A Phase 2, Multiple Cohort Study of Elotuzumab in Combination With Pomalidomide and Low-Dose Dexamethasone (EPd), and in Combination With Nivolumab (EN), in Patients With Multiple Myeloma Relapsed or Refractory to Prior Treatment With Lenalidomide.
Phase: PHASE2
Conditions: Multiple Myeloma
Sponsor: Bristol-Myers Squibb

Page:
1
Protocol Number:
CA204142
IND Number:
100,043
EUDRACT Number
N/A
Date:
27-Apr-2015
Revised Date
08-Mar-2018
Clinical Protocol CA204142
A Phase 2, Multiple Cohort Study of Elotuzumab in Combination with Pomalidomide and Low-
Dose Dexamethasone (EPd), and in Combination with Nivolumab (EN), in Patients with 
Multiple Myeloma Relapsed or Refractory to Prior Treatment with Lenalidomide.
Revised Protocol Number: 03
Study Director & Medical Monitor
Rao Saleem MD, MPH
This document is the confidential and proprietary information of Bristol-Myers Squibb 
Company and its global affiliates (BMS). By reviewing this document, you agree to keep it 
confidential and to use and disclose it solely for the purpose of assessing whether your 
organization will participate in and/or the performance of the proposed BMS-sponsored 
study. Any permitted disclosures will be made only on a confidential "need to know" basis 
within your organization or to your independent ethics committee(s). Any other use, copying, 
disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) that may 
be added to this document is also confidential and proprietary to BMS and must be kept in 
confidence in the same manner as the contents of this document. Any person who receives 
this document without due authorization from BMS is requested to return it to BMS or 
promptly destroy it. All other rights reserved. References to BMS in this protocol may apply 
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Revised Protocol No.: 03
Date: 08-Mar-2018
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to partners to which BMS has transferred obligations, eg, a Contract Research Organization 
(CRO).
Replace all previous version(s) of the protocol with this revised protocol and please provide a copy of this 
revised protocol to all study personnel under your supervision, and archive the previous versions.
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Revised Protocol No.: 03
Date: 08-Mar-2018
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DOCUMENT HISTORY
Document
Date of Issue
Summary of Change
Revised 
Protocol 03
08-Mar-2018
Major changes
•
Revisions required by the FDA based on safety concerns reported for 
patients treated in the Keynote 183 and Keynote 185 studies have 
been incorporated.
•
Incorporation of multiple myeloma program changes for biomarker 
evaluations of the elotuzumab in combination with nivolumab cohort 
(EN)
Revised 
Protocol 02
15-Feb-2017
Incorporate Amendment 02
Amendment 02
15-Feb-2017
•
Allows subjects who received elotuzumab in combination with 
pomalidomide and low-dose dexamethasone (EPd Cohort) to receive 
nivolumab upon progression 
•
Adds a cohort to receive elotuzumab in combination with nivolumab 
in a separate cohort (EN Cohort). 
Revised 
Protocol 01
16-May-2016
Incorporates Amendment 01, Administrative Letters 01 and 02.
Amendment 01
16-May-2016
Major Changes
•
Patients with multiple myeloma who may have received prior 
treatment with elotuzumab outside of a clinical trial are now eligible,
provided the patient did not discontinue treatment due to 
intolerability to elotuzumab
•
The requirement of 6 months or less for relapse to prior treatment 
with lenalidomide has been removed as a criteria for eligibility. 
•
Monthly dosing of elotuzumab will now begin at Cycle 3 rather than 
at Cycle 7.
Administrative 
Letter 02
14-Dec-2015
Personnel changes
Administrative 
Letter 01
21-Sep-2015
Alignment of the following protocol sections with revised washout 
period for study drug:
•
Sections 3.3.1 Age and Reproductive Status
•
Table 5.1-3 Pregnancy Test Note
•
Table 5.3.4-1 Pregnancy Test Note
•
Section 6.4 Pregnancy
Original 
Protocol
27-Apr-2015
Not applicable
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OVERALL RATIONALE FOR REVISED PROTOCOL 03:
 
 
 
 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Title Page
Change in Medical Monitor
Administrative Change
 
 
 
 
 
• Synopsis Study Design
• Section 3.1 Study 
Design and Duration
• Figure 3.1-1 Study 
Design Schematic
Removed the option to add 
nivolumab to EPd cohort, 
removed the option to add 
pomalidomide/lenalidomide 
to the EN cohort, and added 
the option for EN patients to 
crossover to EPd if they not 
respond to EN treatment.
Increased the EN cohort size 
to 30 patients.
• Synopsis Study 
Population
• Section 3.3.1 Inclusion 
Criteria
Modified the number of prior 
lines and type of therapy a EN 
patient must have received to 
be eligible for enrollment
•
Synopsis, Study Design
•
Section 3.3.4 Eligibility 
Criteria for EN Patients 
to Cross-over to EPd 
cohort
Added separate section to 
clarify eligibility criteria for 
crossover patients
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
• Synopsis Statistical 
Considerations
• Section 8 Statistical 
Considerations
Statistical sections have been 
updated to reflect changes in 
study design.
 
 
Section 1.1.6.2 Non-
overlapping toxicities and 
preliminary safety
Added details about non-
overlapping toxicities and 
preliminary safety data
 
 
 
 
 
Section 3.5 
Discontinuation of 
Subjects following any 
Treatment with Study Drug
Modified 
to 
incorporate 
stopping rules and to reflect 
change in study design
 
 
 
Section 4.5 Selection and 
Timing of Dose For Each 
Subject
Tables updated to reflect 
changes in study design
 
 
Section 4.5.10 Stopping 
rules for unacceptable 
toxicity (EN cohort).
Added stopping rules for 
toxicity in the EN cohort
• Table 5.1-1 Screening; 
Screening 
Procedural 
Outline
• Table 5.1-4 CA204142 
Cycles 1 and 2 EN 
Cohort
Specifications for Bone 
Marrow Aspirates/Biopsy 
have been removed from the 
notes sections of the Time and 
Events tables along with 
specific assessment rows and 
replaced with a reference link 
to the sections and tables 
within the protocol that 
 
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
• Table 5.1-5 CA204142 
Cycles 3 and 4 EN 
Cohort
• Table 5.1-6 CA204142 
Cycles 5 and beyond EN 
Cohort
• Section 
5.6.2.1 
Bone 
Marrow 
Aspirate 
Samples
specify the bone marrow 
procedures and assessments. 
• Table 5.1-1 Screening; 
Screening 
Procedural 
Outline
•
 
 
Addition of Buccal Swab 
(Germ 
Line 
Control)
for 
patients enrolled in EN cohort 
per Revised Protocol 03 and 
thereafter. 
 
 
 
 
 
 
 
 
 
Table 
5.1-4 
CA204142 
Cycles 1 and 2 EN Cohort
Deletion of specification for 
timing of thyroid function tests 
in notes 
 
Section 5.4.2 Laboratory 
Assessments for Myeloma
Adjusted to reflect changes in 
study design
 
•
Table 
5.4.2-2, 
Bone 
Marrow Samples for EN 
Cohort
•
Section 5.6.2.1 Bone 
Marrow Aspirate 
Samples
•
Section 5.6.2.2 
Peripheral Blood 
Samples
Table 5.6.2.1-1 Usage of 
bone 
marrow 
aspirate 
samples (EN cohort).
Additional specifications for 
Bone Marrow Samples for EN 
Cohorts added.
 
 
 
 
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SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
 
 
 
Section 6.2.1 Nonserious 
Adverse Event Collection 
and Reporting
Specified 
that 
nonserious 
adverse 
events 
will 
be 
collected until 100 days from 
the last dose of study drug for 
EN and crossover subjects 
only.
NSAEs will still be 
collected for 60 days in EPd 
cohort.
Section 9.2.2 Study 
Records
Dexamethasone 
has 
been 
deleted from this section. 
 
 
 
All
Minor 
formatting 
and 
typographical corrections
 
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SYNOPSIS
Clinical Protocol CA204142
Protocol Title: A Phase 2, Multiple Cohort Study of Elotuzumab in Combination with Pomalidomide and Low-Dose 
Dexamethasone (EPd), and in Combination with Nivolumab (EN), in Patients with Multiple Myeloma Relapsed or 
Refractory to Prior Treatment with Lenalidomide.
Investigational Product(s), Dose and Mode of Administration, Duration of Treatment with Investigational 
Product(s):
Elotuzumab: 10 mg/kg IV - Cycles 1 and 2: Days 1, 8, 15, 22
20 mg/kg IV - Cycle 3 and beyond: Day 1 of each cycle
Pomalidomide: 4 mg PO: 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
Nivolumab:
•
Cycles 1 through 4: 240 mg IV Days 1, 15 of each 28-day cycle
•
Cycles 5 and beyond: 480 mg IV Day 1 of each 28-day cycle
Study Phase: Phase 2
Research Hypothesis:
Elotuzumab/Pomalidomide/Low-Dose Dexamethasone Cohort (EPd) :
Elotuzumab in combination with pomalidomide and low-dose dexamethasone will prolong progression-free survival 
(PFS) in subjects with multiple myeloma (MM) who have relapsed or are refractory or intolerant to a 
lenalidomide-based regimen.
Elotuzumab/Nivolumab Cohort (EN):
The combination of elotuzumab and nivolumab will provide clinical benefit, represented by response rate, in patients 
with relapsed or refractory multiple myeloma (MM) who have received at least 4 prior lines of therapy including a 
proteasome inhibitor (PI), immunomodulatory (IMID), and an anti-CD38 antibody.
Objectives:
Primary EPd Cohort Objective:
•
To estimate the PFS in patients with MM treated by EPd as second- or third-line regimen after relapse or being 
refractory or intolerant to a prior lenalidomide based regimen.
Primary EN Cohort Objective:
•
To estimate the Objective Response Rate (ORR).
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Secondary EPd Objectives
•
Estimate the ORR
•
Estimate the overall survival (OS) Rate
Secondary EN Cohort Objectives:
•
Estimate PFS
•
Estimate OS
 
 
Study Design:
This is a Phase 2, multi-center, open-label, multiple cohort study of elotuzumab in combination with pomalidomide 
and low dose dexamethasone (EPd Cohort) and elotuzumab in combination with nivolumab (EN Cohort) to assess the 
safety and efficacy of this combination therapy for treatment of relapsed or refractory MM patients. 
Approximately 120 subjects will be screened in this study to treat a  minimum of 60 subjects in the EPd Cohort and 
approximately 30 subjects in the EN Cohort. Screen failure rate is approximately 25%. Per Revised Protocol 03, the 
EPd cohort is closed to enrollment.
The estimated duration of enrollment is 18 to 24 months, minimum of 24 months follow-up and study duration of 
about 48 months, estimated from the date first patient, first visit.
If subjects enrolled in the EN cohort do not achieve clinical benefit represented by at least minimal response (≥MR) 
after 2 cycles of treatment or do not achieve an objective response (≥PR) after 5 cycles of treatment, they may cross 
over to the EPd cohort at Day 1 of the subsequent cycle. 
Subjects will continue treatment as long as the subject has clinical benefit from the treatment and do not meet criteria 
for discontinuation.
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Study Population:
Eligible subject must have:
a)
Documented disease progression per International Myeloma Working Group (IMWG) guidelines during or after 
their last anti-myeloma therapy
b)
As of Amendment 02, this criterion has been moved to criterion 2.g.i for clarity.
c)
As of Amendment 02, this criterion has been moved to criterion 2.g.ii for clarity.
d)
Measurable disease at screening, based on central laboratory results, defined as 1 or more of the following:
i) Serum immunoglobulin (Ig)G, IgA, IgM M-protein ≥0.5 g/dL 
ii) Urinary M Protein ≥200 mg urinary M-protein excretion in a 24 hour collection sample
iii)Involved serum free light chain (sFLC) ≥10 mg/dL provided the FLC ratio is abnormal. 
e)
Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
f)
As of Amendment 02, this criterion has been moved to criterion 2.g.iii for clarity.
g)
for the EPd Cohort:
i) Subjects must have received at least 1 but no greater than 2 prior lines of therapy (note: induction and stem 
cell transplants with or without maintenance therapy is considered 1 line of therapy)
ii) Subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive 
cycles (full therapeutic dose) and must have been deemed as relapsed, refractory, or intolerant. Refractory is 
defined as progressing on-treatment or within 60 days of the last dose.
NOTE: lenalidomide-based regimens to which the subject has relapsed or been refractory to is not required 
to be the most recent regimen received. 
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iii)Prior elotuzumab exposure is permitted only if subjects fulfill all of the following:
(1). Did not discontinue elotuzumab due to any intolerable drug-related adverse reaction. 
(2). Did not participate in a prior elotuzumab clinical trial, regardless of treatment assignment
h)
For EN Cohort:
i)
Subjects must have received at least 4 prior lines of therapy including a proteasome inhibitor (PI), an 
immunomodulatory (IMID) agent, and an anti-CD38 antibody.
Subjects not eligible for enrollment include subjects with a) solitary bone or extramedullary plasmacytoma as the only 
evidence of plasma cells dyscrasia; b) monoclonal gammopathy of undetermined significance (MGUS), smoldering 
multiple myeloma (SMM), primary amyloidosis (no active multiple myeloma), Waldenstrom’s macroglobulinemia, 
or POEMS syndrome (plasma cell dyscrasia with poly neuropathy, organomegaly, endocrinopathy, monoclonal 
protein, and skin changes); c) 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); d) with Central Nervous 
System involvement with multiple myeloma.
Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and Non-investigational [Medicinal] 
Products (Non-IP/Non-IMP) as listed:
Study Drug for CA204142
Medication
Potency
IP/Non-IP
Elotuzumab Powder for Solution 
for Infusion
400 mg/vial
IP
Dexamethasone Tablets
2 mg and 4 mg and various 
strengths
Non-IP
Dexamethasone Solution
4 mg/mL, 8 mg/mL and various 
strengths
Non-IP
Nivolumab for Injection
100 mg/vial
IP
Pomalidomide Capsules
1 mg, 2 mg, 3 mg and 4 mg
IP
Study Assessments:
Assessments for safety and efficacy will be conducted as time points indicated on the time and events schedules 
included in Section 5. Safety evaluations include assessments of AEs, clinical laboratory tests (hematology, 
chemistry), vital sign measurements, and physical examination with assessment of ECOG performance score (PS).
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, Table 5.1-3, Table 5.1-4, Table 5.1-5, 
and Table 5.1-6. Assessments for SPEP and UPEP 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.
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Statistical Considerations:
Sample Size: 
EPd Cohort: 
Per Revised Protocol 03, the EPd cohort is closed to enrollment. Screening continued until a minimum of 60 patients 
were enrolled and treated. This total number is based on logistical consideration with statistical properties outlined 
below.
Under the assumptions that:
•
time to progression-free survival is exponentially distributed
•
median time of progression-free survival of 11 months among subjects treated with pomalidomide and 
dexamethasone and will increase to a median of 15 months when elotuzumab is added to the mix
•
an increase of 4 months in median corresponds to relative risk ratio of 0.73 (0.0462 monthly risk in the elotuzumab 
add on and 0.0630 monthly historical risk in the pomalidomide + dexamethasone treated subjects)
Sixty subjects enrolled over a 24-month period are sufficient to detect an increase in median from 11 to 15 months 
with about 70% power in a one-sided test with a 0.05 significance level. 
Assuming a monthly hazard rate of 0.0462, 48 of the 60 treated subjects are expected to have PFS events over a 24 
month follow up period
Power is calculated using PASS12 using the one-sample exponential module where the median is mapped to mean by 
dividing the assumed alternative median by logarithm of 2. The calculated power and event counts are consistent with 
power and event counts based on one sample log rank test where the number of events is calculated assuming relative 
risk ratio of 0.73.
EN Cohort
The planned sample size will be approximately 30 treated subjects; screening will continue until a minimum of 
30 patients are enrolled and treated. For a 30% observed ORR rate, a sample size of N=30 yields an exact confidence 
interval of [0.15, 0.49]. These design parameters ensure a lower bound higher than 15 %
Endpoints:
Primary EPd Endpoint:
PFS is defined as the time from first dosing date to the date of the first documented progression per IMWG uniform 
criteria or death due to any cause, whichever occurs first. Subjects who die without a reported prior progression will 
be considered to have progressed on the date of their death. Subjects who did not progress or die will be censored on 
the date of their last evaluable assessment. Subjects who did not have any on study efficacy assessments and did not 
die will be censored on the first dosing date.
Subjects who switched to subsequent therapy prior to documented progression will be censored on the date of the last 
evaluable assessment prior to the initiation of the new therapy. 
Primary EN Endpoints
ORR is defined as proportion of subjects with best overall response of partial response (PR) or better. Response will 
be determined per IMWG uniform criteria.
Secondary EPd Endpoints
•
Objective Response Rate (ORR) is defined as the proportion of subjects with a best overall response of partial 
response (PR) or better
•
Overall Survival (OS) is defined as the time from first dosing date to the date of death from any cause. A subject 
who has not died will be censored at last known date alive.
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Secondary EN Endpoints:
•
PFS is defined as the time from first dosing date to the date of the first documented progression per IMWG 
uniform criteria or death due to any cause, whichever occurs first. Subjects who die without a reported prior 
progression will be considered to have progressed on the date of their death.
•
OS is defined as the time from first dosing date to the date of death from any cause. A subject who has not died 
will be censored at last known date alive.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Analyses
Demographics and Baseline Characteristics: The demographic and baseline characteristics of patients in the safety 
analysis set will be presented. 
Efficacy Analyses: The efficacy endpoints, progression free survival and objective response rate (ORR), will be 
defined using the International Myeloma Working Group criteria. Responses will be assessed at every treatment cycle 
using central laboratory test results on myeloma urine and serum, local laboratory bone marrow aspiration test, and if 
needed bone marrow and skeletal survey results and CT/MRI assessments. Objective responses will include stringent 
complete response, complete response, very good partial response and partial responses. The objective response rate 
and its 95% confidence interval (CI) using the Clopper-Pearson estimation procedure will be reported. Progression 
free survival and overall survival will be plotted using Kaplan-Meier estimates, and if estimable, median and its 95% 
CI will be reported.
 
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For EPd cohort, the primary analysis of PFS will be conducted when 48 progression events have been observed.
For EN cohort, the primary analyses for ORR will be conducted when enrollment in the EN cohort is complete and 
all enrolled patients treated with the combination have received at least 3 cycles of treatment.
 
 
 
 
 
Safety Analyses
Safety assessments will be performed prior, during and between dosing, and up to 100 days after last treatment in the 
EN cohort, 60 days after the last dose in the EPd cohort and for subjects in the EN cohort who cross-over to the EPd 
cohort but discontinue treatment within 2 cycles of EPd treatment safety assessments will be performed up to 100 days 
after the last dose of nivolumab. The frequency, severity, relationship to combination of drug treatment, seriousness, 
and outcomes of adverse events (AEs) will be reported for the full safety analysis set. AE severity will be graded 
according to the NCI Common Terminology Criteria for Adverse Events 3.0. Results of targeted physical 
examinations prior to each dosing cycle will be presented. Summary statistics on vital signs at screening,  pre-infusion, 
30 minutes after the start of infusion, at end of infusion and 30 minutes after the completion of infusion will be reported 
for Cycle 1 and pre-infusion for Cycle 2 and beyond. Concomitant medications, SAEs, and performance status prior 
to dosing will be presented. The safety analysis set will be used for reporting safety /adverse events.
Biomarker Analyses
No biomarker analysis is planned for the EPd Cohort. In the EN Cohort, the potential association between PD-L1 
expression and clinical efficacy measures, such as overall response, will be assessed using methods such as Fisher’s 
exact test if sample size is large enough to allow meaningful analysis or other methodology as appropriate.
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................ 
DOCUMENT HISTORY .............................................................................................. 
OVERALL RATIONALE FOR REVISED PROTOCOL 03: ..................................... 
SUMMARY OF KEY CHANGES FOR REVISED PROTOCOL 03 ......................... 
SYNOPSIS .................................................................................................................... 
TABLE OF CONTENTS .............................................................................................. 
1. INTRODUCTION AND STUDY RATIONALE .................................................... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2 Research Hypotheses ........................................................................................ 
1.2.1 EPd Cohort .............................................................................................. 
1.2.2 EN Cohort ................................................................................................ 
1.3 Objectives(s) ..................................................................................................... 
1.3.1 Primary Objectives .................................................................................. 
1.3.1.1 EPd Cohort: .................................................................................... 
1.3.1.2 EN Cohort: ...................................................................................... 
1.3.2 Secondary Objectives ............................................................................... 
1.3.2.1 EPd Cohort: .................................................................................... 
1.3.2.2 EN Cohort: ...................................................................................... 
 
