 
and overall for all randomized subjects. Subjects who have a PFS event will be considered as 
current for this analysis. The primary (ITT) definition of PFS will be used for this summary. 
Currentness of OS data will be summarized in months, by computing the time from “last known 
alive” date to data cut-off date. Subjects who have a death event will be considered as current for 
this analysis.
By-subject listings will also be produced to accompany the subject time from last tumor 
assessment table.
7.5.5
Efficacy Assessments
A by subject listing of efficacy will be provided to present the following:
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Percent change in serum and urine M-protein, from baseline and nadir.

Serum free light chain kappa and lambda concentrations and the kappa/lambda ratio.

Serum and urine immunofixation test results.

Corrected calcium results

Results of bone marrow analysis, including plasma cells (%) and clonality of plasma cells.

Radiologic evaluation of extramedullary plasmacytoma and lytic bone lesions
In addition, a plot of the change in mean Serum and Urine M-protein per cycle will be presented. 
7.6
Safety
Safety summaries will be based on the treated subject population, grouped by treatment regimen 
received. A subject’s treatment regimen received will equal the arm to which the subject was
assigned at randomization as long as he did not receive the wrong regimen throughout the study.
7.6.1
Adverse Events
AEs will be categorized using the most recent version of the MedDRA, by system organ class 
(SOC) and preferred term. The severity of AEs will be graded using the NCI CTCAE (v 3.0).
On-study AEs are defined as non-serious and serious AEs with an onset date on or after the first 
dose until 60 days after the last dose. See Section 8.4, Imputing AE Onset Dates, for a discussion 
of imputation rules for incomplete or missing AE onset dates. If the relationship to study drug is 
missing, then the AE will be assumed to be related to study drug.
Unless specified otherwise, AEs will be counted only once per subject within each SOC and 
preferred term, according to their worst CTC grade.
Tables will be sorted by SOC and preferred term, with SOCs ordered by decreasing frequency 
overall and then alphabetically. Preferred terms will be sorted within SOCs by descending 
frequency overall and then alphabetically. The sorting will be done based on the total column when 
arms are presented side-by-side.
The following summaries will be presented by treatment arm:
Frequency tables of the worst grade of on-study AE will be presented: one table with AEs broken 
out by individual grade (1, 2, 3, 4 or 5) and an Any Grade category and another table in which both 
arms are included and grades are grouped as follows “Any, Grade 3-4 and Grade 5.” The last 
summary will be repeated for:

On-study drug-related AEs.

On-study AEs that occurred ≤ Cycle 2 and ≥ Cycle 3.
A by-subject listing of all AEs will be presented.

Exposure-adjusted AE incidence rates (including multiple occurrences of unique events) will
be calculated for each SOC and preferred term.
Exposure-adjusted incidence rate per 100 person-years will be used and will be calculated as:
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ͳͲͲ ൈ
ܶ݋ݐ݈ܽ݊ݑܾ݉݁ݎ݋݂ݑ݊݅ݍݑ݁ܣܧݏ
൮
ݏݑܾ݆݁ܿݐ݀ܽݐ݁݋݂݈ܽݏݐ݀݋ݏ݁݋݂ݏݐݑ݀ݕ݀ݎݑ݃െ
ݏݑܾ݆݁ܿݐ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁݋݂ݏݐݑ݀ݕ݀ݎݑ݃൅͸Ͳ ൅ͳ
͵͸ͷǤʹͷ
൲
and will be displayed along with a count of events
For these additional tables, AEs can be counted multiple times within each SOC and preferred 
term.
A by-subject listing of unique AEs will be provided.
7.6.2
Serious Adverse Events and Adverse Event Leading to Discontinuation
Summaries of worst grade of on-study SAE, both by individual grade (1, 2, 3, 4, or 5, together 
with an Any Grade category) and by grade grouped as “Any, Grade 3-4 and Grade 5” will also be 
presented. This last summary will be repeated for:

On-study drug-related SAEs

On-study AEs leading to discontinuation.