 
 
 
 
 
 
 
 
1.5 Overall Risk/Benefit Assessment ..................................................................... 
2. ETHICAL CONSIDERATIONS .............................................................................. 
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2.1 Good Clinical Practice ...................................................................................... 
2.2 Institutional Review Board/Independent Ethics Committee ............................. 
2.3 Informed Consent.............................................................................................. 
3. INVESTIGATIONAL PLAN ................................................................................... 
3.1 Study Design and Duration ............................................................................... 
3.2 Post Study Access to Therapy ........................................................................... 
3.3 Study Population ............................................................................................... 
3.3.1 Inclusion Criteria ..................................................................................... 
3.3.2 Exclusion Criteria .................................................................................... 
3.3.3 Women of Childbearing Potential ........................................................... 
3.3.4 Eligibility Criteria for EN Patients to Cross-over to EPd cohort. .......... 
 
 
 
 
 
 
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 ..................................................................................... 
4.2 Non-investigational Product ............................................................................. 
4.3 Storage and Dispensing..................................................................................... 
4.3.1 Elotuzumab .............................................................................................. 
4.3.2 Nivolumab ................................................................................................ 
4.3.3 Pomalidomide .......................................................................................... 
4.3.4 Dexamethasone ........................................................................................ 
4.4 Method of Assigning Subject Identification ..................................................... 
4.5 Selection and Timing of Dose for Each Subject ............................................... 
4.5.1 Pomalidomide .......................................................................................... 
4.5.2 Dexamethasone ........................................................................................ 
4.5.3 Elotuzumab .............................................................................................. 
4.5.3.1 Premedication Before Elotuzumab in Subjects Without a Prior 
Infusion Reaction .................................................................................. 
4.5.3.2 Elotuzumab Premedication Regimen in Subjects With a Prior 
Infusion Reaction .................................................................................. 
4.5.3.3 Elotuzumab Infusion Rate ............................................................... 
4.5.4 Nivolumab ................................................................................................ 
4.5.5 Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions
.....................................................................................................................
4.5.5.1 Grade 1 Infusion Reaction .............................................................. 
4.5.5.2 Grade 2 or 3 Infusion Reaction ...................................................... 
4.5.5.3 Grade 4 Infusion Reaction .............................................................. 
4.5.6 Treatment of Nivolumab-Related Infusion Reactions .............................. 
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4.5.7 Management Algorithms for Immune Related Adverse Events ................ 
4.5.8 Dose Delay, Interruption, or Discontinuation for All Subjects ............... 
4.5.8.1 Dose Delay for Elotuzumab ............................................................ 
4.5.8.2 Dose Delay for Dexamethasone ...................................................... 
4.5.8.3 Dose Delay for Pomalidomide ........................................................ 
4.5.8.4 Dose Delay for Nivolumab .............................................................. 
4.5.8.5 Criteria to Resume Treatment with Nivolumab .............................. 
4.5.8.6 Nivolumab Dose Discontinuation ................................................... 
4.5.9 Recommended Dose Reduction ................................................................ 
4.5.9.1 Elotuzumab and Nivolumab ............................................................ 
4.5.9.2 Dexamethasone ............................................................................... 
4.5.9.3 Pomalidomide ................................................................................. 
4.5.10 EN Cohort: Stopping Rules for Unacceptable Toxicity ......................... 
4.6 Blinding/Unblinding ......................................................................................... 
4.7 Treatment Compliance ...................................................................................... 
4.8 Destruction of Study Drug ................................................................................ 
4.9 Return of Study Drug ........................................................................................ 
5. STUDY ASSESSMENTS AND PROCEDURES .................................................... 
5.1 Flow Chart/Time and Events Schedule ............................................................. 
5.1.1 Retesting During Screening Period ......................................................... 
5.2 Study Materials ................................................................................................. 
5.3 Safety Assessments ........................................................................................... 
5.3.1 Imaging Assessment for the Study............................................................ 
5.3.2 Vital Signs, Physical Measurements, and Physical Examination ............ 
5.3.3 Performance Status .................................................................................. 
5.3.4 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 Imaging.............................................................................. 
5.4.3.2 Assessment of Extramedullary Plasmacytoma................................ 
5.4.4 Definitions of Response and Progression Criteria .................................. 
 
 
 
 
 
 
 
5.7 Outcomes Research Assessments ..................................................................... 
5.8 Other Assessments ............................................................................................ 
5.8.1 Pharmacogenomic/Pharmacogenetic Assessments ................................. 
6. ADVERSE EVENTS ................................................................................................ 
6.1 Serious Adverse Events .................................................................................... 
6.1.1 Serious Adverse Event Collection and Reporting .................................... 
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6.2 Nonserious Adverse Events .............................................................................. 
6.2.1 Nonserious Adverse Event Collection and Reporting .............................. 
6.3 Laboratory Test Result Abnormalities .............................................................. 
6.4 Pregnancy .......................................................................................................... 
6.5 Overdose ........................................................................................................... 
6.6 Potential Drug Induced Liver Injury (DILI) ..................................................... 
6.7 Other Safety Considerations ............................................................................. 
7. DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES.......................................................................................................
8. STATISTICAL CONSIDERATIONS...................................................................... 
8.1 Sample Size Determination ............................................................................... 
8.1.1 EPd Cohort .............................................................................................. 
8.1.2 EN Cohort ................................................................................................ 
8.2 Populations for Analyses .................................................................................. 
8.3 Endpoints .......................................................................................................... 
8.3.1 Primary Endpoint(s) ................................................................................ 
8.3.1.1 EPd Cohort ..................................................................................... 
8.3.1.2 EN Cohort ....................................................................................... 
8.3.2 Secondary Endpoint(s) ............................................................................. 
8.3.2.1 EPd Cohort ..................................................................................... 
8.3.2.2 EN Cohort ....................................................................................... 
 
 
 
8.4 Analyses ............................................................................................................ 
8.4.1 Demographics and Baseline Characteristics........................................... 
8.4.2 Efficacy Analyses ..................................................................................... 
8.4.3 Safety Analyses......................................................................................... 
 
 
8.4.6 Outcomes Research Analyses (both cohorts) ........................................... 
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 ................................................................................. 
 
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APPENDIX 1 DEFINITION OF LINES OF THERAPY ............................................ 
 
APPENDIX 2 PERFORMANCE STATUS SCALES ................................................. 
 
APPENDIX 3 PREPARATION AND ADMINISTRATION OF ELOTUZUMAB ... 
 
APPENDIX 4 DEFINITIONS OF RESPONSE AND PROGRESSION CRITERIA 
(MODIFIED FROM IMWG) ................................................................................. 
APPENDIX 5 THE INTERNATIONAL STAGING SYSTEM (ISS) FOR MULTIPLE 
MYELOMA ............................................................................................................ 
APPENDIX 6 POMALIDOMIDE PREGNANCY RISK PREVENTION PLAN ...... 
 
 
 
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1.2
Research Hypotheses
1.2.1
EPd Cohort
Elotuzumab in combination with pomalidomide and low-dose dexamethasone will prolong PFS in 
subjects with MM who have relapsed or are refractory or intolerant to a lenalidomide-based 
regimen.
1.2.2
EN Cohort
The combination of elotuzumab and nivolumab will provide clinical benefit, represented by 
response rate, in patients with relapsed or refractory multiple myeloma (MM) who have received 
at least 4 prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory 
(IMID) agent and an anti-CD38 antibody.
1.3
Objectives(s)
1.3.1
Primary Objectives
1.3.1.1
EPd Cohort:
•
To estimate the PFS in patients with MM treated by EPd as second- or third-line regimen after 
relapse or being refractory or intolerant to a prior lenalidomide-based regimen.
1.3.1.2
EN Cohort:
•
To estimate the ORR.
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1.3.2
Secondary Objectives
1.3.2.1
EPd Cohort:
•
Estimate the ORR
•
Estimate OS Rate
1.3.2.2
EN Cohort:
•
Estimate PFS
•
Estimate OS
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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1.5
Overall Risk/Benefit Assessment
The American Cancer Society has estimated 30,330 new MM cases in the US in 2016, with an 
estimated 12,650 deaths.1 While recent advances in the use of high-dose chemotherapy, targeted 
therapeutics, and stem cell transplantation have improved overall and event-free survival, the 
majority of patients with myeloma will relapse and disease progression is expected for all but a 
small percentage.5 The subjects enrolled in the EPd trial will receive an anti-myeloma regimen of 
pomalidomide + dexamethasone which demonstrated improvements in PFS, OS, and overall 
response in patients with refractory or relapsed and refractory multiple myeloma, including 
patients with disease refractory to both bortezomib and lenalidomide.29 Pomalidomide has gained 
U.S. FDA accelerated approval and EMA approval in this population of MM patients at a dose of 
4 mg, which is the dose being used in this trial.
Since pomalidomide may enhance the activity of NK cells, which are central to the main biological 
activity of elotuzumab, combining both drugs is likely to enhance elotuzumab mediated ADCC 
towards primary myeloma cells in a similar way to that observed with lenalidomide. The 
expectation is that subjects in this trial will derive clinical benefit.
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Pomalidomide is an analogue of thalidomide, which is known to cause severe life-threatening 
human birth defects. Because of this potential toxicity and to avoid fetal exposure, pomalidomide 
is only available under a special restricted distribution program Pomalyst® REMS (Section 4.3.3). 
Subjects may also follow Pomalidomide Pregnancy Risk Prevention Plan (Appendix 6) where 
applicable. All investigators and subjects must fully comply with and participate in the distribution
program in order to participate in this trial.
Elotuzumab as monotherapy or in combination with immunomodulatory agents such as 
thalidomide or lenalidomide is well tolerated. Safety data from an interim analysis of the ongoing 
randomized phase 3 study of lenalidomide and dexamethasone with or without elotuzumab in 
patients with relapsed or refractory multiple myeloma (Eloquent 2) has shown that elotuzumab 
was well tolerated in combination with lenalidomide/dexamethasone, with minimal incremental 
toxicity and no new safety signals. The safety profile of elotuzumab was consistent across IMiD 
combination studies (thalidomide and lenalidomide). As pomalidomide is an analogue of 
thalidomide, a similar safety profile is expected when pomalidomide + dexamethasone is 
combined with elotuzumab. Key elotuzumab adverse events have been infusion related events.14
These have all been managed by medications and resolved in less than 24 hours. The frequency 
and intensity of infusion related adverse events has been mitigated with premedications, including 
corticosteroids, histamine-1 and -2 antagonists, and acetaminophen. Guidelines for the 
management of infusion reactions are also provided in this protocol (See Section 4.5.5).
Nivolumab is approved in multiple solid tumor indications and hematologic malignancies 
(eg, classical Hodgkin lymphoma) based on its favorable benefit/risk assessment. In hematological 
malignancies including multiple myeloma, nivolumab monotherapy was generally well tolerated 
and toxicity profile was similar to that observed in solid tumors. Nivolumab has the potential for 
clinically relevant unique AEs potentially caused by an inflammatory mechanism. These include 
pulmonary toxicity, hepatotoxicity, diarrhea/colitis, endocrinopathies, and nephrotoxicity. To date, 
these unique AEs have been manageable with frequent monitoring, prompt diagnosis, and 
initiation of corticosteroids, dose interruption, and adequate supportive care. The management 
algorithms of the immune-related AEs are included in Appendix 7. 
Because nivolumab and elotuzumab have non-overlapping toxicity profiles, the combination of 
both drugs is not expected to increase toxicities. 
Elotuzumab combination with nivolumab is an experimental therapy and it is possible that 
unforeseen or unanticipated adverse events may occur although both agents have been evaluated 
separately in combination with other agents in multiple myeloma and have known toxicity profiles.
In order to minimize the overall risks to participating subjects, the protocol has inclusion-exclusion 
criteria appropriate to the population, and specific follow-up safety assessments. Adverse events 
and serious adverse events will be reviewed on an ongoing basis by the Medical Monitor and the 
Sponsor’s pharmacovigilance group to look for trends and safety concerns. Stopping rules for 
unexpected toxicity have been incorporated into the protocol. Treatment options in this later line 
relapsed/refractory myeloma setting are limited and it is possible that this combination may 
provide clinical benefit to patients.
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The overall assessment of risk/benefit supports the evaluation of elotuzumab in combination with 
pomalidomide and dexamethasone in multiple myeloma and also the combination of elotuzumab
with nivolumab in the later line relapsed/refractory multiple myeloma setting.
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.
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 
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requirements. The sample informed consent form will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
Investigators must:
1) Provide a copy of the consent form and written information about the study in the language in 
which the subject is most proficient prior to clinical study participation. The language must be 
non-technical and easily understood.
2) Allow time necessary for subject or subject's legally acceptable representative to inquire about 
the details of the study.
3) Obtain an informed consent signed and personally dated by the subject or the subject's legally 
acceptable representative and by the person who conducted the informed consent discussion.
4) Obtain the IRB/IEC’s written approval/favorable opinion of the written 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.
5) If informed consent is initially given by a subject’s legally acceptable representative or legal 
guardian, and the subject subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the subject.
6) Revise the informed consent whenever important new information becomes available that is 
relevant to the subject's consent. The investigator, or a person designated by the investigator, 
should fully inform the subject or the subject's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
subject's willingness to continue participation in the study. This communication should be 
documented.
The confidentiality of records that could identify subjects must be protected, respecting the privacy 
and confidentiality rules applicable to regulatory requirements, the subjects' signed ICF and, in the 
US, the subjects’ signed HIPAA Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to subject records.
Subjects unable to give their written consent (eg, stroke or subjects with or severe dementia) may 
only be enrolled in the study with the consent of a legally acceptable representative. The subject 
must also be informed about the nature of the study to the extent compatible with his or her 
understanding, and should this subject become capable, he or she should personally sign and date 
the consent form as soon as possible. The explicit wish of a subject who is unable to give his or 
her written consent, but who is capable of forming an opinion and assessing information to refuse 
participation in, or to be withdrawn from, the clinical study at any time should be considered by 
the investigator.
The rights, safety, and well-being of the study subjects are the most important considerations and 
should prevail over interests of science and society.
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3.
INVESTIGATIONAL PLAN
3.1
Study Design and Duration
This is a Phase 2, multi-center, open-label, multiple cohort study of elotuzumab in combination 
with pomalidomide and low-dose dexamethasone (EPd Cohort) and elotuzumab in combination
with nivolumab (EN Cohort) to assess the safety and efficacy of these combination therapies for 
treatment of relapsed or refractory MM patients.
In the EPd Cohort, subjects will receive treatment with elotuzumab in combination with 
pomalidomide and low-dose dexamethasone in a 28 day cycle. Subjects will receive 10 mg/kg IV 
elotuzumab on Days 1, 8, 15, and 22 of Cycles 1 and 2. Starting with Cycle 3, subjects will receive 
20 mg/kg on Day 1. 
As of Amendment 02, subjects will also be enrolled in the EN cohort to receive a combination of 
elotuzumab and nivolumab in a 28-day cycle. EN subjects will receive nivolumab 240 mg IV on 
Days 1 and 15 for Cycles 1-4. At Cycle 5 and beyond, subjects will receive 480 mg IV on Day 1. 
Subjects will also receive elotuzumab 10 mg/kg on Days 1, 8, 15, and 22 of Cycles 1 and 2. At 
Cycle 3 and beyond, subjects will receive 20 mg/kg of elotuzumab IV on Day 1. If subjects do not 
achieve clinical benefit represented by at least minimal response (≥MR) after 2 cycles of treatment
or do not achieve an objective response (≥PR) after 5 cycles of treatment, they may cross over to 
the EPd cohort at Day 1 of the subsequent cycles if they also meet the eligibility criteria for cross-
over specified in Section 3.3.4. 
Subjects will continue treatment as long as the subject has clinical benefit from the treatment and 
do not meet criteria for discontinuation.
All subjects will be assessed for safety and response as presented in the Time and Event Tables in 
Section 5. Subjects who are discontinued from further study treatment for reasons other than 
progression will be followed for disease progression. Following disease progression, subjects will 
be followed at least annually for survival.
Approximately 120 subjects will be screened in this study. A minimum of 60 subjects will be 
treated in the EPd Cohort. Approximately 30 subjects will be treated in the EN Cohort. The 
estimated duration of enrollment is 18 to 24 months, and the duration of the study is estimated at 
48 months from the date of first patient, first visit. Per Revised Protocol 03, the EPd cohort is 
closed for enrollment.
The study design schematic is presented in Figure 3.1-1.
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Figure 3.1-1:
Study Design Schematic
3.2
Post Study Access to Therapy
At the conclusion of the study, subjects who continue to demonstrate clinical benefit are eligible 
to receive BMS supplied study drug. Study drug will be provided via an extension of the study, a 
rollover study requiring approval by responsible health authority and ethics committee or through 
another mechanism at the discretion of BMS. BMS reserves the right to terminate access to BMS 
supplied study drug if any of the following occur: a) the marketing application is rejected by 
responsible health authority; b) the study is terminated due to safety concerns; c) the subject can 
obtain medication from a government sponsored or private health program; or d) therapeutic 
alternatives become available in the local market.
3.3
Study Population
For entry into the study, the following criteria MUST be met.
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) All subjects must have documented disease progression per IMWG (Appendix 4) criteria 
during or after their last anti-myeloma therapy.
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b) As of Amendment 02, this criterion has been moved to criterion 2.i.i for clarity.
c) As of Amendment 02, this criterion has been moved to criterion 2.i.ii for clarity. 
d) Per Amendment 1, this criterion is no longer applicable. Specifications previously listed in 
criterion d) have been included in the revised criterion c) above. 
e) Measurable disease at screening, based on central laboratory results, defined as one or more 
of the following:
i)
Serum IgG, IgA, IgM M-protein ≥0.5 g/dL
ii) Urinary M-Protein ≥200 mg urinary M-protein excretion in a 24 hour collection sample 
iii) Involved serum free light chain (sFLC) ≥10 mg/dL provided the FLC ratio is abnormal.
f)
ECOG Performance Status ≤2 (Appendix 2).
g) Subject Re-enrollment: This study permits the re-enrollment of a subject that has 
discontinued the study as a pre-treatment failure (ie, has not been treated). If re-enrolled, 
the subject must be re-consented.
h) As of Amendment 02, this criterion has been moved to criterion 2.i.iii for clarity.
i)
for the EPd Cohort:
i)
Subjects must have received at least 1 but no greater than 2 prior lines of therapy (note: 
induction and stem cell transplants with or without maintenance therapy is considered 
1 line of therapy)
ii) Subjects must have received prior treatment with a lenalidomide-containing regimen 
for at least 2 consecutive cycles (full therapeutic dose) and must have been deemed as 
relapsed, refractory, or intolerant. Refractory is defined as progressing on-treatment or 
within 60 days of the last dose.30
NOTE: lenalidomide-based regimens to which the subject has relapsed or been 
refractory to is not required to be the most recent regimen received. 
iii) Prior elotuzumab exposure is permitted only if subjects fulfill all of the following:
(1).Did not discontinue elotuzumab due to any intolerable drug-related adverse 
reaction. 
(2).Did not participate in a prior elotuzumab clinical trial, regardless of treatment 
assignment
j)
For EN Cohort:
i)
Subjects must have received at least 4 prior lines of therapy including a proteasome 
inhibitor (PI), an immunomodulatory (IMID) agent, and an anti-CD38 antibody. 
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 a negative serum or urine 
pregnancy tests (minimum sensitivity 25 IU/L or equivalent units of HCG), at 10-14 days 
prior to start of study drug; another within 24 hours prior to the start of study drug.
c) Women must not be breastfeeding
d) WOCBP must agree to follow instructions for method(s) of contraception for 1 month 
(4 weeks) before the start of treatment with study drugs, for the duration of treatment with 
study drugs, and for a total of 5 months post-treatment completion. 
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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 while taking 
pomalidomide and for up to 28 days after discontinuing pomalidomide, even if they have 
undergone a successful vasectomy. Male patients must not donate sperm. 
f)
Azoospermic males and WOCBP who are continuously not heterosexually active are 
exempt from contraceptive requirements. However, they must still undergo pregnancy 
testing as described in this section.
g) All subjects must be willing and able to comply with the local pomalidomide risk 
management program or the Pomalidomide Pregnancy Risk Prevention Plan
h) All subjects must agree not to share study medication. 
i)
Male subjects receiving elotuzumab or nivolumab must also agree to follow instructions 
for method(s) of contraception for 1 month (4 weeks) before the start of treatment with 
study drugs, for the duration of treatment with study drugs, and for a total of 7 months post-
treatment completion.
j)
Subjects must be willing to refrain from blood donations during study drug therapy and for 
90 days after therapy.
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on 
the importance of pregnancy prevention and the implications of an unexpected pregnancy 
Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the 
use of highly effective methods of contraception. Highly effective methods of contraception have 
a failure rate of < 1% when used consistently and correctly.
At a minimum, subjects must agree to the use of two methods of contraception, with one method 
being highly effective and the other method being either highly effective or less effective as listed 
below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
•
Male condoms with spermicide
•
Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, 
injectables, implants and intrauterine devices (IUDs) such as Mirena® by WOCBP subject or 
male subject’s WOCBP partner. Female partners of male subjects participating in the study 
may use hormone based contraceptives as one of the acceptable methods of contraception since 
they will not be receiving study drug
•
IUDs, such as ParaGard®
•
Tubal ligation
•
Vasectomy
•
Complete Abstinence*
*Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an 
acceptable form of contraception for all study drugs. Female subjects must continue to have 
pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed 
in the event that the subject chooses to forego complete abstinence.
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LESS EFFECTIVE METHODS OF CONTRACEPTION
•
Diaphragm with spermicide
•
Cervical cap with spermicide
•
Vaginal sponge
•
Male Condom without spermicide
•
Progestin only pills by WOCBP subject or male subject’s WOCBP partner
•
Female Condom*
•
* A male and female condom must not be used together
3.3.2
Exclusion Criteria
1. Target Disease Exceptions: EN and EPd Cohorts
a) Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of 
plasma cells dyscrasia.
b) Subjects with monoclonal gammopathy of undetermined significance (MGUS), 
smoldering multiple myeloma (SMM), primary amyloidosis (no active multiple myeloma), 
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)
d) Subjects with Central Nervous System involvement with multiple myeloma
2. Medical History and Concurrent Diseases - for both cohorts unless otherwise noted.
a) Any serious medical condition, laboratory abnormality, or psychiatric illness that would 
prevent the patient from signing the informed consent form
b) Any serious concurrent medical conditions that may make the patient non-evaluable or put
the patient’s safety at risk
c) Active infection that requires parenteral anti-infective treatment >14 days
d) Unable to tolerate thromboembolic prophylaxis while on the study
e) Severe hypersensitivity reaction to prior IMiD (thalidomide or lenalidomide)
f)
Grade > 2 peripheral neuropathy (per National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) v3.0)
g) Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic 
infection. 
h) Known HIV infection or known acquired immunodeficiency syndrome (AIDS). NOTE: 
Testing for HIV must be performed at sites where mandated locally
i)
Prior or concurrent malignancy, except for the following:
i)
Adequately treated basal cell or squamous cell skin cancer or in-situ carcinoma.
ii) Any other cancer from which the subject has been disease free for > 3 years prior to 
study entry.
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j)
Additionally for EN Cohort:
i)
Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes 
mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, 
psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in 
the absence of an external trigger are permitted to enroll
ii) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg 
daily prednisone equivalent) or other immunosuppressive medications within 14 days of 
initiation of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 
mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
3. Prior therapy or surgery
a) For EPd Cohort
i)
Prior treatment with pomalidomide
ii) Prior participation in an elotuzumab clinical trial regardless of treatment assignment.
iii) Prior discontinuation of treatment with elotuzumab due to intolerable drug-related 
adverse reactions
iv) Use of any anti-myeloma drug therapy within 14 days of the initiation of study drug 
treatment or use of any experimental drug therapy within 28 days of the initiation of 
study drug treatment
v) Treatment with melphalan within 4 weeks of the first dose of study drug
vi) Treatment with corticosteroids (other than the dexamethasone of anti-myeloma 
regimens) 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)
vii)Prior autologous stem cell transplant within 12 weeks of the first dose of study drug
viii)
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 systemic immunosuppressive therapy
ix) 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.
b) For EN Cohort
i)
Prior treatment with elotuzumab or nivolumab (or any PD-1 or PD-L1 inhibitor).
ii) Use of any anti-myeloma drug therapy, within 14 days of the initiation of study drug 
treatment. Bisphosphonate use permitted if initiated prior to first dose of study 
medication
iii) All prior drug-related AEs should have resolved or returned to baseline for the subject 
to be eligible
iv) Prior autologous stem cell transplant within 12 weeks of the first dose of study drug
v) Prior allogeneic stem cell transplant or graft versus host disease (GVHD) within 
12 months of the first dose of study drug, or subjects on topical or systemic 
immunosuppressive therapy for GVHD
vi) Treatment with corticosteroids within 2 weeks of the first dose of study drug, except 
for the equivalent of ≤10 mg prednisone per day or corticosteroids with minimal to no 
systemic absorption (ie, topical or inhaled steroids) or for short course (≤4 days) of 
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40 mg dexamethasone or equivalent for emergency use (baseline M proteins must be 
drawn after this short course and prior to randomization). Adrenal replacement steroid 
doses > 10 mg daily prednisone equivalent, are permitted in the absence of active 
autoimmune disease
vii)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 - For both cohorts:
•
Absolute neutrophil count < 1 x 109/L (without growth factor support within 1 week)
•
Platelets < 75 x 109/L (< 30 x 109/L if ≥50% of bone marrow nucleated cells were 
plasma cells) (without transfusion support within 3 days)
•
Creatinine clearance < 30 ml/min according to the Cockroft-Gault formula:
−Female CrCl = (140 - age in years) x weight in kg x 0.85
72 x serum creatinine in mg/dl
−Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dl
•
Total bilirubin ≥2 x ULN (≥3 x ULN if Gilbert’s syndrome)
•
AST or ALT ≥3x ULN
5. Allergies and Adverse Drug Reaction (For both Cohorts)
a) Known severe hypersensitivity or allergy to dexamethasone, any excipients in elotuzumab, 
formulation or recombinant protein, or any monoclonal antibody
6. Other Exclusion Criteria (For both Cohorts)
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness
3.3.3
Women of Childbearing Potential
A Women of childbearing potential (WOCBP) is defined as any female who has experienced 
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral 
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in 
a woman over age 45 years in the absence of other biological or physiological causes. In addition, 
females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level 
> 40mIU/mL to confirm menopause.
*Females treated with hormone replacement therapy, (HRT) are likely to have artificially 
suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH 
level. The duration of the washout period is a function of the type of HRT used. The duration of 
the washout period below are suggested guidelines and the investigators should use their judgment 
in checking serum FSH levels. If the serum FSH level is > 40 mIU/ml at any time during the 
washout period, the woman can be considered postmenopausal:
•
1 week minimum for vaginal hormonal products (rings, creams, gels)
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•
4 week minimum for transdermal products
•
8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months.
3.3.4
Eligibility Criteria for EN Patients to Cross-over to EPd cohort. 
Crossover to EPd is permitted if:
•
No clinical benefit (≥minimal response) after 2 cycles. 
•
No objective response (≥PR) after 5 cycles of treatment. 
EN patients who cross-over will no longer be treated with nivolumab after the cross-over to the 
EPd cohort. Re-consent is not required for EN patients who cross-over to treatment with EPd. 
EN patients who do not cross-over can continue treatment with EN until discontinuation criteria 
are met, as specified in Section 3.5. 
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.
 
 
 
 
 
 
 
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3.5
Discontinuation of Subjects following any Treatment with Study Drug
Subjects MUST discontinue investigational product (and non-investigational product at the 
discretion of the investigator) for any of the following reasons:
•
Subject’s request to stop study treatment
•
Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the 
opinion of the investigator, indicates that continued participation in the study is not in the best 
interest of the subject
•
Termination of the study by Bristol-Myers Squibb (BMS) or meeting the criteria for stopping 
rules for cohort(Section 4.5.10). 
•
Loss of ability to freely provide consent through imprisonment or involuntary incarceration for 
treatment of either a psychiatric or physical (eg, infectious disease) illness
•
Pregnancy (Subjects must discontinue the study drugs.
•
Progressive Disease (Appendix 4)
•
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 related to elotuzumab must discontinue 
elotuzumab (refer to the Grade 4 Infusion Reaction subsection presented in Section 4.5.5)
Subjects may continue pomalidomide and dexamethasone treatment.
•
Subjects experiencing a Grade 3 or 4 infusion reaction related to nivolumab must discontinue 
nivolumab (only).
•
Subjects experiencing angioedema, Grade 4 rash, exfoliative or bullous rash, Stevens-Johnson 
syndrome, or toxic epidermal necrolysis related to pomalidomide must discontinue 
pomalidomide. Subjects may continue elotuzumab and dexamethasone.
•
Subjects experiencing a 56 day delay in all study drugs (elotuzumab, nivolumab, 
pomalidomide, and dexamethasone) due to an adverse event(s) related to study treatment must 
be discontinued from study drug. Subjects experiencing delays unrelated to study therapy, for 
example due to radiation therapy may delay study treatment up to 84 days. Further delays may 
be allowed after discussion with the medical monitor.
In the case of pregnancy, the investigator must immediately notify the BMS Medical 
Monitor/designee of this event, and treatment with the IMPs would immediately be stopped. In 
most cases, the study drug will be permanently discontinued in an appropriate manner. Please call 
the BMS Medical Monitor within 24 hours of awareness of the pregnancy. If the investigator 
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determines a possible favorable benefit/risk ratio that warrants continuation of study drug 
(ie, allowing restart of study drug if the patient choses to terminate the pregnancy), a discussion 
between the investigator and the BMS Medical Monitor/designee must occur so that permission 
can be granted.
All subjects who discontinue study drug should comply with protocol-specified follow-up 
procedures outlined in Section 5. The only exception to this requirement is when a subject 
withdraws consent for all study procedures including post-treatment study follow-up or loses the 
ability to consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either 
a psychiatric or physical illness).
If study drug is discontinued prior to the subject’s completion of the study, the reason for the 
discontinuation must be documented in the subject’s medical records and entered on the 
appropriate case report form (CRF/eCRF) page.
3.6
Post Study Drug Study Follow up
In this study, PFS is a key endpoint of the study. Post study follow-up is of critical importance and 
is essential to preserving subject safety and the integrity of the study. Subjects who discontinue 
study drug must continue to be followed for collection of PFS. Subjects who discontinue study 
therapy must also continue to be followed for overall survival data in line with Section 5 until 
death or the conclusion of the study.
3.6.1
Withdrawal of Consent
Subjects who request to discontinue study drug will remain in the study and must continue to be 
followed for protocol specified follow-up procedures. The only exception to this is when a subject 
specifically withdraws consent for any further contact with him/her or persons previously 
authorized by subject to provide this information. Subjects should notify the investigator of the 
decision to withdraw consent from future follow-up in writing, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is from further treatment with study drug only or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF/eCRF page. 
In the event that vital status (whether the subject is alive or dead) is being measured, publicly 
available information should be used to determine vital status only as appropriately directed in 
accordance with local law.
3.6.2
Lost to Follow-Up
All reasonable efforts must be made to locate subjects to determine and report their ongoing status. 
This includes follow-up with persons authorized by the subject as noted above. Lost to follow-up 
is defined by the inability to reach the subject after a minimum of three documented phone calls, 
faxes, or emails as well as lack of response by subject to one registered mail letter. All attempts 
should be documented in the subject’s medical records. If it is determined that the subject has died, 
the site will use permissible local methods to obtain the date and cause of death.
If investigator’s use of third-party representative to assist in the follow-up portion of the study has 
been included in the subject’s informed consent, then the investigator may use a Sponsor-retained 
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third-party representative to assist site staff with obtaining subject’s contact information or other 
public vital status data necessary to complete the follow-up portion of the study. The site staff and 
representative will consult publicly available sources, such as public health registries and 
databases, in order to obtain updated contact information. If after all attempts, the subject remains 
lost to follow-up, then the last known alive date as determined by the investigator should be 
reported and documented in the subject’s medical records.
4.
STUDY DRUG
Study drug includes both Investigational [Medicinal] Product (IP/IMP) and Non-investigational 
[Medicinal] Product (Non-IP/Non-IMP) and are listed in Table 4.-1.
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Table 4.-1:
Study Drugs for CA204142
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
300 mg/vial or 400 
mg/vial
IMP
Open Label
Vial 
Refer to the label on the 
container and/or the pharmacy 
manual.
Nivolumab Solution for 
Injection
100 mg (10 mg/mL)
IMP
Open label
Vial
Refer to the label on the 
container and/or the pharmacy 
manual.
Dexamethasone Tablets
2 mg and 4 mg and 
various strengths
Non-IMP
Open-label
Various packing 
configurations
Refer to label on container or 
package insert / summary of 
product characteristics
Dexamethasone Solution
4 mg/mL, 8 mg/mL and 
various strengths
Non-IMP
Open-label
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
IMP
Open label
Various packing 
configurations
Refer to label on container or 
package insert 
Pomalidomide (Pomalyst®), Dexamethasone tablets and solution for IV infusion will be obtained by the investigating site’s standard prescribing procedures.
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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.
4.2
Non-investigational Product
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as non-
investigational products.
In this protocol, non-investigational product(s) are: dexamethasone tablets and concentrate for 
solution for IV infusion, or products used for Elotuzumab premedication Section 4.5.3.1 or 
thromboprophylaxis (Section 3.4.1).
4.3
Storage and Dispensing
The product storage manager should ensure that the study drug is stored in accordance with the
environmental conditions (temperature, light, and humidity) as determined by BMS. If concerns 
regarding the quality or appearance of the study drug arise, the study drug should not be dispensed 
and contact BMS immediately.
Study drug not supplied by BMS will be stored in accordance with the package insert.
Investigational product documentation (whether supplied by BMS or not) must be maintained that 
includes all processes required 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.
The investigator or designee accepts responsibility for documenting traceability and study drug 
integrity in accordance with requirements applicable under law and the standard operating 
procedures (SOPs)/standards of the sourcing pharmacy. These records should include:
•
label identification number or batch number
•
the amount dispensed to and returned by each subject, including unique subject identifiers 
dates and initials of person responsible for Investigational Product dispensing/accountability, 
as per the Delegation of Authority Form.
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4.3.1
Elotuzumab
The lyophilized elotuzumab drug product should be stored at 2° to 8°C. Before administration the 
drug product must be reconstituted with Sterile Water for Injection, USP, and then further diluted 
in 0.9% sodium chloride normal saline, United States Pharmacopoeia (USP), as per the instructions 
in Appendix 3. The dose of elotuzumab to be administered to a subject will be calculated by 
multiplying the subject’s weight (kg) by 10 or 20 mg/kg. The subject’s predose weight on Day 1 
of each cycle will be used to calculate the dose for each cycle. The screening weight can be used 
for the Cycle 1 dose calculation. Each dose should be infused as per instructions in Appendix 3. 
The infusion start and stop time will be recorded in the CRF/eCRF. If the infusion is stopped 
mid-session for any reason, the stop/start time must be recorded together with an explanation. 
Please refer to the pharmacy manual for detailed guidance on storage, preparation and 
administration.
4.3.2
Nivolumab
Nivolumab will be administered at a dose of 240 mg as an intravenous infusion over 30 minutes 
every 2 weeks (Days 1 and 15 of each 28 day cycle) during Cycles 1 through 4. Starting Cycle 5 
and beyond, nivolumab will be administered at a dose of 480 mg as an intravenous infusion over 
30 minutes every 4 weeks (Day 1 of each 28 day cycle). 
Please refer to the nivolumab investigator brochure and/or pharmacy reference sheet for guidelines 
on drug preparation and administration. Flush the intravenous line at the end of infusion.
Nivolumab vials must be stored at a temperature of 2°to 8°C and should be protected from light 
and freezing. Recommended safety measures for preparation and handling of nivolumab include 
laboratory coats and gloves.
4.3.3
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.
Because of this potential toxicity and to avoid fetal exposure to pomalidomide, pomalidomide is 
only available under a special restricted distribution program. This program is called Pomalyst®
REMS. Pomalidomide must only be dispensed to subjects who meet all the conditions of 
Pomalyst® REMS. Subjects who have the potential of pregnancy in Pomalyst® REMS must be 
instructed about contraception and undergo the scheduled pregnancy tests.
Please see the US package insert 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 Pomalyst® REMS.
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4.3.4
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. Marketed product will be utilized for this study and should be stored in accordance 
with the package insert.
4.4
Method of Assigning Subject Identification
After the subject’s eligibility is established and informed consent has been obtained, the subject 
must be enrolled into the study by calling an interactive voice response system (IVRS) to obtain 
the subject number. The following information is required for subject enrollment:
•
Date of Birth
•
Gender
•
Site number
•
Date that informed consent was obtained
Instructions on the use of IVRS will be provided in a separate document.
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4.5
Selection and Timing of Dose for Each Subject
Table 4.5-1:
Treatment Schedule for EPd Cohort and Cross over Patients from EN Cohort
Cycle
Cycle 1
Cycle 2
Cycle 3 and beyondb
Day
1
8
15
22
1
8
15
22
1
8
15
22
Elotuzumab
10 
mg/kg
10 
mg/kg
10 
mg/kg
10 
mg/kg
10 
mg/kg
10 
mg/kg
10 
mg/kg
10 
mg/kg
20 
mg/kg
Dexamethasonea
Pomalidomide
Days 1-21
Days 1-21
Days 1-21
a See Table 4.5.2-1 for the dose of dexamethasone.
b Patients who cross over from the EN cohort will follow the treatment schedule for Cycle 3 and beyond
Table 4.5-2:
Treatment Schedule for the EN Cohort
Cycle
Cycles 1 and 2
Cycles 3 and 4
Cycle 5 and beyond
Day
1
8
15
22
1
8
15
22
1
8
15
22
Elotuzumab
10 
mg/kg
10 
mg/kg
10 
mg/kg
10 
mg/kg
20 
mg/kg
20 
mg/kg
Nivolumab
240 
mg
240 
mg
240 
mg
240 
mg
480 
mg
See Table 4.5.2-2 for dexamethasone IV dose administered as pre-medication for elotuzumab
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4.5.1
Pomalidomide
Pomalidomide 4 mg will be administered orally once daily for the first 3 weeks of a 4-week cycle. 
Pomalidomide should be taken without food (at least 2 hours before or 2 hours after a meal). 
Subjects should not break, chew or open the capsules.
On the days of elotuzumab administration, the dose of pomalidomide is to be administered at 
least 2 hours after completion of elotuzumab dosing. 
Pomalidomide delay should be performed as clinically indicated at the discretion of the 
investigator.
Subjects should be instructed that if a dose of pomalidomide has been missed and it has been less 
than 12 hours since the subject’s regular dosing time, to take pomalidomide as soon as the subject 
remembers. If it has been more than 12 hours, the dose must be skipped. Subjects should not take 
2 doses at the same time
Females of reproductive potential must have negative pregnancy testing and use contraception 
methods before initiating pomalidomide.
4.5.2
Dexamethasone
Dexamethasone for subjects in the EPd cohort will be administered as indicated in Table 4.5.2-1. 
Table 4.5.2-1:
Dexamethasone Dosing, EPd Cohort
Age
Day
1
8
15
22
Cycles 1 and 2
≤ 75 years old
Dexamethasone
(mg)
28 mg PO +
8 mg IVa,b
28 mg PO +
8 mg IVa,b
28 mg PO +
8 mg IVa,b
28 mg PO +
8 mg IVa,b
> 75 years old
Dexamethasone
(mg)
8 mg PO +
8 mg IVa,b
8 mg PO +
8 mg IVa,b
8 mg PO +
8 mg IVa,b
8 mg PO +
8 mg IVa,b
Cycles 3 and beyond
≤ 75 years old
Dexamethasone
(mg)
28 mg PO +
8 mg IVa,b
40 mg PO per 
weekc
40 mg PO per 
weekc
40 mg PO per 
weekc
> 75 years old
Dexamethasone
(mg)
8 mg PO +
8 mg IVa,b
20 mg PO per 
weekc
20 mg PO per 
weekc
20 mg PO per 
weekc
a On days of elotuzumab, infusion dexamethasone will be administered as a split dose of:
28 mg PO, for subjects ≤75 years old or 8 mg PO for subjects > 75 years old (between 3 - 24 hours before the start 
of elotuzumab infusion)
AND
8 mg IV (on the day of elotuzumab infusion at least 45 minutes before the start of infusion)
b If elotuzumab dosing is skipped or discontinued, dexamethasone will be administered orally as in days without 
elotuzumab.
c Note the dexamethasone dose, as elotuzumab is not given on Days 8, 15 and 22 of cycle 3 and beyond.
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At the investigator’s discretion, the oral dexamethasone may be given as a split dose over 
2 consecutive days. Dexamethasone delay should be performed as clinically indicated at the 
discretion of the investigator.
Dexamethasone for subjects in the EN cohort will be administered as indicated in Table 4.5.2-2.
Table 4.5.2-2:
Dexamethasone Dosing: EN Cohort
Age
Day
1
8
15
22
Cycles 1 and 2
All subjects 
Dexamethasone
(mg)
8 mg IVa,b
8 mg IVa,b
8 mg IVa,b
8 mg IVa,b
Cycles 3 and beyond
All subjects
Dexamethasone
(mg)
8 mg IVa,b
--
--
--
a On days of elotuzumab, dexamethasone will be administered as a premedication at dose of 8 mg IV at least 45 
minutes before the start of infusion)
b If elotuzumab dosing is skipped or discontinued, dexamethasone will be not be administered.
4.5.3
Elotuzumab
Elotuzumab will be administered intravenously at a dose of 10 mg/kg weekly (Days 1, 8, 15, and 
22 of a 4-week cycle) of the first 2 cycles and starting Cycle 3, elotuzumab will be administered 
intravenously at a dose of 20 mg/kg of Day 1 of each cycle. A window of -1 to + 3 days is permitted 
in Cycles 1 and 2.
In Cycle 1 and 2, an elotuzumab dose that falls outside of the pre-specified window must be 
skipped.
In Cycles 3 and beyond, elotuzumab dosing may be delayed for up to 1 week as clinically 
indicated. If unable to administer within 1 week, then the dose should be skipped and resumption 
of the elotuzumab continues per the protocol defined schedule.
4.5.3.1
Premedication Before Elotuzumab in Subjects Without a Prior Infusion 
Reaction
On weeks of elotuzumab infusion, the dexamethasone dose for the EPd cohort will be split into a 
PO and IV administration (described in Section 4.5.2), which will also serve as premedication for 
elotuzumab.
Intravenous and PO dexamethasone doses are calculated to provide a total dose that is 
bioequivalent to an oral dose of 40 mg (subjects who are ≤75 years old) or 20 mg (in subjects who 
are > 75 years old). (Dexamethasone 8 mg IV is approximately bioequivalent to 11 mg PO).
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For the EN cohort, dexamethasone will still be administered as a premedication for elotuzumab at 
a dose of 8 mg IV 45-90 minutes prior to initiating the elotuzumab infusion.
In addition, the following must also be administered 45 to 90 minutes before initiating the 
elotuzumab:
•
H1 blocker: diphenhydramine (25 - 50 mg PO or IV) or equivalent
•
H2 blocker: ranitidine (50 mg IV) or equivalent (eg, 150 mg PO)
•
Acetaminophen (650 - 1000 mg PO)
4.5.3.2
Elotuzumab Premedication Regimen in Subjects With a Prior Infusion 
Reaction
To be re-treated with elotuzumab, subjects with a prior infusion reaction must receive H1, H2 
blockers and acetaminophen at maximum doses specified (ie, 50 mg diphenhydramine, 50 mg 
ranitidine [or equivalent], and 650-1000 mg acetaminophen) 45 to 90 minutes before initiating the 
elotuzumab.
Recommended dexamethasone dosing is summarized in Table 4.5.3.2-1.
Decisions to use more aggressive premedication schemes in subjects with prior Grade 1 infusion 
reactions or only one prior Grade 2 infusion reaction must be approved by the Medical Monitor.
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Table 4.5.3.2-1:
Corticosteroid Premedication
For Subjects ≤75 years old
For Subjects > 75 years old
Prior Infusion 
Reaction
Corticosteroid Premedicationa Before Elotuzumab
None or
Only Grade 1 
infusion reactionb
28 mg po dexamethasone (3 - 24 hrs 
before elotuzumab)
AND
8 mg IV dexamethasone at least 45 min 
before elotuzumab 
8 mg po dexamethasone (3 - 24 hrs before 
elotuzumab) 
AND
8 mg IV dexamethasone at least 45 min before 
elotuzumab 
Prior Grade 2 
infusion reactionc
28 mg po dexamethasone (3 - 24 hrs 
before elotuzumab) 
AND
10 mg IV dexamethasone at least 45 min 
before elotuzumab 
8 mg po dexamethasone (3 - 24 hrs before 
elotuzumab) 
AND
10 mg IV dexamethasone at least 45 min 
before elotuzumab 
Prior Grade 3 or 
recurrent Grade 2 
infusion reaction
8 mg oral dexamethasone (12 - 24 hrs 
before elotuzumab) 
AND
8 mg oral dexamethasone (at least 3 hrs 
before elotuzumab, on the same day as 
the infusion) 
AND
18 mg IV dexamethasone at least 45 min 
before elotuzumab
2 mg oral dexamethasone (12 - 24 hrs before 
elotuzumab) 
AND
2 mg oral dexamethasone (at least 3 hrs before 
elotuzumab, on the same day as the infusion) 
AND
12 mg IV dexamethasone at least 45 min 
before elotuzumab
For prior infusion reactions, use maximum doses H1, H2 blockers and acetaminophen as described in Section 4.5.3.1.
a At the discretion of the investigator, the oral dexamethasone component may be given as a split dose 12-24 and 
3 hours before elotuzumab.
b Subjects with prior Grade 1 infusion reaction may be pre-medicated as per Grade 2 infusion reactions.
c Subjects with prior Grade 2 infusion reaction may be pre-medicated as per Grade 3 infusion reactions.
If a subject with a prior Grade 2 to 3 infusion reaction also requires dose reduction of 
dexamethasone, the dexamethasone dose on the days of elotuzumab infusion should be no less 
than 8 mg IV (on the day of elotuzumab infusion at least 45 minutes before elotuzumab).
Subjects with Grade 4 infusion reaction are not eligible to receive additional elotuzumab. These 
subjects may continue to receive pomalidomide and dexamethasone.
4.5.3.3
Elotuzumab Infusion Rate
During the first cycle, the elotuzumab infusion rate will be increased gradually to a maximum of 
5 mL/min as presented in the table below. An infusion rate increase to the next higher level is 
permitted only if no infusion reactions are encountered.
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Table 4.5.3.3-1:
Elotuzumab Infusion Rate
Infusion Rate
Duration of infusion
Volume delivered
Volume remaining
Cycle 1 Dose 1
Approximate Total Duration: 2hrs 50min
262 mL*
0.5 mL/min
30 min
15 mL
247 mL
1 mL/min
30 min
30 mL
217 mL
2 mL/min
110 min
217 mL
0 mL
Cycle 1 Dose 2
Approximate Total Duration: 1hr 13min
262 mL
3 mL/min
30 min
90 mL
172 mL
4 mL/min
43 min
172 mL
0 mL
Cycle 1 Dose 3 and 4
Approximate Total Duration: 53min
262 mL
5 mL/min
53 min
262 mL
0 mL
Cycle 2 +
Approximate Total Duration: 53min
262 mL
5 mL/min
53 min
262 mL
0 mL
* Volume for 80 kg subject. Total volume varies according to the subject weight.
Please note that infusion rate increase to the next higher level only if no infusion reactions 
encountered.
4.5.4
Nivolumab
Nivolumab will be administered at a dose of 240 mg as an intravenous infusion over 30 minutes 
every 2 weeks (Days 1 and 15 of each 28 day cycle) during Cycles 1 through 4. Starting Cycle 5 
and beyond, nivolumab will be administered at a dose of 480 mg as an intravenous infusion over 
30 minutes every 4 weeks (Day 1 of each 28 day cycle).
Nivolumab should be administered before elotuzumab. 
When administering Q2W, subjects may be dosed no less than 12 days from the previous dose. 
There are no premedications recommended for nivolumab on the first cycle.
Nivolumab can be delayed within a 3 day window of Day 1 and Day 15, during cycles 1 through 4, 
as long as the 12 day interval between 2 nivolumab doses is respected. 
When administering Q4W, subjects may be dosed no less than 21 days from the previous dose. 
During cycles 5 and beyond, nivolumab can be delayed within a week.
Doses that fall outside the allowed window, regardless of the schedule, should be skipped.
Subjects should be carefully monitored for infusion reactions during nivolumab administration. If 
an acute infusion reaction is noted, subjects should be managed according to Section 4.5.6.
There will be no dose escalations or reductions of nivolumab allowed. Doses of nivolumab may 
be interrupted, delayed, or discontinued in accordance with Section 4.5.8 depending on how well 
the subject tolerates the treatment.
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4.5.5
Guidelines for Elotuzumab Infusion in Subjects with Infusion Reactions
4.5.5.1
Grade 1 Infusion Reaction
Grade 1 elotuzumab infusion-related reactions by definition do not require intervention; however, 
increased monitoring is recommended.
4.5.5.2
Grade 2 or 3 Infusion Reaction
Infusion reactions during the elotuzumab infusion: For a Grade 2 or 3 elotuzumab 
infusion-related reaction, the infusion must be interrupted. The subject should be treated as 
clinically indicated with one or more of the following medications or interventions: antiemetics, 
antihistamines, analgesics, corticosteroids, leukotriene inhibitors, oxygen inhalation, epinephrine, 
bronchodilators, or other supportive measures as indicated.
Once the elotuzumab infusion-related reaction has resolved to Grade ≤1, the infusion can be 
restarted at 0.5 mL/minute. If symptoms do not recur after 30 minutes, the infusion rate may be 
increased in a stepwise fashion (0.5 mL/minute every 30 minutes) to the rate at which the infusion 
reaction occurred. If no recurrence of the infusion reaction, the escalation regimen can be resumed. 
Subjects who experience an infusion reaction require vital signs to be monitored every 30 minutes 
for 1 or 2 hours after the end of the elotuzumab infusion (as clinically indicated). 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 throughout Section 4.5.3.1
Infusion reactions after the completion of elotuzumab infusion: Should a Grade 2 or 3 infusion 
reaction occur following completion of an elotuzumab infusion, the subject should be treated as 