Drug related AEs leading to discontinuation
By-subject listings of SAEs and AEs leading to study drug discontinuation will be produced.
7.6.3
Adverse Events of Special Interest
7.6.3.1
Infusion Reaction
Infusion reaction is a known elotuzumab toxicity. It will be based on investigator assessment and 
will be defined as any non-serious or serious adverse event judged by the investigator to be infusion 
related and which also occurs on the day of or the day after the elotuzumab infusion. These
summaries will be presented:

Frequency tables of the worst grade of on-study investigator infusion reaction (any grade
and grade 1 through 5) by treatment group. The same summary will be presented with
grades grouped as Any, Grade 3-4 and Grade 5.

Frequency tables of the worst on-study investigator infusion reaction SAE will be also
summarized by treatment group as above.

Frequency of infusion reaction by infusion rate.

Frequency of infusion reaction by elotuzumab concentration

Frequency of infusion reaction by cycle.
By-subject listings of infusion reactions will be produced.
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7.6.3.2
Opportunistic Infections
Multiple myeloma is associated with immune dysfunction and the natural course of the disease 
includes increased infection risk. In addition, elotuzumab may inhibit some cellular components 
of the immune system. Therefore, a thorough characterization of infections will be presented.
Infections will be based on the SOC ‘infections and infestations’ and opportunistic infections 
will be based on clinically pre-defined PT terms (Appendix 2):

Time to onset and duration of first infection

Frequency of infections including opportunistic infections by treatment group.

Absolute lymphocyte count at time of first infection

Kinetics of lymphocyte reduction
7.6.3.3
Second Primary Malignancies
A summary table and a by-subject listing of second primary malignancies (SPM) will be provided.
In addition, exposure-adjusted SPM incidence rates (including multiple occurrences of unique 
events) will be presented by treatment group and will be calculated as follows:
ͳͲͲ ൈ
ܶ݋ݐ݈ܽ݊ݑܾ݉݁ݎ݋݂ݑ݊݅ݍݑ݁ܵܲܯ݁ݒ݁݊ݐݏ
൮
ݏݑܾ݆݁ܿݐ݀݁ܽݐ݄݀ܽݐ݁݋ݎ݈ܽݏݐ݇݊݋ݓ݊݈ܽ݅ݒ݁݀ܽݐ݁െ
ݏݑܾ݆݁ܿݐ݀ܽݐ݁݋݂݂݅ݎݏݐ݀݋ݏ݁݋݂ݏݐݑ݀ݕ݀ݎݑ݃൅ͳ
͵͸ͷǤʹͷ
൲
Information on SPM will be obtained from the on-treatment eCRF page for secondary 
malignancies and the “Survival Status” eCRF page.
7.6.4
Safety in Subgroups
Summaries of all adverse events with  5% frequency, adverse events leading to discontinuation, 
serious adverse events (any grade), and death within 60 days of last dose will be presented for the 
levels of the factors listed below.
In addition summaries by the same factors will be produced for second primary malignancies, 
opportunistic infections and infusion reactions.

Age:

< 65

≥65 up to < 75

≥75 years

Gender (male, female)

Race (White, Black, Asian, Other)

High risk vs. low risk vs. other standard
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Region (North America, Europe, Japan, and Rest of World)

Number of prior lines of therapy (2-3 vs. > 4)

ECOG PS (0 vs. 1 or 2)
The sorting will be the same as for the overall table (not by subgroup). 
7.6.5
Deaths
The number and percentage of deaths and the investigator-reported cause of death will be presented
by treatment group. This will be summarized for all deaths, and for those reported on study 
treatment or within 60 days of discontinuing study treatment.
7.6.6
Clinical Laboratory Evaluations
On-treatment laboratory tests for safety are defined as those that occur after first dose of any study 
therapy until 60 days after last dose of any study therapy. 
The number and percentage of subjects with each worst severity grade for on-study hematology 
parameters (hemoglobin, WBC, ANC, ALC and platelets) will be presented, by treatment group. 
Grades will be categorized as Grade 1, Grade 2, Grade 3, Grade 4, Any Grade and Grade 3-4.
Subjects will be counted only once for each parameter, according to their worst post baseline CTC 
grade. The percentage of subjects with each worst severity grade will be calculated out of the 
number of treated subjects with on-study assessment for lab parameter. Subjects with a no post-
baseline (on-treatment) assessment for a lab parameter will be reported in the “NOT REPORTED” 
category. 
This summary will be repeated for:

Liver parameters (ALT, AST, alkaline phosphatase, albumin and total bilirubin) with available
CTC grades

Renal/electrolyte parameters (sodium, potassium, bicarbonate, calcium, glucose and
creatinine) with available CTC grades
Sodium, potassium, calcium, and random glucose will be presented separately, based on their high 
and low values. 
For blood urea nitrogen (BUN), direct bilirubin and total protein the worst category on-treatment 
will be presented. Results will be categorized as: below upper normal limits, above upper normal
limits or not reported.
For reporting purposes, urea will be converted to BUN, using the conversion factor: 
urea (mmol/L) / 0.357 = BUN (mg/dL).
Subjects experiencing any potential drug induced liver injury (DILI) will be summarized by 
treatment group and overall as follows: 

A summary of the number and percentage of subjects with (AST or ALT > 3 x upper limit of
normal (ULN)) and (Total bilirubin > 2 x ULN and ALP < 2 x ULN) will be presented.
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If any potential cases of DILI are identified then clinical review will be conducted to ensure no 
other immediate apparent possible causes of AT elevation and hyperbilirubinemia are present, 
including but not limited to, viral hepatitis, pre-existing chronic or acute liver disease, or the 
administration of other drugs known to be hepatotoxic.
Note: The timing for total bilirubin rising to > 2 x ULN needs to be concomitant with or within 30
days after ALT or AST rising to > 3 x ULN. ALP needs to be < 2 x ULN at the time of or within 
2 weeks before ALT or AST rising to > 3 x ULN or TBILI > 2 x ULN. This mean a normal ALP 
value ( 2 x ULN) must be present within 2 weeks of either the ALT/AST criteria or the TBILI 
criteria.
A by subject listing of all laboratory data will be provided. A separate listing will be provided for
all subjects potentially experiencing DILI. 
7.6.7
Echocardiogram, MUGA Scan and Electrocardiograms
A by subject listing of electrocardiogram (ECG) data collected at screening will be presented.
7.6.8
Vital Signs, Physical Measurements 
Vital signs parameters (body temperature, seated diastolic and systolic blood pressure and heart 
rate) will be presented by visit and time point in a subject listing. 
7.7
Pharmacokinetic Analysis
Elotuzumab concentrations taken pre (elotuzumab) dose and post-end of infusion, at each 
scheduled visit, will be summarized, by cycle and day, for subjects in the elotuzumab arm only. In 
addition to the standard summary statistics, the geometric mean and % CV will also be presented. 
A by subject listing of elotuzumab concentrations will be provided.
7.8
Anti Drug Antibody Analysis
ADA status of a sample:

Baseline ADA positive sample: ADA is detected in the last sample prior to the first dosing
date/time of elotuzumab.

On study ADA positive sample: after the first dosing date/time of elotuzumab:

ADA is detected in a subject whose baseline is negative

ADA is detected and ADA titer is at least 9-fold or greater () than the baseline positive
ADA titers

On study ADA negative sample: after the first dosing date/time of elotuzumab, no ADA
detected relative to baseline or with a titer lower than the baseline sample.
Anti-drug antibody (ADA) will be summarized for elotuzumab arm only with the following 
categories: 

Baseline ADA Positive Subject: A subject with Baseline ADA Positive Sample
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ADA Positive Subject: A subject with at least one ADA positive sample after the first
elotuzumab dose relative to baseline.