clinically indicated with 1 or more of the following medications or interventions: 
diphenhydramine, acetaminophen, hydrocortisone, H2 inhibitor, leukotriene inhibitor, oxygen 
inhalation, epinephrine, bronchodilators, or other supportive measures as indicated.
Elotuzumab infusions on subsequent weeks after a prior Grade 2 or 3 infusion reaction: 
Subjects with prior Grade 2 or 3 infusion reactions should have the next infusion started at 
0.5 mL/min and then escalated in a stepwise fashion (0.5 mL/minute every 30 minutes) to the rate 
at which the infusion reaction occurred. If no Grade ≥2 infusion reaction occurs, the escalation 
regimen may be resumed and the next infusion may be initiated as planned per the regimen.
4.5.5.3
Grade 4 Infusion Reaction
Subjects with a Grade 4 elotuzumab infusion reaction must have elotuzumab permanently 
discontinued.
4.5.6
Treatment of Nivolumab-Related Infusion Reactions
Since nivolumab contains only human immunoglobulin protein sequences, it is unlikely to be 
immunogenic and induce infusion or hypersensitivity reactions. However, if such a reaction were 
to occur, it might manifest with fever, chills, rigors, headache, rash, pruritus, arthralgia, 
hypotension, hypertension, bronchospasm, or other allergic-like reactions. All Grade 3 or 
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4 infusion reactions should be reported within 24 hours to the study medical monitor and reported 
as an SAE if it meets the criteria. Infusion reactions should be graded according to NCI CTCAE 
(Version 3.0) guidelines.
Treatment recommendations are provided below and may be modified based on local treatment 
standards and guidelines, as appropriate:
For Grade 1 symptoms: (mild reaction; infusion interruption not indicated; intervention not 
indicated):
•
Remain at bedside and monitor subject until recovery from symptoms. The following 
prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg 
(or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg at least 30 minutes before 
additional nivolumab administrations.
For Grade 2 symptoms: (moderate reaction required therapy or infusion interruption but responds 
promptly to symptomatic treatment (eg, antihistamines, non-steroidal anti-inflammatory drugs, 
narcotics, corticosteroids, bronchodilators, IV fluids); prophylactic medications indicated for 
≤24 hours):
•
Stop the nivolumab infusion, begin an IV infusion of normal saline, and treat the subject with 
diphenhydramine 50 mg IV (or equivalent) and/or acetaminophen/paracetamol 325 to 
1000 mg; remain at bedside and monitor subject until resolution of symptoms. Corticosteroid 
and/or bronchodilator therapy may also be administered as appropriate. If the infusion is 
interrupted, then restart the infusion at 50% of the original infusion rate when symptoms 
resolve; if no further complications ensue after 30 minutes, the rate may be increased to 100% 
of the original infusion rate. Monitor subject closely. If symptoms recur, then no further 
nivolumab will be administered at that visit.
•
For future infusions, the following prophylactic premedications are recommended: 
diphenhydramine 50 mg (or equivalent) and/or acetaminophen/paracetamol 325 to 1000 mg 
should be administered at least 30 minutes before nivolumab infusions. If necessary, 
corticosteroids (up to 25 mg of SoluCortef or equivalent) may be used.
For Grade 3 or 4 symptoms: (severe reaction, Grade 3: prolonged [ie, not rapidly responsive to 
symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following 
initial improvement; hospitalization indicated for other clinical sequelae (eg, renal impairment, 
pulmonary infiltrates). Grade 4: Life-threatening; pressor or ventilator support indicated):
•
Immediately discontinue infusion of nivolumab. Begin an IV infusion of normal saline and 
treat the subject as follows: Recommend bronchodilators, epinephrine 0.2 to 1 mg of a 1:1000 
solution for subcutaneous administration or 0.1 to 0.25 mg of a 1:10,000 solution injected 
slowly for IV administration, and/or diphenhydramine 50 mg IV with methylprednisolone 
100 mg IV (or equivalent), as needed. Subject should be monitored until the Investigator is 
comfortable that the symptoms will not recur. Nivolumab will be permanently discontinued. 
Investigators should follow their institutional guidelines for the treatment of anaphylaxis. 
Remain at bedside and monitor subject until recovery of the symptoms.
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In case of late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (eg, oral 
antihistamine or corticosteroids).
4.5.7
Management Algorithms for Immune Related Adverse Events
Immuno-oncology (I-O) agents are associated with AEs that can differ in severity and duration 
than AEs caused by other therapeutic classes. Nivolumab is considered an immuno-oncology agent 
in this protocol. Early recognition and management of AEs associated with immuno-oncology 
agents may mitigate severe toxicity. Management Algorithms have been developed to assist 
investigators in assessing and managing the following groups of AEs:
•
Gastrointestinal
•
Renal
•
Pulmonary
•
Hepatic
•
Endocrinopathy
•
Skin
•
Neurological
The above algorithms are found in Appendix 7 and in the nivolumab Investigator Brochure.
4.5.8
Dose Delay, Interruption, or Discontinuation for All Subjects
Please refer to Sections 4.5.8.1, 4.5.8.2, 4.5.8.3, and 4.5.8.4 for drug-specific delay guidance.
For each cohort, if the dose of one drug in the regimen (ie, pomalidomide, dexamethasone, 
nivolumab, or elotuzumab) is delayed, interrupted, or discontinued, the treatment with the other 
drugs may continue as scheduled. However, in the EPd cohort, if dexamethasone is delayed or 
discontinued discuss ongoing elotuzumab administration with the Medical Monitor. Subjects 
experiencing a 56 day delay in all study drugs due to an adverse event(s) related to study treatment 
must be discontinued from study drug. Subjects experiencing delays unrelated to study therapy, 
for example due to radiation therapy, may delay study treatment after discussion with the medical 
monitor.
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. 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 may continue on study therapy if elotuzumab must be 
discontinued for an adverse event or other reason. Patients are considered still on study therapy 
even if they continue solely on pomalidomide, dexamethasone, or nivolumab.
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4.5.8.1
Dose Delay for Elotuzumab
In Cycles 1 to 2, elotuzumab doses that fall outside of the pre-specified window of -1 to +3 days 
must be skipped.
Beginning with Cycle 3 and beyond, elotuzumab dosing may be delayed for up to 1 week. If unable 
to administer within 1 week, then the dose should be skipped and resumption of the elotuzumab 
continues per the protocol defined schedule.
Subjects experiencing a Grade 4 infusion reaction related to elotuzumab must permanently 
discontinue elotuzumab.
4.5.8.2
Dose Delay for Dexamethasone
Dexamethasone interruption should be performed as clinically indicated at the discretion of the 
investigator.
The weekly dexamethasone that coincides with or is temporally closest to the next elotuzumab 
dosing must be administered as part of the premedication for elotuzumab per the guidance in 
Section 4.5.3.1.
4.5.8.3
Dose Delay for Pomalidomide
Pomalidomide interruption should be performed as clinically indicated at the discretion of the 
investigator.
Subjects should be instructed that if a dose of pomalidomide has been missed and it has been less 
than 12 hours since the subject’s regular dosing time, to take pomalidomide as soon as the subject 
remembers. If it has been more than 12 hours, the dose must be skipped. Subjects should not take 
2 doses at the same time
4.5.8.4
Dose Delay for Nivolumab
Nivolumab administration should be delayed for the following:
•
Any Grade ≥2 non-skin, drug-related adverse event, with the following exceptions:
−
Grade 2 drug-related fatigue or laboratory abnormalities do not require a treatment 
delay/ interruption.
•
Any Grade 3 skin, drug-related adverse event
•
Any Grade 3 drug-related laboratory abnormality, with the following exceptions for 
lymphopenia, AST, ALT, or total bilirubin or asymptomatic amylase or lipase:
−
Grade 3 lymphopenia does not require dose delay/interruption
−
If a subject has a baseline AST, ALT, or total bilirubin that is within normal limits, 
delay/interrupt dosing for drug-related Grade ≥2 toxicity.
−
If a subject has baseline AST, ALT, or total bilirubin within the Grade 1 toxicity range, 
delay/interrupt dosing for drug-related Grade ≥3 toxicity.
−
Any Grade ≥3 drug-related amylase or lipase abnormality that is not associated with 
symptoms or clinical manifestations of pancreatitis does not require dose 
delay/interruption.
•
Any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of 
the investigator, warrants delaying the dose of study medication.
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Subjects who require delay/interruption of nivolumab should be re-evaluated as clinically 
indicated and resume nivolumab dosing, as per the protocol dosing schedule when re-treatment 
criteria are met.
4.5.8.5
Criteria to Resume Treatment with Nivolumab
Subjects may resume treatment with nivolumab when the drug-related AE(s) resolve(s) to 
Grade ≤1 or baseline, with the following exceptions:
•
Subjects may resume treatment in the presence of Grade 2 fatigue
•
Subjects who have not experienced a Grade 3 drug-related skin AE may resume treatment in 
the presence of Grade 2 skin toxicity
−
Subjects with baseline Grade 1 AST/ALT or total bilirubin who require dose 
delays/interruptions for reasons other than a 2-grade shift in AST/ALT or total bilirubin 
may resume treatment in the presence of Grade 2 AST/ALT OR total bilirubin
−
Subjects with combined Grade 2 AST/ALT AND total bilirubin values meeting 
discontinuation parameters (Section 4.5.8.6) should have treatment permanently 
discontinued
•
Drug-related pulmonary toxicity, diarrhea, colitis, uveitis or neurologic toxicity must have 
resolved to baseline before treatment is resumed. Subjects with persistent Grade 1 pneumonitis 
after completion of a steroid taper over at least 1 month may be eligible for retreatment if 
discussed with and approved by the BMS Medical Monitor.
•
Drug-related endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment after consultation with the BMS Medical Monitor
Dose delay/interruption of nivolumab which results in treatment interruption of > 8 weeks require 
treatment discontinuation, with exceptions as noted in Section 4.5.8.6. There will be no dose 
reductions for nivolumab.
4.5.8.6
Nivolumab Dose Discontinuation
Nivolumab treatment should be permanently discontinued for the following:
•
Any Grade 2 drug-related uveitis, eye pain or blurred vision that does not respond to topical 
therapy and does not improve to Grade 1 severity within the re-treatment period OR requires 
systemic treatment
•
Any Grade 3 non-skin, drug-related adverse event lasting > 7 days, with the following 
exceptions for laboratory abnormalities, drug-related uveitis, pneumonitis, bronchospasm, 
hypersensitivity reactions, infusion reactions, and endocrinopathies:
−
Grade 3 drug-related uveitis, pneumonitis, bronchospasm, hypersensitivity reaction, or 
infusion reaction of any duration requires discontinuation
−
Grade 3 drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement do not require discontinuation
−
Grade 3 drug-related laboratory abnormalities do not require treatment discontinuation 
except:
♦Grade 3 drug-related thrombocytopenia > 7 days or associated with bleeding requires 
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discontinuation
♦Any drug-related liver function test (LFT) abnormality that meets the following criteria 
require discontinuation:
•
AST or ALT > 5-10 x ULN for 2 weeks
•
AST or ALT > 10 x ULN
•
Total bilirubin > 5 x ULN
•
Concurrent AST or ALT > 3 x ULN and total bilirubin > 2 x ULN
•
Any Grade 4 drug-related adverse event or laboratory abnormality, except for the 
following events which do not require discontinuation:
−
Grade 4 neutropenia ≤7 days
−
Grade 4 lymphopenia or leukopenia
−
Isolated Grade 4 amylase or lipase abnormalities that are not associated with symptoms or 
clinical manifestations of pancreatitis. The BMS Medical Monitor should be consulted for 
Grade 4 amylase or lipase abnormalities.
−
Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 72 hours 
of their onset
−
Grade 4 drug-related endocrinopathy adverse events, such as adrenal insufficiency, ACTH 
deficiency, hyper- or hypothyroidism, or glucose intolerance, which resolve or are 
adequately controlled with physiologic hormone replacement (corticosteroids, thyroid 
hormones) or glucose-controlling agents, respectively, may not require discontinuation 
after discussion with and approval from the BMS Medical Monitor.
•
Any event that leads to delay in dosing lasting > 8 weeks from the previous dose requires 
discontinuation, with the following exceptions:
−
Dosing delays to allow for prolonged steroid tapers to manage drug-related adverse events 
are allowed. Prior to re-initiating treatment in a subject with a dosing delay lasting 
> 8 weeks from the previous dose, the BMS medical monitor must be consulted. Tumor 
assessments should continue as per protocol even if dosing is delayed/interrupted. Periodic 
study visits to assess safety and laboratory studies should also continue as clinically 
indicated during such dosing delays/interruption.
−
Dosing delays lasting > 8 weeks from the previous dose that occur for non-drug-related 
reasons may be allowed if approved by the BMS medical monitor. Prior to re-initiating 
treatment in a subject with a dosing delay lasting > 8 weeks, the BMS medical monitor 
must be consulted. Tumor assessments should continue as per protocol even if dosing is 
delayed/interrupted. Periodic study visits to assess safety and laboratory studies should 
also continue as clinically indicated during such dosing delays/interruption.
•
Any adverse event, laboratory abnormality, or intercurrent illness which, in the judgment of 
the Investigator, presents a substantial clinical risk to the subject with continued nivolumab 
dosing.
4.5.9
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. Dose 
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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.
4.5.9.1
Elotuzumab and Nivolumab
No dose reduction is allowed for elotuzumab or nivolumab.
4.5.9.2
Dexamethasone
Dexamethasone dose reductions for toxicity related to study drug, must be performed as clinically 
indicated. Recommended management is described in Table 4.5.9.2-1 and Table 4.5.9.2-2. 
Deviations to the recommended dose reductions are allowed based on the clinical judgment of the 
investigator.
Table 4.5.9.2-1:
Dexamethasone Dose Reductions
CTCAE 
Category
Adverse Event
Treatment Adjustment
Gastrointestinal
Dyspepsia, gastric or duodenal 
ulcer, gastritis
Grade 1 - 2 
(requiring medical management)
Treat with a proton pump inhibitor.
If symptoms persist despite above measures, decrease by 
1 dose level.
≥Grade 3 
(requiring hospitalization or 
surgery)
Hold dexamethasone until symptoms are adequately 
controlled. Reduce by 1 dose level and resume along with 
concurrent therapy with a proton pump inhibitor.
If symptoms persist despite above measures, reduce to dose 
level -3 (dose withheld).
Acute pancreatitis
Reduce to dose level -3 (dose withheld).
Cardiovascular
Edema
≥Grade 3 (limiting function and 
unresponsive to therapy or 
anasarca)
Use diuretics as needed, and decrease dexamethasone by 
1 dose level. If edema persists despite above measures, 
decrease by another dose level.
Neurology
Confusion or Mood alteration 
≥Grade 2 (interfering with 
function ± interfering with 
activities of daily living)
Hold dexamethasone until symptoms resolve.
Decrease by 1 dose level and resume.
If symptoms persist despite above measures, decrease by 
another dose level.
Musculoskeletal
Muscle weakness 
≥Grade 2 (symptomatic and 
interfering with function ±
interfering with activities of 
daily living)
Hold dose until muscle weakness is ≤Grade 1.
Decrease dexamethasone by 1 dose level and resume.
If weakness persists despite above measures, decrease by 
another dose level.
Metabolic
Hyperglycemia
≥Grade 3 or higher
Treat with insulin or oral hypoglycemics as needed. If 
uncontrolled despite above measures, decrease by 1 dose 
level until glucose levels are satisfactory.
Constitutional
Insomnia ≥Grade 2
Decrease by 1 dose level and resume.
Dose reduction for persistent Grade 2 or Grade ≥3 AEs believed to be related to dexamethasone 
and not listed above are permitted.
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Contact the medical monitor to discuss dexamethasone premedication for subjects who reach dose 
level -3 or must discontinue dexamethasone due to toxicity.
Table 4.5.9.2-2:
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 - 8 mg
> 75 years old - 12 mg
-2
≤75 years old - 0 mg
8 mg
≤75 years old - 12 mg
N/A
> 75 years old - 0 mg
> 75 years old - 8 mg
-3
≤75 years old - 0 mg 
Contact 
Medical 
Monitor
≤75 years old - 0 mg 
N/A
> 75 years old - 0 mg 
> 75 years old - 0 mg 
4.5.9.3
Pomalidomide
Below are the recommended dose adjustments for the management of NCI CTCAE Grade 3 and 
4 toxicities for thrombocytopenia and neutropenia judged by the investigator to be related to 
pomalidomide. Information in Table 4.5.9.3-1 and Table 4.5.9.3-2 is based on pomalidomide 
prescribing information, which contains additional guidance on pomalidomide dosing.29,31
Table 4.5.9.3-1:
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 4.5.9.3-2:
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 ≥500 per mm3
Resume pomalidomide at 3 mg daily
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Table 4.5.9.3-2:
Treating Neutropenia Related to Pomalidomide
When Neutrophil Count:
Recommended Course:
For each subsequent drop < 500 mm3
Interrupt pomalidomide treatment
Return to ≥500 mm3
Resume pomalidomide at 1 mg less than previous dose
ANC, absolute neutrophil count.
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%.29,31
4.5.10
EN Cohort: Stopping Rules for Unacceptable Toxicity
The rate of AE occurrence will be assessed on an ongoing basis during treatment and within 100 
days of last dose of therapy with nivolumab.
Enrollment in the EN cohort and continued treatment of patients already enrolled in the EN cohort 
will be stopped if either of the safety signals below are observed:
•
Grade 5 adverse events, excluding those due to disease progression: cumulative rate ≥20% 
occurrence in the first 50% of treated patients
•
Grade ≥3 nivolumab immune-related adverse events: ≥10% occurrence in the first 50% of 
treated patients.
4.6
Blinding/Unblinding
Not applicable.
4.7
Treatment Compliance
Starting at Cycle 1, Day 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.
4.8
Destruction of Study Drug
For this study, study drugs (those supplied by BMS or sourced by the investigator) such as partially 
used study drug containers, vials and syringes may be destroyed on site.
Any unused study drugs can only be destroyed after being inspected and reconciled by the 
responsible Study Monitor unless study drug containers must be immediately destroyed as required 
for safety, or to meet local regulations (eg, cytotoxics or biologics).
On-site destruction is allowed provided the following minimal standards are met:
•
On-site disposal practices must not expose humans to risks from the drug.
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•
On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.
•
Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.
•
Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.
•
Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
If conditions for destruction cannot be met the responsible Study Monitor will make arrangements 
for return of study drug.
It is the investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept.
4.9
Return of Study Drug
If study drug will not be destroyed upon completion or termination of the study, all unused and/or 
partially used study drug that was supplied by BMS must be returned to BMS. The return of study 
drug will be arranged by the responsible Study Monitor.
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elotuzumab
5.
STUDY ASSESSMENTS AND PROCEDURES
5.1
Flow Chart/Time and Events Schedule 
Table 5.1-1:
Screening Procedural Outline (CA204142)
Procedure
Screening
Visit 
Notes
Eligibility Assessments
Informed Consent
X
Prior to any screening procedures
Inclusion/Exclusion Criteria
X
Within 14 days prior to first dose of study drug
Medical History/Treatment History
X
Safety Assessments
Physical Examination
X
Includes height and weight within 14 days prior to first dose of study drug
Vital Signs
X
Temperature, BP, HR, within 14 days prior to first dose of study drug
Performance Status (ECOG)
X
Within 14 days prior to first dose of study drug
Serious Adverse Events Assessment
X
Collected from the time of informed consent
Concomitant Medications
X
Within 14 days prior to first dose of study drug
ECG
X
Within 28 days of randomization
Laboratory Assessments 
CBC, differential, platelets
X
Within 14 days prior to first dose of study drug
Chemistry
X
Within 14 days prior to first dose of study drug (See Section 5.3.4)
Serum β2-microglobulin
X
Within 28 days prior to first dose of study drug (Central Lab Analysis) 
Albumin
X
Within 28 days prior to first dose of study drug
Pregnancy Test
X
For WOCBP only, 2 pregnancy tests, one 10 - 14 days prior to start of study drug and one within 24 
hours prior to start of study drug. Urine tests must have a sensitivity of at least 25 IU/L.
Thyroid Function Tests (TFTs)
(reflex to free T3/total T3, free T4 for 
abnormal TSH result).
X
Within 28 days prior to first dose of study drug. Required only after Amendment 02.
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elotuzumab
Table 5.1-1:
Screening Procedural Outline (CA204142)
Procedure
Screening
Visit 
Notes
Hepatitis B surface antigen (HBsAg), 
and hepatitis C antibody (HCV Ab) or 
HCV ribonucleic acid (RNA).
X
Within 28 days prior to first dose of study drug. Required only after Amendment 02.
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Table 5.1-2:
CA204142 Cycles 1 and 2 - EPd Cohort Only
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 – 28
Notes
Safety Assessments
Targeted Physical Examination
X
Perform prior to dosing, include weight
Vital Signs
X
X
X
X
Cycle 1: Measure vital signs pre-elotuzumab infusion, 30 minutes after the 
start of elotuzumab infusion, at the end of infusion, and 30 minutes after 
the completion of infusion
Cycle 2 and beyond: evaluate prior to dosing
Performance Status (ECOG)
X
Evaluate prior to dosing
Serious Adverse Event Assessment
X
X
X
X
Evaluate prior to dosing
Adverse Events Assessment
X
X
X
X
Evaluate prior to dosing
Concomitant Medications
X
X
X
X
Evaluate prior to dosing
Laboratory Tests
CBC, differential, platelets
X
X
X
X
Can be drawn up to 3 days prior to study visit (See Section 5.3.4). Screening 
results are sufficient for Cycle 1
Chemistry
X
Can be drawn up to 3 days prior to study visit 
Pregnancy Test
X
For WOCBP only. Urine tests must have a sensitivity of at least 25 IU/L.
Test within 24 hours of Dose 1 study medication.
Efficacy Assessments
Myeloma Urine and Serum Lab tests
(Central Lab Analysis)
Every 4 weeks from date of
first dose of study drug until disease 
progression
Day 1 of each cycle (except Cycle 1 - refer to Screening visit for defined 
window as listed on Table 5.1-1) (See also: Section 5.4.2)
24-hour urine sample can be collected within ± 7 days of visit, and must be 
obtained in all subjects who have measurable UPEP M protein 
(≥200 mg/24 hours) at baseline with each cycle.
See Section 5.4.2 for subjects without measurable urine M protein at 
baseline and no FLC detected by the serum test.
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CA204142
BMS-901608
elotuzumab
Table 5.1-2:
CA204142 Cycles 1 and 2 - EPd Cohort Only
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 – 28
Notes
Bone Marrow Aspiration/Biopsy
For confirmation of CR if applicable or, 
if clinically indicated at time of suspected 
disease progression
Bone marrow aspirate is mandatory. Bone marrow biopsy is optional.
Bone marrow will be analyzed in local laboratory, with performance of 
IHC and/or flow cytometry to assess for sCR.
Skeletal Imaging
If clinically indicated
CT/MRI assessment 
As clinically indicated
Response per IMWG uniform 
criteria
Every 4 weeks from date of first dose of 
study drug on Cycle 1 Day 1 until 
progression. (Cycles cannot be delayed. 
In the event that the first dose within a 
cycle is delayed or omitted, the tumor 
assessment should still be done on Day 1 
of the cycle and should not be delayed 
until dosing.).
Subjects who discontinue from study treatment for reasons other than 
progression will continue to have tumor assessment every 4 weeks from 
C1D1 until progression.
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Date: 08-Mar-2018
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CA204142
BMS-901608
elotuzumab
Table 5.1-3:
CA204142 Cycles 3 and Beyond - EPd Cohort and Cross-over Patients from EN Cohort
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 - 28
End of 
Treatment
Days 30 & 
60 
post end of 
treatment*
Notes
Safety Assessments
Targeted Physical Examination
X
Perform prior to dosing, includes weight 
Vital Signs
X
X
Evaluate prior to dosing.
Performance Status (ECOG)
X
X
Evaluate prior to dosing
Serious Adverse Event 
Assessment
X
X
X
Evaluate prior to dosing
SAEs will be collected for EPd subjects up to 100 days 
of last dose (per Section 6.1.1).
Adverse Events Assessment
X
X
X
Evaluate prior to dosing
Concomitant Medications
X
X
X
Evaluate prior to dosing
Laboratory Tests
CBC, differential, platelets
X
X
Can be drawn up to 3 days prior to visit. Additional 
samples as clinically indicated.
Chemistry
X
X
Can be drawn up to 3 days prior to visit (See 
Section 5.3.4)
Pregnancy Test
X
X
X
For WOCBP only. Tests must occur within 24 hours 
prior to dosing. The pregnancy test should occur on 
Days 1 of each cycle. Urine tests must have a sensitivity 
of at least 25 IU/L. Pregnancy test must also be 
performed at end of treatment and at 30, 60 and 90 days 
off treatment. The test at 90 days off treatment may be 
performed locally if the patient is not scheduled to return 
to the center for other reasons.
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CA204142
BMS-901608
elotuzumab
Table 5.1-3:
CA204142 Cycles 3 and Beyond - EPd Cohort and Cross-over Patients from EN Cohort
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 - 28
End of 
Treatment
Days 30 & 
60 
post end of 
treatment*
Notes
Efficacy Assessments
Myeloma Urine and Serum 
Lab tests
(Central Lab Analysis)
Every 4 weeks from date of
first dose of study drug until disease progression
Day 1 of each cycle (except Cycle 1 - refer to Screening 
visit for defined window).
24-hour urine sample can be collected within ± 7 days of 
visit and must be obtained in all subjects who have 
measurable UPEP M protein (≥200 mg/24 hours) at 
baseline with each cycle.
See Section 5.4.2 for subjects without measurable urine 
M protein at baseline and no FLC detected by the serum 
test.
Bone Marrow 
Aspiration/Biopsy
For confirmation of CR if applicable or, if clinically indicated at time 
of suspected disease progression
Bone marrow aspirate is mandatory. Bone marrow 
biopsy is optional.
Bone marrow will be analyzed in local laboratory, with 
performance of IHC and/or flow cytometry to assess for 
sCR.
Corrected calcium
Every 4 weeks from the date of the first dose of study drug until 
disease progression, regardless of whether the subject is on study 
therapy or subsequent therapy.
Serum calcium and albumin from peripheral blood at D1 
of each cycle until disease progression, even if subject is 
on subsequent therapy; if used as criterion for disease 
progression, must be confirmed by second value.
Skeletal Imaging
If clinically indicated
CT/MRI assessment 
As clinically indicated
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CA204142
BMS-901608
elotuzumab
Table 5.1-3:
CA204142 Cycles 3 and Beyond - EPd Cohort and Cross-over Patients from EN Cohort
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 - 28
End of 
Treatment
Days 30 & 
60 
post end of 
treatment*
Notes
Response per IMWG uniform 
criteria
Every 4 weeks from date of first dose of study drug on Cycle 1 Day 1 
until progression. (Cycles cannot be delayed. In the event that the first 
dose within a cycle is delayed or omitted, the tumor assessment 
should still be done on Day 1 of the cycle and should not be delayed 
until dosing.).
Subjects who discontinue from study treatment for 
reasons other than progression will continue to have 
tumor assessment every 4 weeks from C1D1 until 
progression.
Following disease progression, subjects will be followed 
at least annually for survival.
* Subjects in the EN cohort who cross-over to the EPd cohort but discontinue treatment within 2 cycles of EPd treatment will still need to undergo 100 day follow-
up visit from last dose of nivolumab to evaluate safety events related to study treatment.
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CA204142
BMS-901608
elotuzumab
Table 5.1-4:
CA204142 Cycles 1 and 2 - EN Cohort
Procedure
Day
1
Day 
8
Day
15
Day
22
Rest Days 
23 – 28
Notes
Safety Assessments
Targeted Physical 
Examination
X
Perform prior to dosing, include weight
Vital Signs
X
X
X
X
Cycle 1: Measure vital signs pre-elotuzumab infusion, 30 minutes after the start of 
elotuzumab infusion, at the end of infusion, and 30 minutes after the completion of 
infusion
Cycle 2 and beyond: Evaluate prior to dosing. 
Vital signs must be collected if infusion related AE occurs.
Performance Status 
(ECOG)
X
Evaluate prior to dosing
Serious Adverse 
Event Assessment
X
X
X
X
Evaluate prior to dosing
Adverse Events 
Assessment
X
X
X
X
Evaluate prior to dosing
Concomitant 
Medications
X
X
X
X
Evaluate prior to dosing
Second Primary 
Malignancy
X
Laboratory Tests
CBC, differential, 
platelets
X
X
X
X
Can be drawn up to 3 days prior to study visit (See Section 5.3.4). Screening results 
are sufficient for Cycle 1
Chemistry
X
Can be drawn up to 3 days prior to study visit 
Pregnancy Test
X
For WOCBP only. Urine tests must have a sensitivity of at least 25 IU/L.
Test within 24 hours of Dose 1 study medication. 
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Date: 08-Mar-2018
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CA204142
BMS-901608
elotuzumab
Table 5.1-4:
CA204142 Cycles 1 and 2 - EN Cohort
Procedure
Day
1
Day 
8
Day
15
Day
22
Rest Days 
23 – 28
Notes
Thyroid stimulating 
hormone (TSH) 
(reflex to free 
T3/total T3, free T4 
for abnormal TSH 
result).
X*
To be performed every *2 cycles (± 7 days) from first dose regardless of dosing 
schedule 
Efficacy Assessments
Myeloma Urine and 
Serum Lab tests
(SPEP/EPEP/sFLC/
Igs)
(Central Lab Analysis)
Every 4 weeks from date of
first dose of study drug until disease progression 
of study drug until disease progression regardless 
of whether subject is on study therapy or 
subsequent therapy 
Day 1 of each cycle (Optional at C1D1 if conducted at screening.)
(See also: Section 5.4.2)
24-hour urine sample can be collected within ± 7 days of visit, and must be 
obtained in all subjects 
Bone Marrow 
Aspiration/Biopsy
For confirmation of CR, if applicable or, if 
clinically indicated at time of suspected disease 
progression (Local Lab analysis)
Bone Marrow plasma cell percentage.
Performance of IHC or flow cytometry to assess for sCR (for subjects with CR).
Corrected Calcium
Every 4 weeks from the date of the first dose of 
study drug until disease progression, regardless 
of whether the subject is on study therapy or 
subsequent therapy.
Serum calcium and albumin from peripheral blood at D1 of each cycle until disease 
progression, even if subject is on subsequent therapy; if used as criterion for 
disease progression, must be confirmed by second value.
Skeletal Imaging
If clinically indicated
CT/MRI assessment 
As clinically indicated and at the time of CR/sCR 
assessments
Response per 
IMWG uniform 
criteria
Every 4 weeks from date of first dose of study 
drug on Cycle 1 Day 1 until progression. (Cycles 
cannot be delayed. In the event that the first dose 
within a cycle is delayed or omitted, the tumor 
assessment should still be done on Day 1 of the 
cycle and should not be delayed until dosing.).
Subjects who discontinue from study treatment for reasons other than progression 
will continue to have tumor assessment every 4 weeks from C1D1 until 
progression.
Response assessments and PD require confirmation (2 consecutive assessments 
made at any time) before the institution of any new therapy.
Revised Protocol No.: 03
Date: 08-Mar-2018
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CA204142
BMS-901608
elotuzumab
Table 5.1-4:
CA204142 Cycles 1 and 2 - EN Cohort
Procedure
Day
1
Day 
8
Day
15
Day
22
Rest Days 
23 – 28
Notes
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CA204142
BMS-901608
elotuzumab
Table 5.1-5:
CA204142 Cycles 3 and 4 - EN Cohort
Procedure
Day 1
Day 8
Day 15
Day 22
Rest Days 
23 – 28
Notes
Safety Assessments
Targeted 
Physical 
Examination
X
Perform prior to dosing, include weight
Vital Signs
X
X
Evaluate prior to dosing. 
Performance 
Status (ECOG)
X
Evaluate prior to dosing
Serious Adverse 
Event 
Assessment
X
X
Evaluate prior to dosing
Adverse Events 
Assessment
X
X
Evaluate prior to dosing
Concomitant 
Medications
X
X
Evaluate prior to dosing
Second Primary 
Malignancy
X
Laboratory Tests
CBC, 
differential, 
platelets
X
Can be drawn up to 3 days prior to study visit (See Section 5.3.4). 
Chemistry
X
Can be drawn up to 3 days prior to study visit 
Pregnancy Test
X
For WOCBP only. Urine tests must have a sensitivity of at least 25 IU/L.
Test within 24 hours. 
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Date: 08-Mar-2018
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CA204142
BMS-901608
elotuzumab
Table 5.1-5:
CA204142 Cycles 3 and 4 - EN Cohort
Procedure
Day 1
Day 8
Day 15
Day 22
Rest Days 
23 – 28
Notes
Thyroid 
stimulating 
hormone (TSH) 
(reflex to free 
T3/total T3, free 
T4 for abnormal 
TSH result).
X*
To be performed every *2 cycles (± 7 days) from first dose regardless of 
dosing schedule.
Efficacy Assessments
Myeloma Urine 
and Serum Lab 
tests
(SPEP/UPEP/sF
LC/Igs)
(Central Lab Analysis)
Every 4 weeks from date of first dose of study drug until 
disease progression regardless of whether subject is on 
study therapy or subsequent therapy 
Day 1 of each cycle (See also: Section 5.4.2)
24-hour urine sample can be collected within ± 7 days of visit, and must be 
obtained in all subjects 
Bone marrow 
aspiration/biopsy
For confirmation of CR, if applicable, or if clinically at the 
time of suspected disease progression (local lab analysis)
Bone marrow plasma cell percentage
Performance of IHC or flow cytometry to assess for sCR (for subjects with 
CR).
Corrected 
Calcium
Every 4 weeks from the date of the first dose of study drug 
until disease progression, regardless of whether the subject 
is on study therapy or subsequent therapy.
Serum calcium and albumin from peripheral blood at D1 of each cycle until 
disease progression, even if subject is on subsequent therapy; if used as 
criterion for disease progression, must be confirmed by second value.
Skeletal Imaging
If clinically indicated
CT/MRI 
assessment 
As clinically indicated and at the time of CR/sCR 
assessments
Response per 
IMWG uniform 
criteria
Every 4 weeks from date of first dose of study drug on 
Cycle 1 Day 1 until progression. (Cycles cannot be 
delayed. In the event that the first dose within a cycle is 
delayed or omitted, the tumor assessment should still be 
done on Day 1 of the cycle and should not be delayed until 
dosing.).
Subjects who discontinue from study treatment for reasons other than 
progression will continue to have tumor assessment every 4 weeks from 
C1D1 until progression.
Response assessments and PD require confirmation (2 consecutive 
assessments made at any time) before the institution of any new therapy.
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Date: 08-Mar-2018
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Clinical Protocol
CA204142
BMS-901608
elotuzumab
Table 5.1-5:
CA204142 Cycles 3 and 4 - EN Cohort
Procedure
Day 1
Day 8
Day 15
Day 22
Rest Days 
23 – 28
Notes
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CA204142
BMS-901608
elotuzumab
Table 5.1-6:
CA204142 Cycles 5 and Beyond - EN Cohort
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 - 28
End of 
Treatment
Days 30 & 100
(+/- 7 days)
post end of 
treatment
Notes
Safety Assessments
Targeted Physical 
Examination
X
Perform prior to dosing, includes weight 
Vital Signs
X
X
Evaluate prior to dosing. 
Performance Status (ECOG)
X
X
Evaluate prior to dosing
Serious Adverse Event 
Assessment
X
X
X
Evaluate prior to dosing
Adverse Events Assessment
X
X
X
Evaluate prior to dosing
Concomitant Medications
X
X
X
Evaluate prior to dosing
Second Primary Malignancy
X
X
X
Laboratory Tests
CBC, differential, platelets
X
X
Can be drawn up to 3 days prior to visit. Additional 
samples as clinically indicated.
Chemistry
X
X
Can be drawn up to 3 days prior to visit (See 
Section 5.3.4)
Revised Protocol No.: 03
Date: 08-Mar-2018
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Clinical Protocol
CA204142
BMS-901608
elotuzumab
Table 5.1-6:
CA204142 Cycles 5 and Beyond - EN Cohort
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 - 28
End of 
Treatment
Days 30 & 100
(+/- 7 days)
post end of 
treatment
Notes
Pregnancy Test
X
X
X
For WOCBP only. Tests must occur within 24 hours prior 
to dosing. The pregnancy test should occur on Days 1 of 
each cycle. Urine tests must have a sensitivity of at least 
25 IU/L. Pregnancy test must also be performed at end 
of treatment and at 30, 60 and 90 days off treatment.
The test at 90 days off treatment may be performed 
locally if the patient is not scheduled to return to the 
center for other reasons.
Thyroid stimulating hormone 
(TSH) (reflex to free T3/total 
T3, free T4 for abnormal TSH 
result).
X
X
To be performed every 2 cycles (± 7 days) from first dose 
regardless of dosing schedule.
Efficacy Assessments
Myeloma Urine and Serum 
Lab tests
(SPEP/UPEP/sFLC/Igs)
(Central Lab Analysis)
Every 4 weeks from date of first dose of study drug until disease 
progression regardless of whether subject is on study therapy or 
subsequent therapy 
Day 1 of each cycle (including Cycle 1 See also 
Section 5.4.2) 
24-hour urine sample can be collected within ± 7 days of 
visit, and must be obtained in all subjects 
Bone marrow 
aspiration/biopsy
For confirmation of CR, if applicable or if clinically indicated at the 
time of suspected disease progression (local lab analysis). 
Bone marrow plasma cell percentage
Performance of IHC or flow cytometry to assess for a 
sCR (for subjects with CR).
Skeletal Imaging
If clinically indicated
CT/MRI assessment 
As clinically indicated
Revised Protocol No.: 03
Date: 08-Mar-2018
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Clinical Protocol
CA204142
BMS-901608
elotuzumab
Table 5.1-6:
CA204142 Cycles 5 and Beyond - EN Cohort
Procedure
Day 
1
Day 
8
Day 
15
Day 
22
Rest Days 
23 - 28
End of 
Treatment
Days 30 & 100
(+/- 7 days)
post end of 
treatment
Notes
Response per IMWG uniform 
criteria
Every 4 weeks from date of first dose of study drug on Cycle 1 Day 
1 until progression. (Cycles cannot be delayed. In the event that the 
first dose within a cycle is delayed or omitted, the tumor assessment 
should still be done on Day 1 of the cycle and should not be delayed 
until dosing.). 
Response assessments (≥PR) and PD require confirmation 
(2 consecutive assessments made at any time before the institution of 
new therapy).
Subjects who discontinue from study treatment for 
reasons other than progression will continue to have 
tumor assessment every 4 weeks from C1D1 until 
progression. 
Following disease progression, subjects will be followed 
at least annually for survival.
Revised Protocol No.: 03
Date: 08-Mar-2018
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Clinical Protocol
CA204142
BMS-901608
elotuzumab
5.1.1
Retesting During Screening Period
Retesting of laboratory parameters and/or other assessments within any single 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 Treatment) 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 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:
•
Instructions and kits for collections, processing, and shipment of blood and tissue samples
•
NCI CTCAE booklets version 3.0
•
Elotuzumab Investigator Brochure
•
Nivolumab Investigator Brochure
•
Pomalidomide (Pomalyst®) Package Insert
•
Site Manual for operation of IVRS
•
Subject Dosing Diary 
•
Serious Adverse Event (SAE) Case Report Form (CRF/eCRF) 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, blood pressure and heart rate) will be recorded as outlined in Table 
5.1-1, Table 5.1-2, Table 5.1-3, Table 5.1-4 , Table 5.1-5, and Table 5.1-6. Blood pressure and 
heart rate should be measured after the subject has been seated quietly for at least 5 minutes prior 
to dosing. On Cycle 1 only, the days of elotuzumab dosing, vital signs monitoring should be 
performed as follows:
•
Prior to the start of the elotuzumab infusion
•
Thirty minutes after the start of infusion
•
At the end of the infusion
•
Thirty minutes post completion of the elotuzumab infusion.
•
Subjects who experience a Grade ≥2 infusion reaction require vital signs to be monitored every 
30 minutes for 1- 2 hours (as clinically indicated) 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, Table 5.1-3, Table 5.1-4, Table 5.1-5, and Table 5.1-6. 
A full physical examination will be performed at the screening visit, whereas a targeted exam will 
occur at Day 1 and during on-treatment up to 3 days prior to dosing and post-treatment visits. A 
targeted physical examination may be performed by a qualified professional guided by the 
examiner’s observations and/or subject complaints on new or changed conditions, symptoms, or 
concerns. Targeted physical exam includes assessment of heart, lung, and abdomen.
5.3.3
Performance Status
Performance assessment will be performed as indicated in Table 5.1-1, Table 5.1-2, Table 5.1-3, 
Table 5.1-4, Table 5.1-5, and Table 5.1-6 using ECOG performance scale and criteria as described 
in Appendix 2.
5.3.4
Laboratory Assessments for Safety
Laboratory assessments for safety will be performed at local laboratories. Safety laboratory 
assessments are listed in Table 5.3.4-1.
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Table 5.3.4-1:
Safety Laboratory Assessments
Safety Laboratory Assessments
Screening as outlined in 
Table 5.1-1. Within 14 days 
of first dose of study drug
Study Visits as outlined in
Table 5.1-2,Table 5.1-3, Table 5.1-4, 
Table 5.1-5, and Table 5.1-6. 
Hematology
CBC
X
X
Differential
X
X
Platelets
X
X
Chemistry
Sodium
X
X
Potassium
X
X
Chloride
X
X
Albumin
X
(within 28 days of first dose 
of study drug) 
X
Alkaline Phosphatase
X
X
ALT (SGPT)
X
X
AST (SGOT)
X
X
Total Bilirubin
X
X
Lactate Dehydrogenase
X
X
BUN (or Urea)
X
X
Creatinine
X
X
Glucose
X
X
Calcium
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 Pregnancy test must also be 
performed at end of treatment, and at
30, 60 and 90 days off treatment. The 
test at 90 days off treatment may be 
performed locally if the patient is not 
scheduled to return to the center for 
other reasons. Urine tests must have a 
sensitivity of at least 25 IU/L.
Hepatitis B surface antigen (HBV sAg, 
Australia antigen) and hepatitis C 
antibody (HCV Ab) or HCV 
ribonucleic acid (RNA)
Xa
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Table 5.3.4-1:
Safety Laboratory Assessments
Safety Laboratory Assessments
Screening as outlined in 
Table 5.1-1. Within 14 days 
of first dose of study drug
Study Visits as outlined in
Table 5.1-2,Table 5.1-3, Table 5.1-4, 
Table 5.1-5, and Table 5.1-6. 
Thyroid stimulating hormone (TSH) 
(reflex to free T3, free T4 or abnormal 
result)
Xa
Xb
a Within 28 days of first dose of study drug
b TSH (reflex to free/total T3, free T4 for abnormal result) to be performed every 2 cycles (± 7 days) from first dose 
regardless of schedule.
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, Table 5.1-3, Table 5.1-4, Table 5.1-5, and Table 5.1-6. Assessments done at local labs 
versus central labs are indicated in Table 5.1-1, Table 5.1-2, Table 5.1-3, Table 5.1-4, Table 5.1-
5, and Table 5.1-6. Assessments for SPEP and UPEP and molecular MRD 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 according to guidelines of the modified IMWG33,34 (Appendix 4) will be used 
for the primary analysis. For the purposes of this study, all subjects’ tumor assessments by 
myeloma laboratory tests should be re-evaluated per the protocol-stated frequency relative to the 
date of first dose of study drug until disease progression based on the modified IMWG criteria, 
irrespective of dose delays or treatment cycle. If subject does not have documented disease 
progression at time of study drug discontinuation, then tumor assessments should still be 
performed according to the same schedule described above until disease progression. 
Subjects will be followed for survival at least once a year by phone after disease progression.
All efficacy laboratory assessments 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). Only if a subject is 
unable to come to the site for a visit to have specimens collected for a central lab (especially after 
study drug discontinuation), a SPEP, UPEP, or sFLC assessment can be performed locally, in lieu 
of a central lab assessment. M protein quantification or Serum Free Light Chain (sFLC) must be 
performed. Any laboratory samples analyzed locally, including for efficacy, must be entered on 
the appropriate CRF/eCRF.
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5.4.2
Laboratory Assessments for Myeloma
Subjects who have urine M protein of zero mg/24 hours at baseline, but have measurable serum 
M-protein, do not have to continue UPEP assessments until SPEP M protein values are 
undetectable. Assessment of UPEP M protein and urine immunofixation at the time of possible 
CR/sCR is mandatory, that is negative urine immunofixation is required to fulfill CR/sCR criteria, 
even in subjects with non-measurable values at baseline. Therefore, when serum immunofixation 
electrophoresis (SIFE) becomes negative, UPEP and urine immunofixation electrophoresis (UIFE)
collection should begin for these subjects. In addition, a UPEP should be collected if clinically 
warranted (for example, signs of disease progression (eg, anemia) even when SPEP M-protein is 
stable).
1) Serum: Serum protein electrophoresis (SPEP) for M protein quantification, immunofixation, 
and quantitative immunoglobulin assay.
a) Immunofixation of serum is required at baseline and to confirm CR regardless of whether 
measurable M-protein was present at baseline.
b) All other serum tests will be followed at each tumor assessment. Confirmation of ≥PR is 
required on 2 consecutive assessments.
2) Urine: 24-hour urine collection electrophoresis for M protein quantification and 
immunofixation.
a) Immunofixation of urine 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 Confirmation of ≥PR is 
required on 2 consecutive assessments.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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5.4.3
Imaging Assessments for Myeloma
5.4.3.1
Skeletal Imaging
Skeletal imaging, by conventional radiography or other methods, for bone lesions will be 
performed within 60 days prior to first dose of study drug in all EPd cohort subjects and within 
28 days in the EN Cohort subjects. Skeletal imaging will be performed on study if clinically 
indicated. 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.
5.4.3.2
Assessment of Extramedullary Plasmacytoma
Computed tomography or MRI should be performed at screening, if clinically indicated, to assess 
for extramedullary 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.
All tumor measurements must be made in millimeters. All documented measurable lesions are to 
be followed throughout the trial. All assessments to be used for tumor response evaluation, 
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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 4 for definitions of response and progression. All criteria are derived from 
IMWG,33,34 except for minor (minimal) response, which is derived from the European Society for 
Blood and Marrow Transplantation (EBMT). All response categories require 2 consecutive 
assessments made before initiation of any new therapy.
 