Persistent Positive: ADA positive sample at 2 or more sequential timepoints at least 3
months apart

Only the Last Sample Positive: ADA positive sample only in the last sampling 
timepoint.

Other Positive: not persistent positive with ADA negative sample in the last sampling  

ADA Negative Subject: A subject with no ADA positive sample after the first elotuzumab
dose relative to baseline.
A by subject listing of all ADA data at each time-point will be provided along with corresponding 
elotuzumab concentration values measured as a part of pharmacokinetic assessments.
7.9
Pharmacogenomic Analysis
The relationship between elotuzumab effect on PFS and high risk cytogenetic abnormality will be 
explored through Cox regression modeling. The following analyses may be conducted depending 
on the number of subjects with available biomarker data in the trial. A separate model will be 
produced for each of the following FISH/cytogenetic abnormalities, which will be categorized as 
positive/negative:

t(4:14)

t(14:16)

del 17p

del(1q)

del(1p)

t(6:14)
Each model will contain treatment, FISH factor and a term for treatment by FISH/cytogenetic 
factor interaction. If treatment by FISH/cytogenetic factor interaction is not significant at the five 
percent level it will be excluded from the model. In addition, the treatment effect (median PFS 
along with corresponding HRs, and 95% CIs) may be computed separately, in the positive and 
negative groups. A similar analysis may be conducted to evaluate the effect on ORR using a 
logistic regression model. 
Similar analyses, as described above, will be conducted to evaluate the relationship between 
baseline SLAMF7 expression on MM cells and NK cells with efficacy (PFS or ORR). 
The level of SLAMF7 protein expression at baseline and at progression, and the change in 
SLAMF7 level, from baseline to progression, will be summarized, by arm, using descriptive 
statistics.
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7.10
Health Related Quality of Life 
The analyses of health related quality of life data will be conducted concurrently with the PFS 
analyses.
Two quality of life (QoL) questionnaires will be used: the M.D. Anderson Symptom Inventory 
Multiple Myeloma module MDASI-MM which measures symptoms, and the EuroQol Group’s 
EQ-5D which measures utilities, and is a preference-based measure of health status.
The EQ 5D is a 5-item questionnaire and a “thermometer” visual analogue scale ranging from 
0 (worst imaginable health state) to 100 (best imaginable health state) that will be administered at 
the same intervals as the other PRO instruments, including at the Screening Visit to assess the 
comparability of the groups at study initiation.
The MDASI-MM module is a valid instrument that asks patients to rate 13 symptoms (“core” 
items) and 6 symptom-related interference items that are common across cancer types and 
treatments. It also assesses 7 multiple myeloma-specific symptom items: bone aches, muscle 
weakness, sore mouth/throat, rash, difficulty concentrating, constipation, and diarrhea.
The key PRO endpoints to be included in the exploratory objectives are the pain, bone aches, and 
fatigue scores of the MDASI-MM scale in addition to the EQ-5D visual analog scale. The mean 
change in PRO scores between baseline and each post-baseline assessment will be summarized by 
treatment arm.
The remaining subscales of MDASI-MM and the EQ-5D summary index scores will also be 
tabulated.
It is possible that the QoL questionnaires are not completed in line with the visit schedule. An
acceptable time delay or “window” during which the questionnaire must be completed is  1 week 
during treatment, at EOT, and the first two visits post treatment, to ensure evaluation of short-term 
toxicity and response. During follow up for EQ-5D, a wider window ( 3 weeks) would be 
acceptable after the first two post-treatment visits. A visit window will be assigned to the scheduled 
visits to ensure that each QoL questionnaire can be assigned to a scheduled visit; for each type of 
questionnaire the one closest to the schedule visit will be assigned.
For PROs, if a multi item subscale has a missing item, then the average of the remaining items will 
be used as the Scale score, as long as at least half the items in that Scale are present.
All analyses will be conducted on randomized subjects with baseline and at least one post-baseline 
assessment.
Descriptive statistics for each instrument will be provided at baseline. 
For each instrument, the questionnaire completion rate will be defined as the proportion of 
questionnaires completed out of the expected number of questionnaires (i.e. the number of subjects 
randomized for baseline visit and still on treatment for post-baseline visits) at each assessment 
point (i.e. Screening, Day 1 of each cycle and End of treatment or study withdrawal). The 
questionnaire completion rate at each assessment point will be presented by treatment group.
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By subject listings of the MDASI-MM and the EuroQol Group’s EQ-5D data will be provided.
7.11
Healthcare Resource Utilization Data
A separate analysis plan will be developed for economic analyses that will be conducted from this 
trial. The economic analyses will combine the resource utilization data from the trial with data on 
unit prices (collected separately) to estimate total costs in preparation for a full-cost analysis.
8
CONVENTIONS
8.1
Baseline Definition
Baseline evaluations will be those performed within 60 days of randomization and prior to first 
dosing date. When an assessment is repeated multiple times within the screening period, the 
baseline evaluation will be the one closest to the first dosing date.
Laboratory tests and procedures (ECG, physical measurement and 2D echocardiogram MUGA, 
skeletal survey and plasmacytoma) done on the first date of dosing will be assumed to have 
occurred prior to dosing and therefore baseline evaluation for those parameters will be those prior 
or on the first dosing date.
8.2
Age Definition
Age (years) will be calculated as:
݀ܽݐ݁݋݂݂݅݊݋ݎ݉݁݀ܿ݋݊ݏ݁݊ݐെ݀ܽݐ݁݋݂ܾ݅ݎݐ݄൅ͳ
͵͸ͷǤʹͷ
8.3
Time Since Initial Diagnosis to Randomization Definition
Time from disease diagnosis to randomization (months) will be calculated as:
݀ܽݐ݁݋݂ݎܽ݊݀݋݉݅ݖܽݐ݅݋݊െ݀ܽݐ݁݋݂݅݊݅ݐ݈݅ܽ݀݅ܽ݃݊݋ݏ݅ݏ൅ͳ
͵ͲǤͶ͵͹ͷ
For the date of cancer diagnosis, the following conventions will be used for imputing partial dates:

If only the day of the month is missing, the 15th of the month will be used to replace the
missing day.

If the day and month are missing or a date is completely missing, it will be considered as
missing.
8.4
Duration and Study Day Definition
In instances in which study period between two dates are to be calculated (for example, duration 
of response, PFS and OS), the convention to be used is as follows: later date – earlier date + 
1 day.
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Study day is calculated as assessment date – first dose date + 1 day, if the assessment is taken on 
or after the first dose day. If the assessment is taken prior to the first dose day, study day will be 
calculated as assessment date – first dose date. Date of first dose is defined as Study Day 1.
8.5
Day Conversion of Date Imputation
Conversion from days to months or years:

1 year = 365.25 days

1 month = 30.4375 days
Imputation for partial or missing progression dates:

If only the day is missing, the 1st of the month will be used to replace the missing day.

If the day and month are missing or a date is completely missing, the date of progression will
be moved back to the last complete tumor assessment date.
In both the cases given above, the imputed date will still be considered an event.
Imputation for partial or missing death dates:

If only the day is missing, the later of the last known alive date and the 1st of the month will be
used to replace the missing day.

If both the day and the month are missing, the later of the last known alive date and Jan 1st will
be used to replace the missing information.
In both the cases given above, the imputed date will still be considered an event.
For partial dates of start of subsequent anti-myeloma therapy, the following conventions will be 
used:

When the day is missing, the alternative therapy will be assumed to start on the first day of the
given month if this day is later than the last dosing date. Otherwise the alternative therapy will
be assumed to start on the day following the last dosing date.