 
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5.7
Outcomes Research Assessments
Not applicable
5.8
Other Assessments
5.8.1
Pharmacogenomic/Pharmacogenetic Assessments
Genetic assessment (FISH) of myeloma cells is optional and 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, these results must be entered into the 
CRF/eCRF. This assessment is considered to be standard of care for myeloma. Aspirates obtained 
will be used to identify prognostic cytogenetic markers that may include: 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).
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)
•
requires inpatient hospitalization or causes prolongation of existing hospitalization (see NOTE
below)
•
results in persistent or significant disability/incapacity
•
is a congenital anomaly/birth defect
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•
is an important medical event (defined as a medical event(s) that may not be immediately life-
threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the subject or may require intervention [eg, medical, 
surgical] to prevent 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)
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 
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100 days of discontinuation of dosing. If applicable, SAEs must be collected that relate to any later 
protocol-specified procedure (eg, a follow-up skin biopsy).
The Investigator must report any SAE that occurs after these time periods and that is believed to 
be related to study drug or protocol-specified procedure.
An SAE report must be completed for any event where doubt exists regarding its seriousness.
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.
6.2.1
Nonserious Adverse Event Collection and Reporting
The collection of nonserious AE information should begin at initiation of study drug until 60 days 
from the last dose of study drug for patients in the EPd cohort and until 100 days from the last dose 
of study drug for the EN cohort. Subjects in the EN cohort who cross-over to the EPd cohort but 
discontinue treatment within 2 cycles of EPd treatment will still need to undergo 100 day follow-
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up visit from last dose of the nivolumab to evaluate safety events related to study treatment.
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/eCRF (paper or electronic).
Completion of supplemental CRF/eCRFs 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/eCRF 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 female study subject 
or female partner of male study subject is pregnant or may have been pregnant at the time of 
investigational product exposure, including during the time to washout (90 days) plus one 
ovulatory cycle (30 days) for a total of 5 months after product administration (female study 
subjects); or plus one spermatogenesis cycle (90 days) for a total of 7 months after product 
administration (female partners of male study subjects), 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 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.
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 
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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)
Specific criteria for identifying potential DILI have not been identified for this protocol. Standard 
medical practice in identifying and monitoring hepatic issues should be followed.
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.
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).
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.
7.
DATA MONITORING COMMITTEE AND OTHER EXTERNAL 
COMMITTEES
Not applicable
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8.
STATISTICAL CONSIDERATIONS
Descriptive statistics (n, mean, median, and standard deviation; minimum, maximum or 
interquartile range) will be provided for the safety analysis and by subgroups based on types of 
prior therapy and line of therapy (2L/3L) groups. Because the sample size for the study is small, 
summary statistics with their associated 95% confidence intervals and tests of hypotheses will be 
based, to the extent possible, using small-sample statistics like the Clopper-Pearson for binomial 
data. Median time-to-event and its 95% confidence interval will be based on the Kaplan-Meier 
(KM) estimation procedure. The KM curves will be presented for time-to-event endpoints.
8.1
Sample Size Determination
8.1.1
EPd Cohort 
Seventy-two subjects will be screened with approximately 17% projected to fail screening. This 
total number is based on logistical consideration with statistical properties outlined below. 
Screening will continue until a minimum of 60 subjects are enrolled and treated.
Under the assumptions that:
•
time to PFS is exponentially distributed
•
median time of PFS is 11 months for subjects treated with pomalidomide + dexamethasone 
and will increase to median of 15 months with the addition of elotuzumab to the treatment mix
•
an increase of 4 months in median corresponds to relative risk ratio of 0.73 (0.0462 monthly 
risk in the elotuzumab add-on and 0.0630 monthly historical risk in the pomalidomide + 
dexamethasone treated-subjects)
Sixty subjects enrolled over a 24-month period are sufficient to detect an increase in median from 
11 to 15 months with about 70% power in a one-sided test with a 0.05 significance level. 
Assuming a monthly hazard rate of 0.0462, 48 of the 60 treated subjects are expected to have PFS 
events over a 24-month follow up period.
Power is calculated using PASS12 using the one-sample exponential module where the median is 
mapped to mean by dividing the assumed alternative median by logarithm of 2. The calculated 
power and event counts are consistent with power and event counts based on one sample log rank 
test where the number of events is calculated assuming relative risk ratio of 0.73.
8.1.2
EN Cohort
The planned sample size will be approximately 30 treated subjects; screening will continue until a 
minimum of 30 patients are enrolled and treated. 
For a 30% observed ORR rate and a sample size of N=30 yields an exact confidence interval of
[0.15, 0.49]. These design parameters ensure a lower bound higher than 15%.
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8.2
Populations for Analyses
•
The safety analysis set consists of subjects who receive at least one dose of study drug. The 
safety analysis set is also the all treated analysis set.
•
The efficacy analysis set is the same as the all treated analysis set.
8.3
Endpoints
8.3.1
Primary Endpoint(s)
8.3.1.1
EPd Cohort
PFS is defined as the time from first dosing date to the date of the first documented progression 
per IMWG uniform criteria or death due to any cause, whichever occurs first. Subjects who die 
without a reported prior progression will be considered to have progressed on the date of their 
death. Subjects who did not progress or die will be censored on the date of their last evaluable 
assessment. Subjects who did not have any on study efficacy assessments and did not die will be 
censored on the first dosing date. 
Subjects who switched to subsequent therapy prior to documented progression will be censored 
on the date of the last evaluable assessment prior to the initiation of the new therapy.
8.3.1.2
EN Cohort
ORR is defined as proportion of subjects with best overall response of partial response (PR) or 
better. Response will be determined per IMWG uniform criteria.
8.3.2
Secondary Endpoint(s)
8.3.2.1
EPd Cohort
•
ORR is defined as proportion of subjects with a best overall response of partial response (PR)
or better. 
•
OS is defined as the time from first dosing date to the date of death from any cause. A subject 
who has not died will be censored at last known date alive.
8.3.2.2
EN Cohort
•
PFS definition: See Section 8.3.1.1
•
OS is defined as the time from first dosing date to the date of death from any cause. A subject 
who has not died will be censored at last known date alive.
 
 
 
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8.4
Analyses
8.4.1
Demographics and Baseline Characteristics
The demographic and baseline characteristics of patients in the safety analysis set will be 
presented. Among the baseline clinical characteristics are patients’ ECOG Performance Status, 
baseline laboratory assessment for safety and efficacy endpoints, number of prior lines of therapy 
and types of previous therapy (Appendix 1), and disease status/stage (Appendix 5) at entry. 
8.4.2
Efficacy Analyses
The efficacy endpoints, PFS and ORR, will be defined using the IMWG criteria. Responses will 
be assessed at every treatment cycle using central laboratory test results on myeloma urine and 
serum, local laboratory bone marrow aspiration test, and if needed bone marrow and skeletal 
survey results and CT/MRI assessments. Objective responses will include stringent complete 
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response, complete response, very good partial response and partial responses. The ORR and its 
95% confidence interval (CI) using the Clopper-Pearson estimation procedure will be reported. 
PFS and OS will be plotted using Kaplan-Meier estimates, and if estimable, median and its 95% 
CI will be reported. Time to response will be analyzed for responders only with summary statistics 
provided. Duration of response will be reported using K-M estimates. The time to event responses 
will be recorded from the first day of the first cycle to the day that an event occurs. If no event 
occurs by the time the study is completed, the patient is censored for that event at the last day of 
subject contact.
For EPd cohort, the primary analysis of PFS will be conducted when 48 progression events have 
been observed.
For EN cohort, the primary analyses for ORR will be conducted when enrollment in the EN cohort 
is complete and all enrolled patients treated with the combination have received at least 3 cycles 
of treatment.
MRD negativity status for subjects in the EN Cohort will be evaluated by time points. The 
frequency of the MRD negativity status and the best MRD negativity status will be summarized 
for the EN cohort. The cross tabulation of the MRD negativity status and BOR will be presented. 
Summary statistics of the MRD levels and their corresponding percent changes from baseline will 
be tabulated by planned study day for the EN cohort. Potential association between the first/best 
MRD negativity status with PFS and OS will be evaluated in all treated patients. Additional details 
will be presented in the Statistical Analysis Plan.
8.4.3
Safety Analyses
Safety assessments will be performed prior, during and between dosing, and up to 100 days after 
the last treatment for the EN cohort and 60 days after the last dose in the EPd cohort and for 
subjects in the EN cohort who cross-over to the EPd cohort but discontinue treatment within 2 
cycles of EPd treatment safety assessments will be performed up to 100 days after the last dose of 
nivolumab. The frequency, severity, relationship to combination of drug treatment, seriousness, 
and outcomes of adverse events (AEs) will be reported for the full safety analysis set. AE severity 
will be graded according to the NCI Common Terminology Criteria for Adverse Events 3.0. 
Results of targeted physical examinations prior to each dosing cycle will be presented.
Summary statistics on vital signs at screening, pre-infusion, 30 minutes after the start of infusion, 
at end of infusion and 30 minutes after the completion of infusion will be reported for each dosing 
cycle. Concomitant medications, SAEs, laboratory parameters, and performance status prior to 
dosing will be presented. The safety analysis set will be used for reporting safety /adverse events.
 
 
 
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8.4.6
Outcomes Research Analyses (both cohorts)
Not applicable.
8.5
Interim Analyses
Administrative interim analyses may be performed at several times prior to completion of the study 
in order to facilitate program decisions and to support presentations or publications.
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
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Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the subject: 
(1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from subjects 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new subjects prior to enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
9.1.2
Monitoring
BMS representatives will review data centrally to identify potential issues to determine a schedule 
of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain CRF/eCRF pages and/or electronic files may serve as the 
source documents.
In addition, the study may be evaluated by BMS internal auditors and government inspectors who 
must be allowed access to CRF/eCRFs, source documents, other study files, and study facilities. 
BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to BMS.
9.1.2.1
Source Documentation
The Investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (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.
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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 CRF/eCRFs, study documentation, informed consent, and enrollment of WOCBP.
9.2
Records
9.2.1
Records Retention
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, or for the period 
specified by BMS, whichever is longer. The investigator must contact BMS prior to destroying 
any records associated with the study.
BMS will notify the investigator when the study records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, IRB). Notice of such 
transfer will be given in writing to BMS.
9.2.2
Study Drug Records
It is the responsibility of the investigator to ensure that a current disposition record of study drug 
(inventoried and dispensed) is maintained at the study site for all investigational products. Records 
or logs must comply with applicable regulations and guidelines and should include:
•
amount received and placed in storage area
•
amount currently in storage area
•
label identification number or batch number
•
amount dispensed to and returned by each subject, including unique subject identifiers
•
amount transferred to another area/site for dispensing or storage
•
nonstudy disposition (eg, lost, wasted)
•
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/eCRF 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 
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enhance understanding of product safety. CRF/eCRFs 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 CRF/eCRFs 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/eCRF 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 CRF/eCRFs.
The completed CRF/ECRF, including any paper or electronic SAE/pregnancy CRF/eCRFs, 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 
CRF/ECRFs, review and approval/signature is completed electronically through the BMS 
electronic data capture tool. The investigator must retain a copy of the CRF/eCRFs including 
records of the changes and corrections.
Each individual electronically signing electronic CRF/eCRFs must meet BMS training 
requirements and must only access the BMS electronic data capture tool using the unique user 
account provided by BMS. User accounts are not to be shared or reassigned to other individuals.
9.3
Clinical Study Report and Publications
A Signatory Investigator must be selected to sign the clinical study report.
For this protocol, the Signatory Investigator will be selected as appropriate based on the following 
criteria:
•
Subject recruitment (eg, among the top quartile of enrollers)
•
Involvement in trial design
•
Regional representation (eg, among top quartile of enrollers from a specified region or country)
•
Other criteria (as determined by the study team)
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
ACTH
adrenocorticotropic Hormone
ADCC
antibody-dependent cell-mediated cytotoxicity
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
HCG
human chorionic gonadotrophin
BMS
Bristol-Myers Squibb
BMSC
bone marrow stromal cells
BOR
best overall response
BP
blood pressure
BUN
blood urea nitrogen
CBC
complete blood count
CFR
code of Federal Regulations 
CI
confidence interval
Cm
centimeter
CR
complete response
CrCLr
creatinine clearance
Cm
centimeter
CRF
case report Form
CSR
clinical study report
dL
deciliter
DOR
duration of response
ECG
electrocardiogram
eCRF
electronic Case Report Form
ECOG
eastern Cooperative Oncology Group
EDC
electronic Data Capture
Eg
exempli gratia (for example)
EMR/EHR
electronic medical/health records
EN
elotuzumab and nivolumab combination cohort
EPd
elotuzumab in combination with pomalidomide and low dose dexamethasone 
FDA
Food and Drug Administration
FISH
fluorescence in situ hybridization
FSH
follicle stimulating hormone
G
gram
GCP
Good Clinical Practice
H
hour
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
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Term
Definition
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
ICH
International Conference on Harmonisation 
Ie
id est (that is)
IEC
Independent Ethics Committee
IHC
immunohistochemistry
IMWG
International Myeloma Working Group
IMP/IP
investigational medicinal products
IND
Investigational New Drug Exemption
I-O
immuno-oncology
IRB
Institutional Review Board
IU
International Unit
IV
intravenous
Kg
kilogram
L
liter
MedDRA
Medical Dictionary for Regulatory Activities
Mg
milligram
Min
minute
mL
milliliter
MR
minimal response
MRD
minimum residual disease
MTD
maximum tolerated dose
μg
microgram
N
number of subjects or observations
N/A
not applicable
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events 
Ng
nanogram
NIMP
non-investigational medicinal products 
ORR
objective response rate
OS
overall survival
PC
plasma cell
PD
pharmacodynamics
PDL-1
programmed death ligand-1
PFS
progression free survival
PK
pharmacokinetics
PR
partial response
PS
performance score
PO
per os (by mouth route of administration)
sCR
stringent complete response
SAE
serious adverse event
SIFE
serum immunofixation electrophoresis
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Term
Definition
sFLC
serum free light chain
SIFE
serum immunofixation electrophoresis
SOP
Standard Operating Procedures
SPEP
serum protein electrophoresis
Subj
subject
T
temperature
T
time
TCR
T Cell Receptor 
TFTs
thyroid function tests
TSH
thyroid stimulating hormone
TTR
time to response
UIFE
urine immunofixation electrophoresis
UPEP
urine protein electrophoresis
USP
United States Pharmacopoeia
VGPR
very good partial response
WOCBP
women of childbearing potential
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APPENDIX 1
DEFINITION OF LINES OF THERAPY
A line of therapy is defined by the 
 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 antilogous stem cell transplantation, followed by maintenance is considered 
one line of therapy. A new line of therapy starts when a planned course of therapy is modified to 
include other treatment agents (alone or in combination) as a result of disease progression, 
relapse, or toxicity. A new line of therapy also starts when a planned period of observation off 
therapy is interrupted by a need for additional treatment for the disease.
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APPENDIX 2
PERFORMANCE STATUS SCALES
STATUS
STATUS
STATUS
ZUBROD-ECOG-WHO
Normal, no complaints
0
Normal activity
Able to carry on normal activities
Minor signs or symptoms of disease
1
Symptoms, but fully 
ambulatory
Cares for self. Unable to carry on normal 
activity or to do active work
2
Symptomatic, but in bed 
< 50% of the day.
Requires considerable assistance and 
frequent medical care
3
Needs to be in bed > 50% of 
the day, but not bedridden
Severely disabled. Hospitalization indicated 
though death non imminent
4
Unable to get out of bed
Dead
5
Dead
 