When the day and the month are missing, the alternative therapy will be assumed to start on
the first day of the given year if this day is latter than the last dosing date. Otherwise the
alternative therapy will be assumed to start on the day following the last dosing date.
8.6
AE, Laboratory Results and Concomitant Medication
Safety data will be handled according to the BMS safety data conventions (described in “Analysis 
of Safety Data - Reference to CT SOP 109”). This document includes descriptions on how to 
analyze AE data as well as how to handle partial dates, missing dates, and unknown end dates 
when analyzing safety data.
The following dictionaries will be used to code medical terms and to derive toxicity grades:

Adverse events and other symptoms will be graded according to the NCI CTC Version 3.0 and
categorized according to the latest version of MedDRA at the time of analysis.

Laboratory results will be classified according to the CTC Version 3.0 grading system.
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All medications will be coded as per the latest version of the WHO Drug dictionary at the time
of analysis.

Tables and listings for laboratory results will be available in SI units and US units.
8.7
Topline Analyses
Outputs covering the following topics will be included in the top-line analyses:
Study conduct:

Relevant eligibility deviations (Table and Listing)
Subject population:

End of Treatment Summary

Accrual by Region

Accrual by stratification factors at randomization

Demographic Characteristics Summary

IVRS Stratification Factors Summary

Baseline Myeloma Characteristics Summary (SI units)

Other Baseline Laboratory Measurements Summary

Risk Factors Results Summary

Prior Systemic Anti-myeloma Therapy

Prior Systemic Therapy Drugs Summary

Refractory Status to Most Recent Line of Therapy Summary

Time from Diagnosis to Randomization Summary

Baseline Physical Measurements Summary
Extent of exposure:

Number of Cycles Summary

Elotuzumab Dose Intensity Summary

Dexamethasone Dose Intensity Summary

Pomalidomide Dose Intensity Summary

Elotuzumab Delay Summary

Elotuzumab Omission Summary

Elotuzumab Infusion Interruption Summary

Pomalidomide Reduction Summary

Pomalidomide Interruption Summary
Tumor response:

Best Overall Response

Best Overall Response Odds Ratio and 95% CI in Subsets (Figure)
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Time to First Response Summary

Kaplan-Meier Plot of Duration of Response
Progression free survival:

Currentness of Follow-Up for PFS Summary

PFS (ITT) Analysis

Kaplan-Meier plot of PFS (ITT) (Figure)

PFS (ITT) Analysis Adjusting for Different Baseline Covariates

PFS (ITT) Hazard Ratio and 95% CI in Subsets (Forest plot)

PFS (Secondary Def.) Analysis

Kaplan-Meier plot of PFS (Secondary Def.) (Figure)

PFS (Secondary Def.) Analysis Adjusting for Different Baseline Covariates

PFS (Secondary Def.) Hazard Ratio and 95% CI in Subsets (Forest plot)
Overall survival:

Currentness of Follow-Up for Overall Survival Summary

Overall Survival Analysis

Overall Survival Analysis Adjusting for Different Baseline Covariates

Kaplan-Meier plot of overall survival (Figure)

Overall survival Hazard Ratio and 95% CI in Subsets (Forest plot)
Safety:

Hematologic Laboratory Test Results Summary of Worst Toxicity Grade - SI Units

Renal and Liver Laboratory Test Results Summary of Worst Toxicity Grade - SI Units

Chemistry Laboratory Test Results Summary of Worst Toxicity Grade - SI Units

Other Laboratory Test Results Summary (BUN, DBILI, TPRO)

Potential Drug Induced Liver Injury Cases Summary - SI Units

Adverse Event Summary by CTC Grade Combined

Related Adverse Event Summary by CTC Grade Combined

Serious Adverse Event Summary by CTC Grade Combined

Related Serious Adverse Event Summary by CTC Grade Combined

Adverse Event Leading to Discontinuation Summary by CTC Grade Combined

Related Adverse Event Leading to Discontinuation Summary by CTC Grade Combined

Infusion Reaction Summary by Common Terminology Criteria

Second Primary Malignancy Summary

Deaths

Deaths within 60 days of last study drug
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Specific tables corresponding to these topics will be identified in a separate Data Presentation Plan.
 
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