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APPENDIX 3
PREPARATION AND ADMINISTRATION OF ELOTUZUMAB
Note: Subjects must be premedicated as described in Section 4.5.4 prior to elotuzumab infusion.
Dose Preparation Instructions
After dilution in normal saline, elotuzumab infusion must be completed within 8 hours if kept at 
room temperature (25 °C). In the United States and Puerto Rico, where a shortage of normal 
saline has been reported, dextrose 5% water (D5W) may be used. Normal saline is the preferred 
diluent and D5W should only be used if normal saline is not available. If a delay is anticipated 
after the dose has been diluted in normal saline, the prepared dose (properly identified) may be 
refrigerated at 2 °C to 8 °C for up to 24 hours. If stored under refrigerated conditions, the study 
drug solution should be equilibrated to room temperature (takes about 2 to 2.5 hours), and the 
container must be gently inverted to thoroughly mix the contents before administration. If the 
storage time limit is exceeded, the prepared dose solution must be discarded and the reason 
documented by the pharmacist in the study drug accountability records.
Elotuzumab will be administered to each subject as an IV infusion, using an automated infusion 
pump set at the appropriate rate according to the dose administration section (see Administration 
Instruction section below). The dose of elotuzumab will be calculated using the subject’s predose 
weight on Day 1 of each cycle (the screening weight can be used for Cycle 1 dose calculation), 
and then added to 0.9% saline for infusion.
Reconstitute elotuzumab lyophilized study drug, as described in steps 1 to 5.
Step 1:  For a 440 mg vial of lyophilized elotuzumab, draw 17 mL of Sterile Water for Injection 
(SWFI), USP into a syringe equipped with an 18-gauge or smaller needle.
Step 2:  Remove the flip-top from the elotuzumab vial.
Step 3:  Place the vial upright on a flat surface and, using standard aseptic techniques, insert the 
syringe needle into the vial through the center of the rubber stopper and deliver 17 mL (into the 
20-mL vial containing 440 mg elotuzumab) SWFI, USP, into the vial. Slowly remove the syringe 
needle out of the vial. The final volume of the reconstituted solution is approximately 17.6 mL, 
which includes the volume displaced by the solid cake. The concentration of elotuzumab in the 
reconstituted solution is approximately 25 mg/mL.
Step 4:  DO NOT SHAKE. Hold the vial upright and gently swirl the solution by rotating the vial 
to dissolve the lyophilized cake. Then gently invert the vial a few times in order to dissolve any 
powder that may be present on top of the vial or the stopper. Finally, hold the vial upright again 
and gently swirl the solution a few more times to dissolve any remaining particles. Avoid 
prolonged or vigorous agitation. DO NOT SHAKE.  
Step 5:  After the remaining solids are completely dissolved, allow the reconstituted solution to 
stand for 5 to 10 minutes.
It is acceptable to have small bubbles and/or foam around the edge of the vial. The reconstituted 
preparation results in a colorless to slightly yellow, clear to slightly opalescent solution 
containing approximately 25 mg/mL of elotuzumab.
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Step 6:  Once the reconstitution is completed, withdraw the calculated drug volume and further 
dilute with 100-500 ml of normal saline into an infusion bag (see Pharmacy Manual for 
additional details). The volume of saline or D5W can be adjusted so as not to exceed 5 mL/kg of 
patient weight at any given dose of elotuzumab. The resulting elotuzumab concentration must be 
from 1.0 mg/mL to 6.0 mg/mL. Elotuzumab solutions are compatible with polyvinyl chloride 
and polyolefin bags. Examples of such bags include Viaflo, MacoPharma Easyflex N, Macoflex 
N, B Braun Excel, and Braun Ecobag.
Drug volume will be calculated based on subject weight: For example, a subject receiving 
10 mg/kg elotuzumab who weighs 80 kg on Day 1 [predose] will require 800 mg of study drug 
for infusion. Withdraw 32 mL of elotuzumab (25 mg/mL) from 2 vials and add to an infusion 
bag already containing 230 mL saline, for a total of 262 mL to be infused. 
Similarly, an 80 kg subject receiving 20 mg/kg elotuzumab [predose] will require 1600 mg of 
study drug for infusion. Withdraw 64 mL of elotuzumab (25 mg/mL) from 4 vials and add to an 
infusion bag already containing 340 mL saline, for a total of 404 mL to be infused.  
Use a new sterile needle for withdrawing solution from each vial.
The same vial must not be used to prepare elotuzumab for more than one subject. Used 
elotuzumab vials will be stored until study drug accountability has been completed by the BMS 
designee, and destruction or return is authorized. Used vials do not need to be refrigerated.
Note: Subjects must be premedicated as described in Section 4.5.4 prior to elotuzumab infusion.
Administration Instructions
The first dose of elotuzumab will be administered following premedications (described in 
Section 4.5.4) to each subject as an IV infusion, using an automated infusion pump set at an 
initial rate of 0.5 mL per minute (30 mL/hour). If the subject does not have an infusion reaction 
within 30 minutes, escalate the infusion rate by 0.5 mL per minute. If the subject still does not 
have an infusion reaction within 30 minutes, escalate the infusion rate to a maximum of 2 mL
per minute (120 mL/hour). If a subject experiences a Grade ≥2 infusion reaction, the infusion 
must be interrupted. Please refer to Section 4.5.5.1 for detailed information on the management 
of infusion reaction and re-initiation of infusion.
The second dose of elotuzumab must be initiated at an infusion rate of 3 mL per minute if no 
infusion reactions were observed with the first elotuzumab infusion. If the subject does not 
experience an infusion reaction during the first 30 minutes of the second dose of elotuzumab, 
escalate the infusion rate to 4 mL per minute.
The third dose of elotuzumab must be initiated at an infusion rate of 5 mL per minute if no 
infusion reactions were reported with the second elotuzumab infusion.
The fourth and subsequent doses of elotuzumab must be initiated at an infusion rate of 5 mL
per minute if no infusion reactions were reported. 
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Elotuzumab Infusion Rate 
The elotuzumab infusion rate will be increased gradually to a maximum of 5 mL/min as 
presented in Table 1. Table 1 represents an example for an 80 kg subject receiving 10mg/kg 
dose. The total volume varies according to the subject weigh and the elotuzumab administered 
dose.
Table 1, Appendix 3: Elotuzumab Infusion Rate Plan 
Infusion Rate
Duration of infusion
Volume delivered
Volume remaining
Cycle 1 Dose 1
Approximate Total Duration: 2hrs 50min
262 mL*
0.5 mL/min
30 min
15 mL
247 mL
1 mL/min
30 min
30 mL
217 mL
2 mL/min
110 min
217 mL
0 mL
Cycle 1 Dose 2
Approximate Total Duration: 1hrs 13min
262 mL
3 mL/min
30 min
90 mL
172 mL
4 mL/min
43 min
172 mL
0 mL
Cycle 1 Dose 3 and 4
Approximate Total Duration: 53min
262 mL
5 mL/min
53 min
262 mL
0 mL
Cycle 2 +
Approximate Total Duration: 53min
262 mL
5 mL/min
53 min
262 mL
0 mL
* Volume for 80 kg subject. Total volume varies according to the subject weight.
Please note that infusion rate increase to the next higher level only if no infusion reactions encountered.
If a subject experiences a Grade ≥2 infusion reaction, the infusion must be interrupted. 
Please refer to Section 4.5.5.1 for detailed information on the management of infusion reaction 
and re-initiation of infusion. If a subject experiences a Grade ≤3 elotuzumab infusion reaction 
that has resolved to Grade ≤1, subsequent infusion rate of elotuzumab should be escalated in a 
stepwise fashion (0.5 mL every 30 minutes as per Section 4.5.5.1).
1. Administer through a low-protein-binding 0.22 - micrometer or smaller in-line filter (placed 
as proximal to the subject as is practical). Prime the infusion line with study drug before 
starting the infusion.
2. Set the IV pump to deliver the infusion at the rate of 0.5 mL per minute (including the drug 
in the line). The total time of infusion will vary depending upon the maximum tolerated 
mL/min infusion rate as discussed above.
3. Record every time the infusion is started and stopped and the reason why the start and stop 
occurred.
4. Monitor the IV setup and the subject’s IV site frequently during infusion, checking for the 
correct infusion rate and IV site infiltration.
5. Ensure that the full volume of elotuzumab is infused.
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After elotuzumab has been infused from the line, discontinue the infusion, disconnect the 
IV tubing, and dispose of materials appropriately according to the facility’s standard procedure.
Note: Subjects must be premedicated as described in Section 4.5.4 prior to elotuzumab infusion.
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APPENDIX 4
DEFINITIONS OF RESPONSE AND PROGRESSION CRITERIA 
(MODIFIED FROM IMWG)
Response Subcategory
Response Criteriaa
Stringent Complete Response 
(sCR)
CR, as defined below, plus the following:
Normal FLC ratiob and absence of clonal cellsc in bone marrow by 
immunohistochemistry or immunofluorescence.
Complete Response (CR)b
Negative immunofixation of serum and urine and disappearance of any soft 
tissue plasmacytomas, and < 5% plasma cells in bone marrow.
Very Good Partial Response 
(VGPR)
Serum and urine M-protein detectable by immunofixation but not on 
electrophoresis or ≥90% reduction in serum M-protein level plus urine 
M-protein level < 100 mg per 24 hour.
Partial Response (PR)
≥50% reduction of serum M-protein and reduction in 24-hour urinary 
M-protein by ≥90% or to < 200 mg per 24 hour. If serum and urine 
M-protein are unmeasurable, a ≥50% decrease in the difference between 
involved and uninvolved FLC levels is required in place of the M-protein 
criteria. In addition to the above criteria, if present at baseline, ≥50% 
reduction in the size of soft tissue plasmacytomas is also required
Minor (Minimal) Response (MR)
25-49% reduction of serum M-protein and reduction in 24-hour urine 
M-protein by 50-89%, which still exceeds 200 mg per 24 hours. In addition, 
if present at baseline, 25-49% reduction in the size of soft tissue 
plasmacytomas is also required. No increase in the size or number of lytic 
bone lesions (development of compression fracture does not exclude 
response).
Stable Disease (SD)
Not meeting criteria for CR, VGPR, PR, MR, or progression.
Progressive disease
Any of the following: 
•
Increase of 25% from lowest response value in any one or more of 
the following:
1.
Serum M-component (absolute increase must be 
≥0.5 g/dL)d and/or
2.
Urine M-component (absolute increase must be ≥200 mg 
per 24 h) and/or
3.
Only in patients without measurable serum and urine 
M-protein levels: the difference between involved and 
uninvolved FLC levels (absolute increase must be 
> 10 mg/dL)
4.
Bone marrow plasma cell percentage (absolute % must be 
≥10%)
•
Definite development of new bone lesions or soft tissue 
plasmacytomas or definite increase in the size of existing bone 
lesions or soft tissue plasmacytomas
•
Development of hypercalcemia (corrected serum calcium 
> 11.5 mg/100 mL) that can be attributed solely to the plasma cell 
proliferative disorder
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a All response categories require 2 consecutive assessments made at any time before the institution of any new 
therapy; all categories also require no known evidence of progressive or new bone lesions if radiographic studies 
were performed. Radiographic studies are not required to satisfy these response requirements. Bone marrow 
assessments need not be confirmed.
b Note clarification to IMWG criteria for coding CR and VGPR in patients in whom the only measurable disease is 
by serum FLC levels: CR in such patients is defined as a normal FLC ratio of 0.26-1.65 in addition to CR criteria 
listed above. VGPR in such patients is defined as a > 90% decrease in the difference between involved and 
uninvolved FLC levels.
c Presence or absence of clonal cells is based upon the κ/λ ratio. An abnormal κ/λ ratio by immunohistochemistry 
and/or immunofluorescence requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting 
presence of an abnormal clone is κ/λ of > 4:1 or < 1:2.
d For progressive disease, serum M-component increase of ≥1 g/dL is sufficient to define progression if starting 
M-component is ≥5 g/dL
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APPENDIX 5
THE INTERNATIONAL STAGING SYSTEM (ISS) FOR MULTIPLE 
MYELOMA
Stage
Criteria
Median Survival 
(months)
Stage I
Serum β2-microglobulin < 3.5 mg/L
Serum albumin ≥3.5 g/dL
62
Stage II
Not stage I or III
(There are two categories for stage II)
serum β2-microglobulin < 3.5 mg/L but serum 
albumin < 3.5 g/dL OR
β2-microglobulin 3.5 to < 5.5 mg/L 
irrespective of the serum albumin level
44
Stage III
Serum β2-microglobulin ≥5.5 mg/L
29
Greipp PR, San Miguel JF, Brian GM, Durie JJ, Crowley BB, Blade J, Boccadoro J, Child A, Avet-Loiseau H, Kyle 
RA, Laheuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I,
Westin J. International Staging System for Multiple Myeloma. J Clin Oncology 2005 23:3412-3420.
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APPENDIX 6
POMALIDOMIDE PREGNANCY RISK PREVENTION PLAN
Appendix 5 only applies to subjects receiving clinical supply of pomalidomide.
Subjects receiving commercial supply of pomalidomide will follow the Pomalyst ® REMS 
program.
1
PREGNANCY PREVENTION RISK MANAGEMENT PLANS
1.1
Pomalidomide (CC-4047) Pregnancy Prevention Risk Management Plan
1.1.1
Pomalidomide Pregnancy Risk Minimization Plan for Celgene Clinical
Trials 
The following Pregnancy Risk Minimization Plan documents are included in this Appendix: 
1) Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth 
Control Methods (Section 1.1.1.1); 
2) Pomalidomide Education and Counselling Guidance Document (Section 1.1.1.2); 
3) Pomalidomide Information Sheet (Section 1.1.1.1).
1. The Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable 
Birth Control Methods document (Section 1.1.1.1) provides the following information:
•
Potential risks to the fetus associated with pomalidomide exposure
•
Definition of Female of Childbearing Potential (FCBP)
•
Pregnancy testing requirements for patients receiving Pomalidomide who are females 
of childbearing potential
•
Acceptable birth control methods for both female of childbearing potential and male 
patients receiving pomalidomide in the study
•
Requirements for counselling of all study patients receiving pomalidomide about 
pregnancy precautions and the potential risks of fetal exposure to pomalidomide
2. The Pomalidomide Education and Counselling Guidance Document (Section 1.1.1.2) must 
be completed and signed by either a trained counsellor or the Investigator at the participating 
clinical center prior to each dispensing of pomalidomide study treatment.  A copy of this 
document must be maintained in the patient records.
3. The Pomalidomide Information Sheet (Section 1.1.1.1) will be given to each patient 
receiving pomalidomide study therapy. The patient must read this document prior to starting 
pomalidomide study treatment and each time they receive a new supply of study drug.
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1.1.1.1
Pomalidomide Risks of Fetal Exposure, Pregnancy Testing Guidelines 
and Acceptable Birth Control Methods 
Risks Associated with Pregnancy
Pomalidomide was found to be teratogenic in a developmental study in rabbits.  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.
Criteria for females of childbearing potential (FCBP)
This protocol defines a female of childbearing potential as a sexually mature woman who: 1) has 
not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) 
for at least 24 consecutive months (ie, has had menses at any time in the preceding 
24 consecutive months).
Counselling
For a female of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (ie, all females of childbearing potential must be counselled concerning the 
following risks and requirements prior to the start of pomalidomide study therapy): 
•
She understands the potential teratogenic risk to the unborn child
•
She understands the need for effective contraception, without interruption, 28 days before 
starting study treatment, throughout the entire duration of study treatment, dose interruption 
and 28 days after the end of study treatment
•
She should be capable of complying with effective contraceptive measures
•
She is informed and understands the potential consequences of pregnancy and the need to 
notify her study doctor immediately if there is a risk of pregnancy
•
She understands the need to commence the study treatment as soon as study drug is 
dispensed following a negative pregnancy test
•
She understands the need and accepts to undergo pregnancy testing based on the frequency 
outlined in this protocol (Section 1.1.1.1)
•
She acknowledges that she understands the hazards and necessary precautions associated 
with the use of pomalidomide
The investigator must ensure that females of childbearing potential:
•
Comply with the conditions for pregnancy risk minimization, including confirmation that she 
has an adequate level of understanding
•
Acknowledge the aforementioned requirements
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For a female NOT of childbearing potential, pomalidomide is contraindicated unless all of the 
following are met (ie, all females NOT of childbearing potential must be counselled concerning 
the following risks and requirements prior to the start of pomalidomide study therapy): 
•
She acknowledges that she understands the hazards and necessary precautions associated 
with the use of pomalidomide
The effect of pomalidomide on spermatogenesis is not known and has not been studied. 
Therefore, male patients taking pomalidomide must meet the following conditions (ie, all males 
must be counselled concerning the following risks and requirements prior to the start of 
pomalidomide study therapy):
•
Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female 
or a female of childbearing potential
•
Understand the need for the use of a condom even if he has had a vasectomy, if engaged in 
sexual activity with a pregnant female or a female of childbearing potential.  
Contraception
Females of childbearing potential (FCBP) enrolled in this protocol must agree to use two reliable 
forms of contraception simultaneously or to practice complete abstinence from heterosexual 
contact during the following time periods related to this study: 1) for at least 28 days before 
starting study drug; 2) while participating in the study; 3) dose interruptions; and 4) for at least 
28 days after study treatment discontinuation. 
The two methods of reliable contraception must include one highly effective method and one 
additional effective (barrier) method. FCBP must be referred to a qualified provider of 
contraceptive methods if needed. The following are examples of highly effective and additional 
effective methods of contraception:  
•
Highly effective methods:
Intrauterine device (IUD)
Hormonal (birth control pills, injections, implants)
Tubal ligation
Partner’s vasectomy
•
Additional effective methods:
Male condom
Diaphragm
Cervical Cap
Because of the increased risk of venous thromboembolism in patients with multiple myeloma 
taking pomalidomide and dexamethasone, combined oral contraceptive pills are not 
recommended. If a patient is currently using combined oral contraception the patient should 
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switch to another one of the effective methods listed above. The risk of venous 
thromboembolism continues for 4−6 weeks after discontinuing combined oral contraception. The 
efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone.
Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk 
of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics 
should be considered particularly in patients with neutropenia. 
Pregnancy testing
Medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/mL must be 
performed for females of childbearing potential, including females of childbearing potential who 
commit to complete abstinence, as outlined below.
Before starting study drug
Female Patients:
FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to 
starting study drug.  The first pregnancy test must be performed within 10-14 days prior to the 
start of study drug and the second pregnancy test must be performed within 24 hours prior to the 
start of study drug.  The patient may not receive study drug until the study doctor has verified 
that the results of these pregnancy tests are negative.
Male Patients:
Must practice complete abstinence or  agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential while participating in the study, during 
dose interruptions and for at least 28 days following study drug discontinuation, even if he has 
undergone a successful vasectomy.  
During study participation and for 28 days following study drug discontinuation 
Female Patients:
FCBP with regular or no menstrual cycles must agree to have pregnancy tests weekly for the 
first 28 days of study participation and then every 28 days while on study, at study 
discontinuation, and at day 28 following study drug discontinuation. If menstrual cycles are 
irregular, the pregnancy testing must occur weekly for the first 28 days and then every 
14 days while on study, at study discontinuation, and at days 14 and 28 following study drug 
discontinuation.  
At each visit, the Investigator must confirm with the FCBP that she is continuing to use two 
reliable methods of birth control.  
Counselling about pregnancy precautions and the potential risks of fetal exposure must be 
conducted at a minimum of every 28 days. 
If pregnancy or a positive pregnancy test does occur in a study patient, study drug must be 
immediately discontinued.
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Pregnancy testing and counselling must be performed if a patient misses her period or if her 
pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be
discontinued during this evaluation.
Females must agree to abstain from breastfeeding during study participation and for at least 
28 days after study drug discontinuation.
Male Patients:
Counseling about the requirement for complete abstinence or condom use during sexual 
contact with a pregnant female or a female of childbearing potential and the potential risks of 
fetal exposure to pomalidomide must be conducted at a minimum of every 28 days.  
If pregnancy or a positive pregnancy test does occur in the partner of a male study patient 
during study participation, the investigator must be notified immediately.
Additional precautions
Patients should be instructed never to give this medicinal product to another person and to 
return any unused capsules to the study doctor at the end of treatment.
Patients should not donate blood during therapy and for at least 28 days following 
discontinuation of study drug.
Male patients should not donate semen or sperm during therapy or for at least 28 days 
following discontinuation of study drug.
Only enough study drug for one cycle of therapy may be dispensed with each cycle of 
therapy. 
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1.1.1.2
Pomalidomide Education and Counselling Guidance Document 
To be completed prior to each dispensing of study drug.
Protocol Number: ____________________________________________
Patient Name (Print): __________________ DOB: _____/_____/_____ (mm/dd/yyyy)
(Check the appropriate box to indicate risk category)
Female:
If female, check one:
FCBP (Female of childbearing potential): sexually mature female who: 1) has not 
undergone a hysterectomy (the surgical removal of the uterus) or bilateral 
oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out 
childbearing potential) for at least 24 consecutive months (ie, has had menses at 
any time during the preceding 24 consecutive months)
NOT FCBP
Male:
Do Not Dispense study drug if:
The patient is pregnant.
No pregnancy tests were conducted for a FCBP.
The patient states she did not use TWO reliable methods of birth control (unless practicing 
complete abstinence of heterosexual contact) [at least 28 days prior to therapy, during 
therapy and during dose interruption].
FCBP:
1. I verified that the required pregnancy tests performed are negative.
2. I counselled FCBP regarding the following:
−
Potential risk of fetal exposure to pomalidomide:  If pomalidomide is taken during 
pregnancy, it may cause birth defects or death to any unborn baby. Females are advised 
to avoid pregnancy while taking pomalidomide. The teratogenic potential of 
pomalidomide in humans cannot be ruled out. FCBP must agree not to become pregnant 
while taking pomalidomide. 
−
Using TWO reliable methods of birth control at the same time or complete abstinence 
from heterosexual contact [at least 28 days prior to therapy, during therapy , during dose 
interruption and 28 days after discontinuation of study drug].
−
That even if she has amenorrhea she must comply with advice on contraception  
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−
Use of one highly effective method and one additional method of birth control AT THE 
SAME TIME. The following are examples of highly effective and additional effective 
methods of contraception:  
♦Highly effective methods:
•
Intrauterine device (IUD)
•
Hormonal (birth control pills, injections, implants)
•
Tubal ligation
•
Partner’s vasectomy
♦Additional effective methods:
•
Male condom
•
Diaphragm
•
Cervical Cap
−
Pregnancy tests before and during treatment, even if the patient agrees not to have 
reproductive heterosexual contact.  Two pregnancy tests will be performed prior to 
receiving study drug, one within 10-14 days and the second within 24 hours of the start of 
study drug.
−
Frequency of pregnancy tests to be done:
−
Every week during the first 28 days of this study and a pregnancy test every 28 days
during the patient’s participation in this study if menstrual cycles are regular or every 14 
days if cycles are irregular.
−
If the patient missed a period or has unusual menstrual bleeding.  
−
When the patient is discontinued from the study and at day 28 after study drug 
discontinuation if menstrual cycles are regular. If menstrual cycles are irregular, 
pregnancy tests will be done at discontinuation from the study and at days 14 and 28 after 
study drug discontinuation.
−
Stop taking study drug immediately in the event of becoming pregnant and to call their 
study doctor as soon as possible. 
−
NEVER share study drug with anyone else.
−
Do not donate blood while taking study drug and for 28 days after stopping study drug.
−
Do not breastfeed a baby while participating in this study and for at least 28 days after 
study drug discontinuation.
−
Do not break, chew, or open study drug capsules.
−
Return unused study drug to the study doctor.
3. Provide Pomalidomide Information Sheet to the patient.
FEMALE NOT OF CHILDBEARING POTENTIAL (NATURAL MENOPAUSE FOR AT 
LEAST 24 CONSECUTIVE MONTHS, A HYSTERECTOMY, OR BILATERAL 
OOPHORECTOMY):
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I counselled the female NOT of childbearing potential regarding the following:
Potential risk of fetal exposure to pomalidomide (Refer to item #2 in FCBP)
NEVER share study drug with anyone else.
Do not donate blood while taking study drug and for 28 days after stopping study drug.
Do not break, chew, or open study drug capsules
Return unused study drug capsules to the study doctor.
Provide Pomalidomide Information Sheet to the patient.
MALE:
I counselled the Male patient regarding the following:
Potential study drug fetal exposure to pomalidomide (Refer to item #2 in FCBP).
To engage in complete abstinence or use a condom when engaging in sexual contact 
(including those who have had a vasectomy) with a pregnant female or a female of 
childbearing potential, while taking study drug, during dose interruptions and for 28 days 
after stopping study drug.
Males should notify their study doctor when their female partner becomes pregnant and 
female partners of males taking study drug should be advised to call their healthcare provider 
immediately if they get pregnant
NEVER share study drug with anyone else.
Do not donate blood while taking study drug and for 28 days after stopping study drug.
Do not donate semen or sperm while taking study drug and for 28 days after stopping study 
drug.
Do not break, chew, or open study drug capsules.
Return unused study drug capsules to the study doctor.
Provide Pomalidomide Information Sheet to the patient.
Investigator/Counsellor Name (Print): ____________________
(circle applicable)
Investigator/Counsellor Signature: _______________________ 
Date: _____/_____/_____
(circle applicable)
**Maintain a copy of the Education and Counselling Guidance Document in the patient records.**
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1.1.1.3
Pomalidomide Information Sheet 
FOR PATIENTS ENROLLED IN CLINICAL RESEARCH STUDIES
Please read this Pomalidomide Information Sheet before you start taking study drug and each 
time you get a new supply. This Pomalidomide Information Sheet does not take the place of an 
informed consent to participate in clinical research or talking to your study doctor or healthcare 
provider about your medical condition or your treatment.  
What is the most important information I should know about pomalidomide?
Pomalidomide may cause birth defects (deformed babies) or death of an unborn baby. 
Pomalidomide is similar to the medicine thalidomide. It is known that thalidomide causes 
life-threatening birth defects. Pomalidomide has not been tested in pregnant women but may 
also cause birth defects. Pomalidomide was found to cause birth defects when tested in 
pregnant rabbits. If you are a female who is able to become pregnant:
Do not take study drug if you are pregnant or plan to become pregnant
You must either not have any sexual relations with a man or use two reliable, separate 
forms of effective birth control at the same time: 
for 28 days before starting study drug
while taking study drug 
during dose interruptions of study drug 
for 28 days after stopping study drug 
You must have pregnancy testing done at the following times:
within 10 – 14 days and again 24 hours prior to the first dose of study drug 
weekly for the first 28 days
every 28 days after the first month or every 14 days if you have irregular menstrual 
periods
if you miss your period or have unusual menstrual bleeding
28 days after the last dose of study drug (14 and 28 days after the last dose if 
menstrual periods are irregular)
Stop taking study drug if you become pregnant during treatment
If you suspect you are pregnant at any time during the study, you must stop study 
drug immediately and immediately inform your study doctor. The study doctor will 
report all cases of pregnancy to Celgene Corporation. 
Do not breastfeed while taking study drug
The study doctor will be able to advise you where to get additional advice on 
contraception.
If you are a female not of childbearing potential:
In order to ensure that an unborn baby is not exposed to pomalidomide, your study doctor will 
confirm that you are not able to become pregnant.
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If you are a male:
The effect of pomalidomide on sperm development is not known and has not been studied. The 
risk to the fetus in females of child bearing potential whose male partner is receiving 
pomalidomide is unknown at this time.  
Male patients (including those who have had a vasectomy) must either not have any sexual 
relations with a pregnant female or a female who can become pregnant, or must use a 
condom during sexual contact with a pregnant female or a female that can become pregnant:
o
While you are taking study drug
o
During dose interruptions of study drug
o
For 28 days after you stop taking study drug  
Male patients should not donate sperm or semen while taking study drug and for 28 days after 
stopping study drug. 
If you suspect that your partner is pregnant any time during the study, you must 
immediately inform your study doctor. The study doctor will report all cases of 
pregnancy to Celgene Corporation. Your partner should call their healthcare provider 
immediately if they get pregnant.
Restrictions in sharing study drug and donating blood:
Do not share study drug with other people. It must be kept out of the reach of 
children and should never be given to any other person.
Do not donate blood while you take study drug and for 28 days after stopping study 
drug. 
Do not break, chew, or open study drug capsules.
You will be supplied with no more than one cycle of study drug 
Return unused study drug capsules to your study doctor.
Additional information is provided in the informed consent form and you can ask your study 
doctor for more information.
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